Recent outputs of the Oklo (Gabon) natural analogue study to nuclear waste disposal

International Nuclear Information System (INIS)

Michaud, V.; Trotignon, L.; Louvat, D.

2000-01-01

In the past twenty five years, the natural nuclear reactors of Oklo have been the subject of numerous detailed studies. First investigated for the physical and neutron aspects of the nuclear reaction, they were then reconsidered because they provide a unique opportunity in the world to study the containment of actinides and fission products in a geological formation over a broad timescale (two billion years). Although the sites investigated do not represent a complete analogue of a repository system, many of the processes studied (mass transfer to the surface, transport, migration / retention), the spatial extent of these processes, and the timescales involved, are compatible with processes liable to occur during the lifespan of a repository for the deep geological disposal of spent nuclear fuel. A fresh program was therefore initiated as a European Commission project in 1990, entitled''Oklo as a natural analog for transfer processes in a radioactive waste repository'- phase 7, and then extended by a phase 2 entitled Oklo, Natural Analogue - Behavior of Nuclear Reaction Products in a Natural Environment''. Researches conducted in phase I served to determine the physical conditions of the operation of the natural reactor, reconstruct the geological history of the reactor environment, and decode the behavior of actinides as well as fission products in the surrounding geological formations. Phase N, which ended in June 1999, had three main objectives: i) to assess radionuclide migration and retention processes from the reactor zones to the geological environment, ii) to define the confinement properties and long-term behavior of geological materials; iii) to test models of processes related to radionuclide migration and retention, and eventually to provide suitable data and scenarios for performance assessment of nuclear waste disposal. This paper proposes a synthesis of the main outputs of the Oklo project to the performance assessment of nuclear waste disposal, the

Titan's organic aerosols: Molecular composition and structure of laboratory analogues inferred from pyrolysis gas chromatography mass spectrometry analysis

Science.gov (United States)

Morisson, Marietta; Szopa, Cyril; Carrasco, Nathalie; Buch, Arnaud; Gautier, Thomas

2016-10-01

Analogues of Titan's aerosols are of primary interest in the understanding of Titan's atmospheric chemistry and climate, and in the development of in situ instrumentation for future space missions. Numerous studies have been carried out to characterize laboratory analogues of Titan aerosols (tholins), but their molecular composition and structure are still poorly known. If pyrolysis gas chromatography mass spectrometry (pyr-GCMS) has been used for years to give clues about their chemical composition, highly disparate results were obtained with this technique. They can be attributed to the variety of analytical conditions used for pyr-GCMS analyses, and/or to differences in the nature of the analogues analyzed, that were produced with different laboratory set-ups under various operating conditions. In order to have a better description of Titan's tholin's molecular composition by pyr-GCMS, we carried out a systematic study with two major objectives: (i) exploring the pyr-GCMS analytical parameters to find the optimal ones for the detection of a wide range of chemical products allowing a characterization of the tholins composition as comprehensive as possible, and (ii) highlighting the role of the CH4 ratio in the gaseous reactive medium on the tholin's molecular structure. We used a radio-frequency plasma discharge to synthetize tholins with different concentrations of CH4 diluted in N2. The samples were pyrolyzed at temperatures covering the 200-700°C range. The extracted gases were then analyzed by GCMS for their molecular identification. The optimal pyrolysis temperature for characterizing the molecular composition of our tholins by GCMS analysis is found to be 600°C. This temperature choice results from the best compromise between the number of compounds released, the quality of the signal and the appearance of pyrolysis artifacts. About a hundred molecules are identified as pyrolysates. A common major chromatographic pattern appears clearly for all the

CO2 Capture with Enzyme Synthetic Analogue

Energy Technology Data Exchange (ETDEWEB)

Cordatos, Harry

2010-11-08

Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

Quark-level analogue of nuclear fusion with doubly heavy baryons.

Science.gov (United States)

Karliner, Marek; Rosner, Jonathan L

2017-11-01

The essence of nuclear fusion is that energy can be released by the rearrangement of nucleons between the initial- and final-state nuclei. The recent discovery of the first doubly charmed baryon , which contains two charm quarks (c) and one up quark (u) and has a mass of about 3,621 megaelectronvolts (MeV) (the mass of the proton is 938 MeV) also revealed a large binding energy of about 130 MeV between the two charm quarks. Here we report that this strong binding enables a quark-rearrangement, exothermic reaction in which two heavy baryons (Λ c ) undergo fusion to produce the doubly charmed baryon and a neutron n (), resulting in an energy release of 12 MeV. This reaction is a quark-level analogue of the deuterium-tritium nuclear fusion reaction (DT → 4 He n). The much larger binding energy (approximately 280 MeV) between two bottom quarks (b) causes the analogous reaction with bottom quarks () to have a much larger energy release of about 138 MeV. We suggest some experimental setups in which the highly exothermic nature of the fusion of two heavy-quark baryons might manifest itself. At present, however, the very short lifetimes of the heavy bottom and charm quarks preclude any practical applications of such reactions.

Molecular methods in nuclear medicine therapy

International Nuclear Information System (INIS)

Lee, Kyung Han

2001-01-01

Nuclear medicine has traditionally contributed to molecular oncology by allowing noninvasive monitoring of tumor metabolism, growth and genetic changes, thereby providing a basis for appropriate biology-based treatment planning. However, NM techniques are now being applied as an active therapeutic tool in novel molecular approaches for cancer treatment. Such areas include research on cancer therapy with radiolabeled ligands or oligonucleotides, and utilization of synergism between NM radiotherapy and gene transfer techniques. Here we will focus on novel aspects of nuclear medicine therapy

A fermionic molecular dynamics technique to model nuclear matter

International Nuclear Information System (INIS)

Vantournhout, K.; Jachowicz, N.; Ryckebusch, J.

2009-01-01

Full text: At sub-nuclear densities of about 10 14 g/cm 3 , nuclear matter arranges itself in a variety of complex shapes. This can be the case in the crust of neutron stars and in core-collapse supernovae. These slab like and rod like structures, designated as nuclear pasta, have been modelled with classical molecular dynamics techniques. We present a technique, based on fermionic molecular dynamics, to model nuclear matter at sub-nuclear densities in a semi classical framework. The dynamical evolution of an antisymmetric ground state is described making the assumption of periodic boundary conditions. Adding the concepts of antisymmetry, spin and probability distributions to classical molecular dynamics, brings the dynamical description of nuclear matter to a quantum mechanical level. Applications of this model vary from investigation of macroscopic observables and the equation of state to the study of fundamental interactions on the microscopic structure of the matter. (author)

Upgrading of analogue cameras using modern PC based computer

International Nuclear Information System (INIS)

Pardom, M.F.; Matos, L.

2002-01-01

Aim: The use of computers along with analogue cameras enables them to perform tasks involving time-activity parameters. The INFORMENU system converts a modern PC computer into a dedicated nuclear medicine computer system with a total cost affordable to emerging economic countries, and easily adaptable to all existing cameras. Materials and Methods: In collaboration with nuclear medicine physicians, an application including hardware and software was developed by a private firm. The system runs smoothly on Windows 98 and its operation is very easy. The main features are comparable to the brand commercial computer systems; such as image resolution until 1024 x 1024, low count loss at high count rate, uniformity correction, integrated graphical and text reporting, and user defined clinical protocols. Results: The system is used in more than 20 private and public institutions. The count loss is less than 1% in all the routine work, improvement of uniformity correction of 3-5 times, improved utility of the analogue cameras. Conclusion: The INFORMENU system improves the utility of analogue cameras permitting the inclusion of dynamic clinical protocols and quantifications, helping the development of the nuclear medicine practice. The operation and maintenance costs were lowered. The end users improve their knowledge of modern nuclear medicine

Comparative study of the interactions between bisphenol-A and its endocrine disrupting analogues with bovine serum albumin using multi-spectroscopic and molecular docking studies.

Science.gov (United States)

Ikhlas, Shoeb; Usman, Afia; Ahmad, Masood

2018-04-24

Interaction studies of bisphenol analogues; biphenol-A (BPA), bisphenol-B (BPB), and bisphenol-F (BPF) with bovine serum albumin (BSA) were performed using multi-spectroscopic and molecular docking studies at the protein level. The mechanism of binding of bisphenols with BSA was dynamic in nature. SDS refolding experiments demonstrated no stabilization of BSA structure denatured by BPB, however, BSA denatured by BPA and BPF was found to get stabilized. Also, CD spectra and molecular docking studies revealed that BPB bound more strongly and induced more conformational changes in BSA in comparison to BPA. Hence, this study throws light on the replacement of BPA by its analogues and whether the replacement is associated with a possible risk, raising a doubt that perhaps BPB is not a good substitute of BPA.

Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

Directory of Open Access Journals (Sweden)

Anastasios Papaioannou

2017-09-01

Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

Molecular Imaging and nuclear medicine: expectations and requirements

International Nuclear Information System (INIS)

Rollo, F.D.

2003-01-01

Molecular Imaging with Nuclear Medicine offers earlier, more accurate and more specific diagnosis, as well as targeted molecular therapy, providing significant improvements in clinical outcomes. (orig.)

[Parathyroid hormone and its analogues - molecular mechanisms of action and efficacy of osteoporosis therapy].

Science.gov (United States)

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.

Parathyroid hormone and its analogues--molecular mechanisms of action and efficacy in osteoporosis therapy.

Science.gov (United States)

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.

Natural Analogue Synthesis Report

Energy Technology Data Exchange (ETDEWEB)

A. M. Simmons

2002-05-01

The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport

NATURAL ANALOGUE SYNTHESIS REPORT

International Nuclear Information System (INIS)

Simmons, A.M.

2004-01-01

The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

Molecular nuclear imaging for targeting and trafficking

International Nuclear Information System (INIS)

Bom, Hee Seung; Min, Jung Jun; Jeong, Hwan-Jeong

2006-01-01

Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99m Tc as a radionuclide. We developed 99m Tc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99m Tc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67 Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99m Tc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99m Tc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

Breast cancer imaging using radiolabelled somatostatin analogues

International Nuclear Information System (INIS)

Dalm, Simone U.; Melis, Marleen; Emmering, Jasper; Kwekkeboom, Dik J.; Jong, Marion de

2016-01-01

Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36–100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22–100%. Furthermore, false negatives and

Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

Energy Technology Data Exchange (ETDEWEB)

Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu (Univ. of Tokyo (Japan))

1990-01-09

Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

Reasoning by analogy: rational foundation of natural analogue studies

International Nuclear Information System (INIS)

Petit, J.-C.

1992-01-01

Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory investigations. Most nuclear countries have hence developed an approach relying on the following research directions: 1. laboratory experiments; 2. in situ testing; 3. modeling; and 4. natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence (if not truly validated). Although the field of natural analogues has grown very rapidly in recent years, receiving support from varied specialists and institutions involved in radioactive waste disposal, there is not yet a full consensus on their actual usefulness. More problematic is the criticism sometimes made that analogical reasoning is not ''true science'' and that information retrieved from the study of natural analogues will always remain questionable. The present paper gives some clues about the exact status of reasoning by analogy, compared to more ''scientific'' ways of deriving information from investigated systems. It is not a thorough discussion of this very complex, and by far too philosophical issue but we hope, at least, to present to readers of papers devoted to natural analogue studies arguments showing that this approach has some sound foundation. (author)

Electron-nuclear dynamics of molecular systems

International Nuclear Information System (INIS)

Diz, A.; Oehrn, Y.

1994-01-01

The content of an ab initio time-dependent theory of quantum molecular dynamics of electrons and atomic nuclei is presented. Employing the time-dependent variational principle and a family of approximate state vectors yields a set of dynamical equations approximating the time-dependent Schroedinger equation. These equations govern the time evolution of the relevant state vector parameters as molecular orbital coefficients, nuclear positions, and momenta. This approach does not impose the Born-Oppenheimer approximation, does not use potential energy surfaces, and takes into account electron-nuclear coupling. Basic conservation laws are fully obeyed. The simplest model of the theory employs a single determinantal state for the electrons and classical nuclei and is implemented in the computer code ENDyne. Results from this ab-initio theory are reported for ion-atom and ion-molecule collisions

Natural analogues, paradigm for manmade repositories for radioactive wastes

International Nuclear Information System (INIS)

Pavelescu, M.; Pavelescu, A.

2004-01-01

Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

Electron-nuclear corellations for photoinduced dynamics in molecular dimers

Science.gov (United States)

Kilin, Dmitri S.; Pereversev, Yuryi V.; Prezhdo, Oleg V.

2003-03-01

Ultrafast photoinduced dynamics of electronic excitation in molecular dimers is drastically affected by dynamic reorganization of of inter- and intra- molecular nuclear configuration modelled by quantized nuclear degree of freedom [1]. The dynamics of the electronic population and nuclear coherence is analyzed with help of both numerical solution of the chain of coupled differential equations for mean coordinate, population inversion, electronic-vibrational correlation etc.[2] and by propagating the Gaussian wavepackets in relevant adiabatic potentials. Intriguing results were obtained in the approximation of small energy difference and small change of nuclear equilibrium configuration for excited electronic states. In the limiting case of resonance between electronic states energy difference and frequency of the nuclear mode these results have been justified by comparison to exactly solvable Jaynes-Cummings model. It has been found that the photoinduced processes in dimer are arranged according to their time scales:(i) fast scale of nuclear motion,(ii) intermediate scale of dynamical redistribution of electronic population between excited states as well as growth and dynamics of electronic -nuclear correlation,(iii) slow scale of electronic population approaching to the quasiequilibrium distribution, decay of electronic-nuclear correlation, and diminishing the amplitude of mean coordinate oscillations, accompanied by essential growth of the nuclear coordinate dispersion associated with the overall nuclear wavepacket width. Demonstrated quantum-relaxational features of photoinduced vibronic dinamical processess in molecular dimers are obtained by simple method, applicable to large biological systems with many degrees of freedom. [1] J. A. Cina, D. S. Kilin, T. S. Humble, J. Chem. Phys. (2003) in press. [2] O. V. Prezhdo, J. Chem. Phys. 117, 2995 (2002).

The research progress of nuclear medicine on cardiovascular molecular imaging

International Nuclear Information System (INIS)

Yin Xiaohua; Zhang Yongxue

2007-01-01

Cardiovascular molecular imaging is a rapidly evolving discipline and its clinical application is promising. Nuclear medicine is playing a leading role in this field with its special superiority of noninvasive, quantifiability, high sensitivity and specificity. It provides broad opportunities for exploring the pathophysiologic process of cardiovascular diseases and monitoring its gene therapy in the molecular level. In this review, we mainly discuss some basic knowledge on cardiovascular molecular imaging, and then focus on the applied research prospect of nuclear medicine radionuclide imaging. (authors)

Isolation and identification of a sibutramine analogue adulterated in slimming dietary supplements.

Science.gov (United States)

Kim, Ji Won; Kweon, Soon Jae; Park, Seon Kyung; Kim, Jung Yeon; Lee, Ji Hyun; Han, Kyoung Moon; Cho, Sooyeul; Kim, Jinho; Han, Soon Young; Kim, Hyoung Ja; Kim, Woo Seong

2013-01-01

A suspected sibutramine analogue was detected in a slimming functional food by an ultra performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (UPLC-ESI-TOF/MS) method. The ultraviolet (UV) spectrum of this suspected compound showed close similarity to that of sibutramine. The sample was extracted with 70% MeOH and isolated by semi-preparative column chromatography. The structure of this compound was identified by spectroscopic analyses (nuclear magnetic resonance [NMR] technique, mass and tandem mass etc.). The structure of the unknown compound was demonstrated to be [(±)-dimethyl-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N,N,3-trimethylbutan-1-amine (molecular formula C17H25NCl2) and named as chloro-sibutramine. Compared with sibutramine, it has one more chlorine atom than the 3-cholorophenyl group so was switched to 3,4-dichlorophenyl. Until now, chloro-sibutramine was isolated for the first time from the undeclared ingredient included in dietary supplements. Although the safety of chloro-sibutramine is unknown, there is a potential health risk to consumers because of a similar skeleton to sibutramine. For public health, this sibutramine analogue has been included in the inspection list of illegal adulterants in Korea.

A silyl andrographolide analogue suppresses Wnt/β-catenin signaling pathway in colon cancer.

Science.gov (United States)

Reabroi, Somrudee; Chairoungdua, Arthit; Saeeng, Rungnapha; Kasemsuk, Teerapich; Saengsawang, Witchuda; Zhu, Weiming; Piyachaturawat, Pawinee

2018-05-01

Hyperactivation of Wnt/β-catenin signaling implicated in oncogenesis of colorectal cancer (CRC) is a potential molecular target for chemotherapy. An andrographolide analogue, 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) has previously been reported to be potently cytotoxic toward cancer cells by unknown molecular mechanisms. The present study explored the anti-cancer activity of analogue 3A.1 on Wnt/β-catenin signaling in colon cancer cells (HT29 cells) which were more sensitive to the others (HCT116 and SW480 cells). Analogue 3A.1 inhibited viability of HT29 cells with IC 50 value of 11.1 ± 1.4 μM at 24 h, which was more potent than that of the parent andrographolide. Analogue 3A.1 also suppressed the proliferation of HT29 cells and induced cell apoptosis in a dose-dependent manner. Its apoptotic activity was accompanied with increased expressions of proteins related to DNA damages; PARP-1 and γ-H2AX. In addition, analogue 3A.1 significantly inhibited T-cell factor and lymphoid enhancer factor (TCF/LEF) promoter activity of Wnt/β-catenin signaling. Accordingly, the expressions of Wnt target genes and β-catenin protein were suppressed. Moreover, analogue 3A.1 increased the activity of GSK-3β kinase, which is a negative regulator responsible for degradation of intracellular β-catenin. This mode of action was further supported by the absence of the effects after treatment with a GSK-3β inhibitor, and over-expression of a mutant β-catenin (S33Y). Our findings reveal, for the first time, an insight into the molecular mechanism of the anti-cancer activity of analogue 3A.1 through the inhibition of Wnt/β-catenin/GSK-3β pathway and provide a therapeutic potential of the andrographolide analogue 3A.1 in CRC treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Analogue Gravity

Directory of Open Access Journals (Sweden)

Carlos Barceló

2011-05-01

Full Text Available Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

PET-based molecular nuclear neuro-imaging

International Nuclear Information System (INIS)

Kim, Jong Ho

2004-01-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

PET-based molecular nuclear neuro-imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

2004-04-01

Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

Developing a programme on molecular nuclear medicine. Proceedings of a technical meeting

International Nuclear Information System (INIS)

2007-07-01

During the last decades, new methodologies have emerged in the molecular nuclear medicine field developed to contribute to the detection, diagnosis, staging and treatment follow-up of human diseases. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are two examples of this methodology that enabled the study of molecular alterations of cell metabolism in the living subject with non-invasive approaches. 18-fluorine fluorodeoxyglucose positron emission tomography (FDG-PET) is used for many disease diagnoses, differential diagnosis and treatment follow-up. Like FDG, new molecules are also being identified and are promising candidates to be used. Molecular imaging studies the expression of genes involved in the evolution of different diseases. This data has been shown to be a reliable prognostic marker, for accurate diagnosis or for predicting response to treatment in certain cases. The use of molecular imaging in the evaluation of exogenous gene therapy and the study of endogenous gene expression in genetic, neurological, cardiovascular and neoplastic diseases will be of significant importance worldwide in the near future. The use of nuclear medicine and molecular imaging for the study of a disease assures the determination of integral parameters for prognosis and diagnosis. The improvement of the therapeutic decisions involved with the stage and prognosis of a disease will certainly add to the clinical studies that are designed for patient care, treatment and survival improvement. Many efforts have been made and will continue in the future to demonstrate the potential of the association of molecular nuclear technology and nuclear medicine imaging, since it has been shown to be useful and applicable to many important diseases. In addition, molecular biology techniques, such as polymerase chain reaction (PCR) and differential gene expression have added important findings to the study of disease pathogenesis. These techniques have

Status of natural analogue studies

International Nuclear Information System (INIS)

Sekine, Keiichi

1994-03-01

This report is based on the materials for the meeting at the Nuclear Safety Commission of Japan held on September 1993. Details are as follows: Alteration of glass as the study of alteration of natural minerals; alteration of uranium minerals, migration of uranium and thorium series radionuclides, alteration of chlorite, fixation of uranium alteration of minerals and migration of uranium as the study of alligator rivers analogue project held at Koongarra uranium deposit, Australia. (author)

Molecularly imprinted solid-phase extraction for selective extraction of bisphenol analogues in beverages and canned food.

Science.gov (United States)

Yang, Yunjia; Yu, Jianlong; Yin, Jie; Shao, Bing; Zhang, Jing

2014-11-19

This study aimed to develop a selective analytical method for the simultaneous determination of seven bisphenol analogues in beverage and canned food samples by using a new molecularly imprinted polymer (MIP) as a sorbent for solid-phase extraction (SPE). Liquid chromatography coupled to triple-quadruple tandem mass spectrometry (LC-MS/MS) was used to identify and quantify the target analytes. The MIP-SPE method exhibited a higher level of selectivity and purification than the traditional SPE method. The developed procedures were further validated in terms of accuracy, precision, and sensitivity. The obtained recoveries varied from 50% to 103% at three fortification levels and yielded a relative standard deviation (RSD, %) of less than 15% for all of the analytes. The limits of quantification (LOQ) for the seven analytes varied from 0.002 to 0.15 ng/mL for beverage samples and from 0.03 to 1.5 ng/g for canned food samples. This method was used to analyze real samples that were collected from a supermarket in Beijing. Overall, the results revealed that bisphenol A and bisphenol F were the most frequently detected bisphenols in the beverage and canned food samples and that their concentrations were closely associated with the type of packaging material. This study provides an alternative method of traditional SPE extraction for screening bisphenol analogues in food matrices.

Using natural analogue studies in the secondary science curriculum

International Nuclear Information System (INIS)

Ebert, E.K.

1995-01-01

This paper discusses an atomic theory unit of a high school chemistry course taught in Nevada. The unit is based on the application of natural analogues to nuclear waste issues. The paper focuses on the students' reactions to the subject material

On the physical interpretation of the nuclear molecular orbital energy.

Science.gov (United States)

Charry, Jorge; Pedraza-González, Laura; Reyes, Andrés

2017-06-07

Recently, several groups have extended and implemented molecular orbital (MO) schemes to simultaneously obtain wave functions for electrons and selected nuclei. Many of these schemes employ an extended Hartree-Fock approach as a first step to find approximate electron-nuclear wave functions and energies. Numerous studies conducted with these extended MO methodologies have explored various effects of quantum nuclei on physical and chemical properties. However, to the best of our knowledge no physical interpretation has been assigned to the nuclear molecular orbital energy (NMOE) resulting after solving extended Hartree-Fock equations. This study confirms that the NMOE is directly related to the molecular electrostatic potential at the position of the nucleus.

Alligator Rivers analogue project

International Nuclear Information System (INIS)

Duerden, P.

1990-01-01

Australian Nuclear Science and Technology Organization has extensively evaluated uranium ore bodies in the Alligator Rivers Uranium Province in Australia as analogues of radioactive waste repositories. The work was extended for a three-year program as an international project based on the Koongarra uranium deposit and sponsored by the OECD Nuclear Energy Agency. The technical program comprises six major sub-projects involving modelling and experimental work: modelling of radionuclide migration; hydrogeology of the Koongarra uranium deposit; uranium/thorium series disequilibria studies; groundwater and colloid studies; fission product studies; transuranic nuclide studies; an outline of the technical programs and a summary of progress in the technical sub-projects is given. This is followed by a series of technical reports which briefly describe current research tasks, and which have been separately indexed

Design of ultra-stable insulin analogues for the developing world

Directory of Open Access Journals (Sweden)

Michael A Weiss

2013-01-01

Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

Lasers in atomic, molecular and nuclear physics

International Nuclear Information System (INIS)

Letokhov, V.S.

1986-01-01

This book presents papers on laser applications in atomic, molecular and nuclear physics. Specifically discussed are: laser isotope separation; laser spectroscopy of chlorophyll; laser spectroscopy of molecules and cell membranes; laser detection of atom-molecule collisions and lasers in astrophysics

High-precision analogue peak detector for X-ray imaging applications

OpenAIRE

Dlugosz, Rafal Tomasz; Iniewski, Kris

2007-01-01

A new analogue high-precision peak detector is presented. Owing to its very low power consumption the circuit is particularly well suited for photon energy detection in multichannel receiver integrated circuits used in nuclear medicine.

Analogue Gravity

Directory of Open Access Journals (Sweden)

Barceló Carlos

2005-12-01

Full Text Available Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

Nuclear medicine imaging instrumentations for molecular imaging

International Nuclear Information System (INIS)

Chung, Yong Hyun; Song, Tae Yong; Choi, Yong

2004-01-01

Small animal models are extensively utilized in the study of biomedical sciences. Current animal experiments and analysis are largely restricted to in vitro measurements and need to sacrifice animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural evolution of the process under study. Imaging techniques can provide repeatedly in vivo anatomic and molecular information noninvasively. Small animal imaging systems have been developed to assess biological process in experimental animals and increasingly employed in the field of molecular imaging studies. This review outlines the current developments in nuclear medicine imaging instrumentations including fused multi-modality imaging systems for small animal imaging

Natural Analogues - One Way to Help Build Public Confidence in the Predicted Performance of a Mined Geologic Repository for Nuclear Waste

Energy Technology Data Exchange (ETDEWEB)

Stuckless, J. S.

2002-02-26

The general public needs to have a way to judge the predicted long-term performance of the potential high-level nuclear waste repository at Yucca Mountain. The applicability and reliability of mathematical models used to make this prediction are neither easily understood nor accepted by the public. Natural analogues can provide the average person with a tool to assess the predicted performance and other scientific conclusions. For example, hydrologists with the Yucca Mountain Project have predicted that most of the water moving through the unsaturated zone at Yucca Mountain, Nevada will move through the host rock and around tunnels. Thus, seepage into tunnels is predicted to be a small percentage of available infiltration. This hypothesis can be tested experimentally and with some quantitative analogues. It can also be tested qualitatively using a variety of analogues such as (1) well-preserved Paleolithic to Neolithic paintings in caves and rock shelters, (2) biological remains preserved in caves and rock shelters, and (3) artifacts and paintings preserved in man-made underground openings. These examples can be found in materials that are generally available to the non-scientific public and can demonstrate the surprising degree of preservation of fragile and easily destroyed materials for very long periods of time within the unsaturated zone.

THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

Energy Technology Data Exchange (ETDEWEB)

G.J. Saulnier Jr; W. Statham

2006-03-10

The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

International Nuclear Information System (INIS)

G.J. Saulnier Jr; W. Statham

2006-01-01

The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 ± 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis

Modeling of NAD+ analogues in horse liver alcohol dehydrogenase

NARCIS (Netherlands)

Beijer, N.A.; Buck, H.M.; Sluyterman, L.A.A.E.; Meijer, E.M.

1990-01-01

So far, the interactions of nicotinamide adenine dinucleotide (NAD+) derivatives with dehydrogenases are not very well understood. This hampers the introduction of NAD+ analogues with improved characteristics concerning industrial application. We have developed an AMBER molecular mechanics model in

In vitro structure-activity relationship of Re-cyclized octreotide analogues

Energy Technology Data Exchange (ETDEWEB)

Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

2010-07-15

Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents.

Science.gov (United States)

Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L; Guzman, Monica L; Crooks, Peter A

2015-03-06

A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Vitamin E analogues and immune response in cancer treatment

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Neužil, Jiří

2007-01-01

Roč. 76, - (2007), s. 463-491 ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

Bentonite deposits as a natural analogue to long-term barriers in a final repository of nuclear waste

International Nuclear Information System (INIS)

Keto, P.

2000-01-01

The geology of bentonite occurrences in Almeria (Spain) and Wyoming (USA) were studied in order to find suitable natural analogue to the longterm mechanical behaviour of the bentonite barrier in the final nuclear waste disposal. The study is based on literature review over both occurrence areas and on fieldwork observations from Almeria, Spain. The deposit areas differ from each other by age, deposition environment, exchangeable cation chemistry, alteration condition, occurrence and deformational features. One of the most important deformational feature in Almeria bentonites was the existence of Tertiary (Middle and Upper Miocene, 6-15.5 Ma old) bentonite intrusion inside/over younger Quaternary (Pleistocene Superior, 0.01-0.72 Ma old) sediments. This was a result of the confining pressure of overlying volcanic rocks and sediments and the high plasticity behaviour of bentonites. According to this observation, the pressure effect in final nuclear waste repositories requires further investigations. The bentonites in Wyoming have survived weathering and shearing without losing their expandability or other properties typical of smectite-rich materials. (orig.)

Uranium, thorium and trace elements in geologic occurrences as analogues of nuclear waste repository conditions

International Nuclear Information System (INIS)

Wollenberg, H.A.; Brookins, D.G.; Cohen, L.H.; Flexser, S.; Abashian, M.; Murphy, M.; Williams, A.E.

1984-01-01

Contact zones between intrusive rocks and tuff, basalt, salt and granitic rock were investigated as possible analogues of nuclear waste repository conditions. Results of detailed studies of contacts between quartz monzonite of Laramide age, intrusive into Precambrian gneiss, and a Tertiary monzonite-tuff contact zone indicate that uranium, thorium and other trace elements have not migrated significantly from the more radioactive instrusives into the country rock. Similar observations resulted from preliminary investigations of a rhyodacite dike cutting basalt of the Columbia River plateau and a kimberlitic dike cutting bedded salt of the Salina basin. This lack of radionuclide migration occurred in hydrologic and thermal conditions comparable to, or more severe than those expected in nuclear waste repository environments and over time periods of the order of concern for waste repositories. Attention is now directed to investigation of active hydrothermal systems in candidate repository rock types, and in this regard a preliminary set of samples has been obtained from a core hole intersecting basalt underlying the Newberry caldera, Oregon, where temperatures presently range from 100 to 265 0 C. Results of mineralogical and geochemical investigations of this core should indicate the alteration mineralogy and behavior of radioelements in conditions analogous to those in the near field of a repository in basalt

Enzymatic synthesis of RNAs capped with nucleotide analogues reveals the molecular basis for substrate selectivity of RNA capping enzyme: impacts on RNA metabolism.

Directory of Open Access Journals (Sweden)

Moheshwarnath Issur

Full Text Available RNA cap binding proteins have evolved to specifically bind to the N7-methyl guanosine cap structure found at the 5' ends of eukaryotic mRNAs. The specificity of RNA capping enzymes towards GTP for the synthesis of this structure is therefore crucial for mRNA metabolism. The fact that ribavirin triphosphate was described as a substrate of a viral RNA capping enzyme, raised the possibility that RNAs capped with nucleotide analogues could be generated in cellulo. Owing to the fact that this prospect potentially has wide pharmacological implications, we decided to investigate whether the active site of the model Paramecium bursaria Chlorella virus-1 RNA capping enzyme was flexible enough to accommodate various purine analogues. Using this approach, we identified several key structural determinants at each step of the RNA capping reaction and generated RNAs harboring various different cap analogues. Moreover, we monitored the binding affinity of these novel capped RNAs to the eIF4E protein and evaluated their translational properties in cellulo. Overall, this study establishes a molecular rationale for the specific selection of GTP over other NTPs by RNA capping enzyme It also demonstrates that RNAs can be enzymatically capped with certain purine nucleotide analogs, and it also describes the impacts of modified RNA caps on specific steps involved in mRNA metabolism. For instance, our results indicate that the N7-methyl group of the classical N7-methyl guanosine cap is not always indispensable for binding to eIF4E and subsequently for translation when compensatory modifications are present on the capped residue. Overall, these findings have important implications for our understanding of the molecular determinants involved in both RNA capping and RNA metabolism.

Evolving a polymerase for hydrophobic base analogues.

Science.gov (United States)

Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

2009-10-21

Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity.

Visualizing the molecular sociology at the HeLa cell nuclear periphery

NARCIS (Netherlands)

Mahamid, Julia; Pfeffer, Stefan; Schaffer, Miroslava; Villa, Elizabeth; Danev, Radostin; Cuellar, Luis Kuhn; Förster, Friedrich|info:eu-repo/dai/nl/412516438; Hyman, Anthony A; Plitzko, Jürgen M; Baumeister, Wolfgang

2016-01-01

The molecular organization of eukaryotic nuclear volumes remains largely unexplored. Here we combined recent developments in cryo-electron tomography (cryo-ET) to produce three-dimensional snapshots of the HeLa cell nuclear periphery. Subtomogram averaging and classification of ribosomes revealed

Analogue MIMO Detection

Directory of Open Access Journals (Sweden)

McNamara Darren

2006-01-01

Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs.

Science.gov (United States)

Sun, Yubo; Kiraly, Alex J; Cox, Michael; Mauerhan, David R; Hanley, Edward N

2018-04-01

Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (Pguinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program.

1H nuclear magnetic resonance studies of the conformation of an ATP analogue at the active site of Na,K-ATPase from kidney medulla

International Nuclear Information System (INIS)

Stewart, J.M.M.; Grisham, C.M.

1988-01-01

1 H nuclear magnetic relaxation measurements have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH 3 ) 4 ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH 4 ) 4 ATP is a competitive inhibitor with respect to MnATP for the Na,K-ATPase and that Mn 2+ bound to a single, high-affinity site on the ATPase can be an effective paramagnetic probe for nuclear relaxation studies of the Na-K-ATPase. From the paramagnetic effect of Mn 2+ bound to the APTase on the longitudinal relaxation rates of the protons of Co(NH 3 ) 4 ATP at the substrate site (at 300 and 361 MHz), Mn-H distances to seven protons on the bound nucleotide were determined. Taken together with previous 31 P nuclear relaxation data, these measurements are consistent with a single nucleotide conformation at the active site. The nucleotide adopts a bent configuration, in which the triphosphate chain lies nearly parallel to the adenine moiety. The glycosidic torsion angle is 35 0 , and the conformation of the ribose ring is slightly N-type. The bound Mn 2+ lies above and in the plane of the adenine ring. The distances from Mn 2+ to N 6 and N 7 are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules. The NMR data also indicate that the structure of the bound ATP analogue is independent of the conformational state of the enzyme

Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

Energy Technology Data Exchange (ETDEWEB)

Skagius, K [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

1993-12-31

The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

Energy Technology Data Exchange (ETDEWEB)

Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

1992-12-31

The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

International Nuclear Information System (INIS)

Skagius, K.; Wingefors, S.

1992-01-01

The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

Classical molecular dynamics simulation of nuclear fuels

International Nuclear Information System (INIS)

Devanathan, R.; Krack, M.; Bertolus, M.

2015-01-01

Molecular dynamics simulation using forces calculated from empirical potentials, commonly called classical molecular dynamics, is well suited to study primary damage production by irradiation, defect interactions with fission gas atoms, gas bubble nucleation, grain boundary effects on defect and gas bubble evolution in nuclear fuel, and the resulting changes in thermomechanical properties. This enables one to obtain insights into fundamental mechanisms governing the behaviour of nuclear fuel, as well as parameters that can be used as inputs for mesoscale models. The interaction potentials used for the force calculations are generated by fitting properties of interest to experimental data and electronic structure calculations (see Chapter 12). We present here the different types of potentials currently available for UO 2 and illustrations of applications to the description of the behaviour of this material under irradiation. The results obtained from the present generation of potentials for UO 2 are qualitatively similar, but quantitatively different. There is a need to refine these existing potentials to provide a better representation of the performance of polycrystalline fuel under a variety of operating conditions, develop models that are equipped to handle deviations from stoichiometry, and validate the models and assumptions used. (authors)

Preparation, characterization and in vitro evaluation of a new nucleotide analogue prodrug cyclodextrin inclusion complexes.

Science.gov (United States)

Diab, Roudayna; Jordheim, Lars P; Degobert, Ghania; Peyrottes, Suzanne; Périgaud, Christian; Dumontet, Charles; Fessi, Hatem

2009-01-01

Bis(tbutyl-S-acyl-2-thioethyl)-cytidine monophosophate is a new cytotoxic mononucleotide prodrug which have been developed to reverse the cellular resistance to nucleoside analogues. Unfortunately, its in vivo utilisation was hampered by its poor water solubility, raising the need of a molecular vector capable to mask its physicochemical characteristics although without affecting its cytotoxic activity. Hydroxypropyl-beta-cyclodextrin was used to prepare the prodrug inclusion complexes, allowing it to be solubilized in water and hence to be used for in vitro and in vivo experiments. A molar ratio of the cyclodextrin: prodrug of 3 was sufficient to obtain complete solubilization of the prodrug. The inclusion complex was characterized by differential scanning calorimetry, which revealed the disappearance of the melting peak of the prodrug suggesting the formation of inclusion complex. Proton Nuclear Magnetic Resonance spectroscopy provided a definitive proof of the inclusion complex formation, which was evidenced by the large chemical shift displacements observed for protons located in the interior of the hydrophobic cyclodextrin cavity. The complex retained its cytotoxic activity as shown by in vitro cell survival assays on murine leukemia cells. These results provided a basis for potential therapeutic applications of co-formulation of this new nucleotide analogue with hydroxypropyl-beta-CD in cancer therapy.

THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

Energy Technology Data Exchange (ETDEWEB)

G. Saulnier and W. Statham

2006-04-16

The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

International Nuclear Information System (INIS)

G. Saulnier; W. Statham

2006-01-01

The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table

Natural analogue studies as supplements to biomineralization research

International Nuclear Information System (INIS)

McNeil, M.B.

1995-01-01

Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu 4 SO 4 (OH) 6· H 2 O] and mineral morphologies unusual in corrosion [malachite, Cu 2 CO 3 (OH) 2 , rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena

Microscopic study of nuclear 'pasta' by quantum molecular dynamics

International Nuclear Information System (INIS)

Watanabe, Gentaro; Sato, Katsuhiko; Yasuoka, Kenji; Ebisuzaki, Toshikazu

2002-01-01

Structure of cold dense matter at subnuclear densities is investigated by quantum molecular dynamics (QMD) simulations. We succeeded in showing that the phases with slab-like and rod-like nuclei etc. and be formed dynamically from hot uniform nuclear matter without any assumptions on nuclear shape. We also observe intermediate phases, which has complicated nuclear shapes. Geometrical structures of matter are analyzed with Minkowski functionals, and it is found out that intermediate phases can be characterized as ones with negative Euler characteristic. Our result suggests the existence of these kinds of phases in addition to the simple 'pasta' phases in neutron star crusts. (author)

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

Energy Technology Data Exchange (ETDEWEB)

Nascimento, Josenaide P. do; Santos, Lourivaldo S.; Carmo, Maria Carolina L. do; Brasil, Davi S.B.; Alves, Claudio N., E-mail: nahum@ufpa.b [Universidade Federal do Para (UFPA), Belem, PA (Brazil). Inst. de Ciencias Exatas e Naturais; Santos, Regina Helena A.; Tozzo, Erica; Ferreira, Janaina G. [Universidade de Sao Paulo (IQSC/USP), Sao Carlos, SP (Brazil). Inst. de Quimica

2010-07-01

The synthesis and X-ray crystal diffraction structure of two analogues of neolignans, 2-(4-chlorophenyl)-1-phenylethanone (20) and 2-[(4-chlorophenyl)thio]-1-(3,4-dimethoxyphenyl) propan-1-one (12) is described. The compound 12 presents activity against intracellular Leishmania donovani and Leishmania amazonensis amastigotes that cause cutaneous and visceral leishmaniasis. In addition, the density functional theory (DFT) with the B3LYP hybrid functional was employed to calculate a set of molecular descriptors for nineteen synthetic analogues of neolignans with antileishmanial activities. Afterwards, the stepwise discriminant analysis was performed to investigate possible relationship between the molecular descriptors and biological activities. Through this analysis the compounds were classified into two groups active and inactive according to their degree of biological activities, and the more important properties were charges on some key atoms, electronic affinity and ClogP. (author)

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

International Nuclear Information System (INIS)

Nascimento, Josenaide P. do; Santos, Lourivaldo S.; Carmo, Maria Carolina L. do; Brasil, Davi S.B.; Alves, Claudio N.; Santos, Regina Helena A.; Tozzo, Erica; Ferreira, Janaina G.

2010-01-01

The synthesis and X-ray crystal diffraction structure of two analogues of neolignans, 2-(4-chlorophenyl)-1-phenylethanone (20) and 2-[(4-chlorophenyl)thio]-1-(3,4-dimethoxyphenyl) propan-1-one (12) is described. The compound 12 presents activity against intracellular Leishmania donovani and Leishmania amazonensis amastigotes that cause cutaneous and visceral leishmaniasis. In addition, the density functional theory (DFT) with the B3LYP hybrid functional was employed to calculate a set of molecular descriptors for nineteen synthetic analogues of neolignans with antileishmanial activities. Afterwards, the stepwise discriminant analysis was performed to investigate possible relationship between the molecular descriptors and biological activities. Through this analysis the compounds were classified into two groups active and inactive according to their degree of biological activities, and the more important properties were charges on some key atoms, electronic affinity and ClogP. (author)

Reasoning by analogy: rational foundation of natural analogue studies. [Application to radioactive waste disposal

Energy Technology Data Exchange (ETDEWEB)

Petit, J.-C. (CEA Centre d' Etudes Nucleaires de Fontenay-aux Roses, (France). DRDD/SESD)

1992-01-01

Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory investigations. Most nuclear countries have hence developed an approach relying on the following research directions: 1. laboratory experiments; 2. in situ testing; 3. modeling; and 4. natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence (if not truly validated). Although the field of natural analogues has grown very rapidly in recent years, receiving support from varied specialists and institutions involved in radioactive waste disposal, there is not yet a full consensus on their actual usefulness. More problematic is the criticism sometimes made that analogical reasoning is not ''true science'' and that information retrieved from the study of natural analogues will always remain questionable. The present paper gives some clues about the exact status of reasoning by analogy, compared to more ''scientific'' ways of deriving information from investigated systems. It is not a thorough discussion of this very complex, and by far too philosophical issue but we hope, at least, to present to readers of papers devoted to natural analogue studies arguments showing that this approach has some sound foundation. (author).

Synthesis and preliminary pharmacological evaluation of asymmetric chloroquine analogues.

Science.gov (United States)

Witiak, D T; Grattan, D A; Heaslip, R J; Rahwan, R G

1981-06-01

Asymmetric chloroquine analogues (1-4) were prepared of known absolute configuration in order to assess stereochemical influences on selected biological activities. Since chloroquine has been shown to possess spasmolytic properties, analogues 1-4 were tested for similar pharmacological effects on smooth-muscle contraction. The (S)- and (R)-chlorochloroquine enantiomers (1 and 2, respectively) were more potent antispasmodics than the less lipophilic (S)- and (R)-hydroxychloroquines (3 and 4, respectively) when tested against KCl- or acetylcholine-induced contractions of the isolated mouse ileum. A membrane stabilizing mechanism of action for the chloroquine analogues is proposed since neither cellular toxicity nor calcium antagonism plays a role in the spasmolytic action of these compounds. Although compounds 1-4 also inhibited PGF2 alpha-induced contractions of the ileum, 1 was significantly more potent than 2; the latter in turn was equipotent to 3 and 4. It is tentatively proposed that 1 may possess stereoselective affinity for the PGF2 alpha receptor in the ileum. This observation may be further exploited to obtain more selective profiles of biological activity through molecular manipulation.

Liposomal delivery systems for anti-cancer analogues of vitamin E

Czech Academy of Sciences Publication Activity Database

Koudelka, S.; Knotigova, P.T.; Masek, J.; Prochazka, L.; Lukac, R.; Miller, A.D.; Neužil, Jiří; Turanek, J.

2015-01-01

Roč. 207, Jun 10 (2015), s. 59-69 ISSN 0168-3659 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Alpha-tocopheryl succinate * Analogues of vitamin E * Anti-cancer drugs Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.441, year: 2015

Molecularly Imprinted Polymers: Thermodynamic and Kinetic Considerations on the Specific Sorption and Molecular Recognition

Directory of Open Access Journals (Sweden)

Kejun Tong

2008-04-01

Full Text Available This article presents a work aiming at thermodynamically and kinetically interpreting the specific sorption and recognition by a molecularly imprinted polymer. Using Boc-L-Phe-OH as a template, the imprinted material was prepared. The result indicates that the prepared polymer can well discriminate the imprint species from its analogue (Boc-D-Phe-OH, so as to adsorb more for the former but less for the latter. Kinetic analysis indicates that this specific sorption, in nature, can be a result of a preferential promotion. The imprint within the polymer causes a larger adsorption rate for the template than for the analogue. Thermodynamic study also implies that the molecular induction from the specific imprint to the template is larger than to the analogue, which thus makes the polymer capable of preferentially alluring the template to bind.

Matrix diffusion model. In situ tests using natural analogues

International Nuclear Information System (INIS)

Rasilainen, K.

1997-11-01

Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories

Exploration of charge states of balanol analogues acting as ATP-competitive inhibitors in kinases.

Science.gov (United States)

Hardianto, Ari; Yusuf, Muhammad; Liu, Fei; Ranganathan, Shoba

2017-12-28

(-)-Balanol is an ATP mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is a tumour promoter, PKC isozymes act as tumour promoters or suppressors, depending on the cancer type. In particular, PKCε is frequently implicated in cancer promotion, making it a potential target for anticancer drugs. To improve isozyme selectivity of balanol, exhaustive structural and activity relationship (SAR) studies have been performed in the last two decades, but with limited success. More recently, fluorination on balanol has shown improved selectivity for PKCε, although the fluorine effect is not yet clearly understood. Understanding the origin to this fluorine-based selectivity will be valuable for designing better balanol-based ATP mimicking inhibitors. Computational approaches such as molecular dynamics (MD) simulations can decipher the fluorine effect, provided that correct charges have been assigned to a ligand. Balanol analogues have multiple ionisable functional groups and the effect of fluorine substitutions on the exact charge state of each analogue bound to PKA and to PKCε needs to be thoroughly investigated in order to design highly selective inhibitors for therapeutic applications. We explored the charge states of novel fluorinated balanol analogues using MD simulations. For different potential charge states of these analogues, Molecular Mechanics Generalized Born Surface Area (MMGBSA) binding energy values were computed. This study suggests that balanol and the most potent fluorinated analogue (5S fluorine substitution on the azepane ring), have charges on the azepane ring (N1), and the phenolic (C6''OH) and the carboxylate (C15''O 2 H) groups on the benzophenone moiety, when bound to PKCε as well as PKA. To the best our knowledge, this is the first study showing that the phenolate group is charged in balanol and its analogues binding to the ATP site of PKCε. Correct charge

Flaviviridae viruses use a common molecular mechanism to escape nucleoside analogue inhibitors

Czech Academy of Sciences Publication Activity Database

Valdés, James J.; Butterill, Philip T.; Růžek, Daniel

2017-01-01

Roč. 492, č. 4 (2017), s. 652-658 ISSN 0006-291X R&D Projects: GA MZd(CZ) NV16-34238A; GA ČR GB14-36098G Institutional support: RVO:60077344 Keywords : Analogue * Flaviviridae * Interrogating * Polymerase * Virus * Water Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 2.466, year: 2016

The development of nuclear medicine molecular imaging: An era of multiparametric imaging

International Nuclear Information System (INIS)

Zhu Yuyuan; Huang Gang

2010-01-01

Nuclear medical molecular imaging is developing toward a multimodality and multitracer future. Abundant complementary data generated from different tracers in different modalities are successfully serving the biological research and clinical treatment. Among the others, PER-MRI has the greatest potential and will be a research of interest in the near future. This article focused on the evolution history on nuclear medicine from single modality to multimodality, single tracer to multitracer. It also gave a brief summary to the identifications, differences, pros and consofmultimodality, multitracer, multiparametric molecular imaging. Issues, problems and challenges concerned with her development and recognition are also discussed. (authors)

Visualizing the molecular sociology at the HeLa cell nuclear periphery.

Science.gov (United States)

Mahamid, Julia; Pfeffer, Stefan; Schaffer, Miroslava; Villa, Elizabeth; Danev, Radostin; Cuellar, Luis Kuhn; Förster, Friedrich; Hyman, Anthony A; Plitzko, Jürgen M; Baumeister, Wolfgang

2016-02-26

The molecular organization of eukaryotic nuclear volumes remains largely unexplored. Here we combined recent developments in cryo-electron tomography (cryo-ET) to produce three-dimensional snapshots of the HeLa cell nuclear periphery. Subtomogram averaging and classification of ribosomes revealed the native structure and organization of the cytoplasmic translation machinery. Analysis of a large dynamic structure-the nuclear pore complex-revealed variations detectable at the level of individual complexes. Cryo-ET was used to visualize previously elusive structures, such as nucleosome chains and the filaments of the nuclear lamina, in situ. Elucidation of the lamina structure provides insight into its contribution to metazoan nuclear stiffness. Copyright © 2016, American Association for the Advancement of Science.

c-MYC G-quadruplex binding by the RNA polymerase I inhibitor BMH-21 and analogues revealed by a combined NMR and biochemical Approach.

Science.gov (United States)

Musso, Loana; Mazzini, Stefania; Rossini, Anna; Castagnoli, Lorenzo; Scaglioni, Leonardo; Artali, Roberto; Di Nicola, Massimo; Zunino, Franco; Dallavalle, Sabrina

2018-03-01

Pyridoquinazolinecarboxamides have been reported as RNA polymerase I inhibitors and represent a novel class of potential antitumor agents. BMH-21, was reported to intercalate with GC-rich rDNA, resulting in nucleolar stress as a primary mechanism of cytotoxicity. The interaction of BMH-21 and analogues with DNA G-quadruplex structures was studied by NMR and molecular modelling. The cellular response was investigated in a panel of human tumor cell lines and protein expression was examined by Western Blot analysis. We explored the ability of BMH-21 and its analogue 2 to bind to G-quadruplex present in the c-MYC promoter, by NMR and molecular modelling studies. We provide evidence that both compounds are not typical DNA intercalators but are effective binders of the tested G-quadruplex. The interaction with c-MYC G-quadruplex was reflected in down-regulation of c-Myc expression in human tumor cells. The inhibitory effect was almost complete in lymphoma cells SUDHL4 characterized by overexpression of c-Myc protein. This downregulation reflected an early and persistent modulation of cMyc mRNA. Given the relevance of c-MYC in regulation of ribosome biogenesis, it is conceivable that the inhibition of c-MYC contributes to the perturbation of nuclear functions and RNA polymerase I activity. Similar experiments with CX-5461, another RNA polymerase I transcription inhibitor, indicate the same behaviour in G-quadruplex stabilization. Our results support the hypothesis that BMH-21 and analogue compounds share the same mechanism, i.e. G-quadruplex binding as a primary event of a cascade leading to inhibition of RNA polymerase I and apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

/sup 1/H nuclear magnetic resonance studies of the conformation of an ATP analogue at the active site of Na,K-ATPase from kidney medulla

Energy Technology Data Exchange (ETDEWEB)

MacD. Stewart, J.M.; Grisham, C.M.

1988-06-28

/sup 1/H nuclear magnetic relaxation measurements have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH/sub 3/)/sub 4/ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH/sub 4/)/sub 4/ATP is a competitive inhibitor with respect to MnATP for the Na,K-ATPase and that Mn/sup 2 +/ bound to a single, high-affinity site on the ATPase can be an effective paramagnetic probe for nuclear relaxation studies of the Na-K-ATPase. From the paramagnetic effect of Mn/sup 2 +/ bound to the APTase on the longitudinal relaxation rates of the protons of Co(NH/sub 3/)/sub 4/ATP at the substrate site (at 300 and 361 MHz), Mn-H distances to seven protons on the bound nucleotide were determined. Taken together with previous /sup 31/P nuclear relaxation data, these measurements are consistent with a single nucleotide conformation at the active site. The nucleotide adopts a bent configuration, in which the triphosphate chain lies nearly parallel to the adenine moiety. The glycosidic torsion angle is 35/sup 0/, and the conformation of the ribose ring is slightly N-type. The bound Mn/sup 2 +/ lies above and in the plane of the adenine ring. The distances from Mn/sup 2 +/ to N/sub 6/ and N/sub 7/ are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules. The NMR data also indicate that the structure of the bound ATP analogue is independent of the conformational state of the enzyme.

Conformational analysis of vitamin D 3 derivatives by molecular mechanics . Part II. 1α,25-dihydroxyvitamin D 3 and analogues

Science.gov (United States)

Mosquera, Ricardo A.; Rios, Miguel A.; Tovar, Clara A.; Maestro, Miguel

1989-10-01

The conformational analysis of vitamin D 3 derivatives, including the biologically active form 1α,25-dihydroxyvitamin D 3 (III) and several synthetic analogues: b-deoxy-1α,25-dihydroxyvitamin D 3 (IV), 3-deoxy-3α-methyl-1α,25-dihydroxyvitamin D 3 (V), 3-deoxy-3β-methyl-1α,25-dihydroxyvitamin D 3 (VI), and 3-deoxy-3,3-dimethyl-1α,25-dihydroxyvitamin D 3 (VII), has been carried out employing Allinger's molecular mechanics method. The results obtained for conformational equilibrium populations are found to be in good agreement with those provided by NMR studies. Comparison of the active form of vitamin D 3 (1α,25-dihydroxyvitamin D 3) with the other species reveals no important geometrical differences.

Glaciation and geosphere evolution - Greenland Analogue Project

International Nuclear Information System (INIS)

Hirschorn, S.; Vorauer, A.; Belfadhel, M.B.; Jensen, M.

2011-01-01

The deep geological repository concept for the long-term management of used nuclear fuel involves the containment and isolation of used nuclear fuel in a suitable geological formation. A key objective of the Canadian Nuclear Waste Management Organization (NWMO) geoscience technical research program is to advance the understanding of geosphere stability and its resilience to perturbations over time frames of relevance to a deep geological repository. Glaciation has been identified as the most probable and intense perturbation relevant to a deep geological repository associated with long-term climate change in northern latitudes. Given that the North American continent has been re-glaciated nine times over the past million years, it is strongly expected that a deep geological repository within a suitable crystalline or sedimentary rock formation in Canada will be subject to glaciation events associated with long-term climate change. As such, NWMO's geoscience research program has placed particular emphasis on investigations of the response of the geosphere to glaciations. As surface conditions change from present day conditions to periglacial, followed by ice-sheet cover of variable thickness and rapid glacial retreat, transient geochemical, hydraulic, mechanical and temperature conditions will be simultaneously imposed on groundwater systems. NWMO research activities related to glaciation events and their impacts on groundwater system evolution are being undertaken using a multi-disciplinary approach aimed at collecting multiple lines of evidence. These investigations include assessment of the: Impact of an ice sheet on groundwater composition at repository depth using the Greenland Ice Sheet as an analogue to future glaciations in North America; Expected physical and temporal surface boundary conditions related to potential future glaciation events by estimating the magnitude and time rate of change of ice sheet thickness, ground surface temperature and

Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities.

Science.gov (United States)

Verlinden, Bianca K; Niemand, Jandeli; Snyman, Janette; Sharma, Shiv K; Beattie, Ross J; Woster, Patrick M; Birkholtz, Lyn-Marie

2011-10-13

A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC(50) values in the 100-650 nM range. Analogues arrested parasitic growth within 24 h of exposure due to a block in nuclear division and therefore asexual development. Moreover, this effect appears to be cytotoxic and highly selective to malaria parasites (>7000-fold lower IC(50) against P. falciparum) and is not reversible by the exogenous addition of polyamines. With this first report of potent antimalarial activity of polyamine analogues containing 3-7-3 or 3-6-3 carbon backbones and substituted terminal urea- or thiourea moieties, we propose that these compounds represent a structurally novel class of antimalarial agents.

International conference on clinical PET and molecular nuclear medicine (IPET 2007). Book of abstracts

Energy Technology Data Exchange (ETDEWEB)

NONE

2007-07-01

The International Atomic Energy Agency is organizing its first international conference on 'Clinical PET and Molecular Nuclear Medicine'. Medical imaging technologies have undergone explosive growth over the past two decades. Today, imaging is at a crossroad, with molecular targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Observing molecular interactions in the living body by the radiotracer technique has become known as 'molecular nuclear medicine'. Molecular nuclear medicine techniques analyze cellular biochemistry and its relationship to disease processes expressed in tissue and organ dysfunction, for diagnostic and therapeutic purposes. People can often have similar manifestations of disease, but no two patients will be the same. Functional radionuclide imaging and positron emission tomography (PET) provide excellent opportunities to follow the pathology in individual patients and therefore provide a means for tailored clinical management. These also provide the means to assess the response to treatment in a safe and non-invasive manner. Changes at molecular and cellular levels provide vital clues for evaluating the effectiveness of chosen clinical treatment plans. This information is expected to have a major impact on understanding disease, disease detection, individualised treatment, and drug development. Recently, considerable attention has been drawn to nuclear medicine with the visualization of biochemical processes in vivo such as PET studies with 18F-FDG in many different organs and in cancerous tissues. With the arrival of PET/CT systems there is a new era of accurate mapping of disease processes. Today, 18F-FDG is the most useful PET tracer for the detection, staging, treatment planning and management of cancer. There is mounting evidence for its competitive advantage over conventional techniques in major medical areas including oncology, cardiology, and neurology. Nuclear medicine is

International conference on clinical PET and molecular nuclear medicine (IPET 2007). Book of abstracts

International Nuclear Information System (INIS)

2007-01-01

The International Atomic Energy Agency is organizing its first international conference on 'Clinical PET and Molecular Nuclear Medicine'. Medical imaging technologies have undergone explosive growth over the past two decades. Today, imaging is at a crossroad, with molecular targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Observing molecular interactions in the living body by the radiotracer technique has become known as 'molecular nuclear medicine'. Molecular nuclear medicine techniques analyze cellular biochemistry and its relationship to disease processes expressed in tissue and organ dysfunction, for diagnostic and therapeutic purposes. People can often have similar manifestations of disease, but no two patients will be the same. Functional radionuclide imaging and positron emission tomography (PET) provide excellent opportunities to follow the pathology in individual patients and therefore provide a means for tailored clinical management. These also provide the means to assess the response to treatment in a safe and non-invasive manner. Changes at molecular and cellular levels provide vital clues for evaluating the effectiveness of chosen clinical treatment plans. This information is expected to have a major impact on understanding disease, disease detection, individualised treatment, and drug development. Recently, considerable attention has been drawn to nuclear medicine with the visualization of biochemical processes in vivo such as PET studies with 18F-FDG in many different organs and in cancerous tissues. With the arrival of PET/CT systems there is a new era of accurate mapping of disease processes. Today, 18F-FDG is the most useful PET tracer for the detection, staging, treatment planning and management of cancer. There is mounting evidence for its competitive advantage over conventional techniques in major medical areas including oncology, cardiology, and neurology. Nuclear medicine is

Rethinking of the criteria for natural analogue study. A case of Tono natural analogue study

International Nuclear Information System (INIS)

Yoshida, Hidekazu

1996-01-01

Natural analogue regarding long-term performance of the geological disposal system for radioactive waste isolation is essentially the study of geochemical process which has been evolved in geological environment. All geochemical studies, however, will not be nominated as natural analogue studies. It is, therefore, important to be clear the criteria for natural analogue study with the view of analogy by following three categories, (1) Conceptual model development, (2) Data provision and (3) Model testing, for the concept of geological disposal and safety assessment model. Rethinking of the criteria for natural analogue study through the case of Tono Natural Analogue Study, and the usefulness of natural analogue study for the safety assessment of geological disposal system in Japan have been presented in this paper. (author)

Nuclear molecular structure in heavy mass systems

International Nuclear Information System (INIS)

Arctaedius, T.; Bargholtz, C.

1989-04-01

A study is made of nuclear molecular configurations involving one heavy mass partner. The stability of these configurations to mass flow and to fission is investigated as well as their population in fusion reactions. It is concluded that shell effects in combination with the effects of angular momentum may be important in stabilizing certain configurations. A possible relation of these configurations to the so called superdeformed states is pointed out. The spectrum of rotational and vibrational trasitions within molecular configurations is investigated. For sufficiently mass-asymmetric systems the engergies of vibrational transitions are comparable to the neutron separation energy. Gamma radiation from such transitions may then be observable above the background of statistical transitions. The gamma spectrum and the directional distribution of the radioation following fusion reactions with 12 C and 16 O are calculated. (authors)

Proceedings of a workshop on molecular nuclear medicine

International Nuclear Information System (INIS)

Reba, R.C.

1992-01-01

The Office of Health and Environmental Research (OHER) of the Department of Energy (DOE) has increased the emphasis on research in structural biology and molecular biology. The Department has increased support substantially in the area of basic molecular and structural biology research. To exploit the advances in these fields, OHER has sought to apply those advances in their other areas of responsibility, e.g., health effects research, environmental biology, and, in particular, nuclear medicine. The applications of biotechnology have contributed greatly to the productive research efforts of molecular biology. These techniques include gene manipulation for targeted gene delivery; characterization of molecular probes for hormone, tumor, and neuroreceptors; the receptor-agonist/antagonist binding interactions; studies of mechanisms of cellular communication; and the development of in vitro diagnostics such as molecular probes for studying the aging process and patients with mental disorders, cancer, and atherosclerosis. The importance of this work is the reasonable expectation that mainly, through an appreciation of the molecular basis of disease, will the most effective and rapid progress be made toward understanding, identifying, solving, and preventing specific disease processes. Critical questions arising before and during the Workshop are how the following technologies can be applied in a practical clinical research or patient management setting: the recombinant DNA methodology, the technology of engineered monoclonal antibodies, the new methods for protein production and purification, and the production of transgenic animals

The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

Science.gov (United States)

Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

2011-11-01

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

Low energy electron-initiated ion-molecule reactions of ribose analogues

International Nuclear Information System (INIS)

Mozejko, P.

2003-01-01

Recent experiments in which plasmid DNA samples were bombarded with low energy ( 2 O, DNA bases, and sugar-phosphate backbone analogues. To this end, the cyclic molecule tetrahydrofuran, and its derivatives, provide useful models for the sugar-like molecules contained in the backbone of DNA. In addition to LEE induced dissociation by processes such as dissociative electron attachment (DEA), molecules may be damaged by ions and neutral species of non-thermal energies created by LEE in the surrounding environment. In this contribution, we investigate with electron stimulated desorption techniques, LEE damage to films of desoxy-ribose analogues in the presence of various molecular coadsorbates, that simulate changes in local molecular environment. In one type of experiments tetrahydrofuran is deposited onto multilayer O2. A desorbed signal of OH - indicates ion-molecule reactions of the type O - + C 4 H 8 O -> OH - + C 4 H 7 O, where the O - was formed initially by DEA to O 2 . Further electron stimulated desorption measurements for tetrahydrofuran and derivatives adsorbed on H 2 O, Kr, N 2 O and CH 3 OH will be presented and discussed

Comparison of 3D quantitative structure-activity relationship methods: Analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis

Science.gov (United States)

Woolfrey, John R.; Avery, Mitchell A.; Doweyko, Arthur M.

1998-03-01

Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as well as two CoMFA models (leave-one-out standard CoMFA and the guided-region selection protocol). Similar r2 and q2 values were obtained by each method, although some striking differences existed between CoMFA contour maps and the HASL output. Each of the four predictive models exhibited a similar ability to predict the activity of a test set of 23 artemisinin analogues, although some differences were noted as to which compounds were described well by either model.

The molecular mechanism of bisphenol A (BPA as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD simulations.

Directory of Open Access Journals (Sweden)

Lanlan Li

Full Text Available Bisphenol A (BPA can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA.

Novel Indole-based Tambjamine-Analogues Induce Apoptotic Lung Cancer Cell Death through p38 Mitogen-Activated Protein Kinase Activation.

Science.gov (United States)

Manuel-Manresa, Pilar; Korrodi-Gregório, Luís; Hernando, Elsa; Villanueva, Alberto; Martínez-García, David; Rodilla, Ananda M; Ramos, Ricard; Fardilha, Margarida; Moya, Juan; Quesada, Roberto; Soto-Cerrato, Vanessa; Pérez-Tomás, Ricardo

2017-07-01

Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells. Expression changes produced after compounds treatment comprised genes related to apoptosis, cell cycle, growth factors and its receptors, protein kinases and topoisomerases, among others. Dysregulation of BCL2 and BIRC5 /survivin genes suggested the apoptotic pathway as the induced molecular cell death mechanism. In fact, activation of several proapoptotic markers (caspase-9, caspase-3, and PARP) and reversion of the cytotoxic effect upon treatment with an apoptosis inhibitor (Z-VAD-FMK) were observed. Moreover, members of the Bcl-2 protein family suffered changes after tambjamine analogues treatment, with a concomitant protein decrease towards the prosurvival members. Besides this, it was observed cellular accumulation of ROS upon compound treatment and an activation of the stress-kinase p38 MAPK route that, when inhibited, reverted the cytotoxic effect of the tambjamine analogues. Finally, a significant therapeutic effect of these compounds was observed in subcutaneous and orthotopic lung cancer mice models. Taken together, these results shed light on the mechanism of action of novel cytotoxic anionophores and demonstrate the therapeutic effects against lung cancer. Mol Cancer Ther; 16(7); 1224-35. ©2017 AACR . ©2017 American Association for Cancer Research.

Mathematical analysis of compressive/tensile molecular and nuclear structures

Science.gov (United States)

Wang, Dayu

Mathematical analysis in chemistry is a fascinating and critical tool to explain experimental observations. In this dissertation, mathematical methods to present chemical bonding and other structures for many-particle systems are discussed at different levels (molecular, atomic, and nuclear). First, the tetrahedral geometry of single, double, or triple carbon-carbon bonds gives an unsatisfying demonstration of bond lengths, compared to experimental trends. To correct this, Platonic solids and Archimedean solids were evaluated as atoms in covalent carbon or nitrogen bond systems in order to find the best solids for geometric fitting. Pentagonal solids, e.g. the dodecahedron and icosidodecahedron, give the best fit with experimental bond lengths; an ideal pyramidal solid which models covalent bonds was also generated. Second, the macroscopic compression/tension architectural approach was applied to forces at the molecular level, considering atomic interactions as compressive (repulsive) and tensile (attractive) forces. Two particle interactions were considered, followed by a model of the dihydrogen molecule (H2; two protons and two electrons). Dihydrogen was evaluated as two different types of compression/tension structures: a coaxial spring model and a ring model. Using similar methods, covalent diatomic molecules (made up of C, N, O, or F) were evaluated. Finally, the compression/tension model was extended to the nuclear level, based on the observation that nuclei with certain numbers of protons/neutrons (magic numbers) have extra stability compared to other nucleon ratios. A hollow spherical model was developed that combines elements of the classic nuclear shell model and liquid drop model. Nuclear structure and the trend of the "island of stability" for the current and extended periodic table were studied.

CEC natural analogue working group

International Nuclear Information System (INIS)

Come, B.; Chapman, N.A.

1986-01-01

The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

Matrix diffusion model. In situ tests using natural analogues

Energy Technology Data Exchange (ETDEWEB)

Rasilainen, K. [VTT Energy, Espoo (Finland)

1997-11-01

Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories. 98 refs. The thesis includes also eight previous publications by author.

Application of natural analogues in the Yucca Mountain project - overview

International Nuclear Information System (INIS)

Simmons, Ardyth M.

2003-01-01

The Natural Analogue Synthesis Report (NASR) [1] provides a compilation of information from analogues that test, corroborate, and add confidence to process models and model predictions pertinent to total system performance assessment (TSPA). The report updated previous work [2] with new literature examples and results of quantitative studies conducted by the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate greater understanding of processes expected to occur during postclosure of a proposed Yucca Mountain repository. Natural analogues, as used here, refer to either natural or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have occurred over long time periods (decades to millenia) and large spatial scales (up to tens of kilometers). In the past, the YMP has used analogues for testing and building confidence in conceptual and numerical process models in a number of ways. Yucca Mountain mineral alteration phases provided a self-analogue for postclosure alteration [3]. Thermodynamic parameters for silica minerals of the Wairakai, New Zealand geothermal field were added to databases used in geochemical modeling [4]. Scoping calculations of radionuclide transport using the Yucca Mountain TSPA numerical model were conducted for the Peqa Blanca site [5]. Eruption parameters from the Cerro Negro volcano, Nicaragua, were used to verify codes that model ash plume dispersion [6]. Analogues have also been used in supplemental science and performance analyses to provide multiple lines of evidence in support of both analyses and model reports (AMRs) [7]; in screening arguments for inclusion or exclusion of features, events, and processes (FEP)s in TSPAs; in the quantification of uncertainties [7]; in expert elicitations of volcanic and seismic hazards [8, 9] and in peer reviews [10]. Natural analogues may be applied

The interaction of new piroxicam analogues with lipid bilayers--a calorimetric and fluorescence spectroscopic study.

Science.gov (United States)

Maniewska, Jadwiga; Szczęśniak-Sięga, Berenika; Poła, Andrzej; Sroda-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

2014-01-01

The purpose of the present paper was to assess the ability of new piroxicam analogues to interact with the lipid bilayers. The results of calorimetric and fluorescence spectroscopic experiments of two new synthesized analogues of piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and fluorescence quenching of fluorescent probes (Laurdan and Prodan), which molecular location within membranes is known with certainty, are shown in present work. The presented results revealed that, depending on the details of chemical structure, the studied compounds penetrated the lipid bilayers.

The use of natural and archaeological analogues for understanding the long-term behavior of nuclear glasses; L'utilisation des analogues naturels et archeologiques pour la comprehension de l'evolution a long terme des verres nucleaires

Energy Technology Data Exchange (ETDEWEB)

Libourel, G.; Verney-Carron, A.; Morlok, A. [CNRS UPR2300, centre de recherches petrographiques et geochimiques (CRPG), Nancy-universite, 15, rue Notre-Dame-des-Pauvres, BP 20, 54501 Vandoeuvre-les-Nancy (France); Libourel, G. [INPL, Ecole nationale superieure de geologie (ENSG), Nancy-universite, rue du Doyen-Marcel-Roubault, BP 20, 54501 Vandoeuvre-les-Nancy (France); Gin, St. [CEA Marcoule, DEN/SECM/LCLT, 30 (France); Sterpenich, J. [G2R, CNRS-UMR 7566, Nancy-universite, BP 70239, 54506 Vandoeuvre-les-Nancy cedex (France); Michelin, A.; Neff, D.; Dillmann, Ph. [Laboratoire archeomateriaux et prevision de l' alteration LAPA/SIS2 M, CEA and CNRS, Bat 637, CEA Saclay, 91191 Gif/Yvette cedex (France); Michelin, A.; Dillmann, Ph. [LMC IRAMAT UMR5060 CNRS (France)

2011-02-15

The knowledge of the long-term behavior of nuclear waste in anticipation of ultimate disposal in a deep geological formation is of prime importance in a waste management strategy. If phenomenological models have been developed to predict the long-term behavior of these materials, validating these models remains a challenge, when considering the time scale of radioactive decay of radionuclides of environmental concern, typically 10{sup 4}-10{sup 5} yrs. Here we show how natural or archaeological analogues provide critical constraints not only on the phenomenology of glass alteration and the mechanisms involved, but also on the ability of experimental short-term data to predict long-term alteration in complex environments. (authors)

Rhyolitic glasses as natural analogues of nuclear waste glasses: behaviour of an Icelandic glass upon natural aqueous corrosion

International Nuclear Information System (INIS)

Magonthier, M.-C.; Petit, J.-C.; Dran, J.-C.

1992-01-01

A detailed study of the altered rims present in narrow fissures of a 52 ka-old Icelandic obsidian reveals the behaviour of transition and heavy elements, as well as the mechanism and kinetics of alteration, during glass/solution interaction. These complex altered rims are alkali depleted and consist of alternating layers of Fe-rich aluminosilicate and aluminium thihydroxide. The elemental partitioning observed on this naturally corroded obsidian is supported by laboratory experiments performed on the same glass, the elemental accumulation being explained by the formation of a hydrosilicate. A good correlation exists between the thickness of the altered rims and that calculated from the amounts of Fe and Ti accumulated locally. Thus, immobile elements can be used reliably as indices of the extent of alteration because only near-equilibrium conditions occur. The good agreement between the experimental hydration rate of obsidians and the progress of natural corrosion, leads to the assumption that ion diffusion is the long-term controlling mechanism of corrosion. Such an assumption is supported by the particular distribution of the immobile elements which is due to ion diffusion and coprecipitation processes (self-organization genesis). These observations have implications for nuclear waste disposal topics and support the validity of obsidians as analogues of nuclear waste glasses with respect to some local environmental constraints induced by waste packaging and disposal. (author)

Natural analogue studies of engineered barrier materials at PNC Tokai, Japan

International Nuclear Information System (INIS)

Kamei, G.; Yusa, Y.; Yamagata, J.; Inoue, K.

1991-01-01

Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory tests. Natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence. Our natural analogue studies for the assessment of long-term durability of engineered barrier materials are outlined. Materials of young age and with simple history are the most suitable for the studies as: 1) properties of the materials tend to deteriorate over the longer term; and 2) detailed quantitative data on the term and on the environmental conditions can be obtained. The framework of our studies includes: 1) clarification of alteration phenomena, 2) examination of the environmental conditions, and 3) support experiments. (author)

Pena Blanca Natural Analogue Project: Summary of activities

International Nuclear Information System (INIS)

Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

2011-01-01

The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

Pena Blanca Natural Analogue Project: Summary of activities

Energy Technology Data Exchange (ETDEWEB)

Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

2011-02-01

The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

Pena blanca natural analogue project: summary of activities

International Nuclear Information System (INIS)

Levy, Schon S.; Goldstein, Steven J.; Abdel-Fattah, Amr I.

2010-01-01

The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

Pena blanca natural analogue project: summary of activities

Energy Technology Data Exchange (ETDEWEB)

Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

2010-12-08

The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

CEC Natural Analogue Working Group

International Nuclear Information System (INIS)

Come, B.; Chapman, N.A.

1989-01-01

The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

Molecular imaging: a new approach to nuclear cardiology

International Nuclear Information System (INIS)

Dobrucki, L.W.; Sinusas, A.J.

2005-01-01

Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentations will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutical angiogenesis

A Natural Analogue for Thermal-Hydrological-Chemical Coupled Processes at the Proposed Nuclear Waste Repository at Yucca Mountain, Nevada

International Nuclear Information System (INIS)

Bill Carey; Gordon Keating; Peter C. Lichtner

1999-01-01

Dike and sill complexes that intruded tuffaceous host rocks above the water table are suggested as natural analogues for thermal-hydrologic-chemical (THC) processes at the proposed nuclear waste repository at Yucca Mountain, Nevada. Scoping thermal-hydrologic calculations of temperature and saturation profiles surrounding a 30-50 m wide intrusion suggest that boiling conditions could be sustained at distances of tens of meters from the intrusion for several thousand years. This time scale for persistence of boiling is similar to that expected for the Yucca Mountain repository with moderate heat loading. By studying the hydrothermal alteration of the tuff host rocks surrounding the intrusions, insight and relevant data can be obtained that apply directly to the Yucca Mountain repository and can shed light on the extent and type of alteration that should be expected. Such data are needed to bound and constrain model parameters used in THC simulations of the effect of heat produced by the waste on the host rock and to provide a firm foundation for assessing overall repository performance. One example of a possible natural analogue for the repository is the Paiute Ridge intrusive complex located on the northeastern boundary of the Nevada Test Site, Nye County, Nevada. The complex consists of dikes and sills intruded into a partially saturated tuffaceous host rock that has stratigraphic sequences that correlate with those found at Yucca Mountain. The intrusions were emplaced at a depth of several hundred meters below the surface, similar to the depth of the proposed repository. The tuffaceous host rock surrounding the intrusions is hydrothermally altered to varying extents depending on the distance from the intrusions. The Paiute Ridge intrusive complex thus appears to be an ideal natural analogue of THC coupled processes associated with the Yucca Mountain repository. It could provide much needed physical and chemical data for understanding the influence of heat

Molecular nuclear cardiac imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Dong Soo; Paeng, Jin Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2004-04-01

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

Molecular nuclear cardiac imaging

International Nuclear Information System (INIS)

Lee, Dong Soo; Paeng, Jin Chul

2004-01-01

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect

Analogues to features and processes of a high-level radioactive waste repository proposed for Yucca Mountain, Nevada

Science.gov (United States)

Simmons, Ardyth M.; Stuckless, John S.; with a Foreword by Abraham Van Luik, U.S. Department of Energy

2010-01-01

Natural analogues are defined for this report as naturally occurring or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have taken place over time periods of decades to millennia and on spatial scales as much as tens of kilometers. Analogues provide an important temporal and spatial dimension that cannot be tested by laboratory or field-scale experiments. Analogues provide one of the multiple lines of evidence intended to increase confidence in the safe geologic disposal of high-level radioactive waste. Although the work in this report was completed specifically for Yucca Mountain, Nevada, as the proposed geologic repository for high-level radioactive waste under the U.S. Nuclear Waste Policy Act, the applicability of the science, analyses, and interpretations is not limited to a specific site. Natural and anthropogenic analogues have provided and can continue to provide value in understanding features and processes of importance across a wide variety of topics in addressing the challenges of geologic isolation of radioactive waste and also as a contribution to scientific investigations unrelated to waste disposal. Isolation of radioactive waste at a mined geologic repository would be through a combination of natural features and engineered barriers. In this report we examine analogues to many of the various components of the Yucca Mountain system, including the preservation of materials in unsaturated environments, flow of water through unsaturated volcanic tuff, seepage into repository drifts, repository drift stability, stability and alteration of waste forms and components of the engineered barrier system, and transport of radionuclides through unsaturated and saturated rock zones.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

In Vitro Evaluation of Molecular Tumor Targets in Nuclear Medicine: Immunohistochemistry Is One Option, but Under Which Conditions?

Science.gov (United States)

Reubi, Jean Claude

2017-12-01

The identification of new molecular targets for diagnostic and therapeutic applications using in vitro methods is an important challenge in nuclear medicine. One such method is immunohistochemistry, increasingly popular because it is easy to perform. This review presents the case for conducting receptor immunohistochemistry to evaluate potential molecular targets in human tumor tissue sections. The focus is on the immunohistochemistry of G-protein-coupled receptors, one of the largest families of cell surface proteins, representing a major class of drug targets and thus playing an important role in nuclear medicine. This review identifies common pitfalls and challenges and provides guidelines on performing such immunohistochemical studies. An appropriate validation of the target is a prerequisite for developing robust and informative new molecular probes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Invariant delineation of nuclear architecture in glioblastoma multiforme for clinical and molecular association.

Science.gov (United States)

Chang, Hang; Han, Ju; Borowsky, Alexander; Loss, Leandro; Gray, Joe W; Spellman, Paul T; Parvin, Bahram

2013-04-01

Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E) stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, multi-reference graph cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear features and their organization have identified 1) statistically significant subtypes based on several morphometric indexes, 2) whether each subtype can be predictive or not, and 3) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at: http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for quality

Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

CERN Document Server

Small, James S

2013-01-01

We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.

Science.gov (United States)

Koch, Maximilian F; Harteis, Sabrina; Blank, Iris D; Pestel, Galina; Tietze, Lutz F; Ochsenfeld, Christian; Schneider, Sabine; Sieber, Stephan A

2015-11-09

Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial π-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Natural analogue synthesis report, TDR-NBS-GS-000027 REV00 ICN02

International Nuclear Information System (INIS)

Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel, M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

2002-01-01

The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

Natural analogue synthesis report, TDR-NBS-GS-000027 rev00 icn02

Energy Technology Data Exchange (ETDEWEB)

Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel,M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

2002-04-01

The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M&O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide release

Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

KAUST Repository

Hasan, Mohammed Nihal

2018-02-09

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

KAUST Repository

Hasan, Mohammed Nihal; Choudhry, Hani; Razvi, Syed Shoeb; Moselhy, Said Salama; Kumosani, Taha Abduallah; Zamzami, Mazin A.; Omran, Ziad; Halwani, Majed A.; Al-Babili, Salim; Abualnaja, Khalid Omer; Al-Malki, Abdulrahman Labeed; Alhosin, Mahmoud; Asami, Tadao

2018-01-01

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Evaluations of Molecular Nuclear Medicine in pediatric urgencies; Evaluaciones de Medicina Nuclear Molecular en urgencias pediatricas

Energy Technology Data Exchange (ETDEWEB)

Martinez-Duncker R, C [Departamento de Medicina Nuclear Molecular, Hospital Infantil de Mexico, Mexico D.F. (Mexico)

2000-07-01

Several diagnostic procedures of Molecular Nuclear Medicine are considered in first choice in clinical evaluation of patients with different illnesses. So, the gammagraphy is the diagnostic form more sensitive to detect alterations of the perfusion on organs and systems such as bones, heart, brain, lungs or kidneys. Also is possible to identify, localize, evaluate the activity of inflammatory processes such as cellulitis, arthritis, osteomyelitis, the abscesses and several primary or metastatic tumours before each other diagnostic technique. In this work is treated about the importance of treatments with radioactive materials have been an important reappearance in last years since with the present capacity to localize specifically intracellular processes (for example, synthesis of DNA) new gateways are opened to research which in coming years would be of great utility. (Author)

Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis

Directory of Open Access Journals (Sweden)

Luc Calvin Owono Owono

2013-01-01

Full Text Available We design here new nanomolar antituberculotics, inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt, by means of structure-based molecular design. 3D models of TMPKmt-inhibitor complexes have been prepared from the crystal structure of TMPKmt cocrystallized with the natural substrate deoxythymidine monophosphate (dTMP (1GSI for a training set of 15 thymidine analogues (TMDs with known activity to prepare a QSAR model of interaction establishing a correlation between the free energy of complexation and the biological activity. Subsequent validation of the predictability of the model has been performed with a 3D QSAR pharmacophore generation. The structural information derived from the model served to design new subnanomolar thymidine analogues. From molecular modeling investigations, the agreement between free energy of complexation (ΔΔGcom and Ki values explains 94% of the TMPKmt inhibition (pKi=-0.2924ΔΔGcom+3.234;R2=0.94 by variation of the computed ΔΔGcom and 92% for the pharmacophore (PH4 model (pKi=1.0206×pKipred-0.0832,  R2=0.92. The analysis of contributions from active site residues suggested substitution at the 5-position of pyrimidine ring and various groups at the 5′-position of the ribose. The best inhibitor reached a predicted Ki of 0.155 nM. The computational approach through the combined use of molecular modeling and PH4 pharmacophore is helpful in targeted drug design, providing valuable information for the synthesis and prediction of activity of novel antituberculotic agents.

Nuclear chemical method for preparation of free carbenium ions and radiochemical investigation of reactions of these particles

International Nuclear Information System (INIS)

Nefedov, V.D.; Sinotova, E.N.; Toropova, M.A.

1980-01-01

Tritium nuclear transformation (β-decay) in the composition of the molecules of hydrocarbons, appearance of primary molecular ions and formation of free carbenium ion are the main items of nuclear-chemical method of preparation of free carbenium ions. The method permits to prepare carbenium ions present in free state, i.e. without counterion and without solvate sheath of variou nitial localization of the charge. The rate of carbenium ion generation is strictly definite and does not depend upon outer conditions. The method suggested permits to prepare carbenium ions in all phases, study their reactions with individual substances in gaseous, liquid and solid states. The study of ion-molecular reactions is carried out using radiochemical method. The analysis of the products is made using the method of gaseous radiochromatography. Development of preparation techniques of carbenium ions and their analogues, study of the reactions of these particles with different classes of compounds, investigation of the effect of different factors upon procedure of ion-molecular reactions are the main directions of the investigations

The Greenland analogue project. Yearly report 2010

Energy Technology Data Exchange (ETDEWEB)

Harper, J; Brinkerhoff, D; Johnson, J [University of Montana, Missoula (United States); Ruskeeniemi, T; Engstroem, J; Kukkonen, I [Geological Survey of Finland (Finland); and others

2012-04-15

A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

The Greenland analogue project. Yearly report 2010

International Nuclear Information System (INIS)

Harper, J.; Brinkerhoff, D.; Johnson, J.; Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I.

2012-04-01

A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

Anisotropic Rotational Diffusion Studied by Nuclear Spin Relaxation and Molecular Dynamics Simulation: An Undergraduate Physical Chemistry Laboratory

Science.gov (United States)

Fuson, Michael M.

2017-01-01

Laboratories studying the anisotropic rotational diffusion of bromobenzene using nuclear spin relaxation and molecular dynamics simulations are described. For many undergraduates, visualizing molecular motion is challenging. Undergraduates rarely encounter laboratories that directly assess molecular motion, and so the concept remains an…

Harmony of computational quantum chemistry and experimental chemistry: Comprehensive DFT studies, microsynthesis, and characterization of mustard gas polysulfide analogues

Science.gov (United States)

Saeidian, Hamid; Faraz, Sajjad Mousavi; Mirjafary, Zohreh; Babri, Mehran

2018-05-01

After microsynthesis, structures of mustard gas polysulfide analogues were characterized using electron impact (EI) mass spectrometry. General EI fragmentation pathways for such compounds are proposed. The structure of sulfur mustard (HD) and its two other polysulfide analogues have been examined through B3LYP/6-311++G(2d, 2p) calculations. Geometrical analysis of HD shows that the calculated bond distances are satisfactorily comparable with experimental results. Calculated NMR chemical shifts for HD also were compared with experimental data, indicating good agreement both for 1H and 13C atoms. The vibrational frequencies of HD and polysulfide analogues have been precisely assigned. At the end, based on visual inspection of lowest unoccupied molecular orbitals and the relative difference in the total energies of their episulfonium ions, relative reactivity of HD and its polysulfide analogues were investigated.

Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

Directory of Open Access Journals (Sweden)

Leonie Harmse

Full Text Available Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05. Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05, with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

Science.gov (United States)

Harmse, Leonie; Dahan-Farkas, Nurit; Panayides, Jenny-Lee; van Otterlo, Willem; Penny, Clement

2015-01-01

Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05). Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05), with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

The chaos and order in nuclear molecular dynamics

International Nuclear Information System (INIS)

Srokowski, T.

1995-01-01

The subject of the presented report is role of chaos in scattering processes in the frame of molecular dynamics. In this model, it is assumed that scattering particles (nuclei) consist of not-interacted components as alpha particles or 12 C, 16 O and 20 Ne clusters. The results show such effects as dynamical in stabilities and fractal structure as well as compound nuclei decay and heavy-ion fusion. The goal of the report is to make the reader more familiar with the chaos model and its application to nuclear phenomena. 157 refs, 40 figs

Diagnostic nuclear medicine. 2. rev. ed.

International Nuclear Information System (INIS)

Schiepers, C.

2006-01-01

The field of nuclear medicine is undergoing rapid expansion, and is evolving into diagnostic molecular imaging. During recent years, dual-modality imaging with PET/CT has gained acceptance and this is currently the fastest-growing technique for oncological imaging applications. The glucose analogue FDG has held its place in diagnostic oncology, assessment of myocardial viability and diagnosis of neuro-degenerative disorders. Peptides have become even more important as imaging agents. The accuracy of hepatobiliary scintigraphy has been enhanced by cholecystokinin. The use of ACE inhibitors in the evaluation of renovascular hypertension has become the standard in renography. New instrumentation has led to faster scanners, and computer development to better image processing software. Automatic processing is more common, and standardization of protocols can be accomplished easily. The field of gene imaging has progressed, although routine clinical applications are not yet available. The present text, supplemented with many detailed and informative illustrations, represents an adjunct to the standard knowledge of diagnostic nuclear medicine and provides both the student and the professional with an overview of developments during the past decade. (orig.)

Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

Science.gov (United States)

Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

2017-08-01

Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear Architecture and Patterns of Molecular Evolution Are Correlated in the Ciliate Chilodonella uncinata.

Science.gov (United States)

Maurer-Alcalá, Xyrus X; Katz, Laura A

2016-06-08

The relationship between nuclear architecture and patterns of molecular evolution in lineages across the eukaryotic tree of life is not well understood, partly because molecular evolution is traditionally explored as changes in base pairs along a linear sequence without considering the context of nuclear position of chromosomes. The ciliate Chilodonella uncinata is an ideal system to address the relationship between nuclear architecture and patterns of molecular evolution as the somatic macronucleus of this ciliate is composed of a peripheral DNA-rich area (orthomere) and a DNA-poor central region (paramere) to form a "heteromeric" macronucleus. Moreover, because the somatic chromosomes of C. uncinata are highly processed into "gene-sized" chromosomes (i.e., nanochromosomes), we can assess fine-scale relationships between location and sequence evolution. By combining fluorescence microscopy and analyses of transcriptome data from C. uncinata, we find that highly expressed genes have the greatest codon usage bias and are enriched in DNA-poor regions. In contrast, genes with less biased sequences tend to be concentrated in DNA abundant areas, at least during vegetative growth. Our analyses are consistent with recent work in plants and animals where nuclear architecture plays a role in gene expression. At the same time, the unusual localization of nanochromosomes suggests that the highly structured nucleus in C. uncinata may create a "gene bank" that facilitates rapid changes in expression of genes required only in specific life history stages. By using "nonmodel" organisms like C. uncinata, we can explore the universality of eukaryotic features while also providing examples of novel properties (i.e., the presence of a gene bank) that build from these features. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Current research in nuclear medicine and molecular imaging in Italy: highlights of the 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging.

Science.gov (United States)

Cuocolo, A

2011-06-01

The 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN) took place in Rimini on March 18-21, 2011 under the chairmanship of Professor Stefano Fanti. The program was of excellent quality and put a further step for the settlement of the standardized AIMN congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success with more than 1100 total participants and more than 360 abstracts received. Of these, 40 abstracts were accepted for oral and 285 for poster presentations. The original investigations presented were related to different areas of nuclear medicine and molecular imaging, with particular focus on advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in well established areas of clinical application, such as oncology, cardiology, neurology, psychiatry, endocrinology, paediatrics, and infection and inflammation. Noteworthy, several presentations at this congress, focusing on quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, identified when nuclear medicine procedures achieved clinical effectiveness for patient care and patient management and further demonstrated that nuclear medicine plays a crucial role in the contemporary medical scenario. This highlights lecture is only a brief summary of the large amount of data presented and discussed, which can be found in much greater detail in the congress abstract book, published as volume 55, supplement 1 of the Q J Nucl Med Mol Imaging in April 2011.

Relation between molecular electronic structure and nuclear spin-induced circular dichroism

DEFF Research Database (Denmark)

Štěpánek, Petr; Coriani, Sonia; Sundholm, Dage

2017-01-01

with spatially localized, high-resolution information. To survey the factors relating the molecular and electronic structure to the NSCD signal, we theoretically investigate NSCD of twenty structures of the four most common nucleic acid bases (adenine, guanine, thymine, cytosine). The NSCD signal correlates...... with the spatial distribution of the excited states and couplings between them, reflecting changes in molecular structure and conformation. This constitutes a marked difference to the nuclear magnetic resonance (NMR) chemical shift, which only reflects the local molecular structure in the ground electronic state....... The calculated NSCD spectra are rationalized by means of changes in the electronic density and by a sum-over-states approach, which allows to identify the contributions of the individual excited states. Two separate contributions to NSCD are identified and their physical origins and relative magnitudes...

Defining the selectivity of processes along the auxin response chain: a study using auxin analogues

Czech Academy of Sciences Publication Activity Database

Simon, Sibu; Kubeš, Martin; Baster, P.; Robert, S.; Dobrev, Petre; Friml, J.; Petrášek, Jan; Zažímalová, Eva

2013-01-01

Roč. 200, č. 4 (2013), s. 1034-1048 ISSN 0028-646X R&D Projects: GA ČR(CZ) GAP305/11/0797 Institutional research plan: CEZ:AV0Z50380511 Keywords : auxin analogues * auxin signalling * auxin transport Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.545, year: 2013

Metal ion interaction with phosphorylated tyrosine analogue monolayers on gold.

Science.gov (United States)

Petoral, Rodrigo M; Björefors, Fredrik; Uvdal, Kajsa

2006-11-23

Phosphorylated tyrosine analogue molecules (pTyr-PT) were assembled onto gold substrates, and the resulting monolayers were used for metal ion interaction studies. The monolayers were characterized by X-ray photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy (IRAS), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS), both prior to and after exposure to metal ions. XPS verified the elemental composition of the molecular adsorbate and the presence of metal ions coordinated to the phosphate groups. Both the angle-dependent XPS and IRAS results were consistent with the change in the structural orientation of the pTyr-PT monolayer upon exposure to metal ions. The differential capacitance of the monolayers upon coordination of the metal ions was evaluated using EIS. These metal ions were found to significantly change the capacitance of the pTyr-PT monolayers in contrast to the nonphosphorylated tyrosine analogue (TPT). CV results showed reduced electrochemical blocking capabilities of the phosphorylated analogue monolayer when exposed to metal ions, supporting the change in the structure of the monolayer observed by XPS and IRAS. The largest change in the structure and interfacial capacitance was observed for aluminum ions, compared to calcium, magnesium, and chromium ions. This type of monolayer shows an excellent capability to coordinate metal ions and has a high potential for use as sensing layers in biochip applications to monitor the presence of metal ions.

How to find the optimal partner--studies of snurportin 1 interactions with U snRNA 5' TMG-cap analogues containing modified 2-amino group of 7-methylguanosine.

Science.gov (United States)

Piecyk, Karolina; Niedzwiecka, Anna; Ferenc-Mrozek, Aleksandra; Lukaszewicz, Maciej; Darzynkiewicz, Edward; Jankowska-Anyszka, Marzena

2015-08-01

Snurportin 1 is an adaptor protein that mediates the active nuclear import of uridine-rich small nuclear RNAs (U snRNA) by the importin-β receptor pathway. Its cellular activity influences the overall transport yield of small ribonucleoprotein complexes containing N(2),N(2),7-trimethylguanosine (TMG) capped U snRNA. So far little is still known about structural requirements related to molecular recognition of the trimethylguanosine moiety by snurportin in solution. Since these interactions are of a great biomedical importance, we synthesized a series of new 7-methylguanosine cap analogues with extended substituents at the exocyclic 2-amino group to gain a deeper insight into how the TMG-cap is adapted into the snurportin cap-binding pocket. Prepared chemical tools were applied in binding assays using emission spectroscopy. Surprisingly, our results revealed strict selectivity of snurportin towards the TMG-cap structure that relied mainly on its structural stiffness and compactness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations

DEFF Research Database (Denmark)

Liin, Sara I; Larsson, Johan E; Barro-Soria, Rene

2016-01-01

. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting...

Use of analogues to build technologists' confidence: NAnet

International Nuclear Information System (INIS)

Noseck, Ulrich

2008-01-01

The relevance of analogues to radioactive waste management stems from the long timescales that have to be considered. Periods up to a million or more years into the future need to be considered and these are beyond experimental investigation and human experience. Within the last years the term 'Natural Analogue' has got a much wider meaning and includes man-made analogues as well. The role of natural analogues in the safety case depends amongst others on the time scale to be covered. Therefore, it is useful to classify them by the time period addressed in the study. Here it is referred to: industrial analogues which started earliest 150 years ago, archaeological analogues, which cover time frames between the past 10 000 and 150 years, and geological analogues, which usually cover time frames of more than 10 000 years and in most cases more than million years. The current interest in analogues in different countries is reflected by several recent review projects with emphasis on the application of natural analogue study results in performance assessment. The most recent international review was performed within the 5. EURATOM Framework of the EC by the NAnet project, a network on the review of natural analogue studies with emphasis on the application of analogues in long-term safety assessment and communication. The overall aim of the NAnet project was to review the past and present use and understanding of natural analogues, and to make recommendations for their future use. The project covered 'traditional' natural analogue studies, such as large-scale investigations of radionuclide transport around uranium ore bodies, and process or mechanistic analogue studies such as those examining natural glass and bentonite clay stability. To complete the picture, a restricted range of other studies of natural systems which employ a similar philosophy to analogues was also included in the scope. These included studies which have examined radionuclide transport and retardation

Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study.

Science.gov (United States)

Węglarz-Tomczak, Ewelina; Burda-Grabowska, Małgorzata; Giurg, Mirosław; Mucha, Artur

2016-11-01

A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC 50 =1-12μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computational modeling of the behavior of nuclear materials (2). Molecular simulations for nuclear materials. Current situation and future perspective

International Nuclear Information System (INIS)

Okita, Taira; Itakura, Mitsuhiro

2017-01-01

Molecular simulations for nuclear materials aim to reproduce atomistic-scale phenomena induced by irradiation and infer the change in material properties. In the present work, recent progress in this field is presented. In particular, the following three topics are explained: (1) Quantification of lattice defects formation process induced by fast neutron collision. (2) Identification of dislocation-channeling mechanism induced by interactions between defect clusters and dislocations. (3) Modeling of the three dimensional movement of defect clusters using molecular dynamics and kinetic Monte Carlo simulations. (author)

Natural and archaeological analogues: a review

International Nuclear Information System (INIS)

Brookins, D.G.

1987-01-01

In this chapter natural analogues in the geomedia for various aspects of radioactive waste disposal are discussed. Particular reference is made to the Okla Natural Reactor in Gabon. Igneous contact zones are discussed and natural analogues of waste-form materials. The importance of archaeological remains and anthropogenic materials left by man, in assessing weathering conditions and serving as radioactive waste analogues, is also emphasised. (UK)

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions.

Science.gov (United States)

Choi, Hongyoon

2018-04-01

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

In silico and in vitro characterization of anti-amyloidogenic activity of vitamin K3 analogues for Alzheimer's disease.

Science.gov (United States)

Huy, Pham Dinh Quoc; Yu, Yao-Chung; Ngo, Son Tung; Thao, Tran Van; Chen, Chin-Piao; Li, Mai Suan; Chen, Yi-Cheng

2013-04-01

Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity. Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ. Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ. The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD. VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD. Copyright © 2012 Elsevier B.V. All rights reserved.

Integration of natural analogue studies within a national confidence-building programme

Energy Technology Data Exchange (ETDEWEB)

Tsuboya, T. [Radioactive Waste Management Funding and Research Centre (RWMC), No. 15 Mori Bldg., 2-8-10 Toranomon, Minato-ku, Tokyo 105-0001 (Japan)]. E-mail: tsuboya@rwmc.or.jp; McKinley, I.G. [National Cooperative for the Disposal of Radioactive Waste (Nagra), Hardstrasse 73, 5430 Wettingen (Switzerland)]. E-mail: ian.mackinley@nagra.ch

2004-07-01

It is now commonly recognised that public acceptance is one of the key factors influencing the feasibility of nuclear waste repositories - or indeed, any major industrial or technical developments. The general antipathy against anything 'radioactive' is further compounded by the difficulty of developing a simple, transparent safety case for a facility deep underground that clearly shows that there is no health risk at any time in the future. Natural analogues have great potential as communication tools within such a safety case. The analogue programme must, however, be embedded in an integrated communication strategy that identifies the key concerns of different critical groups and identifies the most appropriate way to address them. Some of the important characteristics of such a strategy include: demonstration of high levels of competence, openness and honesty of involved organisations (both regulators and implementers); ensuring consistency of policy, procedures and utilisation of technical arguments; recognition of the importance of reacting to feedback from all involved parties. (author)

Vitamin E analogues as a novel group of mitocans: Anti-cancer agents that act by targeting mitochondria

Czech Academy of Sciences Publication Activity Database

Neužil, Jiří; Dong, L.F.; Ramanathapuram, L.; Hahn, T.; Chladová, Miroslava; Wang, X. F.; Zobalová, Renata; Procházka, L.; Gold, M.; Freeman, R.; Turánek, J.; Akporiaye, E.T.; Dyason, J.C.; Ralph, S.J.

2007-01-01

Roč. 28, 5-6 (2007), s. 607-645 ISSN 0098-2997 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50520514 Keywords : tocopherol analogues * apoptosis * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.386, year: 2007

Rapid screening and structural elucidation of a novel sibutramine analogue in a weight loss supplement: 11-desisobutyl-11-benzylsibutramine.

Science.gov (United States)

Mans, Daniel J; Gucinski, Ashley C; Dunn, Jamie D; Gryniewicz-Ruzicka, Connie M; Mecker-Pogue, Laura C; Kao, Jeff L-F; Ge, Xia

2013-09-01

A novel analogue of sibutramine, 11-desisobutyl-11-benzylsibutramine, has been discovered. During routine ion mobility spectrometry (IMS) screening of a weight loss supplement collected at an US FDA import operation facility an unknown peak was observed. Further analysis of the supplement by liquid chromatography-mass spectrometry (LC-MS) and high resolution mass spectrometry revealed an unknown peak with a relative retention time of 1.04 with respect to sibutramine and a predicted formula of C20H24NCl. In order to elucidate the analogue's structure, it was isolated from the supplement and characterized by tandem mass spectrometry and nuclear magnetic resonance (NMR), which revealed the analogue possessed a benzyl moiety at the 11 position in place of the isobutyl group associated with sibutramine. Copyright © 2013. Published by Elsevier B.V.

Novel sponge-like molecularly imprinted mesoporous silica material for selective isolation of bisphenol A and its analogues from sediment extracts

International Nuclear Information System (INIS)

Yang, Jiajia; Li, Yun; Wang, Jincheng; Sun, Xiaoli; Shah, Syed Mazhar; Cao, Rong; Chen, Jiping

2015-01-01

Highlights: • Novel sponge-like molecularly imprinted mesoporous silica was synthesized. • Extraordinarily large specific surface area and highly interconnected 3-D porous network. • High specific adsorption capacity and fast adsorption kinetics for BPA. • Good class-selectivity and clean-up effect for bisphenols in sediment under SPE mode. • Good recoveries and sensitivity for bisphenols using the MISMS–SPE coupled with HPLC–DAD method. - Abstract: Bisphenol A (BPA) imprinted sponge mesoporous silica was synthesized using a combination of semi-covalent molecular imprinting and simple self-assembly process. The molecularly imprinted sponge mesoporous silica (MISMS) material obtained was characterized by FT-IR, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption measurements. The results show that the MISMS possessed a large specific surface area (850.55 m 2 g −1 ) and a highly interconnected 3-D porous network. As a result, the MISMS demonstrated a superior specific adsorption capacity of 169.22 μmol g −1 and fast adsorption kinetics (reaching equilibrium within 3 min) for BPA. Good class selectivity for BPA and its analogues (bisphenol F, bisphenol B, bisphenol E and bisphenol AF) was also demonstrated by the sorption experiment. The MISMS as solid-phase extraction (SPE) material was then evaluated for isolation and clean-up of these bisphenols (BPs) from sediment samples. An accurate and sensitive analytical method based on the MISMS–SPE coupled with HPLC–DAD has been successfully established for simultaneous determination of five BPs in river sediments with detection limits of 0.43–0.71 ng g −1 dry weight (dw). The recoveries of BPs for lyophilizated sediment samples at two spiking levels (50 and 500 ng g −1 dw for each BP) were in the range of 75.5–105.5% with RSD values below 7.5%

Novel sponge-like molecularly imprinted mesoporous silica material for selective isolation of bisphenol A and its analogues from sediment extracts

Energy Technology Data Exchange (ETDEWEB)

Yang, Jiajia [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yun; Wang, Jincheng [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Sun, Xiaoli [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Shah, Syed Mazhar [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Cao, Rong [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Chen, Jiping, E-mail: chenjp@dicp.ac.cn [Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China)

2015-01-01

Highlights: • Novel sponge-like molecularly imprinted mesoporous silica was synthesized. • Extraordinarily large specific surface area and highly interconnected 3-D porous network. • High specific adsorption capacity and fast adsorption kinetics for BPA. • Good class-selectivity and clean-up effect for bisphenols in sediment under SPE mode. • Good recoveries and sensitivity for bisphenols using the MISMS–SPE coupled with HPLC–DAD method. - Abstract: Bisphenol A (BPA) imprinted sponge mesoporous silica was synthesized using a combination of semi-covalent molecular imprinting and simple self-assembly process. The molecularly imprinted sponge mesoporous silica (MISMS) material obtained was characterized by FT-IR, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption–desorption measurements. The results show that the MISMS possessed a large specific surface area (850.55 m{sup 2} g{sup −1}) and a highly interconnected 3-D porous network. As a result, the MISMS demonstrated a superior specific adsorption capacity of 169.22 μmol g{sup −1} and fast adsorption kinetics (reaching equilibrium within 3 min) for BPA. Good class selectivity for BPA and its analogues (bisphenol F, bisphenol B, bisphenol E and bisphenol AF) was also demonstrated by the sorption experiment. The MISMS as solid-phase extraction (SPE) material was then evaluated for isolation and clean-up of these bisphenols (BPs) from sediment samples. An accurate and sensitive analytical method based on the MISMS–SPE coupled with HPLC–DAD has been successfully established for simultaneous determination of five BPs in river sediments with detection limits of 0.43–0.71 ng g{sup −1} dry weight (dw). The recoveries of BPs for lyophilizated sediment samples at two spiking levels (50 and 500 ng g{sup −1} dw for each BP) were in the range of 75.5–105.5% with RSD values below 7.5%.

Capture of organic iodides from nuclear waste by metal-organic framework-based molecular traps.

Science.gov (United States)

Li, Baiyan; Dong, Xinglong; Wang, Hao; Ma, Dingxuan; Tan, Kui; Jensen, Stephanie; Deibert, Benjamin J; Butler, Joseph; Cure, Jeremy; Shi, Zhan; Thonhauser, Timo; Chabal, Yves J; Han, Yu; Li, Jing

2017-09-07

Effective capture of radioactive organic iodides from nuclear waste remains a significant challenge due to the drawbacks of current adsorbents such as low uptake capacity, high cost, and non-recyclability. We report here a general approach to overcome this challenge by creating radioactive organic iodide molecular traps through functionalization of metal-organic framework materials with tertiary amine-binding sites. The molecular trap exhibits a high CH 3 I saturation uptake capacity of 71 wt% at 150 °C, which is more than 340% higher than the industrial adsorbent Ag 0 @MOR under identical conditions. These functionalized metal-organic frameworks also serve as good adsorbents at low temperatures. Furthermore, the resulting adsorbent can be recycled multiple times without loss of capacity, making recyclability a reality. In combination with its chemical and thermal stability, high capture efficiency and low cost, the adsorbent demonstrates promise for industrial radioactive organic iodides capture from nuclear waste. The capture mechanism was investigated by experimental and theoretical methods.Capturing radioactive organic iodides from nuclear waste is important for safe nuclear energy usage, but remains a significant challenge. Here, Li and co-workers fabricate a stable metal-organic framework functionalized with tertiary amine groups that exhibits high capacities for radioactive organic iodides uptake.

Capture of organic iodides from nuclear waste by metal-organic framework-based molecular traps

KAUST Repository

Li, Baiyan

2017-09-01

Effective capture of radioactive organic iodides from nuclear waste remains a significant challenge due to the drawbacks of current adsorbents such as low uptake capacity, high cost, and non-recyclability. We report here a general approach to overcome this challenge by creating radioactive organic iodide molecular traps through functionalization of metal-organic framework materials with tertiary amine-binding sites. The molecular trap exhibits a high CH3I saturation uptake capacity of 71 wt% at 150 °C, which is more than 340% higher than the industrial adsorbent Ag0@MOR under identical conditions. These functionalized metal-organic frameworks also serve as good adsorbents at low temperatures. Furthermore, the resulting adsorbent can be recycled multiple times without loss of capacity, making recyclability a reality. In combination with its chemical and thermal stability, high capture efficiency and low cost, the adsorbent demonstrates promise for industrial radioactive organic iodides capture from nuclear waste. The capture mechanism was investigated by experimental and theoretical methods.Capturing radioactive organic iodides from nuclear waste is important for safe nuclear energy usage, but remains a significant challenge. Here, Li and co-workers fabricate a stable metal-organic framework functionalized with tertiary amine groups that exhibits high capacities for radioactive organic iodides uptake.

A Short Term Analogue Memory

DEFF Research Database (Denmark)

Shah, Peter Jivan

1992-01-01

A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.

Science.gov (United States)

Lepage, Mathieu L; Schneider, Jérémy P; Bodlenner, Anne; Compain, Philippe

2015-11-06

A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars.

Dynamical symmetries of molecular states in atomic, nuclear and hadron physics

International Nuclear Information System (INIS)

Iachello, F.; Cseh, J.; Levai, G.

1995-01-01

The algebraic description of dipole degrees of freedom is discussed. These degrees of freedom are relevant to two and few-body systems, as well as in the collective motion of many-body systems. Applications to molecular, nuclear and hadron spectroscopy are presented. Different internal degrees of freedom can also be coupled to the spatial ones, leading to realistic models of several complex systems. (author)

Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

CERN Document Server

Pickering, J.

2015-06-15

This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

Quantum analogue computing.

Science.gov (United States)

Kendon, Vivien M; Nemoto, Kae; Munro, William J

2010-08-13

We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

Proceedings of the forty third annual conference of Society of Nuclear Medicine India: empowering modern medicine with molecular nuclear medicine

International Nuclear Information System (INIS)

2011-01-01

Theme of the 43rd Annual Conference of the Society of Nuclear Medicine India is 'empowering modem medicine with molecular nuclear medicine'. Keeping the theme in mind, the scientific committee has arranged an attractive and comprehensive program for both physicians and scientists reflecting the multimodality background of Nuclear Medicine and Metabolic Imaging. During this meeting the present status and future prospects of Nuclear medicine are discussed at length by esteemed faculty in dedicated symposia and interesting featured sessions which are immensely facilitate in educating the participants. Nuclear Medicine has come a long way since the first applications of radioiodine in the diagnosis of thyroid disease. The specialty of nuclear medicine in India is growing very rapidly. Technology continues to push the field in new directions and open new pathways for providing optimal care to patients. It is indeed an exciting time in the world of imaging and in the field of nuclear medicine. Innovative techniques in hardware and software offer advantages for enhanced accuracy. New imaging agents, equipment, and software will provide us with new opportunities to improve current practices and to introduce new technology into the clinical protocols. Papers relevant to INIS are indexed separately

Molecular Dynamics of Water in Wood Studied by Fast Field Cycling Nuclear Magnetic Resonance Relaxometry

Directory of Open Access Journals (Sweden)

Xinyu Li

2016-01-01

Full Text Available Water plays a very important role in wood and wood products. The molecular motion of water in wood is susceptible to thermal activation. Thermal energy makes water molecules more active and weakens the force between water and wood; therefore, the water molecules dynamic properties are greatly influenced. Molecular dynamics study is important for wood drying; this paper therefore focuses on water molecular dynamics in wood through fast field cycling nuclear magnetic resonance relaxometry techniques. The results show that the spin-lattice relaxation rate decreases with the Larmor frequency. Nuclear magnetic resonance dispersion profiles at different temperatures could separate the relaxation contribution of water in bigger pores and smaller pores. The T1 distribution from wide to narrow at 10 MHz Larmor frequency reflects the shrinkage of pore size with the higher temperature. The dependence of spin-lattice relaxation rate on correlation time for water molecular motion based on BPP (proposed by Bloembergen, Purcell, and Pound theory shows that water correlation time increases with higher temperature, and its activation energy, calculated using the Arrhenius transformation equation, is 9.06±0.53 kJ/mol.

Synthesis of novel 11-desmethyl analogues of laulimalide by Nozaki-Kishi coupling.

Science.gov (United States)

Paterson, Ian; Bergmann, Hermann; Menche, Dirk; Berkessel, Albrecht

2004-04-15

As a first entry into structurally simplified analogues of the anticancer agent laulimalide, 11-desmethyl compounds 2 and 3 were selected by molecular modeling. The unfavorable diastereoselectivity in the key synthetic step, a Nozaki-Kishi coupling between macrocyclic aldehyde 4 and vinyl iodide 5, was overcome either by use of catalytic amounts of DIANANE-type ligands or L-Selectride reduction of the derived enone. This methodology should allow modular introduction of other, unnatural, side chains. [reaction: see text

Natural analogues for processes affecting disposal of high-level radioactive waste in the vadose zone

Science.gov (United States)

Stuckless, J. S.

2003-04-01

Natural analogues can contribute to understanding and predicting the performance of subsystems and processes affecting a mined geologic repository for high-level radioactive waste in several ways. Most importantly, analogues provide tests for various aspects of systems of a repository at dimensional scales and time spans that cannot be attained by experimental study. In addition, they provide a means for the general public to judge the predicted performance of a potential high-level nuclear waste repository in familiar terms such that the average person can assess the anticipated long-term performance and other scientific conclusions. Hydrologists working on the Yucca Mountain Project (currently the U.S. Department of Energy's Office of Repository Development) have modeled the flow of water through the vadose zone at Yucca Mountain, Nevada and particularly the interaction of vadose-zone water with mined openings. Analogues from both natural and anthropogenic examples confirm the prediction that most of the water moving through the vadose zone will move through the host rock and around tunnels. This can be seen both quantitatively where direct comparison between seepage and net infiltration has been made and qualitatively by the excellent degree of preservation of archaeologic artifacts in underground openings. The latter include Paleolithic cave paintings in southwestern Europe, murals and artifacts in Egyptian tombs, painted subterranean Buddhist temples in India and China, and painted underground churches in Cappadocia, Turkey. Natural analogues also suggest that this diversion mechanism is more effective in porous media than in fractured media. Observations from natural analogues are also consistent with the modeled decrease in the percentage of infiltration that becomes seepage with a decrease in amount of infiltration. Finally, analogues, such as tombs that have ben partially filled by mud flows, suggest that the same capillary forces that keep water in the

Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages.

Science.gov (United States)

Yadav, Umesh C S; Kalariya, Nilesh M; Srivastava, Satish K; Ramana, Kota V

2010-05-15

This study was designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappaB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-kappaB were significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE(2) was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-kappaB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases. Copyright 2010 Elsevier Inc. All rights reserved.

Mineral-modeled ceramics for long-term storage of high-level nuclear wastes

International Nuclear Information System (INIS)

Vance, E.R.

1980-01-01

Over the past ten years, Penn State's Materials Research Laboratory has done extensive work on mineral-modeled ceramics for high-level nuclear waste storage. These ceramics are composed of several mineral analogues that form a monolithic polycrystalline aggregate. Mineral-modeling can be made in a similar fashion to nuclear waste glasses, and their naturally occurring analogues are known to last millions, and even billions, of years in hot, wet conditions. It is believed that such ceramics could reduce dispersal of radionuclides by leaching to a minimum

Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

Directory of Open Access Journals (Sweden)

Jitendra D. Bhosale

2018-04-01

Full Text Available The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.

Applications of the semiclassical spectral method to nuclear, atomic, molecular, and polymeric dynamics

International Nuclear Information System (INIS)

Koszykowski, M.L.; Pfeffer, G.A.; Noid, D.W.

1987-01-01

Nonlinear dynamics plays a dominant role in a variety of important problems in chemical physics. Examples are unimolecular reactions, infrared multiphoton decomposition of molecules, the pumping process of the gamma ray laser, dissociation of vibrationally excited state-selected van der Waals's complexes, and many other chemical and atomic processes. The present article discusses recent theoretical studies on the quasi-periodic and chaotic dynamic aspects of vibrational-rotational states of atomic, nuclear, and molecular systems using the semiclassical spectral method (SSM). The authors note that the coordinates, momenta, and so on, are found using classical mechanics in the studies included in this review. They outline the semiclassical spectral method and a wide variety of applications. Although this technique was first developed ten years ago, it has proved to be tremendously successful as a tool used in dynamics problems. Applications include problems in nonlinear dynamics, molecular and atomic spectra, surface science, astronomy and stellar dynamics, nuclear physics, and polymer physics

Dissolution studies of natural analogues spent fuel and U(VI)-Silicon phases of and oxidative alteration process; Estudios de disolucion de analogos naturales de combustible nuclear irradiado y de fases de U(VI)-Silicio representativas de un proceso de alteracion oxidativa

Energy Technology Data Exchange (ETDEWEB)

Perez Morales, I

2000-07-01

In order to understand the long-term behavior of the nuclear spent fuel in geological repository conditions, we have performed dissolution studies with natural analogues to UO{sub 2} as well as with solid phases representatives of the oxidative alteration pathway of uranium dioxide, as observed in both natural environment and laboratory studies. In all cases, we have studied the influence of the bicarbonate concentration in the dissolution process, as a first approximation to the groundwater composition of a granitic environment, where carbonate is one of the most important complexing agents. As a natural analogue to the nuclear spent fuel some uraninite samples from the Oklo are deposit in Gabon, where chain fission reactions took place 2000 millions years ago, as well as a pitchblende sample from the mine Fe ore deposit, in Salamanca (spain) have been studied. The studies have been performed at 25 and 60 degree centigree and 60 degree centigree, and they have focussed on the determination of both the thermodynamic and the kinetic properties of the different samples studied, using batch and continuous experimental methodologies, respectively. (Author)

The Greenland Analogue Project. Yearly Report 2009

Energy Technology Data Exchange (ETDEWEB)

2010-12-15

A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

The Greenland Analogue Project. Yearly Report 2009

International Nuclear Information System (INIS)

2010-12-01

A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

BALANOL ANALOGUES

DEFF Research Database (Denmark)

1997-01-01

The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid...

Dissolution studies of natural analogues spent fuel and U(VI)-Silicon phases of and oxidative alteration process

International Nuclear Information System (INIS)

Perez Morales, I.

2000-01-01

In order to understand the long-term behavior of the nuclear spent fuel in geological repository conditions, we have performed dissolution studies with natural analogues to UO 2 as well as with solid phases representatives of the oxidative alteration pathway of uranium dioxide, as observed in both natural environment and laboratory studies. In all cases, we have studied the influence of the bicarbonate concentration in the dissolution process, as a first approximation to the groundwater composition of a granitic environment, where carbonate is one of the most important complexing agents. As a natural analogue to the nuclear spent fuel some uraninite samples from the Oklo are deposit in Gabon, where chain fission reactions took place 2000 millions years ago, as well as a pitchblende sample from the mine Fe ore deposit, in Salamanca (spain) have been studied. The studies have been performed at 25 and 60 deg C and 60 deg C, and they have focussed on the determination of both the thermodynamic and the kinetic properties of the different samples studied, using batch and continuous experimental methodologies, respectively. (Author)

Cephalostatin analogues--synthesis and biological activity.

Science.gov (United States)

Flessner, Timo; Jautelat, Rolf; Scholz, Ulrich; Winterfeldt, Ekkehard

2004-01-01

Starting off in the early 90's the field of cephalostatin analogues has continually expanded over the last 10 years. First syntheses prepared symmetric analogues like 14b (119) and 26 (65), which were subsequently desymmetrized to provide analogues like beta-hydroxy ketone 31 (19). Importantly the straightforward approach provided already compounds with mu-molar potency and the same pattern of activity as cephalostatin 1 (1) (see Chapter 2.1). Chemically more demanding, two new methods for the directed synthesis of (bissteroidal) pyrazines were devised and subsequently applied to a wide variety of differently functionalized coupling partners. These new methods allowed for the synthesis of various analogues (Chapter 2.2.; and, last but not least, for the totals synthesis of several cephalostatin natural products; Chapter 1.). Functionalization and derivatization of the 12-position was performed (Chapter 2.1 and 3) and synthetic approaches to establish the D-ring double bond were successfully investigated (Chapter 3). [figure: see text] Dealing synthetically with the spiroketal moiety, novel oxidative opening procedures on monomeric delta 14, 15-steroids were devised as well as intensive studies regarding spiroketal synthesis and spiroketal rearrangements were conducted (Chapter 3.2. and 4.). Last but not least direct chemical modification of ritterazines and cephalostatins were studied, which provided a limited number of ritterazine analogues (Chapter 4.). All these synthetic activities towards analogues are summarized in Fig. 18. During this period of time the growing number of cephalostatins and ritterazines on the one hand and of analogues on the other hand provided several SAR trends, which can guide future analogue synthesis. The combined SAR findings are displayed in Fig. 19. So far it is apparent that: Additional methoxylations or hydroxylations in the steroidal A ring core structure (1-position) are slightly decreasing activity (compare cephalostatin 1 1 to

In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors.

Science.gov (United States)

Park, Jae B

2017-12-13

p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; -20 to -39) and several analogues with ΔE; -34 to -39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; -34 to -39) and in silico scores (Avg. score; -27.5 to -29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; -27.5 to -29.3) were found to inhibit p38 MAPK by 27-31% ( p silico score (Avg. score; -29.2) inhibited p38 MAPK (IC 50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; -29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22-73% ( p silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

CERN Multimedia

CERN. Geneva

2002-01-01

The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4.

Science.gov (United States)

Ty, Nancy; Pontikis, Renée; Chabot, Guy G; Devillers, Emmanuelle; Quentin, Lionel; Bourg, Stéphane; Florent, Jean-Claude

2013-03-01

To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. Copyright © 2013. Published by Elsevier Ltd.

Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.

LENUS (Irish Health Repository)

Mohan, Helen M

2012-06-15

Nuclear receptors are of integral importance in carcinogenesis. Manipulation of classic ligand-activated nuclear receptors, such as estrogen receptor blockade in breast cancer, is an important established cancer therapy. Orphan nuclear receptors, such as nuclear family 4 subgroup A (NR4A) receptors, have no known natural ligand(s). These elusive receptors are increasingly recognized as molecular switches in cell survival and a molecular link between inflammation and cancer. NR4A receptors act as transcription factors, altering expression of downstream genes in apoptosis (Fas-ligand, TRAIL), proliferation, DNA repair, metabolism, cell migration, inflammation (interleukin-8), and angiogenesis (VEGF). NR4A receptors are modulated by multiple cell-signaling pathways, including protein kinase A\\/CREB, NF-κB, phosphoinositide 3-kinase\\/AKT, c-jun-NH(2)-kinase, Wnt, and mitogen-activated protein kinase pathways. NR4A receptor effects are context and tissue specific, influenced by their levels of expression, posttranslational modification, and interaction with other transcription factors (RXR, PPAR-Υ). The subcellular location of NR4A "nuclear receptors" is also important functionally; novel roles have been described in the cytoplasm where NR4A proteins act both indirectly and directly on the mitochondria to promote apoptosis via Bcl-2. NR4A receptors are implicated in a wide variety of malignancies, including breast, lung, colon, bladder, and prostate cancer; glioblastoma multiforme; sarcoma; and acute and\\/or chronic myeloid leukemia. NR4A receptors modulate response to conventional chemotherapy and represent an exciting frontier for chemotherapeutic intervention, as novel agents targeting NR4A receptors have now been developed. This review provides a concise clinical overview of current knowledge of NR4A signaling in cancer and the potential for therapeutic manipulation.

Protective role of benfotiamine, a fat soluble vitamin B1 analogue, in the lipopolysaccharide–induced cytotoxic signals in murine macrophages

Science.gov (United States)

Yadav, Umesh C S; Kalariya, Nilesh M; Srivastava, Satish K; Ramana, Kota V

2010-01-01

The study has been designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of Vitamin B1 effects lipopolysaccharide (LPS) – induced inflammatory signals leading to cytotoxicity in mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of Bcl-2 family of pro-apoptotic proteins, caspase-3 activation and PARP cleavage, altered mitochondrial membrane potential and release of cytochrome-c and apoptosis inducing factor (AIF), phosphorylation and subsequent activation of p38-MAPK, stress activated kinases (SAPK/JNK), Protein kinase C, and cytoplasmic-phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappa B (IκB) and consequent activation and nuclear translocation of redox-sensitive transcription factor NF-κB was significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and other inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE2 were also blocked significantly. Thus, our results elucidate the molecular mechanism of anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophage. Benfotiamine suppresses oxidative stress-induced NF-κB activation and prevents the bacterial endotoxin-induced inflammation indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases. PMID:20219672

Phospholipid analogue distributions of Iranian isolates of candida

International Nuclear Information System (INIS)

Zarei Mahmoudabadi, A.; Brucker, D.B.

2004-01-01

The aim of this study was to analyse polar lipids of candida species isolated from Ahwas (Iran) by fast Atom bombardment mass spectrometry . Nine isolates of Candida Sp. were identified by growth at 45 d ig c , production of chlamydoconidia on cornmeal agar, colonial colour on CHROMagar Candida, germ tube production and ID 32 C kits. Then polar lipids were extracted from freeze-dried cultures and analysed using Fast Atom Bombardment Mass Spectrometry. The most intense carboxylate and phospholipid molecular species anions were of m/z 281 (C 1 8 : 1 ) and m/z 515 (PA 23:2). However, the most intense carboxylate and phospholipid analogues in Candida Parapsilosis were 292 (Un) and 555 (PA 26:3), which differed from other yeasts. Isolates were grouped by single linkage clustering based on correlation coefficient for strain pairs calculated with carboxylate and phospholipid molecular species distributions. Fast Atom Bombardment Mass Spectrometry can differentiate the C. albicans based on analysis of polar lipid distributions.These findings support that differentiation between C. albicans and other species is possible based on polar lipids

Antioxidant and cytotoxic activity of new di- and polyamine caffeine analogues.

Science.gov (United States)

Jasiewicz, Beata; Sierakowska, Arleta; Jankowski, Wojciech; Hoffmann, Marcin; Piorońska, Weronika; Górnicka, Agnieszka; Bielawska, Anna; Bielawski, Krzysztof; Mrówczyńska, Lucyna

2018-04-18

A series of new di- and polyamine-caffeine analogues were synthesized and characterized by NMR, FT-IR and MS spectroscopic methods. To access stability of the investigated caffeine analogues Molecular Dynamic simulations were performed in NAMD 2.9 assuming CHARMM36 force field. To evaluate the antioxidant capacity of new compounds, three different antioxidant assays were used, namely 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH • ) scavenging activity, ferrous ions (Fe 2+ ) chelating activity and Fe 3+ →Fe 2+ reducing ability. In vitro, the ability of new derivatives to protect human erythrocytes against oxidative haemolysis induced by free radical from 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) was estimated. The cytotoxic activity was tested using MCF-7 breast cancer cells and human erythrocytes. All compounds showed the antioxidant capacity depending mostly on their ferrous ions chelating activity. In the presence of AAPH, some derivatives were able to effectively inhibit the oxidative haemolysis. Two derivatives, namely 8-(methyl(2-(methylamino)ethyl)-amino)caffeine and 8-(methyl(3-(methylamino)propyl)amino)caffeine, showed cytotoxic activity against MCF-7 breast cancer cells but not against human erythrocytes. Therefore, it is concluded that the selected di- and polyamine caffeine analogues, depending on their chemical structure, were able to minimize the oxidative stress and to inhibit the tumour cell grow. The confirmed antioxidant and cytotoxic properties of some caffeine derivatives make them attractive for potential applications in food or pharmaceutical industries.

International video project on natural analogues

International Nuclear Information System (INIS)

Guentensperger, Marcel

1993-01-01

A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

Nuclear Medicine Technologists' Perception and Current Assessment of Quality: A Society of Nuclear Medicine and Molecular Imaging Technologist Section Survey.

Science.gov (United States)

Mann, April; Farrell, Mary Beth; Williams, Jessica; Basso, Danny

2017-06-01

In 2015, the Society of Nuclear Medicine and Molecular Imaging Technologist Section (SNMMI-TS) launched a multiyear quality initiative to help prepare the technologist workforce for an evidence-based health-care delivery system that focuses on quality. To best implement the quality strategy, the SNMMI-TS first surveyed technologists to ascertain their perception of quality and current measurement of quality indicators. Methods: An internet survey was sent to 27,989 e-mail contacts. Questions related to demographic data, perceptions of quality, quality measurement, and opinions on the minimum level of education are discussed in this article. Results: A total of 4,007 (14.3%) responses were received. When asked to list 3 words or phrases that represent quality, there were a plethora of different responses. The top 3 responses were image quality, quality control, and technologist education or competency. Surveying patient satisfaction was the most common quality measure (80.9%), followed by evaluation of image quality (78.2%). Evaluation of image quality (90.3%) and equipment functionality (89.4%) were considered the most effective measures. Technologists' differentiation between quality, quality improvement, quality control, quality assurance, and quality assessment seemed ambiguous. Respondents were confident in their ability to assess and improve quality at their workplace (91.9%) and agreed their colleagues were committed to delivering quality work. Of note, 70.7% of respondents believed that quality is directly related to the technologist's level of education. Correspondingly, respondents felt there should be a minimum level of education (99.5%) and that certification or registry should be required (74.4%). Most respondents (59.6%) felt that a Bachelor's degree should be the minimum level of education, followed by an Associate's degree (40.4%). Conclusion: To best help nuclear medicine technologists provide quality care, the SNMMI-TS queried technologists to

Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.

Science.gov (United States)

Johnson, James K; Skoda, Erin M; Zhou, Jianhua; Parrinello, Erica; Wang, Dan; O'Malley, Katherine; Eyer, Benjamin R; Kazancioglu, Mustafa; Eisermann, Kurtis; Johnston, Paul A; Nelson, Joel B; Wang, Zhou; Wipf, Peter

2016-08-11

After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure-activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific SAR response, absence of a readily oxidized sulfur atom, low molecular weight, reduced number of flexible bonds and polar surface area, and drug-likeness score) in the prostate-specific antigen luciferase assay in C4-2-PSA-rl cells to qualify as a new lead structure for prostate cancer drug development.

Physical Characterization of Synthetic Phosphatidylinositol Dimannosides and Analogues in Binary Systems with Phosphatidylcholine

DEFF Research Database (Denmark)

Hubert, Madlen; Larsen, David S; Hayman, Colin M

2014-01-01

Native phosphatidylinositol mannosides (PIMs) from the cell wall of Mycobacterium bovis (M. bovis) and synthetic analogues have been identified to exert immunostimulatory activities. These activities have been investigated using particulate delivery systems containing native mannosylated lipids...... the design of liposome-based delivery systems. In mixed films the phosphoglycolipids were found to be miscible with PC based on evaluation of collapse pressures and deviations of experimental molecular areas from calculated ideal values. Concanavalin A (ConA) agglutination confirmed the presence...

Upgrading of analogue gamma cameras with PC based computer system

International Nuclear Information System (INIS)

Fidler, V.; Prepadnik, M.

2002-01-01

Full text: Dedicated nuclear medicine computers for acquisition and processing of images from analogue gamma cameras in developing countries are in many cases faulty and technologically obsolete. The aim of the upgrading project of International Atomic Energy Agency (IAEA) was to support the development of the PC based computer system which would cost 5.000 $ in total. Several research institutions from different countries (China, Cuba, India and Slovenia) were financially supported in this development. The basic demands for the system were: one acquisition card an ISA bus, image resolution up to 256x256, SVGA graphics, low count loss at high count rates, standard acquisition and clinical protocols incorporated in PIP (Portable Image Processing), on-line energy and uniformity correction, graphic printing and networking. The most functionally stable acquisition system tested on several international workshops and university clinics was the Slovenian one with a complete set of acquisition and clinical protocols, transfer of scintigraphic data from acquisition card to PC through PORT, count loss less than 1 % at count rate of 120 kc/s, improvement of integral uniformity index by a factor of 3-5 times, reporting, networking and archiving solutions for simple MS network or server oriented network systems (NT server, etc). More than 300 gamma cameras in 52 countries were digitized and put in the routine work. The project of upgrading the analogue gamma cameras yielded a high promotion of nuclear medicine in the developing countries by replacing the old computer systems, improving the technological knowledge of end users on workshops and training courses and lowering the maintenance cost of the departments. (author)

Synthesis and Biological Activities of Novel Anthranilic Diamides Analogues Containing Benzo[b]thiophene

Institute of Scientific and Technical Information of China (English)

ZHANG Ji-feng; LIU Chen; LIU Peng-fei; YAN Tao; WANG Bao-lei; XIONG Li-xia; LI Zheng-ming

2013-01-01

A series of novel anthranilic diamides analogues containing benzo[b]thiophenyl ring was designed and synthesized.Their structures were characterized by melting points,1H nuclear magnetic resonance(1H NMR) and high-resolution mass spectrometry(HRMS).The bioassay tests indicate that their insecticidal activities were weak to moderate.Antibacterial tests indicate that some of the compounds showed favourable activity in vitro against Physalospora piricola,Alternaria solani,Cercospora arachidicola,Gibberella sanbinetti and Phytophthora infestans at a dosage of 50 mg/L.

Molecular glasses for nuclear waste encapsulation

International Nuclear Information System (INIS)

Ropp, R.C.

1982-01-01

The use of a molecular glass based upon a polymerized phosphate of aluminum (PAP), indium or gallium overcomes all of the prior objections to use of glass as a high-level nuclear waste (HLW) encapsulation agent. This HLW glass product could not be made to devitrify, dissolved all of the oxides found in calcine, including the difficultly soluble ones, did not form microcrystallites in the melt or subsequent glass-casting, and possessed a hydrolytic etching rate to boiling water even lower than that of HLW-ZBS glass. A precursor compound, M(H 2 PO 4 ) 3 , is prepared, where M is a trivalent metal selected from the group consisting of aluminum, indium and gallium. The impurity level is carefully controlled so as not to exceed 300 ppm total. The precursor crystals may be washed to remove excess phosphoric acid as desired. HLW is added to the crystals and the mixture is then heated at a controlled heating rate to induce solid state polymerization and to form a melt at 1350 degrees C in which the HLW oxides dissolve rapidly

Effects of Quantum Nuclear Delocalisation on NMR Parameters from Path Integral Molecular Dynamics

Czech Academy of Sciences Publication Activity Database

Dračínský, Martin; Hodgkinson, P.

2014-01-01

Roč. 20, č. 8 (2014), s. 2201-2207 ISSN 0947-6539 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-299242 People Institutional support: RVO:61388963 Keywords : density functional calculations * isotope effects * NMR spectroscopy * nuclear delocalisation * path integral molecular dynamics Subject RIV: CC - Organic Chemistry Impact factor: 5.731, year: 2014

Analogue Hawking radiation from astrophysical black-hole accretion

International Nuclear Information System (INIS)

Das, Tapas K

2004-01-01

We show that spherical accretion onto astrophysical black holes can be considered as a natural example of an analogue system. We provide, for the first time, an exact analytical scheme for calculating the analogue Hawking temperature and surface gravity for general relativistic accretion onto astrophysical black holes. Our calculation may bridge the gap between the theory of transonic astrophysical accretion and the theory of analogue Hawking radiation. We show that the domination of the analogue Hawking temperature over the actual Hawking temperature may be a real astrophysical phenomenon, though observational tests of this fact will at best be difficult and at worst might prove to be impossible. We also discuss the possibilities of the emergence of analogue white holes around astrophysical black holes. Our calculation is general enough to accommodate accreting black holes with any mass

Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

Science.gov (United States)

Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

2011-01-01

A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

Preparation, characterization and in vitro evaluation of a new nucleotide analogue prodrug cyclodextrin inclusion complexes.

OpenAIRE

Diab , Roudayna; Jordheim , Lars P; Degobert , Ghania; Peyrottes , Suzanne; Périgaud , Christian; Dumontet , Charles; Fessi , Hatem

2009-01-01

International audience; Bis(tbutyl-S-acyl-2-thioethyl)-cytidine monophosophate is a new cytotoxic mononucleotide prodrug which have been developed to reverse the cellular resistance to nucleoside analogues. Unfortunately, its in vivo utilisation was hampered by its poor water solubility, raising the need of a molecular vector capable to mask its physicochemical characteristics although without affecting its cytotoxic activity. Hydroxypropyl-beta-cyclodextrin was used to prepare the prodrug in...

Alligator Rivers Analogue Project. Final Report - Volume 1

Energy Technology Data Exchange (ETDEWEB)

Duerden, P [Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW (Australia); Lever, D A [AEA Technology, Harwell (United Kingdom); Sverjensky, D A [Johns Hopkins Univ., Baltimore, MD (United States); Townley, L R [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Wembley, WA (Australia). Div. of Water Resources

1992-07-01

This summary report, which highlights the work and findings of the Alligator Rivers Analogue Project (ARAP) is one of a series of 16 volumes, listed below. Detailed descriptions and results are provided in Volumes 2 to 16. Full acknowledgment to individual contributions is provided in the individual reports, and in Appendix I of this report. The findings from the technical studies are discussed in the context of assessments of the long-term performance of geological repositories for radioactive wastes, which are being undertaken in many countries. They are also considered in an integrated 'Scenario Development' approach, aimed to understand the formation of the ore deposit. Despite their inherent uncertainties, the findings provide a basis for assessing the way in which radionuclides will migrate in environments with a variety of geologic settings and over a range of different geologic timescales. Thus, section 2 of this report discusses the concept of using uranium deposits as natural analogues and refers to a number of such studies, including those at the Koongarra deposit in the Alligator Rivers Region of the Northern Territory of Australia. Section 3 reviews early scientific work in the Alligator Rivers Region and summarises the results of the analogue studies undertaken between 1981 and 1987 that were funded by the US Nuclear Regulatory Commission (USNRC) and the UK Department of the Environment (UKDoE). Section 4 describes the objectives of ARAP and the manner in which the study was conducted and provides a general outline of the project and a summary of the findings. A general description of the Koongarra ore deposit, the focus of ARAP, is provided in Section 5, with Sections 6-13 providing summaries of the work carried out to characterise the site in detail and provide data for modelling. Sections 14-18 discuss how this data was used in modelling and how the results may be applied for performance assessment studies. Finally, Section 19 considers the

Alligator Rivers Analogue Project. Final Report - Volume 1

International Nuclear Information System (INIS)

Duerden, P.; Lever, D.A.; Sverjensky, D.A.; Townley, L.R.

1992-01-01

This summary report, which highlights the work and findings of the Alligator Rivers Analogue Project (ARAP) is one of a series of 16 volumes, listed below. Detailed descriptions and results are provided in Volumes 2 to 16. Full acknowledgment to individual contributions is provided in the individual reports, and in Appendix I of this report. The findings from the technical studies are discussed in the context of assessments of the long-term performance of geological repositories for radioactive wastes, which are being undertaken in many countries. They are also considered in an integrated 'Scenario Development' approach, aimed to understand the formation of the ore deposit. Despite their inherent uncertainties, the findings provide a basis for assessing the way in which radionuclides will migrate in environments with a variety of geologic settings and over a range of different geologic timescales. Thus, section 2 of this report discusses the concept of using uranium deposits as natural analogues and refers to a number of such studies, including those at the Koongarra deposit in the Alligator Rivers Region of the Northern Territory of Australia. Section 3 reviews early scientific work in the Alligator Rivers Region and summarises the results of the analogue studies undertaken between 1981 and 1987 that were funded by the US Nuclear Regulatory Commission (USNRC) and the UK Department of the Environment (UKDoE). Section 4 describes the objectives of ARAP and the manner in which the study was conducted and provides a general outline of the project and a summary of the findings. A general description of the Koongarra ore deposit, the focus of ARAP, is provided in Section 5, with Sections 6-13 providing summaries of the work carried out to characterise the site in detail and provide data for modelling. Sections 14-18 discuss how this data was used in modelling and how the results may be applied for performance assessment studies. Finally, Section 19 considers the

Evaluations of Molecular Nuclear Medicine in pediatric urgencies

International Nuclear Information System (INIS)

Martinez-Duncker R, C.

2000-01-01

Several diagnostic procedures of Molecular Nuclear Medicine are considered in first choice in clinical evaluation of patients with different illnesses. So, the gammagraphy is the diagnostic form more sensitive to detect alterations of the perfusion on organs and systems such as bones, heart, brain, lungs or kidneys. Also is possible to identify, localize, evaluate the activity of inflammatory processes such as cellulitis, arthritis, osteomyelitis, the abscesses and several primary or metastatic tumours before each other diagnostic technique. In this work is treated about the importance of treatments with radioactive materials have been an important reappearance in last years since with the present capacity to localize specifically intracellular processes (for example, synthesis of DNA) new gateways are opened to research which in coming years would be of great utility. (Author)

Quantum wavepacket ab initio molecular dynamics: an approach for computing dynamically averaged vibrational spectra including critical nuclear quantum effects.

Science.gov (United States)

Sumner, Isaiah; Iyengar, Srinivasan S

2007-10-18

We have introduced a computational methodology to study vibrational spectroscopy in clusters inclusive of critical nuclear quantum effects. This approach is based on the recently developed quantum wavepacket ab initio molecular dynamics method that combines quantum wavepacket dynamics with ab initio molecular dynamics. The computational efficiency of the dynamical procedure is drastically improved (by several orders of magnitude) through the utilization of wavelet-based techniques combined with the previously introduced time-dependent deterministic sampling procedure measure to achieve stable, picosecond length, quantum-classical dynamics of electrons and nuclei in clusters. The dynamical information is employed to construct a novel cumulative flux/velocity correlation function, where the wavepacket flux from the quantized particle is combined with classical nuclear velocities to obtain the vibrational density of states. The approach is demonstrated by computing the vibrational density of states of [Cl-H-Cl]-, inclusive of critical quantum nuclear effects, and our results are in good agreement with experiment. A general hierarchical procedure is also provided, based on electronic structure harmonic frequencies, classical ab initio molecular dynamics, computation of nuclear quantum-mechanical eigenstates, and employing quantum wavepacket ab initio dynamics to understand vibrational spectroscopy in hydrogen-bonded clusters that display large degrees of anharmonicities.

Synthesis and biological evaluation of febrifugine analogues.

Science.gov (United States)

Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

2014-12-01

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

New perspectives in nuclear imaging

International Nuclear Information System (INIS)

Wagner, H.N. Jr.

1981-01-01

In nuclear medicine, biodistribution is studied by quantitative nuclear imaging; chemistry is translated into radio-pharmacology; physics into instrumentation; and biology into physiology. Nuclear medicine can be thought of as applied physiology and physiological chemistry. The modern nuclear chemist is concerned with molecules, with relating chemical structure to biological distributions, as for iminodiacetate compounds. Using mixed ligand analysis, the hepatobiliary agent, HIDA, developed by Loberg, proved an anionic bis-complex with a charge of minus one. Further studies elsewhere showed that the co-ordination number of technetium was 5 and that an oxo-oxygen was in the apical position. From a series of analogues the amount of the complexes excreted in the bile was found to be directly proportional to the natural log of the molecular weight to charge ratio. The trend is towards the synthesis of labelled compounds whose biodistribution depends on their chemical interaction with structurally specific binding sites, i.e. receptors, enzymes or binding sites of active transport systems. Other examples include amino acids for pancreatic imaging; deoxyglucose for studies of regional brain and heart metabolism; fatty acids for studies of the heart; steroid hormones for breast tumours; and muscarinic compounds for study of the cholinergic system of the heart. Most of these compounds are labelled with 11 C, 18 F or 13 N, available only from cyclotrons, but the extension to the more widely available 123 I and sup(99m)Tc is also proceeding rapidly, stimulated chiefly by the success with the positron-emitting compounds. Advances in nuclear imaging include the development of both positron and single photon emission tomography. Biodistribution studies in man permit measurement of regional as well as global function. Improved perception is being augmented by improved quantification and automation

Assessment of six dissimilarity metrics for climate analogues

Science.gov (United States)

Grenier, Patrick; Parent, Annie-Claude; Huard, David; Anctil, François; Chaumont, Diane

2013-04-01

Spatial analogue techniques consist in identifying locations whose recent-past climate is similar in some aspects to the future climate anticipated at a reference location. When identifying analogues, one key step is the quantification of the dissimilarity between two climates separated in time and space, which involves the choice of a metric. In this communication, spatial analogues and their usefulness are briefly discussed. Next, six metrics are presented (the standardized Euclidean distance, the Kolmogorov-Smirnov statistic, the nearest-neighbor distance, the Zech-Aslan energy statistic, the Friedman-Rafsky runs statistic and the Kullback-Leibler divergence), along with a set of criteria used for their assessment. The related case study involves the use of numerical simulations performed with the Canadian Regional Climate Model (CRCM-v4.2.3), from which three annual indicators (total precipitation, heating degree-days and cooling degree-days) are calculated over 30-year periods (1971-2000 and 2041-2070). Results indicate that the six metrics identify comparable analogue regions at a relatively large scale, but best analogues may differ substantially. For best analogues, it is also shown that the uncertainty stemming from the metric choice does generally not exceed that stemming from the simulation or model choice. A synthesis of the advantages and drawbacks of each metric is finally presented, in which the Zech-Aslan energy statistic stands out as the most recommended metric for analogue studies, whereas the Friedman-Rafsky runs statistic is the least recommended, based on this case study.

Synthesis and anticancer evaluation of spermatinamine analogues

KAUST Repository

Moosa, Basem; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M.

2016-01-01

analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell

Insulin analogues in pregnancy and specific congenital anomalies

DEFF Research Database (Denmark)

de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

2016-01-01

Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant...... women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

Glucagon-like peptide-1 analogues: An overview

Directory of Open Access Journals (Sweden)

Vishal Gupta

2013-01-01

Full Text Available Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia and suppression of glucagon (fasting hyperglycemia, amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly, DPP-4-resistant analogues (lixisenatide, albiglutide, and analogues of human GLP-1 (liraglutide, taspoglutide. Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

Analogue circuits simulation

Energy Technology Data Exchange (ETDEWEB)

Mendo, C

1988-09-01

Most analogue simulators have evolved from SPICE. The history and description of SPICE-like simulators are given. From a mathematical formulation of the electronic circuit the following analysis are possible: DC, AC, transient, noise, distortion, Worst Case and Statistical.

Molecularly targeted therapeutic radiopharmaceuticals

International Nuclear Information System (INIS)

Saw, M.M.

2007-01-01

Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

Uncertainties and credibility building of safety analyses. Natural analogues

International Nuclear Information System (INIS)

Laciok, A.

2001-07-01

The substance of natural analogues and their studies is defined as a complementary method to laboratory and in-situ experiments and modelling. The role of natural analogues in the processes of development of repositories is defined, mainly in performance assessment of repository system and communication with public. The criteria for identification of natural analogues which should be evaluated in the phase of initiation of new studies are specified. Review part of this report is divided to study of natural analogues and study of anthropogenic and industrial analogues. The main natural analogue studies performed in various countries, in different geological setting, with various aims are characterized. New results acquired in recently finished studies are included: Palmottu (2nd phase of project financed by European Commission), Oklo (results of research financed also by European Commission), Maqarin (3rd phase) and other information obtained from last meetings and workshops of NAWG. In view of the fact that programmes of development of deep repositories in Czech and Slovak Republics are interconnected, the natural analogues studies carried out in the Czech republic are incorporated in separate chapter - study of uranium accumulation in Tertiary clays at Ruprechtov site and study of degradation of natural glasses. In final part the areas of natural analogue studies as an integral part of development of deep geological repository are proposed along with characterization of broader context and aspects of realization of these studies (international cooperation, preparation and evaluation of procedures, communication with public). (author)

ACTINOMYCIN D ANALOGUES

DEFF Research Database (Denmark)

1997-01-01

The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

Introduction to electronic analogue computers

CERN Document Server

Wass, C A A

1965-01-01

Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

A novel lunar bed rest analogue.

Science.gov (United States)

Cavanagh, Peter R; Rice, Andrea J; Licata, Angelo A; Kuklis, Matthew M; Novotny, Sara C; Genc, Kerim O; Englehaupt, Ricki K; Hanson, Andrea M

2013-11-01

Humans will eventually return to the Moon and thus there is a need for a ground-based analogue to enable the study of physiological adaptations to lunar gravity. An important unanswered question is whether or not living on the lunar surface will provide adequate loading of the musculoskeletal system to prevent or attenuate the bone loss that is seen in microgravity. Previous simulations have involved tilting subjects to an approximately 9.5 degrees angle to achieve a lunar gravity component parallel to the long-axis of the body. However, subjects in these earlier simulations were not weight-bearing, and thus these protocols did not provide an analogue for load on the musculoskeletal system. We present a novel analogue which includes the capability to simulate standing and sitting in a lunar loading environment. A bed oriented at a 9.5 degrees angle was mounted on six linear bearings and was free to travel with one degree of freedom along rails. This allowed approximately 1/6 body weight loading of the feet during standing. "Lunar" sitting was also successfully simulated. A feasibility study demonstrated that the analogue was tolerated by subjects for 6 d of continuous bed rest and that the reaction forces at the feet during periods of standing were a reasonable simulation of lunar standing. During the 6 d, mean change in the volume of the quadriceps muscles was -1.6% +/- 1.7%. The proposed analogue would appear to be an acceptable simulation of lunar gravity and deserves further exploration in studies of longer duration.

Causal structure of analogue spacetimes

International Nuclear Information System (INIS)

Barcelo, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt

2004-01-01

The so-called 'analogue models of general relativity' provide a number of specific physical systems, well outside the traditional realm of general relativity, that nevertheless are well-described by the differential geometry of curved spacetime. Specifically, the propagation of perturbations in these condensed matter systems is described by 'effective metrics' that carry with them notions of 'causal structure' as determined by an exchange of quasi-particles. These quasi-particle-induced causal structures serve as specific examples of what can be done in the presence of a Lorentzian metric without having recourse to the Einstein equations of general relativity. (After all, the underlying analogue model is governed by its own specific physics, not necessarily by the Einstein equations.) In this paper we take a careful look at what can be said about the causal structure of analogue spacetimes, focusing on those containing quasi-particle horizons, both with a view to seeing what is different from standard general relativity, and what the similarities might be. For definiteness, and because the physics is particularly simple to understand, we will phrase much of the discussion in terms of acoustic disturbances in moving fluids, where the underlying physics is ordinary fluid mechanics, governed by the equations of traditional hydrodynamics, and the relevant quasi-particles are the phonons. It must however be emphasized that this choice of example is only for the sake of pedagogical simplicity and that our considerations apply generically to wide classes of analogue spacetimes

Natural analogues and radionuclide transport model validation

International Nuclear Information System (INIS)

Lever, D.A.

1987-08-01

In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

The Palmottu analogue project

International Nuclear Information System (INIS)

Ahonen, L.; Blomqvist, R.; Suksi, J.

1993-01-01

The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

Directory of Open Access Journals (Sweden)

Bryan L Roth

Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

[Department of the molecular bases of semiotics].

Science.gov (United States)

Ternovyĭ, K S

1995-01-01

Department of molecular basis of semiotics was organized in 1986. The main task of the department was to work out new approaches in estimation of the state of immune and blood system at the tissue, cell and molecular levels, using biochemical, biophysical and molecular biology techniques. There are several main directions of scientific investigations at the department. Most informational methods were collected in "immunological portrait" for differential diagnostic and complex investigation of the immune system of autoimmune patients. This group of techniques was used to study changes in the immune system of Kievites after the Chernobyl disaster. A decrease of complement and thymic serum activity was detected. Antibodies against nuclear components appeared in 20% of donors. And a higher of circulating immune complex of low molecular weight was observed. Low level of thymic serum activity in blood of autoimmune patients with rheumatoid arthritis, lupus erythematosus, diabetes, herpes and other depends on the appearance of zinc-independent timuline inhibitor less then 2000 D. Another kind of thymic hormone inhibitors was detected in thymectomized adult mice. Its effect disappears when zinc added in blood rather due to competition for lymphocyte surface receptors timuline and its inactive analogue than other mechanism. Therapeutic effect of UV irradiation of patients' blood was shown to be closely connected with the changes in thymic serum activity in respect to stabilization of thymic hormone/inhibitor ratio. The immunochemical techniques were used to detect and investigate tumor-associated chromatin antigens in human and animal tumor cells. Antigens not found in normal tissues were detected when using rabbit antibodies against chromatin of rat hepatocarcinoma and human colon and carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and anticancer evaluation of spermatinamine analogues

KAUST Repository

Moosa, Basem

2016-02-04

Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

Science.gov (United States)

Kurz, Thomas; Schlüter, Katrin; Pein, Miriam; Behrendt, Christoph; Bergmann, Bärbel; Walter, Rolf D

2007-07-01

The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM.

Downscaling of surface moisture flux and precipitation in the Ebro Valley (Spain using analogues and analogues followed by random forests and multiple linear regression

Directory of Open Access Journals (Sweden)

G. Ibarra-Berastegi

2011-06-01

Full Text Available In this paper, reanalysis fields from the ECMWF have been statistically downscaled to predict from large-scale atmospheric fields, surface moisture flux and daily precipitation at two observatories (Zaragoza and Tortosa, Ebro Valley, Spain during the 1961–2001 period. Three types of downscaling models have been built: (i analogues, (ii analogues followed by random forests and (iii analogues followed by multiple linear regression. The inputs consist of data (predictor fields taken from the ERA-40 reanalysis. The predicted fields are precipitation and surface moisture flux as measured at the two observatories. With the aim to reduce the dimensionality of the problem, the ERA-40 fields have been decomposed using empirical orthogonal functions. Available daily data has been divided into two parts: a training period used to find a group of about 300 analogues to build the downscaling model (1961–1996 and a test period (1997–2001, where models' performance has been assessed using independent data. In the case of surface moisture flux, the models based on analogues followed by random forests do not clearly outperform those built on analogues plus multiple linear regression, while simple averages calculated from the nearest analogues found in the training period, yielded only slightly worse results. In the case of precipitation, the three types of model performed equally. These results suggest that most of the models' downscaling capabilities can be attributed to the analogues-calculation stage.

Long-term predictions using natural analogues

International Nuclear Information System (INIS)

Ewing, R.C.

1995-01-01

One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10 3 -10 5 years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., open-quotes natural analoguesclose quotes) provide perhaps the only means of partial open-quotes validation,close quotes as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10 3 -10 8 years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the open-quotes validationclose quotes of performance assessments

Molecular dynamics study of a nuclear waste glass matrix with plutonium

International Nuclear Information System (INIS)

Meis, C.; Delaye, J.M.; Ghaleb, D.

1999-01-01

Molecular dynamics simulation techniques were applied to model the incorporation of plutonium in the French nuclear waste glass matrix. Born-Mayer-Huggins analytical potentials were established to characterize short-range interactions between Pu-O and Pu-Pu pairs; the potentials were fitted to the structural properties of plutonium dioxide in the light of a recent experimental study showing that plutonium is found as Pu(IV) in the glass. The transferability of the established potentials to the glass structure is discussed, and the potential parameters are further refined by molecular dynamics simulations in an aluminoborosilicate glass to obtain mean Pu-O interatomic distances and first-neighbor coordination numbers matching the experimental values as closely as possible. Previously published Born-Mayer-Huggins potentials supplemented by Stillinger-Weber three-body terms were used for oxygen-cation and cation-cation interactions. The difficulties encountered in establishing a Pu-O potential that provides satisfactory results in both oxides and glasses are also discussed

In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

Directory of Open Access Journals (Sweden)

Jae B. Park

2017-12-01

Full Text Available p38 Mitogen-activated protein kinase (p38 MAPK is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39 and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39 and in silico scores (Avg. score; −27.5 to −29.3. Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3 were found to inhibit p38 MAPK by 27–31% (p < 0.05 better than those with less scores (ΔE < −27.0. Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2 inhibited p38 MAPK (IC50 = 9.9 μM a little better than its methyl ester with best in silico score (Avg. score; −29.3. To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05 in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may

Insulin analogues and cancer: a note of caution

Directory of Open Access Journals (Sweden)

Joseph A.M.J.L. eJanssen

2014-05-01

Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

Characterisation of insulin analogues therapeutically available to patients

KAUST Repository

Adams, Gary G.

2018-03-29

The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions

Directory of Open Access Journals (Sweden)

Maximiliano Martínez-Cifuentes

2016-12-01

Full Text Available In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA and vertical electron affinities (VEA, as well as vertical detachment energy (VDE. To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f+ and Parr (P+ functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity.

Fungal growth inhibitory properties of new phytosphingolipid analogues.

Science.gov (United States)

Mormeneo, D; Manresa, A; Casas, J; Llebaria, A; Delgado, A

2008-04-01

To study the growth inhibitory properties of a series of phytosphingosine (PHS) and phytoceramide (PHC) analogues. A panel of two yeast (Candida albicans and Saccharomyces cerevisiae) and six moulds (Aspergillus repens, Aspergillus niger, Penicillium chrysogenum, Cladosporium cladosporioides, Arthroderma uncinatum and Penicillium funiculosum) has been used in this study. A series of new PHS and PHC analogues differing at the sphingoid backbone and the functional group at C1 position were synthesized. Among PHS analogues, 1-azido derivative 1c, bearing the natural D-ribo stereochemistry, showed a promising growth inhibitory profile. Among PHC analogues, compound 12, with a bulky N-pivaloyl group and a Z double bond at C3 position of the sphingoid chain, was the most active growth inhibitor. Minimal inhibitory concentration values were in the range of 23-48 micromol l(-1) for 1c and 44-87 micromol l(-1) for 12. Only scattered data on the antifungal activity of phytosphingolipids have been reported in the literature. This is the first time that a series of analogues of this kind are tested and compared to discern their structural requirements for antifungal activity.

Synthesis and evaluation of anticancer natural product analogues based on angelmarin: targeting the tolerance towards nutrient deprivation.

Science.gov (United States)

Magolan, Jakob; Adams, Nathan B P; Onozuka, Hiroko; Hungerford, Natasha L; Esumi, Hiroyasu; Coster, Mark J

2012-05-01

Inspired by nature: Angelmarin is an anticancer natural product with potent antiausterity activity, that is, selective cytotoxicity towards nutrient-deprived, resistant cancer cells. Through structure-activity relationship studies, three analogues were identified as lead compounds for the develpoment of molecular probes for the investigation of the mode of action and biological targets of the antiausterity compounds. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular forensic science of nuclear materials

International Nuclear Information System (INIS)

Wilkerson, Marianne Perry

2010-01-01

We are interested in applying our understanding of actinide chemical structure and bonding to broaden the suite of analytical tools available for nuclear forensic analyses. Uranium- and plutonium-oxide systems form under a variety of conditions, and these chemical species exhibit some of the most complex behavior of metal oxide systems known. No less intriguing is the ability of AnO 2 (An: U, Pu) to form non-stoichiometric species described as AnO 2+x . Environmental studies have shown the value of utilizing the chemical signatures of these actinide oxides materials to understand transport following release into the environment. Chemical speciation of actinide-oxide samples may also provide clues as to the age, source, process history, or transport of the material. The scientific challenge is to identify, measure and understand those aspects of speciation of actinide analytes that carry information about material origin and history most relevant to forensics. Here, we will describe our efforts in material synthesis and analytical methods development that we will use to provide the fundamental science required to characterize actinide oxide molecular structures for forensics science. Structural properties and initial results to measure structural variability of uranium oxide samples using synchrotron-based X-ray Absorption Fine Structure will be discussed.

Insulin analogues with improved absorption characteristics.

Science.gov (United States)

Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

1992-01-01

The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

Science.gov (United States)

Morais, Maurício; Zamora-Carreras, Héctor; Raposinho, Paula D; Oliveira, Maria Cristina; Pantoja-Uceda, David; Correia, João D G; Jiménez, M Angeles

2017-07-15

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ ( CycN-K6 ) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ ( CycN-K7 ). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and 13 C NMR. These results were compared to those of the previously reported analogue c[S-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH₂ ( CycS-C6 ). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC 50 = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC 50 = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC 50 = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle's side chains are favorably positioned for receptor interaction.

Tracking nuclear wave-packet dynamics in molecular oxygen ions with few-cycle infrared laser pulses

International Nuclear Information System (INIS)

De, S.; Bocharova, I. A.; Magrakvelidze, M.; Ray, D.; Cao, W.; Thumm, U.; Cocke, C. L.; Bergues, B.; Kling, M. F.; Litvinyuk, I. V.

2010-01-01

We have tracked nuclear wave-packet dynamics in doubly charged states of molecular oxygen using few-cycle infrared laser pulses. Bound and dissociating wave packets were launched and subsequently probed via a pair of 8-fs pulses of 790 nm radiation. Ionic fragments from the dissociating molecules were monitored by velocity-map imaging. Pronounced oscillations in the delay-dependent kinetic energy release spectra were observed. The occurrence of vibrational revivals permits us to identify the potential curves of the O 2 dication which are most relevant to the molecular dynamics. These studies show the accessibility to the dynamics of such higher-charged molecules.

Natural analogue working group

International Nuclear Information System (INIS)

Come, B.; Chapman, N.

1986-01-01

A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

Science.gov (United States)

Segal, Meirav; Fischer, Bilha

2012-02-28

Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

Possible signatures of nuclear-molecular formation in O+C systems

International Nuclear Information System (INIS)

Tighe, R.J.; Kolata, J.J.; Belbot, M.; Aguilera, E.F.

1993-01-01

The interplay between the elastic, quasielastic, and fusion reaction channels at energies from just above to well below the Coulomb barrier is investigated for O+C systems. Elastic-scattering and quasielastic-scattering angular distributions were measured using the kinematic coincidence technique. Fusion yields were obtained by direct detection of the evaporation residues using a time-of-flight energy spectrometer, at energies from just above to well below the Coulomb barrier. The fusion yields differ significantly from previous work, but the present measurements give barrier parameters consistent with systematics. Comparisons with two-center shell model and coupled-channels predictions show possible indications of nuclear-molecular formation in the elastic, inelastic, and single-neutron transfer channels

Nuclear waste disposal: perspective of a geochemist

International Nuclear Information System (INIS)

Sengupta, Pranesh; Dey, G.K.

2011-01-01

Satisfying the growing requirement in an environment friendly way is one of the most important tasks we need to accomplish these days. Considering the restricted non-renewable energy resources and limited technological progresses achieved in the renewable energy sectors in India, nuclear energy appears to be one of the most lucrative solutions towards the forthcoming energy crisis. Successful implementation of nuclear energy program however requires careful execution of high level nuclear waste management activities. One very important aspect of this process is to identify and develop suitable inert matrix(ces) for conditioning of nuclear waste(s) using natural analogue studies. And this establishes the very vital linkage between geochemical studies and nuclear waste immobilization. One good example of such an interdisciplinary approach can be seen in the methodologies adopted for immobilization of sulfate bearing high level nuclear wastes (SO 4 -HLW). It has been reported on several occasions that sulfur-rich melt get separated from silicate melt within magma chamber. Similar process has also been witnessed within vitrification furnaces whenever an attempt has been made to condition SO 4 -HLW within borosilicate glass matrices. Since such liquid-liquid phase separation leads to multiple difficulties in connection to radionuclide immobilization and plant scale vitrification processes, solutions were sought from natural analogue studies. Such as integrated approach ultimately resulted in establishing two different methodologies e.g. (i) modifying the borosilicate network through introduction of Ba 2+ cation; a process being followed in India and (ii) using phosphatic melt as a host instead of borosilicate melt; a process being followed in Russia. Detail of these two routes and the geochemical linkage in nuclear waste immobilization will be discussed.(author)

A Low-cost Multi-channel Analogue Signal Generator

CERN Document Server

Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

2009-01-01

A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The signal generator was successfully used as independent test bed for the ATLAS Level-1 Trigger Pre-Processor, providing up to 16 analogue signals.

Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

Science.gov (United States)

Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

2015-03-01

We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

Synthesis of an Orthogonal Topological Analogue of Helicene

DEFF Research Database (Denmark)

Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

2013-01-01

The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy r...

Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

NARCIS (Netherlands)

Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

1994-01-01

A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues

Science.gov (United States)

Zhang, Zhenshan; Zheng, Mingyue; Du, Li; Shen, Jianhua; Luo, Xiaomin; Zhu, Weiliang; Jiang, Hualiang

2006-05-01

To find useful information for discovering dual functional inhibitors against both wild type (WT) and K103N mutant reverse transcriptases (RTs) of HIV-1, molecular docking and 3D-QSAR approaches were applied to a set of twenty-five 4,1-benzoxazepinone analogues of efavirenz (SUSTIVA®), some of them are active against the two RTs. 3D-QSAR models were constructed, based on their binding conformations determined by molecular docking, with r 2 cv values ranging from 0.656 to 0.834 for CoMFA and CoMSIA, respectively. The models were then validated to be highly predictive and extrapolative by inhibitors in two test sets with different molecular skeletons. Furthermore, CoMFA models were found to be well matched with the binding sites of both WT and K103N RTs. Finally, a reasonable pharmacophore model of 4,1-benzoxazepinones were established. The application of the model not only successfully differentiated the experimentally determined inhibitors from non-inhibitors, but also discovered two potent inhibitors from the compound database SPECS. On the basis of both the 3D-QSAR and pharmacophore models, new clues for discovering and designing potent dual functional drug leads against HIV-1 were proposed: (i) adopting positively charged aliphatic group at the cis-substituent of C3; (ii) reducing the electronic density at the position of O4; (iii) positioning a small branched aliphatic group at position of C5; (iv) using the negatively charged bulky substituents at position of C7.

On the robustness of entanglement in analogue gravity systems

International Nuclear Information System (INIS)

Bruschi, D E; Friis, N; Fuentes, I; Weinfurtner, S

2013-01-01

We investigate the possibility of generating quantum-correlated quasi-particles utilizing analogue gravity systems. The quantumness of these correlations is a key aspect of analogue gravity effects and their presence allows for a clear separation between classical and quantum analogue gravity effects. However, experiments in analogue systems, such as Bose–Einstein condensates (BECs) and shallow water waves, are always conducted at non-ideal conditions, in particular, one is dealing with dispersive media at non-zero temperatures. We analyse the influence of the initial temperature on the entanglement generation in analogue gravity phenomena. We lay out all the necessary steps to calculate the entanglement generated between quasi-particle modes and we analytically derive an upper bound on the maximal temperature at which given modes can still be entangled. We further investigate a mechanism to enhance the quantum correlations. As a particular example, we analyse the robustness of the entanglement creation against thermal noise in a sudden quench of an ideally homogeneous BEC, taking into account the super-sonic dispersion relations. (paper)

A preliminary feasibility study on natural analogue in Korea

Energy Technology Data Exchange (ETDEWEB)

Kim, Chun Soo; Bae, Dae Seok; Kim, Kyung Su; Koh, Yong Kwon; Park, Byung Yun

2000-03-01

Preliminary study on the assessment of natural analogue study in Korea for the deep geological disposal of high-level radioactive waste was carried out. The project on natural analogue study in other countries are introduced. The uranium-bearing deposit in Okcheon belt are summarized, which reported to be uranium-bearing minerals in order to assess to feasibility for natural analogue study in Korea. Among the uranium-bearing deposits, the Deokpyeong area, reported to be the highest reservoir and grade, are selected as the study site, and the elementary investigation, including survey of radioactivity and geochemistry are carried out. According to the investigation of surface environment, the radioactivity and uranium content in the surface water and shallow groundwater does not show any anormal values. However, the radioactivity is expected to be increased in depth and the groundwater reacted with uranium-bearing graphite formation shows high unanium content, indicating the potential possibility for natural analogue study in Korea. In future, if more detail study are performed, the assessment of natural analogue study in Korea are expected.

Analogue Signal Processing: Collected Papers 1994-95

DEFF Research Database (Denmark)

1996-01-01

This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

Alligator Rivers Analogue project. Geochemistry of 239Pu, 129I, 99Tc and 36Cl

International Nuclear Information System (INIS)

Fabryka-Martin, J.T.; Curtis, D.B.

1992-01-01

One objective of this research programme has been to evaluate the applicability of uranium orebodies as natural analogues for testing radionuclide release-rate models used in performance assessment activities. The investigated nuclides included three of the most persistent radioactive constituents of high-level wastes from nuclear fission power reactors: plutonium-239, iodine-129, and technetium-99. The feasibility of uranium minerals as analogues for the behavior of these nuclear reaction products (NRP) in spent fuel relies upon a capability to characterise NRP concentrations in the source minerals. Measured abundances of natural 239 Pu, 99 Tc and 129 I in uranium ores are compared to calculated abundances in order to evaluate the degree to retention of these radionuclides by the ore. This modelling study also shows the extent to which various NRP are correlated, such that one provides a constraint on the production rates of others. Under most conditions, 36 Cl, another long-lived neutron-capture product found in uranium ores, is shown to be an ideal in-situ monitor of the 235 U fission rate, which is the dominant source term for 129 I and possibly a significant one for 99 Tc. Similarly, 239 Pu/U ratios can be used to establish limits on the 238 U neutron-induced fission rate; the ratios measured in this study suggest that 238 U induced fission comprises 129 I and 99 Tc. 79 refs., 21 tabs., 18 figs

Scientific basis for nuclear waste management XX

International Nuclear Information System (INIS)

Gray, W.J.; Triay, I.R.

1997-01-01

The proceedings are divided into the following topical sections: Glass formulations and properties; Glass/water interactions; Cements in radioactive waste management; Ceramic and crystalline waste forms; Spent nuclear fuel; Waste processing and treatment; Radiation effects in ceramics, glasses, and nuclear waste materials; Waste package materials; Radionuclide solubility and speciation; Radionuclide sorption; Radionuclide transport; Repository backfill; Performance assessment; Natural analogues; Excess plutonium dispositioning; and Chernobyl-related waste disposal issues. Papers within scope have been processed separately for inclusion on the data base

Nuclear molecular halo: the ubiquitous occurrence of van der Waals molecular states near threshold in molecular, nuclear and particle physics

International Nuclear Information System (INIS)

Gai, Moshe

1999-01-01

The observation of large E1 strength near threshold in the electromagnetic dissociation of 11 Li poses a fundamental question: Is the large E1 strength due to the threshold or is it due to a low lying E1 state? Such molecular cluster states were observed in 18 O and in several nuclei near the drip line. We discuss the nature of the threshold effect as well as review the situation in Molecular (and Particle Physics) where such Molecular States are observed near the dissociation limit. We suggest that the situation in 11 Li is reminiscent of the argon-benzene molecule where the argon atom is loosely bound by a polarization (van der Waals) mechanism and thus leads to a very extended object lying near the dissociation limit. Such states are also suggested to dominate the structure of mesons [α 0 (980), f 0 (975)] and baryons [λ(1405)] with proposed Kaon molecular structure (Dalitz) near threshold. The inspection of such states throughout Physics allows us to gain insight into this phenomenon and suggest that a new collective Molecular Dipole Degree of Freedom plays a major role in the structure of hadrons (halo nuclei, mesons and baryons), and that quantitative tools such as the E1 Molecular Sum Rule are useful for elucidating the nature of the observed low lying E1 strength in halo nuclei. (author)

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

Directory of Open Access Journals (Sweden)

Arno Verlee

2017-02-01

Full Text Available For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonylbenzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m-sulfamoylbenzamide analogues.

On Using Current Steering Logic in Mixed Analogue-digital Circuits

DEFF Research Database (Denmark)

Lehmann, Torsten

1998-01-01

The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition......, a high-swing current steering buffer for driving analogue switches or external digital signals is proposed....

UK Natural Analogue Coordinating Group: fourth annual report

International Nuclear Information System (INIS)

Read, D.; Hooker, P.J.

1992-01-01

HMIP has a research programme investigating some naturally radioactive sites as geochemical analogues of radionuclide migration. All of the analogue sites under investigation, both in the U.K. and overseas, are located where elevated uranium concentrations occur naturally. Coordination of the programme is achieved through the UK Natural Analogue Co-ordinating Group (NACG) which has met three times in this reporting period. The NACG is steered by the British Geological Survey. Its purpose is to ensure that the different research projects have an integrated function aimed at increasing our understanding of natural geochemical processes. Effort is also being expended in testing research models which may be used in such assessments. (author)

Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

Science.gov (United States)

Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

2017-06-02

Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular phylogeny of the Oriental butterfly genus Arhopala (Lycaenidae, Theclinae) inferred from mitochondrial and nuclear genes

NARCIS (Netherlands)

Megens, H.J.W.C.; Nes, Van W.J.; Moorsel, van C.H.M.; Pierce, N.E.; Jong, de R.

2004-01-01

We present a phylogeny for a selection of species of the butterfly genus Arhopala Boisduval, 1832 based on molecular characters. We sequenced 1778 bases of the mitochondrial genes Cytochrome Oxidase 1 and 2 including tRNALeu, and a 393-bp fragment of the nuclear wingless gene for a total of 42

Membrane and Nuclear Permeabilization by Polymeric pDNA Vehicles: Efficient Method for Gene Delivery or Mechanism of Cytotoxicity?

Science.gov (United States)

Grandinetti, Giovanna; Smith, Adam E.; Reineke, Theresa M.

2012-01-01

The aim of this study is to compare the cytotoxicity mechanisms of linear PEI to two analogous polymers synthesized by our group: a hydroxyl-containing poly(L-tartaramidoamine) (T4) and a version containing an alkyl chain spacer poly(adipamidopentaethylenetetramine) (A4) by studying the cellular responses to polymer transfection. We have also synthesized analogues of T4 with different molecular weights (degrees of polymerization of 6, 12, and 43) to examine the role of molecular weight on the cytotoxicity mechanisms. Several mechanisms of polymer-induced cytotoxicity are investigated, including plasma membrane permeabilization, the formation of potentially harmful polymer degradation products during transfection including reactive oxygen species, and nuclear membrane permeabilization. We hypothesized that since cationic polymers are capable of disrupting the plasma membrane, they may also be capable of disrupting the nuclear envelope, which could be a potential mechanism of how the pDNA is delivered into the nucleus (other than nuclear envelope breakdown during mitosis). Using flow cytometry and confocal microscopy, we show that the polycations with the highest amount of protein expression and toxicity, PEI and T443, are capable of inducing nuclear membrane permeability. This finding is important for the field of nucleic acid delivery in that not only could direct nucleus permeabilization be a mechanism for pDNA nuclear import but also a potential mechanism of cytotoxicity and cell death. We also show that the production of reactive oxygen species is not a main mechanism of cytotoxicity, and that the presence or absence of hydroxyl groups as well as polymer length plays a role in polyplex size and charge in addition to protein expression efficiency and toxicity. PMID:22175236

The role of natural analogues in performance assessment

International Nuclear Information System (INIS)

Ewing, R.C.

1992-01-01

One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10 3 - 10 5 years) required by regulatory agencies for performance assessment. The direct verification of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems provide perhaps the only means of partial verification, as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (m to km) and temporal (10 3 - 10 8 years) scales, and in highly complex terranes in which unknown synergisms may effect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the verification of performance assessments

Analogue computer display of accelerator beam optics

International Nuclear Information System (INIS)

Brand, K.

1984-01-01

Analogue computers have been used years ago by several authors for the design of magnetic beam handling systems. At Bochum a small analogue/hybrid computer was combined with a particular analogue expansion and logic control unit for beam transport work. This apparatus was very successful in the design and setup of the beam handling system of the tandem accelerator. The center of the stripper canal was the object point for the calculations, instead of the high energy acceleration tube a drift length was inserted into the program neglecting the weak focusing action of the tube. In the course of the installation of a second injector for heavy ions it became necessary to do better calculations. A simple method was found to represent accelerating sections on the computer and a particular way to simulate thin lenses was adopted. The analogue computer system proved its usefulness in the design and in studies of the characteristics of different accelerator installations over many years. The results of the calculations are in very good agreement with real accelerator data. The apparatus is the ideal tool to demonstrate beam optics to students and accelerator operators since the effect of a change of any of the parameters is immediately visible on the oscilloscope

Children's (Pediatric) Nuclear Medicine

Medline Plus

Full Text Available ... Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential ... or imaging device that produces pictures and provides molecular information. In many centers, nuclear medicine images can ...

Analogue Signal Processing: Collected Papers 1996-97

DEFF Research Database (Denmark)

1997-01-01

This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

Análogos de insulina Insulin analogues

Directory of Open Access Journals (Sweden)

Manuel E. Licea Puig

2006-12-01

diabetes mellitus (DM. The recombinant technology of deoxyribonucleic acid (DNA has allowed the development of human insulin; however, this has not totally solved the problems related to immunogenecity, among other problems. Therefore, the new technologies are applied to create insulin analogues. It is our purpose to review relevant pharmacological and clinical aspects related to the insulin analogues, as well as their usefulness in the treatment of DM. The insulin analogues result from biochemical modifications of human insulin. These modifications of the insulin molecule alter not only the absorption, but also the beginning and duration of the action, which offer advantages over the conventional insulins. At present, there are three rapid acting insulin analogues: insulin lispro, insulin aspart and glulisine; and three long acting analogues; glargine, detemir and albulin. Albulin is the latest long acting analogue reported. At present, it is being subjected to various in vitro and in vivo studies. Besides, there have been developed diverse formulations where the rapid acting insulin analogues are premixed with the long acting analogues. The rapid acting insulin analogues have showed a modest global benefit against the conventional insulins in type 1 diabetics. The long acting analogues focus their attention in those persons with DM with nocturnal hypoglycemic episodes. Longer term studies are necessary to confirm the safety and benefits of these preparations, as well as to determine their effect on the micro- and macroangiopathic complications of DM.

Diagnostic and therapeutic capabilities of modern nuclear medicine

International Nuclear Information System (INIS)

Lee Myung-Chul, M.D

2007-01-01

growths, brain epilepsies and neurovascular disorders. In lung cancer and colorectal cancer, recurrence FDG-PET, now as FDG-PET/CT, is the method of choice in prostate cancer, impalpable axillary nodes in breast cancer and ovarian cancer. Peptide receptor scintigraphy stared in 1989 with the in vivo demonstration of somatostatin-receptor-positive tumors in patients using radioiodinated somatostatin analogue. Later, other radiolabeled somatostatin analogues were developed. [In-111-DTPA0]octreotide is a radiopharmaceutical with great potential for the visualization of somatostatin-receptor-positive tumors. Pain associated with bone metastases is a common clinical problem which contributes to patient morbidity and reduced quality of life. Symptoms associated with this pain include depression, anxiety, fear and loss of independence. The use of bone-seeking radiopharmaceutical was first reported almost 50 years ago, and there are now compelling data to support their use as an effective - and cost effective - approaches to pain palliation. With the ability of PET machines to capture direct images of cellular and molecular growth condition changes, research and treatment using PET systems quickly progressed in the United States, Europe, Korea and Japan. PET will play an active role in providing these molecular imaging techniques for refining the definition of radiation beams in RTP. Other areas of interest are the investigation of tumor-targeting agents, gene imaging and different PET tracers to improve the characterization of target cells. Technologic advances, such as the ability to acquire gated PET scans, will improve the accuracy of target cell characterization

Isolation and structural characterization of a novel sibutramine analogue, chlorosipentramine, in a slimming dietary supplement, by using HPLC-PDA, LC-Q-TOF/MS, FT-IR, and NMR.

Science.gov (United States)

Yun, Jisuk; Shin, Kye Jung; Choi, Jangduck; Jo, Cheon-Ho

2018-05-01

A novel sibutramine analogue was detected in a slimming formula by high performance liquid chromatography with a photo diode detector array (HPLC-PDA). The unknown compound exhibited an ultraviolet (UV) spectrum that was similar to that of chlorosibutramine, despite having a different HPLC retention time. Further analysis of the slimming formula by LC-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) showed that the unknown compound had the formula C 18 H 27 Cl 2 N. To elucidate the structure of this new sibutramine analogue, the target compound in the slimming formula was isolated on a preparative-LC system equipped with a PDA. After analysis by fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy, the unknown compound was identified as a sibutramine analogue in which the iso-butyl group on the side chain is replaced with an iso-pentyl group. This new sibutramine analogue was identified to be 1-(1-(3,4-dichlorophenyl)cyclobutyl)-N,N,4-trimethylpentan-1-amine and has been named as chlorosipentramine. Copyright © 2018 Elsevier B.V. All rights reserved.

Chemopreventive properties of curcumin analogues ...

African Journals Online (AJOL)

Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

Science.gov (United States)

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-02-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

Insulin analogues and severe hypoglycaemia in type 1 diabetes

DEFF Research Database (Denmark)

Kristensen, P L; Hansen, L S; Jespersen, M J

2012-01-01

The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

How stakeholders view the use of analogues in safety cases: PAMINA

International Nuclear Information System (INIS)

Atherton, Elizabeth; Bailey, Lucy

2008-01-01

The aim of this presentation is to provide an overview of some research that has been undertaken in the UK to investigate stakeholders' views of analogues. There are various reasons for using analogues including: to try and explain difficult concepts; to compare disposal facility features with familiar and/or natural systems; to provide an alternative, non-numerical line of reasoning to support the Safety Case conclusions; to provide evidence of behaviour over very long timescales, that cannot be achieved in the laboratory. There are some dangers when using analogues that people should be aware of: the analogue conditions may not be the same as those found in a disposal facility, so the analogue may have limited application. Some analogues may have negative implications, for example artefacts that have corroded. Analogues can be taken too far and used in inappropriate ways to try and support an assumption. So it is important to find out how stakeholders view the use of analogues in a safety case. NDA is involved in an EC funded project called Pamina (Performance Assessment Methodologies in Application). The project involves 26 partners from 11 European countries, plus other associated members and runs for 3 years from October 2006 to October 2009. The NDA is involved in several parts of the project: Exploring issues of modelling uncertainty; Evaluating effectiveness of approaches for communicating safety cases with stakeholders. NDA ran a workshop in October 2007 in Manchester. The aims of the workshop were to explore how different methods of communicating aspects of a safety case were received by stakeholders. The workshop presented stakeholders with: Examples of different repository concepts; Descriptions of barrier performance; Different ways of presenting numerical results; Use of natural analogues

Defining reference conditions for acidified waters using a modern analogue approach

International Nuclear Information System (INIS)

Simpson, Gavin L.; Shilland, Ewan M.; Winterbottom, Julie M.; Keay, Janey

2005-01-01

Analogue matching is a palaeolimnological technique that aims to find matches for fossil sediment samples from a set of modern surface sediment samples. Modern analogues were identified that closely matched the pre-disturbance conditions of eight of the UK Acid Waters Monitoring Network (AWMN) lakes using diatom- and cladoceran-based analogue matching. These analogue sites were assessed in terms of hydrochemistry, aquatic macrophytes and macro-invertebrates as to their suitability for defining wider hydrochemical and biological reference conditions for acidified sites within the AWMN. The analogues identified for individual AWMN sites show a close degree of similarity in terms of their hydrochemical characteristics, aquatic macrophytes and, to a lesser extent, macro-invertebrate fauna. The reference conditions of acidified AWMN sites are inferred to be less acidic than today and to support a wider range of acid-sensitive aquatic macrophyte and macro-invertebrate taxa than that recorded in the AWMN lakes over the period of monitoring since 1988. - The use of a palaeolimnological technique to identify modern ecological reference analogues for acidified lakes is demonstrated

Isolation of nucleotide binding site-leucine rich repeat and kinase resistance gene analogues from sugarcane (Saccharum spp.).

Science.gov (United States)

Glynn, Neil C; Comstock, Jack C; Sood, Sushma G; Dang, Phat M; Chaparro, Jose X

2008-01-01

Resistance gene analogues (RGAs) have been isolated from many crops and offer potential in breeding for disease resistance through marker-assisted selection, either as closely linked or as perfect markers. Many R-gene sequences contain kinase domains, and indeed kinase genes have been reported as being proximal to R-genes, making kinase analogues an additionally promising target. The first step towards utilizing RGAs as markers for disease resistance is isolation and characterization of the sequences. Sugarcane clone US01-1158 was identified as resistant to yellow leaf caused by the sugarcane yellow leaf virus (SCYLV) and moderately resistant to rust caused by Puccinia melanocephala Sydow & Sydow. Degenerate primers that had previously proved useful for isolating RGAs and kinase analogues in wheat and soybean were used to amplify DNA from sugarcane (Saccharum spp.) clone US-01-1158. Sequences generated from 1512 positive clones were assembled into 134 contigs of between two and 105 sequences. Comparison of the contig consensuses with the NCBI sequence database using BLASTx showed that 20 had sequence homology to nuclear binding site and leucine rich repeat (NBS-LRR) RGAs, and eight to kinase genes. Alignment of the deduced amino acid sequences with similar sequences from the NCBI database allowed the identification of several conserved domains. The alignment and resulting phenetic tree showed that many of the sequences had greater similarity to sequences from other species than to one another. The use of degenerate primers is a useful method for isolating novel sugarcane RGA and kinase gene analogues. Further studies are needed to evaluate the role of these genes in disease resistance.

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues.

Directory of Open Access Journals (Sweden)

Geoffrey D Coxon

Full Text Available Defining the pharmacological target(s of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61 or HadC (at Val85, Lys157 or Thr123, which are components of the β-hydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors.

Cobalamin analogues in humans

DEFF Research Database (Denmark)

Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

2013-01-01

BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...

Concise synthesis of new bridged-nicotine analogues

DEFF Research Database (Denmark)

Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

2012-01-01

This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively.......This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

NARCIS (Netherlands)

Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

2010-01-01

P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels

Climate Analogues for agricultural impact projection and adaptation – a reliability test

Directory of Open Access Journals (Sweden)

Swen P.M. Bos

2015-10-01

Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

Radionuclides for nuclear medicine: a nuclear physicists' view

Czech Academy of Sciences Publication Activity Database

Cantone, M.; Haddad, F.; Harissopoulos, S.; Jensen, M.; Jokinen, A.; Koster, U.; Lebeda, Ondřej; Ponsard, B.; Ratzinger, U.; Stora, T.; Tarkanyi, F.; Van Duppen, P.

2013-01-01

Roč. 40, 2 Supplement (2013), S257-S257 ISSN 1619-7070. [Annual Congress of the European Association of Nuclear Medicine (EANM). 19.10.2013-23.10.2013, Lyon] Institutional support: RVO:61389005 Keywords : nuclear physics for medicine * EANM * medical radionuclides Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy

International Nuclear Information System (INIS)

Kesel, Andreas J.

2003-01-01

The synthesis of retinoid vitamin A-vitamin B 6 conjugate analogues from a vitamin B 6 coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5 ' -O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H 2 O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy ( 1 H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2 ' C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2 ' C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5 ' -O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV

Confocal μ-XRF, μ-XAFS, and μ-XRD Studies of Sediment from a Nuclear Waste Disposal Natural Analogue Site and Fractured Granite Following a Radiotracer Migration Experiment

International Nuclear Information System (INIS)

Denecke, Melissa A.; Brendebach, Boris; Rothe, Joerg; Simon, Rolf; Janssens, Koen; Nolf, Wout de; Vekemans, Bart; Falkenberg, Gerald; Somogyi, Andrea; Noseck, Ulrich

2007-01-01

Combined μ-XRF, μ-XAFS, and μ-XRD investigations of a uranium-rich tertiary sediment, from a nuclear repository natural analogue site, and a fractured granite bore core section after a column tracer experiment using a Np(V) containing cocktail have been performed. Most μ-XRF/μ-XAFS measurements are recorded in a confocal geometry to provide added depth information. The U-rich sediment results show uranium to be present as a tetravalent phosphate and that U(IV) is associated with As(V). Arsenic present is either As(V) or As(0). The As(0) forms thin coatings on the surface of pyrite nodules. A hypothesis for the mechanism of uranium immobilization is proposed, where arsenopyrite acted as reductant of ground water dissolved U(VI) leading to precipitation of less soluble U(IV) and thereby forming As(V). Results for the granite sample show the immobilized Np to be tetravalent and associated with facture material

Activity Prediction of Schiff Base Compounds using Improved QSAR Models of Cinnamaldehyde Analogues and Derivatives

Directory of Open Access Journals (Sweden)

Hui Wang

2015-10-01

Full Text Available In past work, QSAR (quantitative structure-activity relationship models of cinnamaldehyde analogues and derivatives (CADs have been used to predict the activities of new chemicals based on their mass concentrations, but these approaches are not without shortcomings. Therefore, molar concentrations were used instead of mass concentrations to determine antifungal activity. New QSAR models of CADs against Aspergillus niger and Penicillium citrinum were established, and the molecular design of new CADs was performed. The antifungal properties of the designed CADs were tested, and the experimental Log AR values were in agreement with the predicted Log AR values. The results indicate that the improved QSAR models are more reliable and can be effectively used for CADs molecular design and prediction of the activity of CADs. These findings provide new insight into the development and utilization of cinnamaldehyde compounds.

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Final report of the Peña Blanca natural analogue project

Energy Technology Data Exchange (ETDEWEB)

Levy, Schön S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Goldstein, Steven Joel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Abdel-Fattah, Amr I. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Amato, Ronald S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Anthony, Elizabeth [Univ. of Texas, El Paso, TX (United States); Cook, Paul [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Dobson, Patrick F. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fayek, Mostafa [Univ. of Manitoba, Winnipeg (Canada); French, Diana [Univ. of Texas, El Paso, TX (United States); Garza, Rodrigo de [Univ. Autonoma de Chihuahua (Mexico); Ghezzehei, Teamrat [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goodell, Philip C. [Univ. of Texas, El Paso, TX (United States); Harder, Steven H. [Univ. of Texas, El Paso, TX (United States); Ku, Teh-Lung [Univ. of Southern California, Los Angeles, CA (United States); Luo, Shangde [Univ. of Southern California, Los Angeles, CA (United States); Murrell, Michael Tildon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Norman, Deborah E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Nunn, Andrew J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Oliver, Ronald [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pekar-Carpenter, Katrina [Univ. of Texas, El Paso, TX (United States); Rearick, Michael Sean [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ren, Minghua [Univ. of Texas, El Paso, TX (United States); Reyes-Cortes, Ignacio [Univ. Autonoma de Chihuahua (Mexico); Pineda, Jose Alfredo [El Instituto de Ecologia (INECOL) (Mexico); Saulnier, George [AREVA Federal Services LLC, Charlotte, NC (United States); Tarimala, Sowmitri [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Walton, John [Univ. of Texas, El Paso, TX (United States)

2016-10-04

The Peña Blanca region, 50 km north of Chihuahua City, Chihuahua, México, was a target of uranium exploration and mining by the Mexican government. After mining ceased in 1981, researchers became interested in this region as a study area for subsurface uranium migration with relevance to geologic disposal of nuclear waste. Many studies related to this concept were conducted at the Nopal I mine site located on a cuesta (hill) of the Sierra Peña Blanca. This site has geologic, tectonic, hydrologic, and geochemical similarities to Yucca Mountain, Nevada, a formerly proposed site for a high-level nuclear-waste repository in the unsaturated zone. The U.S. Department of Energy (U.S. DOE), Office of Civilian Radioactive Waste Management (OCRWM), sponsored studies at Nopal I in the 1990s and supported the drilling of three research wells – PB1, PB2, and PB3 – at the site in 2003. Beginning in 2004, the Peña Blanca Natural Analogue Project was undertaken by U.S. DOE, OCRWM to develop a three-dimensional conceptual model of the transport of uranium and its radiogenic daughter products at the Nopal I site.

Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

DEFF Research Database (Denmark)

Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.

2008-01-01

An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures...

3-alkyl fentanyl analogues: Structure-activity-relationship study

OpenAIRE

Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

2012-01-01

Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

Rheological and physical characteristics of crustal-scaled materials for centrifuge analogue modelling

Science.gov (United States)

Waffle, Lindsay; Godin, Laurent; Harris, Lyal B.; Kontopoulou, M.

2016-05-01

We characterize a set of analogue materials used for centrifuge analogue modelling simulating deformation at different levels in the crust simultaneously. Specifically, we improve the rheological characterization in the linear viscoelastic region of materials for the lower and middle crust, and cohesive synthetic sands without petroleum-binding agents for the upper crust. Viscoelastic materials used in centrifuge analogue modelling demonstrate complex dynamic behaviour, so viscosity alone is insufficient to determine if a material will be an effective analogue. Two series of experiments were conducted using an oscillating bi-conical plate rheometer to measure the storage and loss moduli and complex viscosities of several modelling clays and silicone putties. Tested materials exhibited viscoelastic and shear-thinning behaviour. The silicone putties and some modelling clays demonstrated viscous-dominant behaviour and reached Newtonian plateaus at strain rates clays demonstrated elastic-dominant power-law relationships. Based on these results, the elastic-dominant modelling clay is recommended as an analogue for basement cratons. Inherently cohesive synthetic sands produce fine-detailed fault and fracture patterns, and developed thrust, strike-slip, and extensional faults in simple centrifuge test models. These synthetic sands are recommended as analogues for the brittle upper crust. These new results increase the accuracy of scaling analogue models to prototype. Additionally, with the characterization of three new materials, we propose a complete lithospheric profile of analogue materials for centrifuge modelling, allowing future studies to replicate a broader range of crustal deformation behaviours.

Molecular Recognition Involving Anthraquinone Derivatives and Molecular Clips

Science.gov (United States)

Alaparthi, Madhubabu

In the past, we have demonstrated that 1,8-anthraquinone-18-crown-5 (1) and its heterocyclic derivatives act as luminescent hosts for a variety of cations of environmental and clinical concern. We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene - 9,10-dione in a 1:1 ratio (2,3, and 6). These sensors bind metal ions in a 1:1 ratio (7 and 8), and the optical properties of the new complexes were examined and the sulfur and selenium analogues show that selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was competitive for Ca(II) ion. Selective reduction of 1 yields secondary alcohols where either one or both of the anthraquinone carbonyl groups has been reduced ( 15 and 9). A new mechanism for the fluorescence detection of metal cations in solution is introduced involving a unique keto-enol tautomerization. Reduction of 1 yields the doubly reduced secondary alcohol, 9. 9 acts as a chemodosimeter for Al(III) ion producing a strong blue emission due to the formation of the anthracene fluorophore, 10, via dehydration of the internal secondary alcohol in DMSO/aqueous solution. The enol form is not the most thermodynamically stable form under these conditions however, and slowly converts to the keto form 11.. Currently we are focusing on cucurbituril derivatives, also described as molecular clips due to their folded geometry used as molecular recognition hosts. We first investigated the synthesis and characterization of aromatic methoxy/catechol terminated cucurbituril units that act as hosts for small solvent molecules, such as CH2Cl2, CH3CN, DMF, and MeOH, through dual pi...H-C T

Labelling and evaluation of new stabilised neurotensin (8-13) analogues for SPET

International Nuclear Information System (INIS)

Chavatte, K.; Terriere, D.; Jeannin, L.

1998-01-01

Neurotensin (8-13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH 2 -NH) isostere. DTPA analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the low nanomolar range in combination with a biological half live in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111 In-DTPA-NT(8-13) analogues showed a major clearance from the blood through the kidneys. 125 I-labelled Neurotensin (8-13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. It is strongly suggested that stabilised neurotensin (8-13) analogues whether labelled with In-111, I-123 and the near future with Tc-99m, may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of different NT-receptor positive tumours like non-endocrine pancreas carcinoma, small cell lung carcinoma or colon adeno carcinoma. It is enticing to speculate that metabolically stabilised Neurotensin (8-13) analogues labelled with an appropriate isotope might be useful in therapy of different human cancers. (author)

Thymidine analogues to assess microperfusion in human tumors

International Nuclear Information System (INIS)

Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C.

2005-01-01

Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation

Analogues of estradiol as potential breast tumor imaging agents

International Nuclear Information System (INIS)

Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

1984-01-01

The radioiodinated analogue of estradiol, 11β-methoxy-17α-[/sup 125/I]iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11β-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11β-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study

The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

Energy Technology Data Exchange (ETDEWEB)

Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius (Bergab Consulting Geologists, Goeteborg (Sweden))

2010-09-15

This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

International Nuclear Information System (INIS)

Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius

2010-09-01

This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

Nuclear sound

International Nuclear Information System (INIS)

Wambach, J.

1991-01-01

Nuclei, like more familiar mechanical systems, undergo simple vibrational motion. Among these vibrations, sound modes are of particular interest since they reveal important information on the effective interactions among the constituents and, through extrapolation, on the bulk behaviour of nuclear and neutron matter. Sound wave propagation in nuclei shows strong quantum effects familiar from other quantum systems. Microscopic theory suggests that the restoring forces are caused by the complex structure of the many-Fermion wavefunction and, in some cases, have no classical analogue. The damping of the vibrational amplitude is strongly influenced by phase coherence among the particles participating in the motion. (author)

Iodination and stability of somatostatin analogues: comparison of iodination techniques. A practical overview.

Science.gov (United States)

de Blois, Erik; Chan, Ho Sze; Breeman, Wouter A P

2012-01-01

For iodination ((125/127)I) of tyrosine-containing peptides, chloramin-T, Pre-Coated Iodo-Gen(®) tubes and Iodo-Beads(®) (Pierce) are commonly used for in vitro radioligand investigations and there have been reliant vendors hereof for decades. However, commercial availability of these radio-iodinated peptides is decreasing. For continuation of our research in this field we investigated and optimized (radio-)iodination of somatostatin analogues. In literature, radioiodination using here described somatostatin analogues and iodination techniques are described separately. Here we present an overview, including High Performance Liquid Chromatography (HPLC) separation and characterisation by mass spectrometry, to obtain mono- and di-iodinated analogues. Reaction kinetics of (125/127)I iodinated somatostatin analogues were investigated as function of reaction time and concentration of reactants, including somatostatin analogues, iodine and oxidizing agent. To our knowledge, for the here described somatostatin analogues, no (127)I iodination and optimization are described. (Radio-)iodinated somatostatin analogues could be preserved with a >90% radiochemical purity for 1 month after reversed phase HPLC-purification.

From BPA to its analogues: Is it a safe journey?

Science.gov (United States)

Usman, Afia; Ahmad, Masood

2016-09-01

Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? Copyright © 2016. Published by Elsevier Ltd.

A pulse amplitude dividing circuit for nuclear applications

International Nuclear Information System (INIS)

Ediss, C.; McQuarrie, S.A.

1981-01-01

A pulse dividing circuit has been developed to provide analogue and digital outputs proportional to the ratio of the amplitudes of two nuclear pulses. Input pulses ranging from 200 mV to 10 V may be processed by the device. The pulse dividing circuit has been successfully incorporated as part of a small gamma camera. (orig.)

Molecular growth in clusters of polycyclic aromatic hydrocarbons induced by collisions with ions

International Nuclear Information System (INIS)

Delaunay, Rudy

2016-01-01

This thesis concerns the experimental study of the interaction between low energy ions (keV range) and neutral isolated molecules or clusters of polycyclic aromatic hydrocarbons (PAH) in the gas phase. The use of ionising radiations on these complex molecular systems of astrophysical interest allowed to highlight processes of statistical fragmentation, corresponding to the redistribution of the energy through the degrees of freedom of the target, and non-statistical fragmentation, linked to binary collisions of the ions on the nuclei of the target. A mechanism of intermolecular growth in clusters of PAH is observed. It is associated to the ultrafast (≤ ps) formation of fragments inside the clusters following binary collisions. The presence of a molecular environment around the fragments formed during the interaction may initiate a process of reactivity between the fragments and the molecules of the clusters. More precisely, the study focusses on the importance of the electronic stopping power SE and the nuclear stopping power SN of the projectile ion. It shows that the molecular growth is enhanced when SN is higher than SE. This can be explained by the fact that the deposit of energy is mainly due to the interaction with the nuclei of the target. The process of growth has been observed for all the molecules of PAH studied during this thesis and also for nitrogenated analogues of the molecule of anthracene. This demonstrates that molecular growth may be efficiently induced by collisions of low energy ions with clusters of PAH. (author) [fr

Design of a saturated analogue and digital current transducer

International Nuclear Information System (INIS)

Pross, Alexander

2002-01-01

This project describes the development of a new analogue and digital current transducer, providing a range of new theoretical design methods for these novel devices. The main control feature is the limit cycling operation, and the novel use of the embedded sigma-delta modulator sensor structure to derive a low component count digital sensor. The research programme was initiated into the design, development and evaluation of a novel non-Hall sensing analogue and digital current transducer. These transducers are used for measurement of high currents in power systems applications. The investigation is concerned with a new design which uses a magnetic ferrite core without an air gap for current measurement. The motivation for this work was to design a new control circuit which provides a low component count, and utilises the non-linear properties of the magnetic ferrite core to transmit direct current. The use of a limit cycle control circuit was believed to be particularly suitable for the analogue and digital transducers, for two main reasons: the low component count, and the output signal is directly digital. In line with the motivations outlined above, the outcome of the research has witnessed the design, development and evaluation of a practically realisable analogue and digital current transducer. The design procedure, which is documented in this thesis, is considered to be a major contribution to the field of transducers design and development using a control systems approach. Mathematical models for both analogue and digital transducers were developed and the resulting model based predictions were found to be in good agreement with measured results. Simplification of the new model sensing device was achieved by approximating the non-linear ferrite core using FFT analysis. This is also considered to be a significant contribution. The development analogue and digital current censors employed a sampled data control systems design and utilised limit cycling

Group fellowship training in nuclear spectroscopy instrumentation maintenance at the Seibersdorf Laboratories

International Nuclear Information System (INIS)

Xie, Y.; Abdel-Rassoul, A.A.

1989-01-01

Nuclear spectroscopy instruments are important tools for nuclear research and applications. Several types of nuclear spectrometers are being sent to numerous laboratories in developing countries through technical co-operation projects. These are mostly sophisticated systems based on different radiation detectors, analogue and digital circuitry. In most cases, they use microprocessor or computer techniques involving software and hardware. Maintenance service and repair of these systems is a major problem in many developing countries because suppliers do not set up service stations. The Agency's Laboratories at Seibersdorf started conducting group fellowship training on nuclear spectroscopy instrumentation maintenance in 1987. This article describes the training programme

Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity

DEFF Research Database (Denmark)

Laursen, Jane B.; de Visser, P.C.; Nielsen, H.K.

2002-01-01

in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH2Cl2 (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis...

Natural analogues for containment-providing barriers for a HLW repository in salt

Energy Technology Data Exchange (ETDEWEB)

Wolf, J.; Noseck, U.

2015-06-15

In 2005, a German research project was started to develop a novel approach to prove safety for a HLW repository in a salt formation, to refine the safety concept, to identify open scientific issues and to define necessary R&D work. This project aimed at identifying the key information for a HLW repository in salt. One important question is how this information may be best fulfilled by natural analogue studies. This question is answered by starting a review of the required key information needs of the safety case (post-closure phase) in order to assess whether or not these requirements can be supported by natural analogues information. In order to structure the review and to address the key elements of the safety concepts, three types of natural analogues are distinguished: (i) natural analogues for the integrity of the geological barrier, (ii) natural analogues for the integrity of the geotechnical barriers and (iii) natural analogues for release scenarios. For the safety case in salt type (i) and (ii) are of highest importance and are treated in this paper. The assessment documented in this paper on the one hand indicates the high potential benefit of natural analogues for a safety case in salt and on the other hand helps to focus the available human and financial resources for the safety case on the most safety-relevant aspects. (authors)

GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

Science.gov (United States)

Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

2013-01-01

The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

Science.gov (United States)

Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

2017-11-30

YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Geological safety aspects of nuclear waste disposalin in Finland

Energy Technology Data Exchange (ETDEWEB)

Ahonen, L; Hakkarainen, V; Kaija, J; Kuivamaki, A; Lindberg, A; Paananen, M; Paulamaki, S; Ruskeeniemi, T

2011-07-01

The management of nuclear waste from Finnish power companies is based on the final geological disposal of encapsulated spent fuel at a depth of several hundreds of metres in the crystalline bedrock. Permission for the licence requires that the safety of disposal is demonstrated in a safety case showing that processes, events and future scenarios possibly affecting the performance of the deep repository are appropriately understood. Many of the safety-related issues are geological in nature. The Precambrian bedrock of Finland has a long history, even if compared with the time span considered for nuclear waste disposal, but the northern location calls for a detailed study of the processes related to Quaternary glaciations. This was manifested in an extensive international permafrost study in northern Canada, coordinated by GTK. Hydrogeology and the common existence of saline waters deep in the bedrock have also been targets of extensive studies, because water chemistry affects the chemical stability of the repository near-field, as well as radionuclide transport. The Palmottu natural analogue study was one of the international high-priority natural analogue studies in which transport phenomena were explored in a natural geological system. Currently, deep biosphere processes are being investigated in support of the safety of nuclear waste disposal. (orig.)

Nuclear molecular states

International Nuclear Information System (INIS)

Abe, Y.

1975-01-01

The effects of polarization on the stability of α-cluster structures in 8 Be and 12 C nuclei are studied in the intrinsic states. The extent of the polarization of α-clusters is investigated by employing a molecular-orbital model. Two α-cluster structure of 8 Be is shown to be extremely stable, and a triangular configuration of three α-clusters is also shown to be stable, but the polarizations of α-clusters are found rather large. Gruemmer--Faessler's method is discussed and their results are shown to be trivial

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

International Nuclear Information System (INIS)

Armaković, Stevan; Armaković, Sanja J.; Holodkov, Vladimir; Pelemiš, Svetlana

2016-01-01

We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S_1−T_1). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S_1−T_1) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S_1−T_1), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

Cross-reactivity of amphetamine analogues with Roche Abuscreen radioimmunoassay reagents

International Nuclear Information System (INIS)

Cody, J.T.

1990-01-01

Cross-reactivity of amphetamine analogues with the Abuscreen amphetamine radioimmunoassay reagents was determined for both the standard and high specificity antibody systems. Compounds tested included 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxyamphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxyamphetamine (MDA), N,N-dimethyl-3,4-methylenedioxyamphetamine and N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine, 2,5-dimethoxy-4-methylamphetamine (DOM), and 3,4,5-trimethoxyphenethylamine (mescaline). Blank negative reference material was spiked with 1,000 to 100,000 ng/mL of the amphetamine analogue and used as sample in the assays. MDA was the only analogue that showed cross reactivity equal to or greater than that of amphetamine. None of the other analogue compounds demonstrated a positive result at even the highest concentration; however several showed depressed counts at various concentration levels

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

Science.gov (United States)

Bharate, Sandip B; Bhutani, Kamlesh K; Khan, Shabana I; Tekwani, Babu L; Jacob, Melissa R; Khan, Ikhlas A; Singh, Inder Pal

2006-03-15

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

Science.gov (United States)

Luger, Peter; Dittrich, Birger; Tacke, Reinhold

2015-09-14

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

Molecular Dynamics-based Simulations of Bulk/Interfacial Structures and Diffusion Behaviors in Nuclear Waste Glasses

Energy Technology Data Exchange (ETDEWEB)

Du, Jincheng

2018-03-16

This NEUP Project aimed to generate accurate atomic structural models of nuclear waste glasses by using large-scale molecular dynamics-based computer simulations and to use these models to investigate self-diffusion behaviors, interfacial structures, and hydrated gel structures formed during dissolution of these glasses. The goal was to obtain realistic and accurate short and medium range structures of these complex oxide glasses, to provide a mechanistic understanding of the dissolution behaviors, and to generate reliable information with predictive power in designing nuclear waste glasses for long-term geological storage. Looking back of the research accomplishments of this project, most of the scientific goals initially proposed have been achieved through intensive research in the three and a half year period of the project. This project has also generated a wealth of scientific data and vibrant discussions with various groups through collaborations within and outside of this project. Throughout the project one book chapter and 14 peer reviewed journal publications have been generated (including one under review) and 16 presentations (including 8 invited talks) have been made to disseminate the results of this project in national and international conference. Furthermore, this project has trained several outstanding graduate students and young researchers for future workforce in nuclear related field, especially on nuclear waste immobilization. One postdoc and four PhD students have been fully or partially supported through the project with intensive training in the field material science and engineering with expertise on glass science and nuclear waste disposal

Synthesis of Naphthyl-, Quinolin- and Anthracenyl Analogues of Clofibric Acid as PPARα Agonists.

Science.gov (United States)

Giampietro, Letizia; Ammazzalorso, Alessandra; Bruno, Isabella; Carradori, Simone; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giancristofaro, Antonella; Maccallini, Cristina; Amoroso, Rosa

2016-03-01

PPARα is a ligand activated transcription factor belonging to the nuclear receptor subfamily, involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPARα activation is important in steatosis, inflammation and fibrosis in preclinical models of non-alcoholic fatty liver disease identifying a new potential therapeutic area. In this work, three series of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized. In an effort to obtain new compounds active as PPARα agonists, these molecules were evaluated for PPARα transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPARα; noteworthy, optically active naphthyl derivatives activated PPARα better than corresponding parent compound. © 2015 John Wiley & Sons A/S.

Theoretical studies on nuclear spin selective quantum dynamics of non-linear molecules; Theoretische Untersuchung zur Quantendynamik der Kernspinisomere nicht-linearer Molekuele

Energy Technology Data Exchange (ETDEWEB)

Grohmann, Thomas

2012-05-31

In this thesis the wave packet dynamics of nuclear spin isomers of polyatomic molecules after interaction with static and time-dependent magnetic fields and moderate intense nonresonant laser pulses is investigated. In particular, the process of inducing (internal) molecular rotation as well as alignment of molecules by manipulating their rotational or rotational-torsional degrees of freedom is studied. In the first part of the thesis all theoretical concepts for identifying nuclear spin isomers and for describing their quantum dynamics will be discussed. Especially the symmetrization postulate and themolecular symmetry group will be introduced and illustrated for some examples of molecules. These concepts will be extended to the case of identifying nuclear spin isomers in the presence of an external field. In the second part it is shown for nitromethane that magnetic fields are able to induce unidirectional rotations in opposite directions for different nuclear spin isomers of molecules containing methyl groups if the dipolar interaction is included. Additionally, it is demonstrated that different nuclear spin isomers of a chemical compound may show different alignment after the interaction with a moderate intense laser pulse. As shown for the rigid symmetric top propadien and the rigid asymmetric tops ethene and analogues, distinct pairs of nuclear spin isomers show at certain points in time a complementary behavior: while one isomer is showing alignment the partner isomer is showing anti-alignment. Moreover, it is illustrated that not every nuclear spin isomer can be aligned equally efficient. The alignment of non-rigid molecules is considered as well. As an example for a molecule with feasible torsion in the electronic ground state, the alignment of diboron tetrafluoride is investigated. It becomes apparent that not only rotational but also the torsional dynamics of the molecules is nuclear spin selective; different nuclear spin isomers have at distinct points

The Planetary Terrestrial Analogues Library (PTAL)

Science.gov (United States)

Werner, S. C.; Dypvik, H.; Poulet, F.; Rull Perez, F.; Bibring, J.-P.; Bultel, B.; Casanova Roque, C.; Carter, J.; Cousin, A.; Guzman, A.; Hamm, V.; Hellevang, H.; Lantz, C.; Lopez-Reyes, G.; Manrique, J. A.; Maurice, S.; Medina Garcia, J.; Navarro, R.; Negro, J. I.; Neumann, E. R.; Pilorget, C.; Riu, L.; Sætre, C.; Sansano Caramazana, A.; Sanz Arranz, A.; Sobron Grañón, F.; Veneranda, M.; Viennet, J.-C.; PTAL Team

2018-04-01

The Planetary Terrestrial Analogues Library project aims to build and exploit a spectral data base for the characterisation of the mineralogical and geological evolution of terrestrial planets and small solar system bodies.

Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays

OpenAIRE

Ryo Nishihara; Masahiro Abe; Shigeru Nishiyama; Daniel Citterio; Koji Suzuki; Sung Bae Kim

2017-01-01

Spectral overlaps among the multiple optical readouts commonly cause optical contamination in fluorescence and bioluminescence. To tackle this issue, we created five-different lineages of coelenterazine (CTZ) analogues designed to selectively illuminate a specific luciferase with unique luciferase selectivity. In the attempt, we found that CTZ analogues with ethynyl or styryl groups display dramatically biased bioluminescence to specific luciferases and pHs by modifying the functional groups ...

Molecular genotyping of Colletotrichum species based on arbitrarily primed PCR, A + T-Rich DNA, and nuclear DNA analyses

Science.gov (United States)

Freeman, S.; Pham, M.; Rodriguez, R.J.

1993-01-01

Molecular genotyping of Colletotrichum species based on arbitrarily primed PCR, A + T-rich DNA, and nuclear DNA analyses. Experimental Mycology 17, 309-322. Isolates of Colletotrichum were grouped into 10 separate species based on arbitrarily primed PCR (ap-PCR), A + T-rich DNA (AT-DNA) and nuclear DNA banding patterns. In general, the grouping of Colletotrichum isolates by these molecular approaches corresponded to that done by classical taxonomic identification, however, some exceptions were observed. PCR amplification of genomic DNA using four different primers allowed for reliable differentiation between isolates of the 10 species. HaeIII digestion patterns of AT-DNA also distinguished between species of Colletotrichum by generating species-specific band patterns. In addition, hybridization of the repetitive DNA element (GcpR1) to genomic DNA identified a unique set of Pst 1-digested nuclear DNA fragments in each of the 10 species of Colletotrichum tested. Multiple isolates of C. acutatum, C. coccodes, C. fragariae, C. lindemuthianum, C. magna, C. orbiculare, C. graminicola from maize, and C. graminicola from sorghum showed 86-100% intraspecies similarity based on ap-PCR and AT-DNA analyses. Interspecies similarity determined by ap-PCR and AT-DNA analyses varied between 0 and 33%. Three distinct banding patterns were detected in isolates of C. gloeosporioides from strawberry. Similarly, three different banding patterns were observed among isolates of C. musae from diseased banana.

Role of nuclear dynamics in the asymmetric molecular-frame photoelectron angular distributions for C 1s photoejection from CO2

International Nuclear Information System (INIS)

Miyabe, S.; Haxton, D. J.; Rescigno, T. N.; McCurdy, C. W.

2011-01-01

We report the results of semiclassical calculations of the asymmetric molecular-frame photoelectron angular distributions for C 1s ionization of CO 2 measured with respect to the CO + and O + ions produced by subsequent Auger decay, and show how the decay event can be used to probe ultrafast molecular dynamics of the transient cation. The fixed-nuclei photoionization amplitudes were constructed using variationally obtained electron-molecular-ion scattering wave functions. The amplitudes are then used in a semiclassical manner to investigate their dependence on the nuclear dynamics of the cation. The method introduced here can be used to study other core-level ionization events.

Molecular dynamics simulation of Xe bubble nucleation in nanocrystalline UO2 nuclear fuel

International Nuclear Information System (INIS)

Moore, Emily; René Corrales, L.; Desai, Tapan; Devanathan, Ram

2011-01-01

Highlights: ► We simulated the interactions of defects and fission gas with grain boundaries in nuclear fuel. ► We observed the formation of Xe bubble nuclei that are difficult to observe experimentally. ► The bubble nuclei form by vacancy-assisted diffusion of Xe atoms. ► We also observed the initial stages of grain boundary motion. ► The study offers insights to the design of nuclear fuel to control fission gas release. - Abstract: We have performed molecular dynamics (MD) simulations to investigate the dynamical interactions between vacancy defects, fission gas atoms (Xe), and grain boundaries in a model of polycrystalline UO 2 nuclear fuel with average grain diameter of about 20 nm. We followed the mobility and aggregation of Xe atoms in the vacancy-saturated model compound for up to 2 ns. During this time we observed the aggregation of Xe atoms into nuclei, which are possible precursors to Xe bubbles. The nucleation was driven by the migration of Xe atoms via vacancy-assisted diffusion. The Xe clusters aggregate faster than grain boundary diffusion rates and are smaller than experimentally observed bubbles. As the system evolves towards equilibrium, the Xe atom cluster growth slows down significantly, and the lattice relaxes around the cluster. These simulations provide insights into fundamental physical processes that are inaccessible to experiment.

Synthesis and antioxidant activity of peptide-based ebselen analogues.

Science.gov (United States)

Satheeshkumar, Kandhan; Mugesh, Govindasamy

2011-04-18

A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration. Copyright �

Phylogeny and systematics of the brake fern genus Pteris (Pteridaceae) based on molecular (plastid and nuclear) and morphological evidence.

Science.gov (United States)

Zhang, Liang; Zhang, Li-Bing

2018-01-01

The brake fern genus Pteris belongs to Pteridaceae subfamily Pteridoideae. It is one of the largest fern genera and has been estimated to contain 200-250 species distributed on all continents except Antarctica. Previous studies were either based on plastid data only or based on both plastid and nuclear data but the sampling was small. In addition, an infrageneric classification of Pteris based on morphological and molecular evidence has not been available yet. In the present study, based on molecular data of eight plastid markers and one nuclear marker (gapCp) of 256 accessions representing ca. 178 species of Pteris, we reconstruct a global phylogeny of Pteris. The 15 major clades identified earlier are recovered here and we further identified a new major clade. Our nuclear phylogeny recovered 11 of these 16 major clades, seven of which are strongly supported. The inclusion of Schizostege in Pteris is confirmed for the first time. Based on the newly reconstructed phylogeny and evidence from morphology, distribution and/or ecology, we classify Pteris into three subgenera: P. subg. Pteris, P. subg. Campteria, and P. subg. Platyzoma. The former two are further divided into three and 12 sections, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Conjugate dynamical systems: classical analogue of the quantum energy translation

International Nuclear Information System (INIS)

Torres-Vega, Gabino

2012-01-01

An aspect of quantum mechanics that has not been fully understood is the energy shift generated by the time operator. In this study, we introduce the use of the eigensurfaces of dynamical variables and commutators in classical mechanics to study the classical analogue of the quantum translation of energy. We determine that there is a conjugate dynamical system that is conjugate to Hamilton's equations of motion, and then we generate the analogue of the time operator and use it in the translation of points along the energy direction, i.e. the classical analogue of the Pauli theorem. The theory is illustrated with a nonlinear oscillator model. (paper)

Laser ionization of molecular clusters

International Nuclear Information System (INIS)

Desai, S.; Feigerle, C.S.

1995-01-01

Multiphoton ionization coupled with mass spectrometry was used to investigate molecular cluster distributions. Three examples will be discussed in this presentation. First, in studies of neat nitric oxide clusters, (NO) m , an interesting odd-even intensity alternation was observed and will be discussed in terms of electron-pairing considerations. In a separate study, the binary clusters comprising nitric oxide and methane preferentially form a stoichiometric cluster made up of repeating units of (NO) 2 CH 4 . These presumably represent a particularly strongly bound open-quotes van der Waalsclose quotes subunit. Finally, in similar studies of neat carbon disulfide clusters, (CS 2 ) m , additional photon absorption after the two-photon ionization step stimulates a series of intracluster ion-molecular reactions leading to formation of S m + and (CS) m + polymers, as well as intermediate species such as S m + (CS 2 ). This molecular cluster analogue of open-quotes laser snowclose quotes will be described in detail

Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays.

Science.gov (United States)

Nishihara, Ryo; Abe, Masahiro; Nishiyama, Shigeru; Citterio, Daniel; Suzuki, Koji; Kim, Sung Bae

2017-04-19

Spectral overlaps among the multiple optical readouts commonly cause optical contamination in fluorescence and bioluminescence. To tackle this issue, we created five-different lineages of coelenterazine (CTZ) analogues designed to selectively illuminate a specific luciferase with unique luciferase selectivity. In the attempt, we found that CTZ analogues with ethynyl or styryl groups display dramatically biased bioluminescence to specific luciferases and pHs by modifying the functional groups at the C-2 and C-6 positions of the imidazopyradinone backbone of CTZ. The optical contamination-free feature was exemplified with the luciferase-specific CTZ analogues, which illuminated anti-estrogenic and rapamycin activities in a mixture of optical probes. This unique bioluminescence platform has great potential for specific and high throughput imaging of multiple optical readouts in bioassays without optical contamination.

Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

Directory of Open Access Journals (Sweden)

B. Leterme

2012-08-01

Full Text Available The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from −42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain, considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from −69% to −14% compared to the present-day climate.

Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

Energy Technology Data Exchange (ETDEWEB)

Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

2016-02-15

We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

DEFF Research Database (Denmark)

Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

2009-01-01

of alkylated compounds in liposomes, it was demonstrated that the MTX-analogue partitioned into the water phase and thereby became available for cell uptake. It was concluded that liposomes containing alkylated MTX-analogues show promise as a drug delivery system, although the MTX-analogue needs to be more......Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

Progress on molecular imaging

International Nuclear Information System (INIS)

Chen Quan; Zhang Yongxue

2011-01-01

Molecular imaging is a new era of medical imaging,which can non-invasively monitor biological processes at the cellular and molecular level in vivo, including molecular imaging of nuclear medicine, magnetic resonance molecular imaging, ultrasound molecular imaging,optical molecular imaging and molecular imaging with X-ray. Recently, with the development of multi-subjects amalgamation, multimodal molecular imaging technology has been applied in clinical imaging, such as PET-CT and PET-MRI. We believe that with development of molecular probe and multi-modal imaging, more and more molecular imaging techniques will be applied in clinical diagnosis and treatment. (authors)

Molecular studies by electron spectroscopy

International Nuclear Information System (INIS)

Hansteen, J.M.

1977-01-01

Experience gained in experimental nuclear physics has played a large role in the development of electron spectroscopy as a powerful tool for studying chemical systems. The use of ESCA (Electron Spectroscopy for Chemical Analysis) for the mapping of molecular properties connected with inner as well as outer electron shells is reviewed, mainly from a phenomological point of view. Molecular Auger electron spectroscopy is described as a means of gaining information on details in molecular structure, simultaneously being extensively applied for surface studies. Future highly promising research areas for molecular electron spectroscopy are suggested to be (e,2e) processes as well as continued exploitation of synchrotron radiation from high energy nuclear devices. (Auth.)

Peramivir analogues bearing hydrophilic side chains exhibit higher activities against H275Y mutant than wild-type influenza virus.

Science.gov (United States)

Chiu, Din-Chi; Lin, Tzu-Chen; Huang, Wen-I; Cheng, Ting-Jen; Tsai, Keng-Chang; Fang, Jim-Min

2017-11-29

Peramivir is an effective anti-influenza drug in the clinical treatment of influenza, but its efficacy toward the H275Y mutant is reduced. The previously reported cocrystal structures of inhibitors in the mutant neuraminidase (NA) suggest that the hydrophobic side chain should be at the origin of reduced binding affinity. In contrast, zanamivir having a hydrophilic glycerol side chain still possesses high affinity toward the H275Y NA. We thus designed five peramivir analogues (5-9) carrying hydrophilic glycol or glycerol side chains, and evaluated their roles in anti-influenza activity, especially for the H275Y mutant. The synthetic sequence involves a key step of (3 + 2) cycloaddition reactions between alkenes and nitrile oxides to construct the scaffold of peramivir carrying the desired hydrophilic side chains and other appropriate functional groups. The molecular docking experiments reveal that the hydrophilic side chain can provide extra hydrogen bonding with the translocated Glu-276 residue in the H275Y NA active site. Thus, the H275Y mutant may be even more sensitive than wild-type virus toward the peramivir analogues bearing hydrophilic side chains. Notably, the peramivir analogue bearing a glycerol side chain inhibits the H275Y mutant with an IC 50 value of 35 nM, which is better than the WSN virus by 9 fold.

Synthesis of the 4’-desmethoxy analogue of RU79115

Directory of Open Access Journals (Sweden)

MICHEL KLICH

2004-11-01

Full Text Available The synthesis, and biological activity in vitro of the 4’-desmethoxy analogue (3 of RU 79115 (2 is described. Comparison of the biological activity of the two analogues clearly indicated the importance of the 4’-methoxy group in conferring good gyrase B inhibitory activity as well as antibacterial activity.

State selective reactions of cosmic dust analogues at cryogenic temperatures

International Nuclear Information System (INIS)

Perry, James Samuel Anthony

2001-01-01

Molecular hydrogen (H 2 ) is the most abundant molecule in interstellar space. It is crucial for initiating all of the chemistry in the Interstellar Medium (ISM) and consequently plays an important role in star formation. However, the amount of H 2 believed to exist in the ISM cannot be accounted for by formation through gas-phase reactions alone. The current, widely accepted theory, is that H 2 forms on the surface of cosmic dust grains. These grains are thought to be composed of amorphous forms of carbon or silicates with temperatures of around 10 K. This thesis describes a new experiment that has been constructed to study H 2 formation on the surface of cosmic dust analogues and presents the initial experimental results. The experiment simulates, through ultra-high vacuum and the use of cryogenics, the conditions of the ISM where cosmic dust grains and H 2 molecules exist. During the experiment, a beam of atomic hydrogen is aimed at a cosmic dust analogue target. H 2 formed on the target's surface is ionised using a laser spectroscopy technique known as Resonance Enhanced Multiphoton lonisation (REMPI) and detected using time-of-flight mass spectrometry. The sensitivity of REMPI is such that H 2 molecules can be ionised in selective internal energy states. This allows the rovibrational populations of the H 2 molecules desorbing from the cosmic dust targets to be determined, providing information on the energy budget of the H 2 formation process in the ISM. Preliminary results from the experiment show that H 2 molecules formed on a diamond-like-carbon surface have a significant non-thermal population of excited vibrational and rotational energy states. (author)

Nucleoside analogues are activated by bacterial deoxyribonucleoside kinases in a species-specific manner

DEFF Research Database (Denmark)

Sandrini, Michael; Clausen, Anders; On, Stephen L. W.

2007-01-01

To investigate the bactericidal activity of antiviral and anticancer nucleoside analogues against a variety of pathogenic bacteria and characterize the activating enzymes, deoxyribonucleoside kinases (dNKs). Several FDA-approved nucleoside analogue drugs were screened for their potential bacteric......-specific manner. Therefore, nucleoside analogues have a potential to be employed as antibiotics in the fight against emerging multiresistant bacteria....

Characterization of iodinated adrenomedullin derivatives suitable for lung nuclear medicine

Energy Technology Data Exchange (ETDEWEB)

Fu Yan; Letourneau, Myriam; Chatenet, David [Laboratoire d' etudes moleculaires et pharmacologiques des peptides, INRS-Institut Armand-Frappier, Ville de Laval, Qc, H7V 1B7 (Canada); Dupuis, Jocelyn [Research Center, Montreal Heart Institute, Montreal, Qc (Canada); Department of Medicine, University of Montreal, Montreal, Qc (Canada); Fournier, Alain, E-mail: alain.fournier@iaf.inrs.ca [Laboratoire d' etudes moleculaires et pharmacologiques des peptides, INRS-Institut Armand-Frappier, Ville de Laval, Qc, H7V 1B7 (Canada)

2011-08-15

Introduction: We have recently demonstrated the effectiveness of 99m-technetium adrenomedullin (AM) as a new molecular lung imaging agent that could provide significant advantages for the diagnosis and follow-up of disorders affecting the pulmonary circulation such as pulmonary embolism and pulmonary hypertension. Having the possibility to conjugate the targeting molecule with different radionuclides would offer more flexibility and potential advantages depending on clinical situations. Since various iodine isotopes are currently used in nuclear medicine and in pharmacological studies, we have evaluated which iodination method should be privileged in order to produce a good iodinated AM-derived nuclear medicine agent. Methods: Synthetic AM was labeled with iodine through chemical and lactoperoxidase oxidation methods. Position of the iodine atom on the peptide was determined by MALDI-TOF mass spectrometry analysis following cyanogen bromide cleavage and carboxypeptidase Y digestion. Binding affinity of iodinated AM analogues was evaluated by competition and saturation binding experiments on dog lung preparations. Results: In this study, we demonstrated that, upon lactoperoxidase oxidation, iodination occurred at Tyr{sup 1} and that this radioligand retained higher binding affinity and specificity over preparations obtained through chemical oxidation. Conclusions: These results emphasize the fact that even a small chemical modification, i.e. iodination, might deeply modify the pharmacological profile of a compound and support observations that the C-terminal tail of human AM plays an important role in the AM receptor binding process. Consequently, incorporation of a radionuclide to produce an AM-based nuclear medicine agent should privilege the N-terminus of the molecule.

A Low-cost Multi-channel Analogue Signal Generator

CERN Document Server

Muller, F; Shen, W; Stamen, R

2009-01-01

A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The implementation of the signal generator is presented as well as an application where it was successfully utilized.

A regulator's perspective on the use of analogues for regulatory confidence

International Nuclear Information System (INIS)

Ruiz, Carmen

2008-01-01

The NAA Study, promoted and coordinated by the CSN, was carried out in collaboration with ENRESA by CIEMAT and three Spanish Universities UZ, UDC and UCM. The 3 year Study, included in the CSN's R and D Programme, started in 1999, is focussed on Deep Geological disposal (DGD). CSN motivation for NA Analogues arose in 1997 as result of the emerging approaches to increase the confidence in the Safety Assessment (SA) considering multiple lines of reasoning show in: some international documents and some national regulation. After a first preliminary (1997-1998) study, the CSN noticed the large amount and dispersion of the information about NNA, and decided to launch a deeper Study with the aims of: Collecting and reviewing the results of all the relevant studies on analogues developed in the last decades in systematic way; Reaching a better understanding of their potential and real application to the SA and for communication purposes. The results of the Analogue Study has been structured in several documents with different levels of detail and technical content addressed to different audiences. Analogue studies are a source of knowledge for the understanding of the long-term behavior of DGD systems. They represent a complementary method to increase Confidence Building within PA. In the majority of the cases, analogues have been used to transmit information on generic aspects of the geological concept an easily understood message. The need to simplify the content to facilitate their understanding may imply different information to different audiences. Analogue studies are: Considered within the multiple lines of reasoning to increase the confidence in the SA; A source of knowledge for the understanding of the long-term behavior of DGD systems. They represent a complementary method to increase Confidence Building within SA. There are few examples of the direct use of data from natural analogue projects in the consulted SA. They are promoted by International organisations

Signals of a phase transition in nuclear multifragmentation: molecular-dynamics approximation

International Nuclear Information System (INIS)

Kiselev, S.M.

1989-01-01

The signals of a liquid-gas-like phase transition proposed recently by X.Campi are analyzed for the reactions Ca+Ca at E/A=400, 800MeV, Nb+Nb at E/A=150, 400,650,800MeV, La+La at E/A=800 MeV and Ne+U at E/A=400 MeV simulated on the basis of the molecular-dynamical model. For the symmetrical systems at E/A≥400 MeV the manifestations of a phase transition are conditioned by the peripheral collisions whereas for the reactions Nb+Nb at E/A=150 MeV and Ne+U at E/A=400 MeV the quasicentral events are a main source of the signals. The manifestations depend weakly on the projectile energy and become more pronounced for a more heavy nuclear system. 15 refs.; 3 figs

Present Status of Nuclear Energy

Czech Academy of Sciences Publication Activity Database

Wagner, Vladimír

2013-01-01

Roč. 2013, SI (2013), s. 89-94 ISSN 0375-8842. [European Nuclear Forum. Praha, 12.05.2013-13.05.2013] Institutional support: RVO:61389005 Keywords : nuclear energy * nuclear reactors * electricity production Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

Arginine-, D-arginine-vasopressin, and their inverso analogues in micellar and liposomic models of cell membrane: CD, NMR, and molecular dynamics studies

Czech Academy of Sciences Publication Activity Database

Lubecka, E. A.; Sikorska, E.; Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Ciarkowski, J.

2015-01-01

Roč. 44, č. 8 (2015), s. 727-743 ISSN 0175-7571 Institutional support: RVO:61388963 Keywords : antidiuretic agonists * anionic-zwitterionic micelles * liposomes * inverso analogues Subject RIV: CC - Organic Chemistry Impact factor: 1.444, year: 2015 http://link.springer.com/article/10.1007/s00249-015-1071-4/fulltext.html

Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

Science.gov (United States)

Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

2017-09-01

Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

Complete mitochondrial genomes and nuclear ribosomal RNA operons of two species of Diplostomum (Platyhelminthes: Trematoda): a molecular resource for taxonomy and molecular epidemiology of important fish pathogens.

Science.gov (United States)

Brabec, Jan; Kostadinova, Aneta; Scholz, Tomáš; Littlewood, D Timothy J

2015-06-19

The genus Diplostomum (Platyhelminthes: Trematoda: Diplostomidae) is a diverse group of freshwater parasites with complex life-cycles and global distribution. The larval stages are important pathogens causing eye fluke disease implicated in substantial impacts on natural fish populations and losses in aquaculture. However, the problematic species delimitation and difficulties in the identification of larval stages hamper the assessment of the distributional and host ranges of Diplostomum spp. and their transmission ecology. Total genomic DNA was isolated from adult worms and shotgun sequenced using Illumina MiSeq technology. Mitochondrial (mt) genomes and nuclear ribosomal RNA (rRNA) operons were assembled using established bioinformatic tools and fully annotated. Mt protein-coding genes and nuclear rRNA genes were subjected to phylogenetic analysis by maximum likelihood and the resulting topologies compared. We characterised novel complete mt genomes and nuclear rRNA operons of two closely related species, Diplostomum spathaceum and D. pseudospathaceum. Comparative mt genome assessment revealed that the cox1 gene and its 'barcode' region used for molecular identification are the most conserved regions; instead, nad4 and nad5 genes were identified as most promising molecular diagnostic markers. Using the novel data, we provide the first genome wide estimation of the phylogenetic relationships of the order Diplostomida, one of the two fundamental lineages of the Digenea. Analyses of the mitogenomic data invariably recovered the Diplostomidae as a sister lineage of the order Plagiorchiida rather than as a basal lineage of the Diplostomida as inferred in rDNA phylogenies; this was concordant with the mt gene order of Diplostomum spp. exhibiting closer match to the conserved gene order of the Plagiorchiida. Complete sequences of the mt genome and rRNA operon of two species of Diplostomum provide a valuable resource for novel genetic markers for species delineation and

Accumulation of radium in relation to some chemical analogues in Dicranopteris linearis

International Nuclear Information System (INIS)

Chao, J.H.; Chuang, C.Y.

2011-01-01

This study elucidates the uptake and accumulation of radium in the field-growing fern Dicranopteris linearis by relating the radium concentration to some potential chemical analogues, including alkaline earth metals, rare earth elements, and some important heavy metals. Time-dependent accumulation of radium and these chemical analogues for D. linearis were described by the 228 Th/ 228 Ra activity ratio, an index for inferring plant age. The correlation between radium and these elements was assessed by statistical analysis and used as a reference to elucidate the uptake and accumulation of radium in relation to the chemical analogues. Analytical and statistical results showed that the concentrations of alkaline earth metals (except for Mg) rare earth elements and some heavy metals in D. linearis increased linearly with plant age. These elements, exhibiting a similar accumulation pattern to radium and significant correlation coefficients with radium, were considered as the chemical analogues to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and most of these analogues in D. linearis exceeded 1, consistent with the definition of hyper-accumulator plants.

Rethinking therapeutic decisions for hepatitis B infection in Syria: insights into molecular monitoring.

Science.gov (United States)

Habbal, Wafa; Monem, Fawza

2012-10-19

Hepatitis B virus patients are usually treated in Syria with alpha interferon and nucleos(t)ide analogues. Genotypic viral factors causing inadequate response or relapse following initial response are not routinely investigated. This study aimed to explore and discuss local therapeutic decisions from a molecular perspective. Fifty patients with hepatitis B from Syria were tested for HBV genotyping and drug-resistance mutations by DNA sequencing. All patients had genotype D, which is characterized by relatively low response to interferon-based therapy. Drug-resistant viral mutant variants were detected in one fifth of the enrolled patients, and distributed similarly in both nucleos(t)ide analogues-naïve and -treated patients. However, nucleos(t)ide analogues-based therapy was associated with the existence of more mutations and hence increased resistance. Investigating HBV genotypes and drug-resistance mutations to support treatment decisions is critically needed for efficient therapy and patients' survival.

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

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Patrick Rabe

2014-08-01

Full Text Available Tropodithietic acid (TDA is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed.

Somatostatin analogues labelled with 99mTc

International Nuclear Information System (INIS)

Obenaus, Esteban R.; Crudo, Jose L.; Edreira, Martin M.; Castiglia, Silvia G.

1999-01-01

Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr 3 -Octreotide. Both analogues have been labelled with 99m Tc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr 3 -Octreotide with HYNIC. The biological distribution of HYNIC-Tyr 3 -Octreotide has been studied in rats. (author)

Boron hydride analogues of the fullerenes

International Nuclear Information System (INIS)

Quong, A.A.; Pederson, M.R.; Broughton, J.Q.

1994-01-01

The BH moiety is isoelectronic with C. We have studied the stability of the (BH) 60 analogue of the C 60 fullerene as well as the dual-structure (BH) 32 icosahedron, both of them being putative structures, by performing local-density-functional electronic calculations. To aid in our analysis, we have also studied other homologues of these systems. We find that the latter, i.e., the dual structure, is the more stable although the former is as stable as one of the latter's lower homologues. Boron hydrides, it seems, naturally form the dual structures used in algorithmic optimization of complex fullerene systems. Fully relaxed geometries are reported as well as electron affinities and effective Hubbard U parameters. These systems form very stable anions and we conclude that a search for BH analogues of the C 60 alkali-metal supeconductors might prove very fruitful

Is hybridic positron emission tomography/computerized tomography the only option? The future of nuclear medicine and molecular imaging.

Science.gov (United States)

Grammaticos, Philip; Zerva, Cherry; Asteriadis, Ioannis; Trontzos, Christos; Hatziioannou, Kostas

2007-01-01

sources of radiation" b) nuclear radiation and c) molecular nuclear medicine. The "European Journal of Nuclear Medicine and Molecular Imaging" shall have to erase the three last words of its title and be renamed. As Professor Abass Alavi et al (2007), have mentioned: "Is PET/CT the only option?" In favor of PET/CT are the following: Attenuation correction (AC) and better anatomical localization of lesions visualized with PET. Also PET/CT can be used as a diagnostic CT scanner (dCT). Against using the PET/CT scanners are the following arguments: a) This equipment is not necessary because we can always ask the Radiologists for a dCT scan. Many patients have already done a dCT scan at the time they are referred for a PET scan to the Nuclear Medicine Department. b) The absolute clinical indications for PET/CT with the use of a contrast agent, are under investigation. c) Although there is at present a list of indications suggested for the PET/CT scanner, there are studies disputing some of these indications, as for example in metastatic colon cancer where a high diagnostic accuracy for PET study alone, has been reported. d) The option of AC performed by the PET/CT scanner has also been questioned. Artifacts may be up to 84%. e) The PET/CT is expensive, time consuming, space occupying, and needs additional medical and technical personnel. f) Not to mention the extra radiation dose to the patients. g) Shall we inform those young medical students who wish to become nuclear medicine physicians, to hold their decision till the content of future Nuclear Medicine is clarified? We may suggest that: Our specialty could be renamed as: "Clinical Nuclear Medicine" and include additional "proper certified education" on the PET/CT equipment. The PET/CT scanner should remain in the Nuclear Medicine Department where Radiologists could act as advisors.

Equivalent molecular mass of cytosolic and nuclear forms of Ah receptor from Hepa-1 cells determined by photoaffinity labeling with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin

International Nuclear Information System (INIS)

Prokipcak, R.D.; Okey, A.B.

1990-01-01

The structure of the Ah receptor previously has been extensively characterized by reversible binding of the high affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report the use of [ 3 H]2,3,7,8-tetrachlorodibenzo-p-dioxin as a photoaffinity ligand for Ah receptor from the mouse hepatoma cell line Hepa-1c1c9. Both cytosolic and nuclear forms of Ah receptor could be specifically photoaffinity-labeled, which allowed determination of molecular mass for the two forms under denaturing conditions. After analysis by fluorography of polyacrylamide gels run in the presence of sodium dodecyl sulfate, molecular mass for the cytosolic form of Ah receptor was estimated at 92,000 +/- 4,300 and that for the nuclear form was estimated at 93,500 +/- 3,400. Receptor in mixture of cytosol and nuclear extract (each labeled separately with [ 3 H]2,3,7,8-tetrachlorodibenzo-p-dioxin) migrated as a single band. These results are consistent with the presence of a common ligand-binding subunit of identical molecular mass in both cytosolic and nuclear complexes

Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

Science.gov (United States)

Nolan, David; Mallal, Simon

2003-02-01

The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

In vitro and in vivo potency of insulin analogues designed for clinical use.

Science.gov (United States)

Vølund, A; Brange, J; Drejer, K; Jensen, I; Markussen, J; Ribel, U; Sørensen, A R; Schlichtkrull, J

1991-11-01

Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono- or di-meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP-G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr-NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vivo potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.

Analyses of volatile organic compounds and refractory organic residues coming from the heating of interstellar ice analogues

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Danger Grégoire

2014-02-01

Full Text Available We use Very High Resolution Mass Spectrometry for analyses of the soluble fraction of yellow stuff produced in laboratory. Their analyses show that they are composed of molecules with high molecular weight (m/z>4000. Fragmentations suggest that grafted molecules constitute a part of them. Hexamethylenetetramine derivatives have also been detected. First results and further analytical developments will be presented to facilitate the understanding of the residue composition and of its chemical evolution. Furthermore, we present for the first time the concept of the VAHIIA project which concerns the analysis of volatiles coming from the heating of interstellar ice analogues.

Inner/Outer nuclear membrane fusion in nuclear pore assembly: biochemical demonstration and molecular analysis.

Science.gov (United States)

Fichtman, Boris; Ramos, Corinne; Rasala, Beth; Harel, Amnon; Forbes, Douglass J

2010-12-01

Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in double nuclear membranes, which carry out nucleocytoplasmic exchange. The mechanism of nuclear pore assembly involves a unique challenge, as it requires creation of a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel has little evolutionary precedent. Here we mapped inner/outer nuclear membrane fusion in NPC assembly biochemically by using novel assembly intermediates and membrane fusion inhibitors. Incubation of a Xenopus in vitro nuclear assembly system at 14°C revealed an early pore intermediate where nucleoporin subunits POM121 and the Nup107-160 complex were organized in a punctate pattern on the inner nuclear membrane. With time, this intermediate progressed to diffusion channel formation and finally to complete nuclear pore assembly. Correct channel formation was blocked by the hemifusion inhibitor lysophosphatidylcholine (LPC), but not if a complementary-shaped lipid, oleic acid (OA), was simultaneously added, as determined with a novel fluorescent dextran-quenching assay. Importantly, recruitment of the bulk of FG nucleoporins, characteristic of mature nuclear pores, was not observed before diffusion channel formation and was prevented by LPC or OA, but not by LPC+OA. These results map the crucial inner/outer nuclear membrane fusion event of NPC assembly downstream of POM121/Nup107-160 complex interaction and upstream or at the time of FG nucleoporin recruitment.

Prussian Blue Analogues of Reduced Dimensionality

NARCIS (Netherlands)

Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

2012-01-01

Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

Megamasers: Molecular Diagnostics of the Nuclear Ism

Science.gov (United States)

Baan, Willem A.; Klöckner, Hans-R.

2005-01-01

Molecular emissions are powerful tracers of intense heating and star-formation processes in galactic nuclei. In this paper we consider the characteristics of molecular Megamaser emission among the population of (Ultra-) Luminous Infrared Galaxies that are powered by intense star-formation or accretion onto a massive compact object. In addition, we consider the systematic behavior of the line emission of high-density tracer molecules. An evolutionary scenario is presented for ULIRGs that may explain the molecular line ratios observed in the population of FIR galaxies.

Receptor-isoform-selective insulin analogues give tissue-preferential effects

DEFF Research Database (Denmark)

Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi

2011-01-01

The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can...... be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI...... (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI...

The Valles natural analogue project

International Nuclear Information System (INIS)

Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

1994-12-01

The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and 39 Ar/ 4O isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks

Aspartame and Its Analogues

Science.gov (United States)

Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

1981-04-01

The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

Analogue studies at the french atomic commission (CEA)

International Nuclear Information System (INIS)

Petit, J.C.

1986-06-01

The different research activities of the French Atomic Energy Commission in the analogue study field are presented. Most of them are conducted in collaboration with major research organisations, both french and international. In fact, the scientific community has been associated to these programmes at different steps of their realisation. The brief description presented illustrates the great diversity and complementarity of actions conducted by CEA for better understanding, through the study of natural analogues, the basic processes that will rule the long term behaviour of high level radwaste materials in a repository and hence contributing to hopefully guaranty disposal safety

Molecular nanomagnets: Syntheses and characterization of high nuclearity transition metal complexes

Science.gov (United States)

Foguet-Albiol, Maria D.

2006-12-01

High nuclearity transition metal complexes have attracted a lot of attention because of their aesthetically pleasant structures and/or their potential applications. The fusion of the world of magnetism with the exciting research in physics and chemistry led to the realization of interesting types of materials that can function as nanoscale magnetic particles. The study of the magnetism of inorganic complexes and especially the study of these molecular nanomagnets (or single-molecule magnets, SMMs) is a field that has generated intense interest in the scientific community. Interest in these molecular nanomagnets arises as part of a broader investigation of nanomagnetism (and nanotechnology), as these represent the ultimate step in device miniaturization. The primary purpose of this dissertation is the development of new synthetic methods intended for the preparation of novel single-molecule magnets (SMMs). The definition of the "bottom-up approach" is to increase the size of molecules by adding new magnetic centers; this is attractive but does not actually reflect how the chemistry takes place. Various strategies have been employed in developing the aforementioned synthetic methods which include the use of mononuclear as well as preformed clusters as starting materials; and the introduction of new alcohol based ligands as N-methyldiethanolamine (mdaH2) and triethanolamine (teaH3), since currently only a few alcohol based ligands have been used by different research groups. Many of these efforts have led to the isolation of new polynuclear Mn clusters with nuclearities ranging all the way from four to thirty-one. Additionally, a family of related Fe7 complexes has been synthesized. The transition metal cluster chemistry has also been extended to nickel-containing species. Many of these polynulear transition metal complexes function as single-molecule magnets. An additional research direction discussed herein is the study of the exchange-coupled dimer of single

Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

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Maarten Walmagh

2015-06-01

Full Text Available Trehalose (α-d-glucopyranosyl α-d-glucopyranoside is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals, medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside, offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis.

Superconductive analogue of spin glasses

International Nuclear Information System (INIS)

Feigel'man, M.; Ioffe, L.; Vinokur, V.; Larkin, A.

1987-07-01

The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

Molecular dynamics for dense matter

International Nuclear Information System (INIS)

Maruyama, Toshiki; Chiba, Satoshi; Watanabe, Gentaro

2012-01-01

We review a molecular dynamics method for nucleon many-body systems called quantum molecular dynamics (QMD), and our studies using this method. These studies address the structure and the dynamics of nuclear matter relevant to neutron star crusts, supernova cores, and heavy-ion collisions. A key advantage of QMD is that we can study dynamical processes of nucleon many-body systems without any assumptions about the nuclear structure. First, we focus on the inhomogeneous structures of low-density nuclear matter consisting not only of spherical nuclei but also of nuclear “pasta”, i.e., rod-like and slab-like nuclei. We show that pasta phases can appear in the ground and equilibrium states of nuclear matter without assuming nuclear shape. Next, we show our simulation of compression of nuclear matter which corresponds to the collapsing stage of supernovae. With the increase in density, a crystalline solid of spherical nuclei changes to a triangular lattice of rods by connecting neighboring nuclei. Finally, we discuss fragment formation in expanding nuclear matter. Our results suggest that a generally accepted scenario based on the liquid–gas phase transition is not plausible at lower temperatures. (author)

Molecular dynamics for dense matter

Science.gov (United States)

Maruyama, Toshiki; Watanabe, Gentaro; Chiba, Satoshi

2012-08-01

We review a molecular dynamics method for nucleon many-body systems called quantum molecular dynamics (QMD), and our studies using this method. These studies address the structure and the dynamics of nuclear matter relevant to neutron star crusts, supernova cores, and heavy-ion collisions. A key advantage of QMD is that we can study dynamical processes of nucleon many-body systems without any assumptions about the nuclear structure. First, we focus on the inhomogeneous structures of low-density nuclear matter consisting not only of spherical nuclei but also of nuclear "pasta", i.e., rod-like and slab-like nuclei. We show that pasta phases can appear in the ground and equilibrium states of nuclear matter without assuming nuclear shape. Next, we show our simulation of compression of nuclear matter which corresponds to the collapsing stage of supernovae. With the increase in density, a crystalline solid of spherical nuclei changes to a triangular lattice of rods by connecting neighboring nuclei. Finally, we discuss fragment formation in expanding nuclear matter. Our results suggest that a generally accepted scenario based on the liquid-gas phase transition is not plausible at lower temperatures.

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

Science.gov (United States)

Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

2017-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues.

Science.gov (United States)

Kalaitzis, John A

2013-01-01

The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aromatic polyketide pathway which is genetically coded by the 21.3 kb enc gene cluster in S. maritimus. Characterization of the enc biosynthesis gene cluster and subsequent manipulation of it via heterologous expression and/or mutagenesis enabled the discovery of other enc-based metabolites that were produced in only very minor amounts in the wild type. Also described are techniques used to harness the enterocin biosynthetic machinery in order to generate unnatural enc-derived polyketide analogues. This review focuses upon the molecular methods used in combination with classical natural products detection and isolation techniques to access minor metabolites of the S. maritimus secondary metabolome.

The Algebra of a q-Analogue of Multiple Harmonic Series

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Yoshihiro Takeyama

2013-10-01

Full Text Available We introduce an algebra which describes the multiplication structure of a family of q-series containing a q-analogue of multiple zeta values. The double shuffle relations are formulated in our framework. They contain a q-analogue of Hoffman's identity for multiple zeta values. We also discuss the dimension of the space spanned by the linear relations realized in our algebra.

Naturally occurring crystalline phases: analogues for radioactive waste forms

International Nuclear Information System (INIS)

Haaker, R.F.; Ewing, R.C.

1981-01-01

Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included

Naturally occurring crystalline phases: analogues for radioactive waste forms

Energy Technology Data Exchange (ETDEWEB)

Haaker, R.F.; Ewing, R.C.

1981-01-01

Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

Design, Synthesis and Cytotoxic Evaluation of o-Carboxamido Stilbene Analogues

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Mohamad Nurul Azmi

2013-11-01

Full Text Available Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50 = 16.68 µM, colon cancer HT-29 (IC50 = 7.51 µM and breast cancer MCF-7 (IC50 = 21.24 µM, respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

Synthesis and biological evaluation of cis-locked vinylogous combretastatin-A4 analogues: derivatives with a cyclopropyl-vinyl or a cyclopropyl-amide bridge.

Science.gov (United States)

Ty, Nancy; Kaffy, Julia; Arrault, Alban; Thoret, Sylviane; Pontikis, Renée; Dubois, Joelle; Morin-Allory, Luc; Florent, Jean-Claude

2009-03-01

A series of novel combretastatin A4 analogues, in which the cis-olefinic bridge is replaced by a cyclopropyl-vinyl or a cyclopropyl-amide moiety, were synthesized and evaluated for inhibition of tubulin polymerization and antiproliferative activity. The derivative 9a with a (cis,E)-cyclopropyl-vinyl unit is the most promising compound. As expected, molecular docking of 9a has shown that only one of the cis-cyclopropyl enantiomers is a good ligand for tubulin.

Aerosolized droplet mediated self-assembly of photosynthetic pigment analogues and deposition onto substrates.

Science.gov (United States)

Shah, Vivek B; Biswas, Pratim

2014-02-25

Self-assembled photosynthetic molecules have a high extinction coefficient and a broad absorption in the infrared region, and these properties can be used to improve the efficiency of solar cells. We have developed a single-step method for the self-assembly of synthetic chlorin molecules (analogues of native bacteriochlorophylls) in aerosolized droplets, containing a single solvent and two solvents, to synthesize biomimetic light-harvesting structures. In the single-solvent approach, assembly is promoted by a concentration-driven process due to evaporation of the solvent. The peak absorbance of Zn(II) 3-(1-hydroxyethyl)-10-phenyl-13(1)-oxophorbine (1) in methanol shifted from 646 nm to 725 nm (∼ 80 nm shift) after assembly, which is comparable to the shift observed in the naturally occurring assembly of bacteriochlorophyll c. Although assembly is thermodynamically favorable, the kinetics of self-assembly play an important role, and this was demonstrated by varying the initial concentration of the pigment monomer. To overcome kinetic limitations, a two-solvent approach using a volatile solvent (tetrahydrofuran) in which the dye is soluble and a less volatile solvent (ethanol) in which the dye is sparingly soluble was demonstrated to be effective. The effect of molecular structure is demonstrated by spraying the sterically hindered Zn(II) 3-(1-hydroxyethyl)-10-mesityl-13(1)-oxophorbine (2), which is an analogue of 1, under similar conditions. The results illustrate a valuable and facile aerosol-based method for the formation of films of supramolecular assemblies.

Transdermal delivery of a melanotropic peptide hormone analogue

International Nuclear Information System (INIS)

Dawson, B.V.; Hadley, M.E.; Kreutzfeld, K.; Dorr, R.T.; Hruby, V.J.; Al-Obeidi, F.; Don, S.

1988-01-01

We previously reported that topical application of [Nl3 4 ,D-Phe 7 ]alpha-MSH, a superpotent analogue of alpha-melanocyte stimulating hormone, to mice induces a darkening of follicular melanocytes throughout the skin. We now report that the melanotropin analogue can be delivered across mouse but not rat skin in an in vitro model system. Passage of the analogue from the topically applied vehicle (polyethylene glycol) across the skin into a subcutaneous receiving vessel was demonstrated by both bioassay as well as by radioimmunoassay. The bioassay data demonstrate that percutaneous absorption of the melanotropin did not result in loss of biological activity of the peptide. The differential penetration of the peptide across rodent skin reveals that one cannot predict percutaneous absorption of a substance across the stratum corneum from studies on a single species. The present results are the first to demonstrate, by direct quantitative measurements, that a bioactive peptide can be delivered across the vertebrate integument in vitro. These studies point out the potential of a topically applied melanotropin for tanning of the skin and possibly for treatment of certain hypopigmentary disorders

Manipulating lightcone fluctuations in an analogue cosmic string

Directory of Open Access Journals (Sweden)

Jiawei Hu

2018-02-01

Full Text Available We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

Manipulating lightcone fluctuations in an analogue cosmic string

Science.gov (United States)

Hu, Jiawei; Yu, Hongwei

2018-02-01

We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

Fermionic molecular dynamics for colliding and decaying nuclei

International Nuclear Information System (INIS)

Feldmeier, H.; Schnack, J.

1993-11-01

Fermionic Molecular Dynamics models a system of fermions by means of a trial many-body state composed of an antisymmetrized product of single-particle states which are localized gaussians in coordinate and momentum space. The parameters specifying them are the analogue to the variables in classical molecular dynamics. The time-dependent variational principle yields the equations of motion which are solved for collisions of 12 C+ 12 C and deexcitations of 12 C. The collisions show a great variety of phenomena including explosion, sequential fragmentation and multifragmentation. The deexcitation for nuclei with E * /A ∼ 5MeV is dominated by particle evaporation on time scales of the order of 10 -20 s or longer. (orig.)

Paleocorrosion studies in deep sea sediments and the geological disposal of nuclear wastes

International Nuclear Information System (INIS)

Fehrenbach, L.; Maurette, M.; Guichard, F.; Havette, A.; Monaco, A.

1984-01-01

Uncertainties still surround assessment of the safety of disposal of nuclear wastes incorporated into 'radwaste' matrices. This is mostly due to the long time required for radioactive decay of 237 Np. The present work explores the usefulness of an experimental approach in 'paleocorrosion', which should help in minimizing such uncertainties. In this approach, polished sections of sediments containing high concentrations of natural analogues of radwaste matrices are subjected to element micromapping. Thus it is possible to characterize the long-term interactions of such analogues in their geological repositories, and to identify which generate reaction aureoles and protective and/or unprotective coatings. These analogues include grains incorporated in deep sea sediments (uraninite and quartz from the Oklo uranium ore deposit; volcanic ash particles; magnetic cosmic spherules). The present results indicate that uraninite should be a much more durable radwaste matrix than any type of glass in deep sea sediments. (orig./TWO)

Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

Energy Technology Data Exchange (ETDEWEB)

Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

2010-08-15

Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

Optimization of gefitinib analogues with potent anticancer activity.

Science.gov (United States)

Yin, Kai-Hao; Hsieh, Yi-Han; Sulake, Rohidas S; Wang, Su-Pei; Chao, Jui-I; Chen, Chinpiao

2014-11-15

The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

Science.gov (United States)

Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

2018-04-13

tumors as well as significantly increased accumulation in the kidneys and red marrow. It has great potential to be used in PRRT for NET tumors with lower dose and less frequency of administration. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

Directory of Open Access Journals (Sweden)

Michelle Visagie

Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

Investigations of the Formation of Molecular Hydrogen on Dust Grain Analogues

Science.gov (United States)

Vidali, Gianfranco; Roser, Joseph E.; Manico, Giulio; Pirronello, Valerio

2002-01-01

In the last four years we have been working to investigate the formation of molecular hydrogen on surfaces of materials of astrophysical interest, such as silicates, carbonaceous particles and ices, and in conditions approximating the ones present in a variety of astrophysical environments. Our experimental studies - the first of their kind and complemented with computer simulations and theoretical analyses - have given not only hydrogen recombination rates under different ISM conditions, but they have also offered new insights into this fundamental astrophysical problem. Here we summarize our experimental methods and most significant results.

Difference in brain activations during appreciating paintings and photographic analogues

Directory of Open Access Journals (Sweden)

Yoshinori eMizokami

2014-07-01

Full Text Available Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies’ measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogues which included corresponding real images. We prepared for famous painters’ pictures and their photographic analogues which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogues including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogues. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

The role of nuclear techniques in the long-term prediction of radionuclide transport

International Nuclear Information System (INIS)

Airey, P.L.; Duerden, P.

1985-01-01

Problems associated with the long-term prediction of the migration of radionuclides, and the role of natural analogues in reducing the inherent uncertainties are discussed. Particular reference is made to the evaluation of uranium ore bodies in the Alligator Rivers region, Northern Territory, as analogues of high-level radioactive waste repositories. A range of nuclear techniques has been used to identify the role of colloids, of alpha recoil and of mineralogy in transport. Specific mention is made of a method being developed which enables models of the migration of solute through fractured rock to be assessed via a combination of alpha track, fission track and PIXE/PIGME techniques

The use of natural analogues in the long-term extrapolation of glass corrosion processes

International Nuclear Information System (INIS)

Lutze, W.; Grambow, B.; Ewing, R.C.; Jercinovic, M.J.

1987-01-01

One of the most critical aspects of nuclear waste management is the extrapolation of materials and systems behavior from short term experiments, typically on the order of one year, over comparatively very long periods of time. Safety and risk analyses have to rely on extrapolations and the respective findings have to be evaluated in the frame of licensing procedures. In this unique situation, any source of information that can lend support to the credibility of predicted behavior, should be exploited and investigated with great care. There are natural systems, e.g. the Oklo reactor, which can provide evidence of radionuclide migration over very long periods of time and thus help to answer specific questions of interest. Natural glasses and minerals can serve as analogues for both glass and crystalline nuclear waste forms, and the alteration of the natural materials can be studied to infer information on the behavior of the man-made products in geologic environments. This paper reviews most of the work performed by the authors and their colleagues in this field together with information available from literature and discusses the extent to which natural glasses can be used to validate or verify predictions. (author)

Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review

Directory of Open Access Journals (Sweden)

Arezoo Rafiee Parhizgar

2017-03-01

Full Text Available Antimalarial drugs with the 4-aminoquinoline scaffold such as the important drugs, chloroquine (CQ and amodiaquine (AQ, have been used to prevent and treat malaria for many years. The importance of these drugs is related to their simple usage, high efficacy, affordability, and cost-effectiveness of their synthesis. In recent years, with the spread of parasite resistance to CQ and cross-resistance to its other analogues have decreased their consumption in many geographical areas. On the other hand, AQ is an effective antimalarial drug which its usage has been restricted due to hepatic and hematological toxicities. The significance of the quinoline ring at quinoline-based antimalarial drugs has prompted research centers and pharmaceutical companies to focus on the design and synthesis of new analogues of these drugs, especially CQ and AQ analogues. Accordingly, various derivatives have been synthesized and evaluated in vitro and in vivo against the resistant strains of the malaria parasite to solve the problem of drug resistance. Also, the pharmacokinetic properties of these compounds have been evaluated to augment their efficacy and diminish their toxicity. Some of these analogues are currently in clinical and preclinical development. Consequently, the recent researches showed yet 4-aminoquinoline scaffold is active moiety in new compounds with antiplasmodial activity. Hence, the aim of this review article is to introduce of the novel synthetic analogues of CQ and AQ, which may constitute the next generation of antimalarial drugs with the 4-aminoquinoline scaffold.

Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review.

Science.gov (United States)

Parhizgar, Arezoo Rafiee; Tahghighi, Azar

2017-03-01

Antimalarial drugs with the 4-aminoquinoline scaffold such as the important drugs, chloroquine (CQ) and amodiaquine (AQ), have been used to prevent and treat malaria for many years. The importance of these drugs is related to their simple usage, high efficacy, affordability, and cost-effectiveness of their synthesis. In recent years, with the spread of parasite resistance to CQ and cross-resistance to its other analogues have decreased their consumption in many geographical areas. On the other hand, AQ is an effective antimalarial drug which its usage has been restricted due to hepatic and hematological toxicities. The significance of the quinoline ring at quinoline-based antimalarial drugs has prompted research centers and pharmaceutical companies to focus on the design and synthesis of new analogues of these drugs, especially CQ and AQ analogues. Accordingly, various derivatives have been synthesized and evaluated in vitro and in vivo against the resistant strains of the malaria parasite to solve the problem of drug resistance. Also, the pharmacokinetic properties of these compounds have been evaluated to augment their efficacy and diminish their toxicity. Some of these analogues are currently in clinical and preclinical development. Consequently, the recent researches showed yet 4-aminoquinoline scaffold is active moiety in new compounds with antiplasmodial activity. Hence, the aim of this review article is to introduce of the novel synthetic analogues of CQ and AQ, which may constitute the next generation of antimalarial drugs with the 4-aminoquinoline scaffold.

Synthesis of tritium labelled phosphonate analogues of sphinganine-1-phosphate

International Nuclear Information System (INIS)

Schick, Andreas; Schwarzmann, Guenter; Kolter, Thomas; Sandhoff, Konrad

1997-01-01

Tritiated phosphonate analogues 9 and 10 are prepared as analogues of sphinganine-1-phosphate 4. The key step in this synthesis is the catalytic tritiation of the triple bond in reduction of the protected diethyl-3-(S)-tert.-butoxycarbonylamino -4-hydroxy-5-tridecinyl-1-phosphonate by means of sodium boro[ 3 H]hydride as tritium source. These compounds are synthesized to study their metabolic stability and to evaluate their biological properties. (author)

Transport Properties of the Nuclear Pasta Phase with Quantum Molecular Dynamics

Science.gov (United States)

Nandi, Rana; Schramm, Stefan

2018-01-01

We study the transport properties of nuclear pasta for a wide range of density, temperature, and proton fractions, relevant for different astrophysical scenarios adopting a quantum molecular dynamics model. In particular, we estimate the values of shear viscosity as well as electrical and thermal conductivities by calculating the static structure factor S(q) using simulation data. In the density and temperature range where the pasta phase appears, the static structure factor shows irregular behavior. The presence of a slab phase greatly enhances the peak in S(q). However, the effect of irregularities in S(q) on the transport coefficients is not very dramatic. The values of all three transport coefficients are found to have the same orders of magnitude as found in theoretical calculations for the inner crust matter of neutron stars without the pasta phase; therefore, the values are in contrast to earlier speculations that a pasta layer might be highly resistive, both thermally and electrically.

Molecular HIV screening.

Science.gov (United States)

Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

2013-09-01

Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

Lessons from nature. The behaviour of technical and natural barriers in the geological disposal of spent nuclear fuel

International Nuclear Information System (INIS)

Marcos, N.

2002-01-01

This work deals with the study of the long-term performance of materials and elements involved in the near- and far-field of an underground nuclear waste repository. Materials and elements occurring in nature are similar, or at least analogous, to the materials and elements manufactured or processed by man. Also, natural processes may be similar to those envisaged as occurring in a nuclear waste repository. This similarity makes it possible to study the behaviour of those materials in nature and to compare it with the behaviour of the manufactured materials to be used in a repository. As many materials and elements have been in the natural environment for long time periods (thousands to million of years), the data obtained can be extrapolated to estimate the future evolution of similar components in a nuclear waste repository. Thinking by analogy is the process of comparison, with those materials, elements and environments used to perform the studies that allow the comparison to be regarded as natural analogues. The Hyrkkoelae U-Cu mineralisation (SW Finland) was studied as an analogue to the behaviour of copper canisters in crystalline bedrock. This analogue could also address the interaction between copper corrosion products and uranium. Copper sulphides are shown to retain up to 25% of uranium as U (IV) even if oxidizing conditions prevail. Furthermore, uranium was observed in smectite (main component of bentonite) associated with native copper and cuprite, which constitutes an analogue to the behaviour of the repository near-field materials in a natural oxidizing environment. In addition to the Hyrkkoelae analogue, the issue of irreversible sorption or uranium immobilization is also addressed, in the studies of the boulder rock near Haemeenlinna. The behaviour of U, Th, and rare earth elements (REE) as analogues to the long-lived actinides is also evaluated in groundwater and rock samples at Olkiluoto (SW Finland). U and Th were shown to be released more easily

Nuclear waste disposal research and studies on natural groundwater colloids in Finland

International Nuclear Information System (INIS)

Vuorinen, U.

1995-01-01

In Finland there are two programmes carrying out studies on the safe disposal of nuclear fuel. One programme is funded by the nuclear power producing companies and the other one is publicly financed. Different natural sites are being investigated within the two programme of the nuclear power producing companies, while the publicly financed programme is concentrating its investigations on the Finnish natural analogue site at Palmottu. Both programmes are briefly discussed. Within both programmes some studies on natural groundwater colloids have been performed. However, a characterization of organic colloids has been performed on only one occasion so far. The colloid studies and results are discussed. (authors). 8 refs

The chaos and order in nuclear molecular dynamics; Chaos i porzadek w jadrowej dynamice molekularnej

Energy Technology Data Exchange (ETDEWEB)

Srokowski, T. [Institute of Nuclear Physics, Cracow (Poland)

1995-12-31

The subject of the presented report is role of chaos in scattering processes in the frame of molecular dynamics. In this model, it is assumed that scattering particles (nuclei) consist of not-interacted components as alpha particles or {sup 12}C, {sup 16}O and {sup 20}Ne clusters. The results show such effects as dynamical in stabilities and fractal structure as well as compound nuclei decay and heavy-ion fusion. The goal of the report is to make the reader more familiar with the chaos model and its application to nuclear phenomena. 157 refs, 40 figs.

Signatures of attosecond electronic–nuclear dynamics in the one-photon ionization of molecular hydrogen: analytical model versus ab initio calculations

International Nuclear Information System (INIS)

Medišauskas, Lukas; Ivanov, Misha Yu; Morales, Felipe; Plimak, Lev; Smirnova, Olga; Palacios, Alicia; González-Castrillo, Alberto; Martín, Fernando

2015-01-01

We present an analytical model based on the time-dependent WKB approximation to reproduce the photoionization spectra of an H 2 molecule in the autoionization region. We explore the nondissociative channel, which is the major contribution after one-photon absorption, and we focus on the features arising in the energy differential spectra due to the interference between the direct and the autoionization pathways. These features depend on both the timescale of the electronic decay of the autoionizing state and the time evolution of the vibrational wavepacket created in this state. With full ab initio calculations and with a one-dimensional approach that only takes into account the nuclear wavepacket associated to the few relevant electronic states we compare the ground state, the autoionizing state, and the background continuum electronic states. Finally, we illustrate how these features transform from molecular-like to atomic-like by increasing the mass of the system, thus making the electronic decay time shorter than the nuclear wavepacket motion associated with the resonant state. In other words, autoionization then occurs faster than the molecular dissociation into neutrals. (paper)

Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

DEFF Research Database (Denmark)

Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

2017-01-01

Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer...... potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

2. Scientific meeting of Chilean Nuclear Energy Commission. Abstracts; Segundas jornadas cientificas de la Comision Chilena de Energia Nuclear. Resumenes

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-10-01

This publication includes 33 papers in the fields on analytical methods nuclear and conventional, atomic and molecular physics, ionizing radiations, nuclear and non nuclear materials, radiological protection and nuclear safety.

Native copper as a natural analogue for copper canisters

International Nuclear Information System (INIS)

Marcos, N.

1989-12-01

This paper discusses the occurrence of native copper as found in geological formations as a stability analogue of copper canisters that are planned to be used for the disposal of spent nuclear fuel in the Finnish bedrock. A summary of several publications on native copper occurrences is presented. The present geochemical and geohydrological conditions in which copper is met with in its metallic state show that metallic copper is stable in a wide range of temperatures. At low temperatures native copper is found to be stable where groundwater has moderate pH (about 7), low Eh (< +100 mV), and low total dissolved solids, especially chloride. Microscopical and microanalytical studies were carried out on a dozen of rock samples containing native copper. The results reveal that the metal shows no significant alteration. Only the surface of copper grains is locally coated. In the oldest samples there exist small corrosion cracks; the age of the oldest samples is over 1,000 million years. A review of several Finnish groundwater studies suggests that there are places in Finland where the geohydrological conditions are favourable for native copper stability. (orig.)

Molecularly imprinted poly (methacrylamide-co-methacrylic acid) composite membranes for recognition of curcumin

International Nuclear Information System (INIS)

Wang Ping; Hu Wenming; Su Weike

2008-01-01

In this study, molecularly imprinted poly (methacrylamide-co-methacrylic acid) composite membranes with different ratio of methacrylamide (MAM) versus methacrylic acid (MAA) were prepared via UV initiated photo-copolymerization on the commercial filter paper. Curcumin was chosen as the template molecule. Infra-red (IR) spectroscopy was used to study the binding mechanism between the imprinted sites and the templates. The morphology of the resultant membranes was visualized by scanning electron microscopy (SEM). Static equilibrium binding and recognition properties of the imprinted composite membranes to curcumin (cur-I) and its analogues demethoxycurcumin (cur-II) or bisdemethoxycurcumin (cur-III) were tested. The results showed that curcumin-imprinted membranes had the best recognition ability to curcumin compared to its analogues. From the results, the biggest selectivity factor of α cur-I/cur-II and α cur-I/cur-III were 1.50 and 5.94, and they were obtained from the composite membranes in which MAM/MAA were 1:4 and 0:1, respectively. The results of this study implied that the molecularly imprinted composite membranes could be used as separation membranes for curcumin enrichment

The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

Directory of Open Access Journals (Sweden)

Christian Montag

2015-12-01

Full Text Available Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications. Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

PENGEMBANGAN BERAS ANALOG DENGAN MEMANFAATKAN JAGUNG PUTIH [Development of White Corn-Based Rice Analogues

Directory of Open Access Journals (Sweden)

Santi Noviasari*

2013-12-01

Full Text Available White corn can be utilized as a source of non-rice carbohydrate in the manufacture of rice analogues. The rice analogues with rice-like characteristics were produced by an extrusion technique. The aim of this research was to develop rice analogues from white corn and to evaluate their physicochemical and sensory properties. The study was conducted in several stages, i.e. preparation, formulation, and physicochemical and sensory properties evaluation. The physicochemical properties of rice analogues evaluated included proximate nutritional composition, dietary fiber concentration, cooking time, water loss rate, color, and whiteness percentage, while their sensory preferences were evaluated using hedonic scale test. The rice analogues made of Pulut Harapan and Lokal Purbalingga corns (4.34:65.66% added with 30% sago starch, was found to be the most preferred. The moisture, ash, protein, fat, carbohydrate, and dietary fiber composition of this rice analog was 9.32, 0.38, 6.86, 1.22, 91.54, and 5.35%, respectively.

Do film soundtracks contain nonlinear analogues to influence emotion?

Science.gov (United States)

Blumstein, Daniel T; Davitian, Richard; Kaye, Peter D

2010-12-23

A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses.

Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

KAUST Repository

Zhang, Xiaomei; Bocca, Silvina Maria; Franchi, Anahí ; Anderson, Sandra; Kaur, Mandeep; Bajic, Vladimir B.; Oehninger, Sergio Carlos

2010-01-01

were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues

Molecular Structure Laboratory. Fourier Transform Nuclear Magnetic Resonance (FTNMR) Spectrometer and Ancillary Instrumentation at SUNY Geneseo

Energy Technology Data Exchange (ETDEWEB)

Geiger, David K [State Univ. of New York (SUNY), Geneseo, NY (United States)

2015-12-31

An Agilent 400-MR nuclear magnetic resonance (NMR) spectrometer and ancillary equipment were purchased, which are being used for molecular structure elucidation.  The instrumentation is housed in a pre-existing facility designed specifically for its use. This instrument package is being used to expand the research and educational efforts of the faculty and students at SUNY-Geneseo and is made available to neighboring educational institutions and business concerns.  Funds were also used for training of College personnel, maintenance of the instrumentation, and installation of the equipment.

Molecular Diffusion through Cyanobacterial Septal Junctions

Directory of Open Access Journals (Sweden)

Mercedes Nieves-Morión

2017-01-01

Full Text Available Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N2-fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO2 through oxygenic photosynthesis provide the heterocysts with reduced carbon and heterocysts provide the vegetative cells with fixed nitrogen. Intercellular molecular transfer has been traced with fluorescent markers, including calcein, 5-carboxyfluorescein, and the sucrose analogue esculin, which are observed to move down their concentration gradient. In this work, we used fluorescence recovery after photobleaching (FRAP assays in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 to measure the temperature dependence of intercellular transfer of fluorescent markers. We find that the transfer rate constants are directly proportional to the absolute temperature. This indicates that the “septal junctions” (formerly known as “microplasmodesmata” linking the cells in the filament allow molecular exchange by simple diffusion, without any activated intermediate state. This constitutes a novel mechanism for molecular transfer across the bacterial cytoplasmic membrane, in addition to previously characterized mechanisms for active transport and facilitated diffusion. Cyanobacterial septal junctions are functionally analogous to the gap junctions of metazoans.

The Dense Molecular Gas and Nuclear Activity in the ULIRG IRAS 13120–5453

Energy Technology Data Exchange (ETDEWEB)

Privon, G. C.; Treister, E. [Instituto de Astrofśica, Facultad de Física, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 22 (Chile); Aalto, S.; Falstad, N.; Muller, S.; Costagliola, F. [Department of Earth and Space Sciences, Chalmers University of Technology, Onsala Space Observatory, SE-439 94 Onsala (Sweden); González-Alfonso, E. [Universidad de Alcalá, Departamento de Física y Matemáticas, Campus Universitario, E-28871 Alcalá de Henares, Madrid (Spain); Sliwa, K. [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); Armus, L. [Spitzer Science Center, California Institute of Technology, MS 220-6, Pasadena, CA, 91125 (United States); Evans, A. S. [Department of Astronomy, University of Virginia, Charlottesville, VA 22903 (United States); Garcia-Burillo, S. [Observatorio de Madrid, OAN-IGN, Alfonso XII, 3, E-28014-Madrid (Spain); Izumi, T. [Institute of Astronomy, School of Science, The University of Tokyo, 2-21-1 Osawa, Mitaka, Tokyo 181-0015 (Japan); Sakamoto, K. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, 10617, Taipei, Taiwan (China); Werf, P. van der [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Chu, J. K. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

2017-02-01

We present new Atacama Large Millimeter/submillimeter Array Band 7 (∼340 GHz) observations of the dense gas tracers HCN, HCO{sup +}, and CS in the local, single-nucleus, ultraluminous infrared galaxy IRAS 13120–5453. We find centrally enhanced HCN (4–3) emission, relative to HCO{sup +} (4–3), but do not find evidence for radiative pumping of HCN. Considering the size of the starburst (0.5 kpc) and the estimated supernovae rate of ∼1.2 yr{sup −1}, the high HCN/HCO{sup +} ratio can be explained by an enhanced HCN abundance as a result of mechanical heating by the supernovae, though the active galactic nucleus and winds may also contribute additional mechanical heating. The starburst size implies a high Σ{sub IR} of 4.7 × 10{sup 12} L {sub ⊙} kpc{sup −2}, slightly below predictions of radiation-pressure limited starbursts. The HCN line profile has low-level wings, which we tentatively interpret as evidence for outflowing dense molecular gas. However, the dense molecular outflow seen in the HCN line wings is unlikely to escape the Galaxy and is destined to return to the nucleus and fuel future star formation. We also present modeling of Herschel observations of the H{sub 2}O lines and find a nuclear dust temperature of ∼40 K. IRAS 13120–5453 has a lower dust temperature and Σ{sub IR} than is inferred for the systems termed “compact obscured nuclei (CONs)” (such as Arp 220 and Mrk 231). If IRAS 13120–5453 has undergone a CON phase, we are likely witnessing it at a time when the feedback has already inflated the nuclear ISM and diluted star formation in the starburst/active galactic nucleus core.

Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients.

Science.gov (United States)

Serrano-Arévalo, Mónica L; Mosqueda-Taylor, Adalberto; Domínguez-Malagón, Hugo; Michal, Michal

2015-01-01

The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 Candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), Acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm.

Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities.

Science.gov (United States)

Thakkar, Sampark S; Thakor, Parth; Ray, Arabinda; Doshi, Hiren; Thakkar, Vasudev R

2017-10-15

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1 H NMR, 13 C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulation of a small molecule analogue of a lithium ionomer in an external electric field

Energy Technology Data Exchange (ETDEWEB)

Waters, Sara M.; McCoy, John D., E-mail: mccoy@nmt.edu; Brown, Jonathan R. [Department of Materials Engineering, New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801 (United States); Frischknecht, Amalie L. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States)

2014-01-07

We have investigated the ion dynamics in lithium-neutralized 2-pentylheptanoic acid, a small molecule analogue of a precise poly(ethylene-co-acrylic acid) lithium ionomer. Atomistic molecular dynamics simulations were performed in an external electric field. The electric field causes alignment of the ionic aggregates along the field direction. The energetic response of the system to an imposed oscillating electric field for a wide range of frequencies was tracked by monitoring the coulombic contribution to the energy. The susceptibility found in this manner is a component of the dielectric susceptibility typically measured experimentally. A dynamic transition is found and the frequency associated with this transition varies with temperature in an Arrhenius manner. The transition is observed to be associated with rearrangements of the ionic aggregates.

q-bosons and the q-analogue quantized field

International Nuclear Information System (INIS)

Nelson, C.A.

1994-01-01

The q-analogue coherent states |z > q are used to identify physical signatures for the presence of a q-analogue quantized radiation field in the | > q classical limit where |z| is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/|z|) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H N = ℎω(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (ΔN) 2 / → 0 as |z| → ∞. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, φ q , still exhibits normal classical behavior. The standard number-phase uncertainty-relation, ΔN Δφ q = 1/2, and the approximate commutation relation, [N,φ q ] = i, still hold for the single-mode q-analogue quantized field. So, N and φ q are almost canonically conjugate operators in the |z > q classical limit. The |z > q CS's minimize this uncertainty relation for moderate |z| 2

Higher-dimensional analogues of Donaldson-Witten theory

International Nuclear Information System (INIS)

Acharya, B.S.; Spence, B.

1997-01-01

We present a Donaldson-Witten-type field theory in eight dimensions on manifolds with Spin(7) holonomy. We prove that the stress tensor is BRST exact for metric variations preserving the holonomy and we give the invariants for this class of variations. In six and seven dimensions we propose similar theories on Calabi-Yau threefolds and manifolds of G 2 holonomy, respectively. We point out that these theories arise by considering supersymmetric Yang-Mills theory defined on such manifolds. The theories are invariant under metric variations preserving the holonomy structure without the need for twisting. This statement is a higher-dimensional analogue of the fact that Donaldson-Witten field theory on hyper-Kaehler 4-manifolds is topological without twisting. Higher-dimensional analogues of Floer cohomology are briefly outlined. All of these theories arise naturally within the context of string theory. (orig.)

Symmetries in molecular and nuclear physics

International Nuclear Information System (INIS)

Iachello, F.

1987-01-01

Algebric techniques (interacting boson and boson-fermion models) used in the study of nuclear structures, and are able to predict properties of complex nuclei with high accuracy described. (M.C.K.) [pt

Molecular imaging in oncology

International Nuclear Information System (INIS)

Weber, W.A.

2007-01-01

Molecular imaging is generally defined as noninvasive and quantitative imaging of targeted macromolecules and biological processes in living organisms. A characteristic of molecular imaging is the ability to perform repeated studies and assess changes in biological processes over time. Thus molecular imaging lends itself well for monitoring the effectiveness of tumor therapy. In animal models a variety of techniques can be used for molecular imaging. These include optical imaging (bioluminescence and fluorescence imaging), magnetic resonance imaging (MRI) and nuclear medicine techniques. In the clinical setting, however, nuclear medicine techniques predominate, because so far only radioactive tracers provide the necessary sensitivity to study expression and function of macromolecules non-invasively in patients. Nuclear medicine techniques allows to study a variety of biological processes in patients. These include the expression of various receptors (estrogen, androgen, somatostatin receptors and integrins). In addition, tracers are available to study tumor cell proliferation and hypoxia. The by far most commonly used molecular imaging technique in oncology is, however, positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG-PET). FDG-PET permits non-invasive quantitative assessment of the accelerated exogenous glucose use of malignant tumors. Numerous studies have now shown that reduction of tumor FDG-uptake during therapy allows early prediction of tumor response and patient survival. Clinical studies are currently underway to determine whether FDG-PET can be used to individualize tumor therapy by signaling early in the course of therapy the need for therapeutic adjustments in patients with likely non-responding tumors. (orig.)

Making Connections in Math: Activating a Prior Knowledge Analogue Matters for Learning

Science.gov (United States)

Sidney, Pooja G.; Alibali, Martha W.

2015-01-01

This study investigated analogical transfer of conceptual structure from a prior-knowledge domain to support learning in a new domain of mathematics: division by fractions. Before a procedural lesson on division by fractions, fifth and sixth graders practiced with a surface analogue (other operations on fractions) or a structural analogue (whole…

Molecular systematics of Indian Alysicarpus (Fabaceae) based on analyses of nuclear ribosomal DNA sequences.

Science.gov (United States)

Gholami, Akram; Subramaniam, Shweta; Geeta, R; Pandey, Arun K

2017-06-01

Alysicarpus Necker ex Desvaux (Fabaceae, Desmodieae) consists of ~30 species that are distributed in tropical and subtropical regions of theworld. In India, the genus is represented by ca. 18 species, ofwhich seven are endemic. Sequences of the nuclear Internal transcribed spacer from38 accessions representing 16 Indian specieswere subjected to phylogenetic analyses. The ITS sequence data strongly support the monophyly of the genus Alysicarpus. Analyses revealed four major well-supported clades within Alysicarpus. Ancestral state reconstructions were done for two morphological characters, namely calyx length in relation to pod (macrocalyx and microcalyx) and pod surface ornamentation (transversely rugose and nonrugose). The present study is the first report on molecular systematics of Indian Alysicarpus.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Science.gov (United States)

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

Application of 3D-QSAR, Pharmacophore, and Molecular Docking in the Molecular Design of Diarylpyrimidine Derivatives as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors.

Science.gov (United States)

Liu, Genyan; Wang, Wenjie; Wan, Youlan; Ju, Xiulian; Gu, Shuangxi

2018-05-11

Diarylpyrimidines (DAPYs), acting as HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs), have been considered to be one of the most potent drug families in the fight against acquired immunodeficiency syndrome (AIDS). To better understand the structural requirements of HIV-1 NNRTIs, three-dimensional quantitative structure⁻activity relationship (3D-QSAR), pharmacophore, and molecular docking studies were performed on 52 DAPY analogues that were synthesized in our previous studies. The internal and external validation parameters indicated that the generated 3D-QSAR models, including comparative molecular field analysis (CoMFA, q 2 = 0.679, R 2 = 0.983, and r pred 2 = 0.884) and comparative molecular similarity indices analysis (CoMSIA, q 2 = 0.734, R 2 = 0.985, and r pred 2 = 0.891), exhibited good predictive abilities and significant statistical reliability. The docking results demonstrated that the phenyl ring at the C₄-position of the pyrimidine ring was better than the cycloalkanes for the activity, as the phenyl group was able to participate in π⁻π stacking interactions with the aromatic residues of the binding site, whereas the cycloalkanes were not. The pharmacophore model and 3D-QSAR contour maps provided significant insights into the key structural features of DAPYs that were responsible for the activity. On the basis of the obtained information, a series of novel DAPY analogues of HIV-1 NNRTIs with potentially higher predicted activity was designed. This work might provide useful information for guiding the rational design of potential HIV-1 NNRTI DAPYs.

Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

Science.gov (United States)

Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

2017-05-01

This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

Benzoheterocyclic amodiaquine analogues with potent antiplasmodial activity: synthesis and pharmacological evaluation.

Science.gov (United States)

Ongarora, Dennis S B; Gut, Jiri; Rosenthal, Philip J; Masimirembwa, Collen M; Chibale, Kelly

2012-08-01

The synthesis and evaluation of antiplasmodial activity of benzothiazole, benzimidazole, benzoxazole and pyridine analogues of amodiaquine is hereby reported. Benzothiazole and benzoxazole analogues with a protonatable tertiary nitrogen atom possessed excellent activity against the W2 and K1 chloroquine resistant strains of Plasmodium falciparum, with IC(50)s ranging from 7 to 22 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

New analogues of Cucurbita maxima trypsin inhibitor III (CMTI III) with simplified structure.

Science.gov (United States)

Rolka, K; Kupryszewski, G; Rózycki, J; Ragnarsson, U; Zbyryt, T; Otlewski, J

1992-10-01

Seven new analogues of trypsin inhibitor CMTI III were obtained by solid-phase peptide synthesis. Three analogues contained only two, instead of three, disulfide bridges, whereas the molecules of the next four analogues were shortened at the N- and/or C-terminus. The elimination of one disulfide bridge in CMTI III induces a decrease in the association equilibrium constants by 6-7 orders of magnitude, whereas the removal of one, two or three amino-acid residues at the N- and/or C-terminus does not significantly affect the activity.

0+ analogue state in 118Sb from 117Sn(p,nγ) reaction

International Nuclear Information System (INIS)

Pal, J.; Dey, C.C.; Bose, S.; Sinha, B.K.; Chatterjee, M.B.; Mahapatra, D.P.

1996-01-01

The analogue of the 0 + ground state in 118 Sn has been observed in the compound nucleus 118 Sb through 117 Sn(p,nγ) 117 Sb reaction. The neutron decays of this analogue resonance have been studied from the deexciting γ-rays of the residual nucleus 117 Sb. From off resonance excitation functions, spin assignments have been made to states in 117 Sb, on the basis of Hauser-Feshbach formalism. The resonance parameters of the isobaric analogue resonance have been determined, including the total, proton and neutron decay widths. (orig.)

Differential Top10 promoter regulation by six tetracycline analogues in plant cells

Science.gov (United States)

Love, John; Allen, George C.; Gatz, Christiane; Thompson, William F.; Brown, C. S. (Principal Investigator)

2002-01-01

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

Electron and nuclear dynamics of molecular clusters in ultraintense laser fields. IV. Coulomb explosion of molecular heteroclusters.

Science.gov (United States)

Last, Isidore; Jortner, Joshua

2004-11-01

In this paper we present a theoretical and computational study of the temporal dynamics and energetics of Coulomb explosion of (CD4)(n) and (CH4)(n) (n=55-4213) molecular heteroclusters in ultraintense (I=10(16)-10(19) W cm(-2)) laser fields, addressing the manifestation of electron dynamics, together with nuclear energetic and kinematic effects on the heterocluster Coulomb instability. The manifestations of the coupling between electron and nuclear dynamics were explored by molecular dynamics simulations for these heteroclusters coupled to Gaussian laser fields (pulse width tau=25 fs), elucidating outer ionization dynamics, nanoplasma screening effects (being significant for Icharges and masses. Nonuniform heterocluster Coulomb explosion (eta >1) manifests an overrun effect of the light ions relative to the heavy ions, exhibiting the expansion of two spatially separated subclusters, with the light ions forming the outer subcluster at the outer edge of the spatial distribution. Important features of the energetics of heterocluster Coulomb explosion originate from energetic triggering effects of the driving of the light ions by the heavy ions (C(4+) for I=10(17)-10(18) W cm(-2) and C(6+) for I=10(19) W cm(-2)), as well as for kinematic effects. Based on the CVI assumption, scaling laws for the cluster size (radius R(0)) dependence of the energetics of uniform Coulomb explosion of heteroclusters (eta=1) were derived, with the size dependence of the average (E(j,av)) and maximal (E(j,M)) ion energies being E(j,av)=aR(0) (2) and E(j,M)=(5a/3)R(0) (2), as well as for the ion energy distributions P(E(j)) proportional to E(j) (1/2); E(j)1) result in an isotope effect, predicting the enhancement (by 9%-11%) of E(H,av) for Coulomb explosion of (C(4+)H(4) (+))(eta) (eta=3) relative to E(D,av) for Coulomb explosion of (C(4+)D(4) (+))(eta) (eta=1.5), with the isotope effect being determined by the ratio of the kinematic parameters for the pair of Coulomb exploding clusters

Kahalalide F analogues from the mucous secretion of Indian sacoglossan mollusc Elysia ornata

Digital Repository Service at National Institute of Oceanography (India)

Ciavatta, M.L.; PrabhaDevi; Carbone, M.; Mathieu, V.; Kiss, R.; Casapullo, A.; Gavagnin, M.

, better delivery, or longer half-life. More than 150 analogues were obtained by solid phase peptide synthesis8,9 and more recently a semi-synthetic approach to produce KF analogues starting from natural KF has been also performed.10In parallel...

Systematic Review of the Cost Effectiveness of Insulin Analogues in Type 1 and Type 2 Diabetes Mellitus.

Science.gov (United States)

Shafie, Asrul Akmal; Ng, Chin Hui; Tan, Yui Ping; Chaiyakunapruk, Nathorn

2017-02-01

Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses. Current evidence indicates that insulin analogues are cost effective for T1DM; however, evidence for their use in T2DM is not convincing. Additional evidence regarding compliance and efficacy is required to support the broader use of long-acting and biphasic insulin analogues in T2DM. The value of insulin analogues depends strongly on reductions in hypoglycaemia event rates and its efficacy in lowering glycated haemoglobin

From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

International Nuclear Information System (INIS)

Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

1991-01-01

Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

NUCLEAR CHEMISTRY ANNUAL REPORT 1970

Energy Technology Data Exchange (ETDEWEB)

Authors, Various

1971-05-01

Papers are presented for the following topics: (1) Nuclear Structure and Nuclear Properties - (a) Nuclear Spectroscopy and Radioactivity; (b) Nuclear Reactions and Scattering; (c) Nuclear Theory; and (d) Fission. (2) Chemical and Atomic Physics - (a) Atomic and Molecular Spectroscopy; and (b) Hyperfine Interactions. (3) Physical, Inorganic, and Analytical Chemistry - (a) X-Ray Crystallography; (b) Physical and Inorganic Chemistry; (c) Radiation Chemistry; and (d) Chemical Engineering. (4) Instrumentation and Systems Development.

Insulin biosimilars: the impact on rapid-acting analogue-based therapy.

Science.gov (United States)

Franzè, S; Cilurzo, F; Minghetti, P

2015-04-01

The impending expiration of patent protection for recombinant insulins provides the opportunity to introduce cost-saving copies, named biosimilars, onto the market. Although there is broad experience in the production and characterisation of insulins, the development of copies is still a challenge. In this paper, the main features of insulins and the EU regulatory framework for their biosimilar products are reviewed. The main focus is on rapid-acting insulin analogues (Humalog(®); Novolog(®)/NovoRapid(®); Apidra(®)). Since they differ by one or two amino acids in chain B, production of one biosimilar for all three drug products is not feasible. However, from post-marketing-collected clinical data, rapid-acting insulin analogues seem to have similar therapeutic efficacy. It is reasonable to suppose that, for prescription to treatment-naïve patients, the cheaper biosimilar would be the preferred choice of physicians, either spontaneously or induced by health insurance. Therefore, its introduction will affect the market share of all the other rapid-acting insulin analogues.

Report of the IAEA Nuclear Data Section to the International Nuclear Data Committee for the period January 2002 - December 2003

Energy Technology Data Exchange (ETDEWEB)

Nichols, Alan L [ed.

2004-05-01

This report contains descriptions of the major activities of the IAEA Nuclear Data Section in 2002 and 2003 for review by the International Nuclear Data Committee (INDC). Information is provided on the staff and budget, atomic, molecular and nuclear data activities of the Nuclear Data Centre, coordination of the Nuclear Data Centre Networks, nuclear data development projects, technology transfer, and computer support. This information is complemented by descriptions of other relevant activities in the reporting period, including meetings and publications. The atomic and molecular data programmes are presented to the INDC for information only, since those specific activities are reviewed in depth by the A+M Subcommittee of the International Fusion Research Council. (author)

Report of the IAEA Nuclear Data Section to the International Nuclear Data Committee for the period January 2000 - December 2001

International Nuclear Information System (INIS)

Nichols, A.L.

2002-05-01

This report contains descriptions of the major activities of the IAEA Nuclear Data Section in 2000 and 2001 for review by the International Nuclear Data Committee (INDC). Information is provided on the staff and budget, atomic, molecular and nuclear data activities of the Nuclear Data Center, coordination of the Nuclear Data Center Networks, nuclear data development projects, technology transfer, and computer support. This information is complemented by descriptions of other relevant activities in the reporting period, including meetings and publications. The atomic and molecular data programmes are presented to the INDC for information only, since those specific activities are reviewed in depth by the A+M Subcommittee of the International Fusion Research Council. (author)

Andrographolide and analogues in cancer prevention.

Science.gov (United States)

Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

2015-01-01

Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

The monoamine oxidase inhibition properties of selected structural analogues of methylene blue

International Nuclear Information System (INIS)

Delport, Anzelle; Harvey, Brian H.; Petzer, Anél; Petzer, Jacobus P.

2017-01-01

The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC 50 = 0.0037 μM), Nile blue (IC 50 = 0.0077 μM) and 1,9-dimethyl methylene blue (IC 50 = 0.018 μM) exhibiting higher potency inhibition compared to MB (IC 50 = 0.07 μM). Nile blue also represents a potent MAO-B inhibitor with an IC 50 value of 0.012 μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. - Highlights: • MB analogues, cresyl violet and Nile blue, are high potency MAO-A inhibitors. • Nile blue also represents a potent MAO-B inhibitor. • Potent MAO-A inhibition should alert to potential serotonin toxicity.

The monoamine oxidase inhibition properties of selected structural analogues of methylene blue

Energy Technology Data Exchange (ETDEWEB)

Delport, Anzelle [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Harvey, Brian H. [Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Pharmacology, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Petzer, Anél [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Petzer, Jacobus P., E-mail: jacques.petzer@nwu.ac.za [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa)

2017-06-15

The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC{sub 50} = 0.0037 μM), Nile blue (IC{sub 50} = 0.0077 μM) and 1,9-dimethyl methylene blue (IC{sub 50} = 0.018 μM) exhibiting higher potency inhibition compared to MB (IC{sub 50} = 0.07 μM). Nile blue also represents a potent MAO-B inhibitor with an IC{sub 50} value of 0.012 μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. - Highlights: • MB analogues, cresyl violet and Nile blue, are high potency MAO-A inhibitors. • Nile blue also represents a potent MAO-B inhibitor. • Potent MAO-A inhibition should alert to potential serotonin toxicity.

The IAEA report on the role of natural analogues in performance assessment

International Nuclear Information System (INIS)

Vovk, I.F.

1989-01-01

A working draft of the report was prepared with the assistance of a group of consultants who met in Vienna from 29 June to 3 July 1987. The draft was revised by an Advisory Group meeting in Vienna from 2 to 6 November 1987 and examined by the Technical Review Committee on Underground Disposal of Radioactive Waste (TRCUD) convened in Vienna from 15 to 19 February 1988. TRCUD recommended it for publication as a Technical Reports Series. The document appraises the use of natural analogues in improving confidence in the soundness of performance assessments for deep underground disposal of long-lived wastes. For this purpose it reviews several available performance assessments and identifies on this basis factors, processes or parameters which are important to their results, assesses the requirements for validation in each area and identifies those areas where analogues are appropriate. A special section is devoted to discussion of the quantitative and qualitative roles of the analogues. A number of conclusions reflect the state-of-the-art and may guide further natural analogue studies

Bentonite analogue research related to geological disposal of radioactive waste: current status and future outlook

International Nuclear Information System (INIS)

Reijonen, H.M.; Russel, A.W.

2015-01-01

The practice of utilising natural analogues in assessing the long-term behaviour of various components of geological repositories for radioactive waste is already well established in most disposal programmes. Numerous studies on bentonites, focussing on bentonite interaction with other components of the engineered barrier system and a range of host rock environments, are present in the literature. In this article, recent bentonite natural analogue studies are briefly reviewed, and gaps in the current literature identified, with the aim of (1) suggesting where relevant new information could be obtained by data mining published bentonite natural analogue studies with a new focus on current safety case requirements, (2) collecting relevant information by revisiting known bentonite analogue sites and conducting investigations with more appropriate analytical techniques, and (3) identifying novel study sites where, for example, bentonite longevity in very dilute to highly saline groundwater conditions can be studied. It must be noted that the use of natural analogues in safety case development is likely to be site and repository design-specific in nature and thus emphasis is placed on the appropriate use of relevant natural analogue data on bentonite longevity. (authors)

Bentonite analogue research related to geological disposal of radioactive waste: current status and future outlook

Energy Technology Data Exchange (ETDEWEB)

Reijonen, H.M. [Saanio and Rickkola Oy, Helsinki (Finland); Russel, A.W. [Bedrock Geosciences, Auenstein (Switzerland)

2015-06-15

The practice of utilising natural analogues in assessing the long-term behaviour of various components of geological repositories for radioactive waste is already well established in most disposal programmes. Numerous studies on bentonites, focussing on bentonite interaction with other components of the engineered barrier system and a range of host rock environments, are present in the literature. In this article, recent bentonite natural analogue studies are briefly reviewed, and gaps in the current literature identified, with the aim of (1) suggesting where relevant new information could be obtained by data mining published bentonite natural analogue studies with a new focus on current safety case requirements, (2) collecting relevant information by revisiting known bentonite analogue sites and conducting investigations with more appropriate analytical techniques, and (3) identifying novel study sites where, for example, bentonite longevity in very dilute to highly saline groundwater conditions can be studied. It must be noted that the use of natural analogues in safety case development is likely to be site and repository design-specific in nature and thus emphasis is placed on the appropriate use of relevant natural analogue data on bentonite longevity. (authors)

Combinatorial Solid-Phase Synthesis of Balanol Analogues

DEFF Research Database (Denmark)

Nielsen, John; Lyngsø, Lars Ole

1996-01-01

The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...

DOTA-derivatives of octreotide dicarba-analogues with high affinity for somatostatin sst2,5 receptors

Science.gov (United States)

Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

2017-02-01

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

water alteration processes and kinetics of basaltic glasses, natural analogue of nuclear glasses

International Nuclear Information System (INIS)

Techer, I.; Advocat, Th.; Vernaz, E.; Lancelot, J.R.; Liotard, J.M.

1997-01-01

Dissolution experiments of a basaltic glass were carried out at 90 deg C for different reaction progresses. The initial dissolution rate was compared with values obtained for rhyolitic glass and the R7T7 nuclear glass. The activation energy was also determined by computing literature data. The results provide similar reactional mechanism for basaltic and nuclear glasses. Dissolution rates measured under saturation conditions were compared to theoretical dissolution rates. These ones were calculated using two kinetic models: the first rate equation is the Grambow's law which only takes into account ortho-silica acid activity; the second rate equation was proposed by Daux et al., where silica and aluminum are combined to formulate the affinity. The comparison between experimental and theoretical results point out that these two models are not appropriate to describe the alteration kinetic of basaltic glasses. (authors)

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

OpenAIRE

Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

2016-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

Science.gov (United States)

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

International Nuclear Information System (INIS)

Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

1989-01-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel 6 ]LH-RH (SB-05) and [Ac-D-Nal(2) 1 ,D-Phe(pCl) 2 ,D-Pal(3) 3 ,Arg 5 ,D-Mel 6 ,D-Ala 10 ]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel 6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells

Numerical Nuclear Second Derivatives on a Computing Grid: Enabling and Accelerating Frequency Calculations on Complex Molecular Systems.

Science.gov (United States)

Yang, Tzuhsiung; Berry, John F

2018-06-04

The computation of nuclear second derivatives of energy, or the nuclear Hessian, is an essential routine in quantum chemical investigations of ground and transition states, thermodynamic calculations, and molecular vibrations. Analytic nuclear Hessian computations require the resolution of costly coupled-perturbed self-consistent field (CP-SCF) equations, while numerical differentiation of analytic first derivatives has an unfavorable 6 N ( N = number of atoms) prefactor. Herein, we present a new method in which grid computing is used to accelerate and/or enable the evaluation of the nuclear Hessian via numerical differentiation: NUMFREQ@Grid. Nuclear Hessians were successfully evaluated by NUMFREQ@Grid at the DFT level as well as using RIJCOSX-ZORA-MP2 or RIJCOSX-ZORA-B2PLYP for a set of linear polyacenes with systematically increasing size. For the larger members of this group, NUMFREQ@Grid was found to outperform the wall clock time of analytic Hessian evaluation; at the MP2 or B2LYP levels, these Hessians cannot even be evaluated analytically. We also evaluated a 156-atom catalytically relevant open-shell transition metal complex and found that NUMFREQ@Grid is faster (7.7 times shorter wall clock time) and less demanding (4.4 times less memory requirement) than an analytic Hessian. Capitalizing on the capabilities of parallel grid computing, NUMFREQ@Grid can outperform analytic methods in terms of wall time, memory requirements, and treatable system size. The NUMFREQ@Grid method presented herein demonstrates how grid computing can be used to facilitate embarrassingly parallel computational procedures and is a pioneer for future implementations.

The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position

International Nuclear Information System (INIS)

Byun, Youngjoo; Yan Junhua; Al-Madhoun, A.S.; Johnsamuel, Jayaseharan; Yang Weilian; Barth, R.F.; Eriksson, Staffan; Tjarks, Werner

2004-01-01

Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase 1 in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues

Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China

International Nuclear Information System (INIS)

Song, Shanjun; Song, Maoyong; Zeng, Luzhe; Wang, Thanh; Liu, Runzeng; Ruan, Ting; Jiang, Guibin

2014-01-01

Extensive use of bisphenol A and its analogues has caused increasing concern over the potential adverse health impacts of these chemicals. In this study, the presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A was the most frequently observed analogue (geometric mean: 20.5 ng/g dw). Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84 ng/g dw) were found with similar frequency. Other BP analogues such as tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were identified for the first time in sewage sludge in China. Significant correlations were found among BP concentrations, but no relationships were found with wastewater treatment plant characteristics. Profiles of the relative estradiol equivalents suggested that the estrogenic potential of BP mixtures may be associated with the occurrence and contributions of specific analogues. -- Highlights: • The profiles of various bisphenols were studied initially in sludge in China. • Analogous abundances were found for BPA, BPS and BPF. • Halo-substituted BPs have similar portions with BPA and its ascendant alternatives. • BPAF, TCBPA, BPE and DHBP were identified for the first time in sludge in China. -- We analyzed the profiles of bisphenol analogues in 52 sewage sludge samples with several bisphenols identified for the first time in wastewater treatment plants in China

Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

International Nuclear Information System (INIS)

Liu, Yongxin; Liu, Dan; Wang, Cheng

2015-01-01

Trivalent metal-based MIL-53 (Al 3+ , Cr 3+ , Fe 3+ , In 3+ ) compounds are interesting metal–organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ 2 -OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn 2+ , Co 2+ , Ni 2+ ), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted. - Graphical abstract: The recent development of bivalent metal-based MIL-53 analogues (Mn 2+ , Co 2+ , Ni 2+ ) on their synthetic strategies, properties and potential applications was reviewed. - Highlights: • Structure features of bivalent metal-based MIL-53 analogues are illustrated. • Important properties and application are presented. • Host–guest interactions are main impetus for liquid-phase separation. • Promising directions of bivalent metal-based MIL-53 analogues are highlighted

Ultrasound exfoliation of inorganic analogues of graphene

Czech Academy of Sciences Publication Activity Database

Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

2014-01-01

Roč. 9, APR (2014), s. 1-14 ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

Nuclear EGFR as a molecular target in cancer

International Nuclear Information System (INIS)

Brand, Toni M.; Iida, Mari; Luthar, Neha; Starr, Megan M.; Huppert, Evan J.; Wheeler, Deric L.

2013-01-01

The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell’s nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future

Conformation of glycomimetics in the free and protein-bound state: structural and binding features of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man.

Science.gov (United States)

Mikkelsen, Lise Munch; Hernáiz, María José; Martín-Pastor, M; Skrydstrup, Troels; Jiménez-Barbero, Jesús

2002-12-18

The conformational properties of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man in solution have been carefully analyzed by a combination of NMR spectroscopy and time-averaged restrained molecular dynamics. It has been found that both the alpha-1,3- and the alpha-1,6-glycosidic linkages show a major conformational averaging. Unusual Phi ca. 60 degrees orientations for both Phi torsion angles are found. Moreover, a major conformational distinction between the natural compound and the glycomimetic affects to the behavior of the omega(16) torsion angle around the alpha-1 --> 6-linkage. Despite this increased flexibility, the C-glycosyl analogue is recognized by three mannose binding lectins, as shown by NMR (line broadening, TR-NOE, and STD) and surface plasmon resonance (SPR) methods. Moreover, a process of conformational selection takes place, so that these lectins probably bind the glycomimetic similarly to the way they recognize the natural analogue. Depending upon the architecture and extension of the binding site of the lectin, loss or gain of binding affinity with respect to the natural analogue is found.

Challenges in nuclear molecular physics

Energy Technology Data Exchange (ETDEWEB)

Betts, R.R. [Argonne, IL (United States). Physics Division, National Laboratory]|[Chicago, IL, Univ. (United States). Dep. Physics

1997-09-01

Despite over thirty years of experimental and theoretical effort in the study of molecular resonance and cluster phenomena in nuclei, fundamental questions still remain to be answered. The most important of these relate precisely to those experimental quantities which would directly prove the underlying nature of the phenomenon-decay widths and transition strengths. The status of the understanding of these quantities is reviewed and new experiments suggested.

In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2

Directory of Open Access Journals (Sweden)

Nunung Yuniarti

2012-03-01

Full Text Available Curcumin has been widely reported as an anti-inflammatory agent isolated from the plant Curcuma longa L. (turmeric. This anti-inflammatory activity was associated with the ability of this compound to inhibit the activity of both cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2 in arachidonic acid metabolism. Dual COX-1 and COX-2 inhibitors are preferred to be employed in the therapy of chronic inflammatory diseases compared to selective inhibitors, since it was reported that the use of selective inhibitors led to severe adverse side effect. In the present study, in vitro and in silico assays on curcumin and its analogues as dual inhibitors for both COX-1 and COX-2 were performed. The results provide theoretical contribution in understanding the ligand-protein interactions at the molecular level to develop new curcumin analogues which possess better anti-inflammatory activity as well as to avoid unsolicited side effects.

Two billion year old natural analogs for nuclear waste disposal: the natural nuclear fission reactors in Gabon (Africa)

International Nuclear Information System (INIS)

Gauthier-Lafaye, F.

2002-01-01

Two billion years ago, the increase of oxygen in atmosphere and the high 235 U/ 238 U uranium ratio (> 3%) made possible the occurrence of natural nuclear reactors on Earth. These reactors are considered to be a good natural analogue for nuclear waste disposal. Their preservation during such a long period of time is mainly due to the geological stability of the site, the occurrence of clays surrounding the reactors and acting as an impermeable shield, and the occurrence of organic matter that maintained the environment in reducing conditions, favourable for the stability of uraninite. Hydrogeochemical studies and modelling have shown the complexity of the geochemical system at Oklo and Bangombe (Gabon) and the lack of precise data about uranium and fission products retention and migration mechanisms in geological environments. (author)

Photoaffinity labeling of undecaprenyl pyrophosphate synthetase with a farnesyl pyrophosphate analogue

International Nuclear Information System (INIS)

Baba, T.; Muth, J.; Allen, C.M.

1985-01-01

The prenyl transferase undecaprenyl pyrophosphate synthetase was partially purified from the cytosolic fraction of Escherichia coli. Its enzymic products were characterized as a family of cis-polyprenyl phosphates, which ranged in carbon number from C55 to C25. The enzyme is constituted of two subunits of approximately 30,000 molecular weight. A radiolabeled photolabile analogue of t,t-farnesyl pyrophosphate, [ 3 H]2-diazo-3-trifluoropropionyloxy geranyl pyrophosphate, was shown to label Lactobacillus plantarum and E. coli undecaprenyl pyrophosphate synthetase on UV irradiation in the presence of isopentenyl pyrophosphate and divalent cations. The only labeled polypeptide migrated on electrophoresis in a sodium dodecyl sulfate-polyacrylamide gel at a molecular weight of approximately 30,000. No protein was radiolabeled when the natural substrate, t,t-farnesyl pyrophosphate was included in the irradiation mixture. Irradiation in the presence of MgCl 2 without isopentenyl pyrophosphate gave less labeling of the polypeptide. Irradiation with only isopentenyl pyrophosphate gave little labeling of the polypeptide. When the enzyme was irradiated with 3H-photoprobe, [ 14 C]isopentenyl pyrophosphate, and MgCl 2 , the labeled polypeptide gave a ratio of 14 C/ 3 H that indicated the product must also bind to the enzyme on irradiation. These results demonstrate the ability to radiolabel the allylic pyrophosphate binding site and possibly product binding site of undecaprenyl pyrophosphate synthetase by a process which is favored when both cosubstrate and divalent cations are present

15. International symposium on nuclear electronics and International seminar CAMAC-92

International Nuclear Information System (INIS)

1993-01-01

The proceedings of the 25. International symposium on nuclear electronics and the CAMAC-92 seminar are presented. The problems on creation of new effective systems for acquisition and processing the information in the field of high energies, spectroscopy and by radiation control at reactors are considered in the reports. Equipment interfaces, analogue-numerical converters, programmed controllers, etc, accomplished relative to the CAMAC and FASTBUS standards are described

Synthesis and Insecticidal Activities of Novel Analogues of Chlorantraniliprole Containing Nitro Group

Institute of Scientific and Technical Information of China (English)

FENG Qi; WANG Ming-zhong; XIONG Li-xia; LIU Zhi-li; LI Zheng-ming

2011-01-01

Twelve novel analogues of chlorantraniliprole containing nitro group were synthesized,and their structures were characterized by 1H NMR and high-resolution mass spectrometry(HRMS).Their evaluated insecticidal activities against oriental armyworm(Mythimna separata) indicate that the nitro-containing analogues showed favorable insecticidal activities,while the activity of compounds 5g at 0.25 mg/L was 40%,but still lower than chlorantraniliprole.

New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

DEFF Research Database (Denmark)

Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

1997-01-01

In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A.

Science.gov (United States)

Ullah, Mohd Fahad; Shamim, Uzma; Hanif, Sarmad; Azmi, Asfar S; Hadi, Sheikh M

2009-11-01

Epidemiological studies have indicated that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. In order to explore the chemical basis of chemopreventive activity of genistein, in this paper we have examined the structure-activity relationship between genistein and its structural analogue biochanin A. We show that both genistein and its methylated derivative biochanin A are able to mobilize nuclear copper in human lymphocyte, leading to degradation of cellular DNA. However, the relative rate of DNA breakage was greater in the case of genistein. Further, the cellular DNA degradation was inhibited by copper chelator (neocuproine/bathocuproine) but not by compounds that specifically bind iron and zinc (desferrioxamine mesylate and histidine, respectively). We also compared the antioxidant activity of the two isoflavones against tert-butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was found to be more effective than biochanin A in providing protection against oxidative stress induced by tert-butylhydroperoxide. It would therefore appear that the structural features of isoflavones that are important for antioxidant properties are also the ones that contribute to their pro-oxidant action through a mechanism that involves redox cycling of chromatin-bound nuclear copper.

2. Scientific meeting of Chilean Nuclear Energy Commission. Abstracts

International Nuclear Information System (INIS)

2000-10-01

This publication includes 33 papers in the fields on analytical methods nuclear and conventional, atomic and molecular physics, ionizing radiations, nuclear and non nuclear materials, radiological protection and nuclear safety

Somatostatin analogue scintigraphy and tuberculosis: case report

International Nuclear Information System (INIS)

Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

2005-01-01

Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

MARSI: metabolite analogues for rational strain improvement

DEFF Research Database (Denmark)

Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

2018-01-01

reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

Nuclear waste repository research at the micro- to nanoscale

Science.gov (United States)

Schäfer, T.; Denecke, M. A.

2010-04-01

Micro- and nano-focused synchrotron radiation techniques to investigate determinant processes in contaminant transport in geological media are becoming especially an increasingly used tool in nuclear waste disposal research. There are a number of reasons for this but primarily they are driven by the need to characterize actinide speciation localized in components of heterogeneous natural systems. We summarize some of the recent research conducted by researchers of the Institute of Nuclear Waste Disposal (INE) at the Karlsruhe Institute of Technology using micro- and nano-focused X-ray beams for characterization of colloids and their interaction with minerals and of elemental and phase distributions in potential repository host rocks and actinide speciation in a repository natural analogues sample. Such investigations are prerequisite to ensuring reliable assessment of the long term radiological safety for proposed nuclear waste disposal sites.

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

Science.gov (United States)

Yoon, Hye Jin; Kong, Sun-Young; Park, Min-Hye; Cho, Yongsung; Kim, Sung-Eun; Shin, Jae-Yeon; Jung, Sunghye; Lee, Jiyoun; Farhanullah; Kim, Hyun-Jung; Lee, Jeewoo

2013-11-15

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Brookhaven electron analogue, 1953--1957

Energy Technology Data Exchange (ETDEWEB)

Plotkin, M.

1991-12-18

The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

The Brookhaven electron analogue, 1953--1957

International Nuclear Information System (INIS)

Plotkin, M.

1991-01-01

The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary

Studies of natural analogues and geological systems

International Nuclear Information System (INIS)

Brandberg, F.; Grundfelt, B.; Hoeglund, L.; Skagius K.; Karlsson, F.; Smellie, J.

1993-04-01

This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

Molecular Fingerprinting Approach in Plant Species Evaluation for a Nuclear Power Programme

International Nuclear Information System (INIS)

Azhar Mohamed

2011-01-01

Deoxyribonucleic acid (DNA) as a tool for marker technology is found to be remarkable, advanced and exciting in recent years. DNA markers are valuable tools and important in various plant breeding analyses for identification, gene mapping, marker systems and mutagenesis response. As gene expression is related to concurrent cellular activities and is mobilised in the adaptation of plants to adverse environmental conditions, changes at the DNA levels can be detected simultaneously. The changes also reflect response onto plant traits in which selection for better quality plant materials can be made and/or used as bio-indicator response in tracking any environmental change. The objective of the present study is to show Inter Simple Sequence Repeat (ISSR) markers as an important technique in differentiating plant DNA genomic in various species for the evaluation of their diversity and radiation effects in population. The technique has been found to be rapid, simple, reliable and robust in generating molecular fingerprinting database in bio surveillance for a nuclear power programme. (author)

Safety case for the disposal of spent nuclear fuel at Olkiluoto. Complementary considerations 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-12-15

Complementary Considerations sits within Posiva Oy's Safety Case 'TURVA-2012' report portfolio and has the objective of enhancing confidence in the outcomes of the safety assessment for a spent nuclear fuel repository to be constructed at Olkiluoto, Finland. The main emphasis in this report is on the evidence and understanding that can be gained from observations at the site, including its regional geological environment, and from natural and anthropogenic analogues for the repository, its components and the processes that affect safety. In particular, the report addresses diverse and less quantifiable types of evidence and arguments that are enclosed to enhance confidence in the outcome of the safety assessment. These complementary considerations have been described as evaluations, evidence and qualitative supporting arguments that lie outside the scope of the other reports of the quantitative safety assessment. The experience with natural analogues for the long-term durability of the materials involved and the extent of processes provides high confidence in our understanding of the disposal system and its evolution. For each engineered barrier and key process, there is increasing analogue evidence to support the conceptual models and parameters. Regarding the suitability of the Olkiluoto site to host a spent fuel repository, a number of factors have been identified that indicate the suitability of crystalline host rock in general, and that of the Olkiluoto site in particular. The report also provides radiation background information for the use of complementary indicators, which aid in putting the results of the safety analysis presented in Assessment of Radionuclide Release Scenarios for the Repository System and Biosphere Assessment in a broader perspective to show that the radiation originating from a spent nuclear fuel repository remains in most cases much below natural background radiation or that caused by non-nuclear industries. (orig.)

Safety case for the disposal of spent nuclear fuel at Olkiluoto. Complementary considerations 2012

International Nuclear Information System (INIS)

2012-12-01

Complementary Considerations sits within Posiva Oy's Safety Case 'TURVA-2012' report portfolio and has the objective of enhancing confidence in the outcomes of the safety assessment for a spent nuclear fuel repository to be constructed at Olkiluoto, Finland. The main emphasis in this report is on the evidence and understanding that can be gained from observations at the site, including its regional geological environment, and from natural and anthropogenic analogues for the repository, its components and the processes that affect safety. In particular, the report addresses diverse and less quantifiable types of evidence and arguments that are enclosed to enhance confidence in the outcome of the safety assessment. These complementary considerations have been described as evaluations, evidence and qualitative supporting arguments that lie outside the scope of the other reports of the quantitative safety assessment. The experience with natural analogues for the long-term durability of the materials involved and the extent of processes provides high confidence in our understanding of the disposal system and its evolution. For each engineered barrier and key process, there is increasing analogue evidence to support the conceptual models and parameters. Regarding the suitability of the Olkiluoto site to host a spent fuel repository, a number of factors have been identified that indicate the suitability of crystalline host rock in general, and that of the Olkiluoto site in particular. The report also provides radiation background information for the use of complementary indicators, which aid in putting the results of the safety analysis presented in Assessment of Radionuclide Release Scenarios for the Repository System and Biosphere Assessment in a broader perspective to show that the radiation originating from a spent nuclear fuel repository remains in most cases much below natural background radiation or that caused by non-nuclear industries. (orig.)

Safety case for the disposal of spent nuclear fuel at Olkiluoto. Complementary considerations 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-12-15

Complementary Considerations sits within Posiva Oy's Safety Case 'TURVA-2012' report portfolio and has the objective of enhancing confidence in the outcomes of the safety assessment for a spent nuclear fuel repository to be constructed at Olkiluoto, Finland. The main emphasis in this report is on the evidence and understanding that can be gained from observations at the site, including its regional geological environment, and from natural and anthropogenic analogues for the repository, its components and the processes that affect safety. In particular, the report addresses diverse and less quantifiable types of evidence and arguments that are enclosed to enhance confidence in the outcome of the safety assessment. These complementary considerations have been described as evaluations, evidence and qualitative supporting arguments that lie outside the scope of the other reports of the quantitative safety assessment. The experience with natural analogues for the long-term durability of the materials involved and the extent of processes provides high confidence in our understanding of the disposal system and its evolution. For each engineered barrier and key process, there is increasing analogue evidence to support the conceptual models and parameters. Regarding the suitability of the Olkiluoto site to host a spent fuel repository, a number of factors have been identified that indicate the suitability of crystalline host rock in general, and that of the Olkiluoto site in particular. The report also provides radiation background information for the use of complementary indicators, which aid in putting the results of the safety analysis presented in Assessment of Radionuclide Release Scenarios for the Repository System and Biosphere Assessment in a broader perspective to show that the radiation originating from a spent nuclear fuel repository remains in most cases much below natural background radiation or that caused by non-nuclear industries. (orig.)

Perspectives in molecular imaging through translational research, human medicine, and veterinary medicine.

Science.gov (United States)

Berry, Clifford R; Garg, Predeep

2014-01-01

The concept of molecular imaging has taken off over the past 15 years to the point of the renaming of the Society of Nuclear Medicine (Society of Nuclear Medicine and Molecular Imaging) and Journals (European Journal of Nuclear Medicine and Molecular Imaging) and offering of medical fellowships specific to this area of study. Molecular imaging has always been at the core of functional imaging related to nuclear medicine. Even before the phrase molecular imaging came into vogue, radionuclides and radiopharmaceuticals were developed that targeted select physiological processes, proteins, receptor analogs, antibody-antigen interactions, metabolites and specific metabolic pathways. In addition, with the advent of genomic imaging, targeted genomic therapy, and theranostics, a number of novel radiopharmaceuticals for the detection and therapy of specific tumor types based on unique biological and cellular properties of the tumor itself have been realized. However, molecular imaging and therapeutics as well as the concept of theranostics are yet to be fully realized. The purpose of this review article is to present an overview of the translational approaches to targeted molecular imaging with application to some naturally occurring animal models of human disease. © 2013 Published by Elsevier Inc.

Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

DEFF Research Database (Denmark)

Kromann, Hasse; Sløk, Frank A; Stensbøl, Tine B

2002-01-01

Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are bot...... antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs....

Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus.

Science.gov (United States)

de Ronde, A; van Dooren, M; van Der Hoek, L; Bouwhuis, D; de Rooij, E; van Gemen, B; de Boer, R; Goudsmit, J

2001-01-01

Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT). Follow-up of the fate of these resistant HIV-1 strains in four newly infected individuals revealed that they were readily replaced by sensitive strains. The RT of the resistant viruses changed at amino acid 215 from tyrosine (Y) to aspartic acid (D) or serine (S), with asparagine (N) as a transient intermediate, indicating the establishment of new wild types. When we introduced these mutations and the original threonine (T)-containing wild type into infectious molecular clones and assessed their competitive advantage in vitro, the order of fitness was in accord with the in vivo observations: 215Y types with D, S, or N residues at position 215 may be warranted in order to estimate the threat to long-term efficacy of regimens including nucleoside analogues.

Natural analogue study on engineered barriers for underground disposal of radioactive wastes

International Nuclear Information System (INIS)

Araki, K.; Motegi, M.; Emoto, Y.; Kaji, Y.; Ikari, S.; Nada, T.; Watanabe, T.

1989-01-01

This is a report to develop the natural analogue methodology for the assessment of the life of the engineered barriers beyond the time period of normal experiments, 1000 years, for the disposal of low-level radioactive wastes with activity levels greater than those of wastes acceptable for shallow land burial in Japan. Geological and archeological events and objects available for the assessment of the possible life of each engineered barrier are surveyed. Taking heavy precipitation into account in Japan, a long-term, zero-release engineered barrier system using long-term durable materials based on the natural analogue events and objects is proposed along with the conventional type of water permeable engineered barrier system. The combination of the material quality and the environment that could be achieved within the repository is important for the long-term durability of the engineered barrier material. It is proposed that for the natural analogue study a physico-chemical methodology, which may be referred to as the physico-chemical natural history, is necessary to get parameters from the natural analogue events for the long-term assessment of the disposal system

Nuclear hydrogen production: re-examining the fusion option

International Nuclear Information System (INIS)

Baindur, S.

2007-01-01

This paper describes a scheme for nuclear hydrogen production by fusion. The basic idea is to use nuclear energy of the fuel (hydrogen plasma) to produce molecular hydrogen fro carbon-free hydrogen compounds. The hydrogen is then stored and utilized electrochemically in fuel cells or chemically as molecular hydrogen in internal combustion engines

Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

Energy Technology Data Exchange (ETDEWEB)

Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

2010-01-01

Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

Fuzzy logic-based analogue forecasting and hybrid modelling of horizontal visibility

Science.gov (United States)

Tuba, Zoltán; Bottyán, Zsolt

2018-04-01

Forecasting visibility is one of the greatest challenges in aviation meteorology. At the same time, high accuracy visibility forecasts can significantly reduce or make avoidable weather-related risk in aviation as well. To improve forecasting visibility, this research links fuzzy logic-based analogue forecasting and post-processed numerical weather prediction model outputs in hybrid forecast. Performance of analogue forecasting model was improved by the application of Analytic Hierarchy Process. Then, linear combination of the mentioned outputs was applied to create ultra-short term hybrid visibility prediction which gradually shifts the focus from statistical to numerical products taking their advantages during the forecast period. It gives the opportunity to bring closer the numerical visibility forecast to the observations even it is wrong initially. Complete verification of categorical forecasts was carried out; results are available for persistence and terminal aerodrome forecasts (TAF) as well in order to compare. The average value of Heidke Skill Score (HSS) of examined airports of analogue and hybrid forecasts shows very similar results even at the end of forecast period where the rate of analogue prediction in the final hybrid output is 0.1-0.2 only. However, in case of poor visibility (1000-2500 m), hybrid (0.65) and analogue forecasts (0.64) have similar average of HSS in the first 6 h of forecast period, and have better performance than persistence (0.60) or TAF (0.56). Important achievement that hybrid model takes into consideration physics and dynamics of the atmosphere due to the increasing part of the numerical weather prediction. In spite of this, its performance is similar to the most effective visibility forecasting methods and does not follow the poor verification results of clearly numerical outputs.

Design and synthesis of biotin analogues reversibly binding with streptavidin.

Science.gov (United States)

Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

2015-04-01

Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

18F-Labelled metomidate analogues as adrenocortical imaging agents

International Nuclear Information System (INIS)

Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

2009-01-01

Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.