Sample records for antagonist mi-319 restores

  1. An MDM2 antagonist (MI-319 restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals

    Directory of Open Access Journals (Sweden)

    Yang Dajun


    Full Text Available Abstract Background MI-319 is a synthetic small molecule designed to target the MDM2-P53 interaction. It is closely related to MDM2 antagonists MI-219 and Nutlin-3 in terms of the expected working mechanisms. The purpose of this study was to evaluate anti-lymphoma activity of MI-319 in WSU-FSCCL, a B-cell follicular lymphoma line. For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments. Results MI-319 was shown to bind to MDM2 protein with an affinity slightly higher than that of MI-219 and Nutlin-3. Nevertheless, cell growth inhibition and gene expression profiling experiments revealed that the three compounds have quite similar potency against the tumor cell lines tested in this study. In vitro, MI-319 exhibited the strongest anti-proliferation activity against FSCCL and four patient cells, which all have wild-type p53. Data obtained from Western blotting, cell cycle and apoptosis analysis experiments indicated that FSCCL exhibited strong cell cycle arrest and significant apoptotic cell death; cells with mutant p53 did not show significant apoptotic cell death with drug concentrations up to 10 μM, but displayed weaker and differential cell cycle responses. In our systemic mouse model for FSCCL, MI-319 was tolerated well by the animals, displayed effectiveness against FSCCL-lymphoma cells in blood, brain and bone marrow, and achieved significant therapeutic impact (p 28% (%ILS, 14.4 days increase in median survival days. Conclusion Overall, MI-319 probably has an anti-lymphoma potency equal to that of MI-219 and Nutlin-3. It is a potent agent against FSCCL in vitro and in vivo and holds the promises to be developed further for the treatment of follicular lymphoma that retains wild-type p53.

  2. The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat. (United States)

    Lieben, Cindy K J; Blokland, Arjan; Sik, Ayhan; Sung, Eric; van Nieuwenhuizen, Petra; Schreiber, Rudy


    Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.

  3. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P


    Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral chroma...

  4. Restoring forests

    DEFF Research Database (Denmark)

    Jacobs, Douglass F.; Oliet, Juan A.; Aronson, James;


    Forest loss and degradation is occurring at high rates but humankind is experiencing historical momentum that favors forest restoration. Approaches to restoration may follow various paradigms depending on stakeholder objectives, regional climate, or the degree of site degradation. The vast amount...

  5. Voice restoration

    NARCIS (Netherlands)

    Hilgers, F.J.M.; Balm, A.J.M.; van den Brekel, M.W.M.; Tan, I.B.; Remacle, M.; Eckel, H.E.


    Surgical prosthetic voice restoration is the best possible option for patients to regain oral communication after total laryngectomy. It is considered to be the present "gold standard" for voice rehabilitation of laryngectomized individuals. Surgical prosthetic voice restoration, in essence, is alwa

  6. ramic restorations

    Directory of Open Access Journals (Sweden)

    Ashish R Jain


    Full Text Available Rehabilitation of a patient with severely worn dentition after restoring the vertical dimension is a complex procedure and assessment of the vertical dimension is an important aspect in these cases. This clinical report describes the full mouth rehabilitation of a patient who was clinically monitored to evaluate the adaptation to a removable occlusal splint to restore vertical dimension for a period 1 month and provisional restorations to determine esthetic and functional outcome for a period of 3 months. It is necessary to recognizing that form follows function and that anterior teeth play a vital role in the maintenance of oral health. Confirmation of tolerance to changes in the vertical dimension of occlusion (VDO is of paramount importance. Articulated study casts and a diagnostic wax-up can provide important information for the evaluation of treatment options. Alteration of the VDO should be conservative and should not be changed without careful consideration.

  7. Opioid Antagonist Impedes Exposure. (United States)

    Merluzzi, Thomas V.; And Others


    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  8. Site Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Noynaert, L.; Bruggeman, A.; Cornelissen, R.; Massaut, V.; Rahier, A


    The objectives, the programme, and the achievements of the Site Restoration Department of SCK-CEN in 2000 are summarised. Main activities include the decommissioning of the BR3 PWR-reactor as well as other clean-up activities, projects on waste minimisation and activities related to the management of decommissioning projects. The department provides consultancy and services to external organisations.

  9. Restorative neuroscience

    DEFF Research Database (Denmark)

    Andres, Robert H; Meyer, Morten; Ducray, Angélique D


    There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of...

  10. Environmental Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Zeevaert, T.; Vanmarcke, H


    The objectives of SCK-CEN's programme on environmental restoration are (1) to optimize and validate models for the impact assessment from environmental, radioactive contaminations, including waste disposal or discharge; (2) to support the policy of national authorities for public health and radioactive waste management. Progress and achievements in 1997 are reported.

  11. Tetrahydroindolizinone NK1 antagonists. (United States)

    Bao, Jianming; Lu, Huagang; Morriello, Gregori J; Carlson, Emma J; Wheeldon, Alan; Chicchi, Gary G; Kurtz, Marc M; Tsao, Kwei-Lan C; Zheng, Song; Tong, Xinchun; Mills, Sander G; DeVita, Robert J


    A new class of potent NK(1) receptor antagonists with a tetrahydroindolizinone core has been identified. This series of compounds demonstrated improved functional activities as compared to previously identified 5,5-fused pyrrolidine lead structures. SAR at the 7-position of the tetrahydroindolizinone core is discussed in detail. A number of compounds displayed high NK(1) receptor occupancy at both 1 h and 24 h in a gerbil foot tapping model. Compound 40 has high NK(1) binding affinity, good selectivity for other NK receptors and promising in vivo properties. It also has clean P(450) inhibition and hPXR induction profiles.

  12. Site Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Noynaert, L.; Bruggeman, A.; Cornelissen, R.; Massaut, V.; Rahier, A


    The objectives, the programme, and the achievements of SCK-CEN's Site Restoration Department for 2001 are described. Main activities include the decommissioning of the BR3 PWR-reactor as well as other clean-up activities, projects on waste minimisation and the management of spent fuel and the flow of dismantled materials and the recycling of materials from decommissioning activities based on the smelting of metallic materials in specialised foundries. The department provides consultancy and services to external organisations and performs R and D on new techniques including processes for the treatment of various waste components including the reprocessing of spent fuel, the treatment of tritium, the treatment of liquid alkali metals into cabonates through oxidation, the treatment of radioactive organic waste and the reconditioning of bituminised waste products.

  13. Global Ecosystem Restoration Index

    DEFF Research Database (Denmark)

    Fernandez, Miguel; Garcia, Monica; Fernandez, Nestor


    The Global ecosystem restoration index (GERI) is a composite index that integrates structural and functional aspects of the ecosystem restoration process. These elements are evaluated through a window that looks into a baseline for degraded ecosystems with the objective to assess restoration...

  14. Restorative dentistry for children. (United States)

    Donly, Kevin J


    This article discusses contemporary pediatric restorative dentistry. Indications and contraindications for the choice of different restorative materials in different clinical situations, including the risk assessment of the patient, are presented. The specific use of glass ionomer cement or resin-modified glass ionomer cement, resin-based composite, and stainless steel crowns is discussed so that preparation design and restoration placement is understood.

  15. Linking restoration ecology with coastal dune restoration (United States)

    Lithgow, D.; Martínez, M. L.; Gallego-Fernández, J. B.; Hesp, P. A.; Flores, P.; Gachuz, S.; Rodríguez-Revelo, N.; Jiménez-Orocio, O.; Mendoza-González, G.; Álvarez-Molina, L. L.


    Restoration and preservation of coastal dunes is urgently needed because of the increasingly rapid loss and degradation of these ecosystems because of many human activities. These activities alter natural processes and coastal dynamics, eliminate topographic variability, fragment, degrade or eliminate habitats, reduce diversity and threaten endemic species. The actions of coastal dune restoration that are already taking place span contrasting activities that range from revegetating and stabilizing the mobile substrate, to removing plant cover and increasing substrate mobility. Our goal was to review how the relative progress of the actions of coastal dune restoration has been assessed, according to the ecosystem attributes outlined by the Society of Ecological Restoration: namely, integrity, health and sustainability and that are derived from the ecological theory of succession. We reviewed the peer reviewed literature published since 1988 that is listed in the ISI Web of Science journals as well as additional references, such as key books. We exclusively focused on large coastal dune systems (such as transgressive and parabolic dunefields) located on natural or seminatural coasts. We found 150 articles that included "coastal dune", "restoration" and "revegetation" in areas such as title, keywords and abstract. From these, 67 dealt specifically with coastal dune restoration. Most of the studies were performed in the USA, The Netherlands and South Africa, during the last two decades. Restoration success has been assessed directly and indirectly by measuring one or a few ecosystem variables. Some ecosystem attributes have been monitored more frequently (ecosystem integrity) than others (ecosystem health and sustainability). Finally, it is important to consider that ecological succession is a desirable approach in restoration actions. Natural dynamics and disturbances should be considered as part of the restored system, to improve ecosystem integrity, health and

  16. Synthesis of potential mescaline antagonists. (United States)

    DeSantis, F; Nieforth, K A


    1-[2-(3,4,5-Trimethoxyphenyl)ethyl]-3-pyrroline, 2-(3,4,5-trimethoxybenzyl)-1,2,3,6-tetrahydropyridine, N-n-propylmescaline, N-cyclopropylmethylmescaline, and N-allylmescaline were synthesized as potential mescaline antagonists. The ability of these compounds to antagonize mescaline-induced disruption of swim behavior is also given.

  17. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B


    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...


    Institute of Scientific and Technical Information of China (English)

    PENGDun-Ren; XIAOShao-Bo


    An ideal antagonist of LHRH is one which can act on the pitutary to inhibit LHRH-stimulatod LH / FSH secretion by competitive occupying the LHRH receptor in the pitutary gland. Its action should be very specific, fast and highly effective, the durations

  19. Glutamate antagonists limit tumor growth



    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N...

  20. Restoring the worn dentition. (United States)

    Ibsen, R L; Ouellet, D F


    Strong dental materials and dental porcelains are providing dentists with restorative opportunities that are more conservative because they require less destruction of healthy tooth structure and yield a more esthetic result. In cases of severe wear due to attrition, abrasion, and erosion, this process can be stopped, restoring the esthetics and function by using proper techniques and materials. The case report described in this article demonstrates the conservative restoration of severe wear due to attrition and erosion. Teeth were lengthened, wear was restored, and further wear was ceased by using a combination of bonded porcelain, a heat, light, and self-cure resin system, and a new glass-ionomer restorative material. The result was a strong, durable restoration (that required no anesthesia) with high esthetics.

  1. Watershed Restoration Project

    Energy Technology Data Exchange (ETDEWEB)

    Julie Thompson; Betsy Macfarlan


    In 2003, the U.S. Department of Energy issued the Eastern Nevada Landscape Coalition (ENLC) funding to implement ecological restoration in Gleason Creek and Smith Valley Watersheds. This project was made possible by congressionally directed funding that was provided through the US Department of Energy, Energy Efficiency and Renewable Energy, Office of the Biomass Program. The Ely District Bureau of Land Management (Ely BLM) manages these watersheds and considers them priority areas within the Ely BLM district. These three entities collaborated to address the issues and concerns of Gleason Creek and Smith Valley and prepared a restoration plan to improve the watersheds’ ecological health and resiliency. The restoration process began with watershed-scale vegetation assessments and state and transition models to focus on restoration sites. Design and implementation of restoration treatments ensued and were completed in January 2007. This report describes the restoration process ENLC undertook from planning to implementation of two watersheds in semi-arid Eastern Nevada.

  2. Toponymic Restoration in Irkutsk

    Directory of Open Access Journals (Sweden)

    Alexander Snarsky


    Full Text Available The article analyzes the discussion on restoration of historical names of public spaces in Irkutsk. It also reviews different approaches to the problem that appeared in the historical science and publicism. The author says about the necessity of a strictly historical approach to the toponymic restoration.

  3. Guiding Restoration Principles (United States)


    restoration of important ecosystem functions requires reintegrating landscapes or restorating the func- tional aspects of landscapes ( Risser 1992...51-64. Risser , P. G. 1992. Landscape ecology approach to ecosystem rehabilitation. Pages 37-46 in M. L. Wali (ed.), Ecosystem Rehabilitation

  4. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly


    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  5. Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Varshney, R.; Kale, R.K. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)


    Rat liver microsomes were irradiated with {gamma}-rays at a dose of 1.31 Gy s{sup -1}. The extent of lipid peroxidation, measured in terms of malondialdehyde (MDA) formed, increased with radiation dose. The presence of calmodulin antagonists during irradiation decreased lipid peroxidation. The order of their protective efficiency was: chlorpromazine (CPZ)>promethazine (PMZ)>trimeprazine (TMZ). Their protective effect was diminished in the presence of ferrous (Fe{sup 2+}) ions and was restored on addition of EDTA. However, calmodulin antagonists considerably inhibited radiation-induced lipid peroxidation in the presence of ferric (Fe{sup 3+}) ions. Calmodulin antagonists also decreased the cytochrome P-450 content of microsomes. These results are discussed with respect to their applicability to radiotherapy. A possible mechanism for the inhibition of radiation-induced lipid peroxidation is suggested. (author).

  6. Restoring primary anterior teeth. (United States)

    Waggoner, William F


    A variety of esthetic restorative materials are available for restoring primary incisors. Knowledge of the specific strengths, weakness, and properties of each material will enhance the clinician's ability to make the best choice of selection for each individual situation. Intracoronal restorations of primary teeth may utilize resin composites, glass ionomer cements, resin-modified ionomers, or polyacid-modified resins. Each has distinct advantages and disadvantages and the clinical conditions of placement may be a strong determining factor as to which material is utilized. Full coronal restoration of primary incisors may be indicated for a number of reasons. Crowns available for restoration of primary incisors include those that are directly bonded onto the tooth, which generally are a resin material, and those crowns that are luted onto the tooth and are some type of stainless steel crown. However, due to lack of supporting clinical data, none of the crowns can be said to be superior to the others under all circumstances. Though caries in the mandibular region is rare, restorative solutions for mandibular incisors are needed. Neither stainless steel crowns nor celluloid crown forms are made specifically for mandibular incisors. Many options exist to repair carious primary incisors, but there is insufficient controlled, clinical data to suggest that one type of restoration is superior to another. This does not discount the fact that dentists have been using many of these crowns for years with much success. Operator preferences, esthetic demands by parents, the child's behavior, and moisture and hemorrhage control are all variables which affect the decision and ultimate outcome of whatever restorative treatment is chosen.

  7. Image restoration scale space (United States)

    Alvarez, Luis; Mazorra, L.; Santana, F.


    We present a study of some image resoration techniques based on partial differential equations. We study separately the denoising problem and the restoration of discontinuities. We analyze the capabilities of the differential operators to restore images. In particular, we analyze a number of models present in the literature, and we present comparative results. Finally, we present a model based in the combination of the anisotropic diffusion of Alvarez, Lions, and Morel and the shock filters of Osher and Rudin.

  8. New antagonist agents of neuropeptide y receptors

    Directory of Open Access Journals (Sweden)

    Ignacio Aldana


    Full Text Available In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists will be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.

  9. Wear Behavior of Ceramic CAD/CAM Crowns and Natural Antagonists

    Directory of Open Access Journals (Sweden)

    Ella A. Naumova


    Full Text Available Objective: Evaluation of wear behavior of computer-aided design/computer-aided manufacturing (CAD/CAM crowns from various restorative materials and natural antagonists. Method: Full CAD/CAM crowns fabricated with nanoceramic resin (Lava Ultimate (LU, a glass ceramic in a resin interpenetrating matrix (Vita Enamic (VE and a lithium silicate reinforced ceramic enriched with zirconia (Vita Suprinity (VS were cemented on human molars. The crown and antagonists were subjected to simulated chewing. 3D data sets, before and after the chewing simulation, were generated and matched. Occlusal surface roughness, vertical and volume loss of the crowns and antagonists were analyzed. Results: Crown roughness was significantly different between the LU and VE groups after chewing simulation. Crown vertical loss differed in all groups. The highest crown volume loss was found in the LU group, and the lowest in the VE group. Comparisons between the LU and VE groups and the LU and VS groups were significantly different. The highest antagonist volume loss was reached in the VE group, the lowest was in the LU group. Conclusion: Roughness increased after chewing simulation. LU crowns are the most natural antagonist-friendly; these were the most susceptible to vertical and volume loss. Of the tested materials, the VE crowns are the most stable regarding occlusion.

  10. Antagonists of the kappa opioid receptor. (United States)

    Urbano, Mariangela; Guerrero, Miguel; Rosen, Hugh; Roberts, Edward


    The research community has increasingly focused on the development of OPRK antagonists as pharmacotherapies for the treatment of depression, anxiety, addictive disorders and other psychiatric conditions produced or exacerbated by stress. Short-acting OPRK antagonists have been recently developed as a potential improvement over long-acting prototypic ligands including nor-BNI and JDTic. Remarkably the short-acting LY2456302 is undergoing phase II clinical trials for the augmentation of the antidepressant therapy in treatment-resistant depression. This Letter reviews relevant chemical and pharmacological advances in the identification and development of OPRK antagonists.

  11. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正


    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  12. [Comparative study of effects of Escherichia coli M-17 exometabolites and fructooligosaccharides on the growth and antagonistic activity of Lactobacilli]. (United States)

    Vakkhitov, T Ia; Dobrolezh, O V; Petrov, L N; Verbitskaia, N B; Zadaura, E Iu


    Facts concerning the evaluation of the influence of E. coli M17 exometabolites and fructooligosaccharides (FOS) on the growth and antagonistic activity of lactobacilli are presented. As revealed by these facts, preparation "Aktoflor" accelerates the growth of lactobacillary cultures, increases the final yield of biomass and antagonistic activity. E. coli M17 exometabolites contained in "Aktoflor" have been shown to be more active in comparison with FOS. The character of their influence on lactobacilli is discussed and the conclusion is made that the restoration and maintenance of eubiosis is greatly determined by the pool of metabolites excreted by the bacteria.

  13. Challenges of ecological restoration

    DEFF Research Database (Denmark)

    Halme, Panu; Allen, Katherine A.; Aunins, Ainars


    The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many ecosys...

  14. [Influence of implant restoration on traditional restoration idea]. (United States)

    Liu, H C


    Implant restoration affected the traditional restoration idea. Artificial implant restoration has a profound influence on the design of dental restoration. Implant supported prostheses have not only changed the method of oral rehabilitation, but also integrated revolutionary concept with the traditional treatment protocol. By using implants, posterior missing molars can be effectively restored and thus eliminating the disadvantages of traditional removable partial denture for Kennedy classification Ⅰ, Ⅱ partically edentulous dentition. Full edentulous arch can also be restored with implant fixed denture which provide much better oral health related quality of life compared with the traditional complete denture. It is useful to master the theory and skills of artificial implant restoration, and to provide a reference for the restoration of oral physiological function.

  15. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C


    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  16. Papahanaumokuakea - Laysan Island Restoration 2010 (United States)

    US Fish and Wildlife Service, Department of the Interior — The Goal of the Laysan Island Restoration is to restore Laysan to a "Pristine" state which would require minimal monitoring and habitat for Endemic Endangered...

  17. Adaptive wiener image restoration kernel (United States)

    Yuan, Ding


    A method and device for restoration of electro-optical image data using an adaptive Wiener filter begins with constructing imaging system Optical Transfer Function, and the Fourier Transformations of the noise and the image. A spatial representation of the imaged object is restored by spatial convolution of the image using a Wiener restoration kernel.

  18. Restoring proximal caries lesions conservatively with tunnel restorations

    Directory of Open Access Journals (Sweden)

    Chu CH


    Full Text Available Chun-Hung Chu1, May L Mei,1 Chloe Cheung,1 Romesh P Nalliah2 1Faculty of Dentistry, The University of Hong Kong, Hong Kong, People's Republic of China; 2Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA Abstract: The tunnel restoration has been suggested as a conservative alternative to the conventional box preparation for treating proximal caries. The main advantage of tunnel restoration over the conventional box or slot preparation includes being more conservative and increasing tooth integrity and strength by preserving the marginal ridge. However, tunnel restoration is technique-sensitive and can be particularly challenging for inexperienced restorative dentists. Recent advances in technology, such as the contemporary design of dental handpieces with advanced light-emitting diode (LED and handheld comfort, offer operative dentists better vision, illumination, and maneuverability. The use of magnifying loupes also enhances the visibility of the preparation. The advent of digital radiographic imaging has improved dental imaging and reduced radiation. The new generation of restorative materials has improved mechanical properties. Tunnel restoration can be an option to restore proximal caries if the dentist performs proper case selection and pays attention to the details of the restorative procedures. This paper describes the clinical technique of tunnel restoration and reviews the studies of tunnel restorations. Keywords: operative, practice, tunnel preparation, composite, amalgam, glass ionomer

  19. Relativistic Linear Restoring Force (United States)

    Clark, D.; Franklin, J.; Mann, N.


    We consider two different forms for a relativistic version of a linear restoring force. The pair comes from taking Hooke's law to be the force appearing on the right-hand side of the relativistic expressions: d"p"/d"t" or d"p"/d["tau"]. Either formulation recovers Hooke's law in the non-relativistic limit. In addition to these two forces, we…

  20. Translating the N-methyl-D-aspartate receptor antagonist model of schizophrenia to treatments for cognitive impairment in schizophrenia. (United States)

    Meltzer, Herbert Y; Rajagopal, Lakshmi; Huang, Mei; Oyamada, Yoshihiro; Kwon, Sunoh; Horiguchi, Masakuni


    The N-methyl-D-aspartate receptor (NMDAR) antagonists, phencyclidine (PCP), dizocilpine (MK-801), or ketamine, given subchronically (sc) to rodents and primates, produce prolonged deficits in cognitive function, including novel object recognition (NOR), an analog of human declarative memory, one of the cognitive domains impaired in schizophrenia. Atypical antipsychotic drugs (AAPDs) have been reported to improve declarative memory in some patients with schizophrenia, as well as to ameliorate and prevent the NOR deficit in rodents following scNMDAR antagonist treatment. While the efficacy of AAPDs to improve cognitive impairment in schizophrenia (CIS) is limited, at best, and controversial, single doses of all currently available AAPDs so far tested transiently restore NOR in rodents following scNMDAR antagonist treatment. Typical antipsychotic drugs (APDs), e.g. haloperidol and perphenazine, are ineffective in this rodent model, and may be less effective as treatments of some domains of CIS. Serotonergic mechanisms, including, but not limited to serotonin (5-HT)2A and 5-HT7 antagonism, 5-HT(1A), and GABA(A) agonism, contribute to the efficacy of the AAPDs in the scNMDAR antagonist rodent models, which are relevant to the loss of GABA interneuron/hyperglutamate hypothesis of the etiology of CIS. The ability of sub-effective doses of the atypical APDs to ameliorate NOR in the scNMDAR-treated rodents can be restored by the addition of a sub-effective dose of the 5-HT(1A) partial agonist, tandospirone, or the 5-HT7 antagonist, SB269970. The mGluR2/3 agonist, LY379268, which itself is unable to restore NOR in the scNMDAR-treated rodents, can also restore NOR when given with lurasidone, an AAPD. Enhancing cortical and hippocampal dopamine and acetylcholine efflux, or both, may contribute to the restoration of NOR by the atypical APDs. Importantly, co-administration of lurasidone, tandospirone, or SB269970, with PCP, to rodents, at doses 5-10 fold greater than those

  1. Auxin-Oxylipin Crosstalk: Relationship of Antagonists

    Institute of Scientific and Technical Information of China (English)

    Maik Hoffmann; Mathias Hentrich; Stephan Pollmann


    Phytohormones regulate a wide array of developmental processes throughout the life cycle of plants. Herein, the various plant hormones may interact additively, synergistically, or antagonistically. By their cooperation they create a delicate regulatory network whose net output largely depends on the action of specific phytohormone combinations rather than on the independent activities of separate hormones. While most classical studies of plant hormonal control have focused mainly on the action of single hormones or on the synergistic interaction of hormones in regulating various developmental processes, recent work is beginning to shed light on the crosstalk of nominally antagonistic plant hormones, such as gibberellins and auxins with oxylipins or abscisic acid. In this review, we summarize our current understanding of how two of the first sight antagonistic plant hormones, i.e. auxins and oxylipins,interact in controlling plant responses and development.

  2. Skjern River Restoration Counterfactual

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel


    heritage. While the meanders of the Skjern River were reconstructed according to its assumed course in 1870s, the embanked canal, which was the main feature and symbol of a comprehensive cultivation project from the 1960s, was deconstructed and reduced to incomprehensible traces of the past. Not only did...... history and more openness towards constant change. In this approach the idea of palimpsest as metaphor for the cultural landscape plays an important role. Rather than being an obstacle for the restoration of nature, the historical layer following the comprehensive cultivation project from the 1960s...

  3. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE


    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  4. Why are mineralocorticoid receptor antagonists cardioprotective?

    NARCIS (Netherlands)

    W. Chai (Wenxia); A.H.J. Danser (Jan)


    textabstractTwo clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effe

  5. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua


    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  6. Technologies for lake restoration

    Directory of Open Access Journals (Sweden)

    Helmut KLAPPER


    Full Text Available Lakes are suffering from different stress factors and need to be restored using different approaches. The eutrophication remains as the main water quality management problem for inland waters: both lakes and reservoirs. The way to curb the degradation is to stop the nutrient sources and to accelerate the restoration with help of in-lake technologies. Especially lakes with a long retention time need (eco- technological help to decrease the nutrient content in the free water. The microbial and other organic matter from sewage and other autochthonous biomasses, causes oxygen depletion, which has many adverse effects. In less developed countries big reservoirs function as sewage treatment plants. Natural aeration solves problems only partly and many pollutants tend to accumulate in the sediments. The acidification by acid rain and by pyrite oxidation has to be controlled by acid neutralizing technologies. Addition of alkaline chemicals is useful only for soft waters, and technologies for (microbial alkalinization of very acidic hardwater mining lakes are in development. The corrective measures differ from those in use for eutrophication control. The salinization and water shortage mostly occurs if more water is used than available. L. Aral, L. Tschad, the Dead Sea or L. Nasser belong to waters with most severe environmental problems on a global scale. Their hydrologic regime needs to be evaluated. The inflow of salt water at the bottom of some mining lakes adds to stability of stratification, and thus accumulation of hydrogen sulphide in the monimolimnion of the meromictic lakes. Destratification, which is the most used technology, is only restricted applicable because of the dangerous concentrations of the byproducts of biological degradation. The contamination of lakes with hazardous substances from industry and agriculture require different restoration technologies, including subhydric isolation and storage, addition of nutrients for better self


    Institute of Scientific and Technical Information of China (English)


    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit+ bosentan group and Nit+ losartan group. Nitroglycerin tolerance was induced by 2-day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg- 1· d- 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg- 1· d- 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit+ losartan group and Nit+ bosentan group compared with Nit group [(31.95± 4.45 ) % vs (21.00± 3.69 ) % , P Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance .

  8. Archived film analysis and restoration

    NARCIS (Netherlands)

    Rares, A.


    The progressive degradation of current film archives poses a serious threat to the preservation of our cultural and technical heritage. Digitization and digital restoration are currently the most viable solutions for the long term preservation and high quality restoration of filmed material. They al


    Directory of Open Access Journals (Sweden)

    Darrell Fox


    Full Text Available This paper explores the links and connections between social work and restorative justice. After a brief description of social work, restorative justice and family group conferencing, I will explore some the complementary theoretical links and practice applications, critically examining the potential implications and opportunities for social work practitioners and academics in relation to practice.

  10. Mineralocorticoid and glucocorticoid receptor antagonists in animal models of anxiety

    NARCIS (Netherlands)

    Korte, SM; KorteBouws, GAH; Koob, GF; DeKloet, ER; Bohus, B


    The behavioral effects of intracerebroventricular (ICV) administration of a specific mineralocorticoid receptor (MR) antagonist [RU28318 (10-50 ng/2 mu l)], a glucocorticoid receptor (GR) antagonist [RU38486 (1-50 ng/2 mu l)], or both antagonists (50 ng/2 mu l), were studied in two different animal

  11. High affinity retinoic acid receptor antagonists: analogs of AGN 193109. (United States)

    Johnson, A T; Wang, L; Gillett, S J; Chandraratna, R A


    A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.

  12. Novel benzimidazole-based MCH R1 antagonists. (United States)

    Carpenter, Andrew J; Al-Barazanji, Kamal A; Barvian, Kevin K; Bishop, Michael J; Britt, Christy S; Cooper, Joel P; Goetz, Aaron S; Grizzle, Mary K; Hertzog, Donald L; Ignar, Diane M; Morgan, Ronda O; Peckham, Gregory E; Speake, Jason D; Swain, Will R


    The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.

  13. Interfering with Resistance to Smoothened Antagonists by Inhibition of the PI3K Pathway in Medulloblastoma (United States)

    Buonamici, Silvia; Williams, Juliet; Morrissey, Michael; Wang, Anlai; Guo, Ribo; Vattay, Anthony; Hsiao, Kathy; Yuan, Jing; Green, John; Ospina, Beatrice; Yu, Qunyan; Ostrom, Lance; Fordjour, Paul; Anderson, Dustin L.; Monahan, John E.; Kelleher, Joseph F.; Peukert, Stefan; Pan, Shifeng; Wu, Xu; Maira, Sauveur-Michel; Garcia-Echeverria, Carlos; Briggs, Kimberly J.; Watkins, D. Neil; Yao, Yung-mae; Lengauer, Christoph; Warmuth, Markus; Sellers, William R.; Dorsch, Marion


    Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in medulloblastoma. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for treating this disease. However, acquired resistance has emerged as a challenge to targeted therapeutics and may limit their anti-cancer efficacy. Here, we describe novel mechanisms of acquired resistance to Smo antagonists in medulloblastoma. NVP-LDE225, a potent and selective Smo antagonist, inhibits Hh signaling and induces tumor regressions in allograft models of medulloblastoma that are driven by mutations of Patched (Ptch), a tumor suppressor in the Hh pathway. However, evidence of resistance was observed during the course of treatment. Molecular analysis of resistant tumors revealed distinct resistance mechanisms. Chromosomal amplification of Gli2, a downstream effector of Hh signaling, or more rarely point mutations in Smo led to reactivated Hh signaling and restored tumor growth. Unexpectedly, analysis of pathway gene-expression signatures selectively deregulated in resistant tumors identified increased phosphoinositide 3-kinase (PI3K) signaling as another potential resistance mechanism. Probing the functional relevance of increased PI3K signaling, we demonstrated that the combination of NVP-LDE225 with the PI3K class I inhibitor NVP-BKM120 or the dual PI3K/mTOR inhibitor NVP-BEZ235 markedly delayed the development of resistance. Our findings have important clinical implications for future treatment strategies in medulloblastoma. PMID:20881279

  14. The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

    Directory of Open Access Journals (Sweden)

    Twum eAnsah


    Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

  15. [Cutaneous adverse effects of TNFalpha antagonists]. (United States)

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F


    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  16. Restoration of optic neuropathy

    Directory of Open Access Journals (Sweden)

    You SW


    . Many genes, such as Bcl-2, PTEN, and mTOR, are crucial in cell proliferation, axon guidance, and growth during development, and play important roles in the regeneration and extension of RGC axons. With transgenic mice and related gene regulations, robust regeneration of RGC axons has been observed after ON injury in laboratories. Although various means of experimental treatments such as cell transplantation and gene therapy have achieved significant progress in neuronal survival, axonal regeneration, and restoration of the visual function after ON injury, many unresolved scientific problems still exist for their clinical applications. Therefore, we still need to overcome hurdles before developing effective therapy to treat optic neuropathy diseases in patients. Keywords: retinal ganglion cells, optic nerve injury, neuronal survival, axonal regeneration, vision restoration

  17. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans


    Kleynhans, Janke


    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  18. The Justification of Antagonistic Response to Wrongdoing


    Goldman, David Michael


    There is a strong Western tradition of opposing angry, hostile, or antagonistic reactions to wrongdoing. In the twentieth century, leaders like Mahatma Gandhi and Dr. Martin Luther King, Jr. counseled responding to wrongdoing with forgiveness and love rather than anger, hate, or vindictiveness.This ideal has taken on an exalted status in Western culture. Gandhi and King are widely regarded as moral saints. And yet sometimes antagonism seems deeply appropriate. Consider a very serious wrong: s...

  19. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    Full Text Available BACKGROUND: In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents. CONCLUSIONS/SIGNIFICANCE: We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  20. The Hip Restoration Algorithm (United States)

    Stubbs, Allston Julius; Atilla, Halis Atil


    Summary Background Despite the rapid advancement of imaging and arthroscopic techniques about the hip joint, missed diagnoses are still common. As a deep joint and compared to the shoulder and knee joints, localization of hip symptoms is difficult. Hip pathology is not easily isolated and is often related to intra and extra-articular abnormalities. In light of these diagnostic challenges, we recommend an algorithmic approach to effectively diagnoses and treat hip pain. Methods In this review, hip pain is evaluated from diagnosis to treatment in a clear decision model. First we discuss emergency hip situations followed by the differentiation of intra and extra-articular causes of the hip pain. We differentiate the intra-articular hip as arthritic and non-arthritic and extra-articular pain as surrounding or remote tissue generated. Further, extra-articular hip pain is evaluated according to pain location. Finally we summarize the surgical treatment approach with an algorithmic diagram. Conclusion Diagnosis of hip pathology is difficult because the etiologies of pain may be various. An algorithmic approach to hip restoration from diagnosis to rehabilitation is crucial to successfully identify and manage hip pathologies. Level of evidence: V. PMID:28066734

  1. From the Cover: Glutamate antagonists limit tumor growth (United States)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy


    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  2. Fernald restoration: ecologists and engineers integrate restoration and cleanup

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Eric; Homer, John


    As cleanup workers excavate pits and tear down buildings at the Fernald site in southwest Ohio, site ecologists are working side-by-side to create thriving wetlands and develop the early stages of forest, prairie, and savanna ecosystems to restore natural resources that were impacted by years of site operations. In 1998, the U.S. Department of Energy-Fernald Office (DOE-FN) and its cleanup contractor, Fluor Fernald, Inc., initiated several ecological restoration projects in perimeter areas of the site (e.g., areas not used for or impacted by uranium processing or waste management). The projects are part of Fernald's final land use plan to restore natural resources over 904 acres of the 1,050-acre site. Pete Yerace, the DOE-FN Natural Resource Trustee representative is working with the Fernald Natural Resource Trustees in an oversight role to resolve the state of Ohio's 1986 claim against DOE for injuries to natural resources. Fluor Fernald, Inc., and DOE-FN developed the ''Natural Resource Restoration Plan'', which outlines 15 major restoration projects for the site and will restore injured natural resources at the site. In general, Fernald's plan includes grading to maximize the formation of wetlands or expanded floodplain, amending soil where topsoil has been removed during excavation, and establishing native vegetation throughout the site. Today, with cleanup over 35 percent complete and site closure targeted for 2006, Fernald is entering a new phase of restoration that involves heavily remediated areas. By working closely with engineers and cleanup crews, site ecologists can take advantage of remediation fieldwork (e.g., convert an excavated depression into a wetland) and avoid unnecessary costs and duplication. This collaboration has also created opportunities for relatively simple and inexpensive restoration of areas that were discovered during ongoing remediation. To ensure the survival of the plant material in heavily

  3. VT River Restoration Data in Lamoille County (United States)

    Vermont Center for Geographic Information — (Link to Metadata) Documented river and riparian buffer restoration projects in Lamoille County, Vermont. Restoration includes buffer plantings (trees and shrubs),...


    Institute of Scientific and Technical Information of China (English)

    张建梅; 陈永红; 王晓红; 唐朝枢


    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n =6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment ofnitroglycerin patch (0. 05mg/h). Angiotensin I1 receptor antagonist losartan (10mg ·kg-1·d-1) and endothe-lin receptor antagonist bosentan ( 100 mg·kg-1· d-1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effec-tive percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentangroup compared with Nit group [(31.95±4.45) % vs (21.00±3.69) %, P <0.01and (33. 18±6. 16)% vs (21.00±3.69 ) %, P < 0. 01 , respectivelyl. The maximal vessel relaxation induced by SNP was thesame in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response toSNP) was found in tolerant group[ (34 ±10) nmol/L, P < 0. 01 ]. The ET-1 amounts in plasma and vasculartissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P<0. 01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartangroup compared with those in Nit group ( P < 0.01 ). Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance.

  5. Papahanaumokuakea - Laysan Island Restoration 2011 (United States)

    US Fish and Wildlife Service, Department of the Interior — This project supports restoration activities at Laysan Island. Staff and volunteers continue efforts to eradicate alien invasive species such as Indian dropseed...

  6. Papahanaumokuakea - Laysan Island Restoration 2009 (United States)

    US Fish and Wildlife Service, Department of the Interior — This project will support restoration activities at Laysan Island. Staff and volunteers continue efforts to eradicate alien invasive species such as Indian dropseed...

  7. Wetland Restoration and Sediment Removal (United States)

    US Fish and Wildlife Service, Department of the Interior — In 2008, Minnesota’s Private Lands Program and Wetland Management Districts began to compare different methods of restoring prairie pothole wetlands to see if there...

  8. Basic research for environmental restoration

    Energy Technology Data Exchange (ETDEWEB)


    The Department of Energy (DOE) is in the midst of a major environmental restoration effort to reduce the health and environmental risks resulting from past waste management and disposal practices at DOE sites. This report describes research needs in environmental restoration and complements a previously published document, DOE/ER-0419, Evaluation of Mid-to-Long Term Basic Research for Environmental Restoration. Basic research needs have been grouped into five major categories patterned after those identified in DOE/ER-0419: (1) environmental transport and transformations; (2) advanced sampling, characterization, and monitoring methods; (3) new remediation technologies; (4) performance assessment; and (5) health and environmental effects. In addition to basic research, this document deals with education and training needs for environmental restoration. 2 figs., 6 tabs.

  9. [Pulp response to restorative materials]. (United States)

    Advokaat, J G


    Restorations may affect the pulp negatively, rather due to microleakage than to toxic properties of the materials used. Hyperalgesia occurs more frequently after restoration with composite resins than with amalgam, though the resins in contrast to amalgam may be bonded to the enamel margins. A number of recommendations are presented in order to minimize the marginal gap between cavity walls and amalgam and to prevent marginal fracture.

  10. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;


    A high degree of structural heterogeneity of the GABAA receptors (GABAARs) has been revealed and is reflected in multiple receptor subtypes. The subunit composition of GABAAR subtypes is believed to determine their localization relative to the synapses and adapt their functional properties...... to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...

  11. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson


    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

  12. THE RESTORATIVE CLASSROOM: Using Restorative Approaches to Foster Effective Learning

    Directory of Open Access Journals (Sweden)

    Reviewed by Martha A. BROWN


    Full Text Available The book is divided into three sections. Part One, chapters 1-3, provides the reader with a framework for understanding relational and restorative pedagogy based on the Five Key Restorative Themes: Everyone has their own unique and equally valued perspectives Thoughts influence emotions, emotions influence actions Empathy and consideration Needs and unmet needs Collective responsibility for problem solving and decision making. (Hopkins, 2011, p.32These five themes form the basis for the rest of the book. Part Two, chapters 4-9, describes a range of restorative practices and exercises, such as mixers, circles, and community-building games, as well as the step-by-step instructions on how to implement and conduct them. Part Three, Chapter 10, succinctly discusses the whole-school approach, which is explained in greater detail in Just Schools (Hopkins, 2004. Still, Hopkins would be remiss not to emphasize the need for the whole-school adoption of restorative practices based on current school effectiveness and improvement literature, and again asserts that "developing a restorative staffroom and staff team is likely to be a pre-requisite for a successful, high-achieving school" (Hopkins, 2011, p. 225.

  13. Antioxidant effects of calcium antagonists in rat brain homogenates. (United States)

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T


    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  14. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  15. Sexually antagonistic selection in human male homosexuality. (United States)

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni


    Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  16. Activins and activin antagonists in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Alev Deli; Emanuel Kreidl; Stefan Santifaller; Barbara Trotter; Katja Seir; Walter Berger; Rolf Schulte-Hermann; Chantal Rodgarkia-Dara; Michael Grusch


    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo-or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

  17. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter


    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects....... In resistance arteries, the long-lasting contractile effects can only be partly and reversibly relaxed by low-molecular-weight ET(A) antagonists (ERAs). However, the neuropeptide calcitonin-gene-related peptide selectively terminates binding of ET1 to ET(A). We propose that ET1 binds polyvalently to ET(A......) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  18. Zebrafish phenotypic screen identifies novel Notch antagonists. (United States)

    Velaithan, Vithya; Okuda, Kazuhide Shaun; Ng, Mei Fong; Samat, Norazwana; Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Shaari, Khozirah; Cheong, Sok Ching; Tan, Pei Jean; Patel, Vyomesh


    Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27(KIP1). Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.

  19. Evaluation of H2 receptor antagonists in chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    Minocha Y


    Full Text Available H1-antagonist (hydroxyzine hydrochloride in dosage of 10 mg-25 mg thrice a day failed to elicit satisfactory response in 60 out of 170 patients of chronic idiopathic urticaria. Additional administration of H2-antagonist (cimetidine in dosage of 200 mg four times a day, in patients not responding earlier to H1-antagonist alones exhibited moderate to good improvement of various parameters of urticaria in approximately 85% patients

  20. Restoration of primary anterior teeth: review of the literature. (United States)

    Lee, Jacob K


    This paper reviews the published data on restorations of primary anterior teeth. The discussion includes Class III restorations, Class V restorations, various forms of full coronal restorations, atraumatic restorative technique (ART) and recommendations for future research.

  1. 76 FR 46149 - Financial Assistance: Wildlife Restoration, Sport Fish Restoration, Hunter Education and Safety (United States)


    ... Assistance: Wildlife Restoration, Sport Fish Restoration, Hunter Education and Safety; Final Rule #0;#0... Restoration, Hunter Education and Safety AGENCY: Fish and Wildlife Service, Interior. ACTION: Final rule... Restoration, Sport Fish Restoration, and Hunter Education and Safety (Enhanced Hunter Education and...

  2. Methodology for ranking restoration options

    DEFF Research Database (Denmark)

    Jensen, Per Hedemann


    The work described in this report has been performed as a part of the RESTRAT Project FI4P-CT95-0021a (PL 950128) co-funded by the Nuclear Fission Safety Programme of the European Commission. The RESTRAT project has the overall objective of developinggeneric methodologies for ranking restoration...... techniques as a function of contamination and site characteristics. The project includes analyses of existing remediation methodologies and contaminated sites, and is structured in the following steps:-characterisation of relevant contaminated sites -identication and characterisation of relevant restoration...... techniques -assessment of the radiological impact -development and application of a selection methodology for restoration options -formulation ofgeneric conclusions and development of a manual The project is intended to apply to situations in which sites with nuclear installations have been contaminated...

  3. Conservative preparations for cast restorations. (United States)

    Shillingburg, H T


    Partial veneer crowns still play a role in modern restorative dentistry. They must be used in the right situation with thoughtful treatment planning, and they must be done well in accordance with certain principles. Three-quarter crowns are less retentive than full crowns, but they can be used successfully as single unit restorations and retainers for short span bridges. Retention can be enhanced by the use of proximal boxes. The M.O.D. onlay, a modified inlay with occlusal coverage, minimizes the damaging effects of stress generated by occlusal forces. There is little indication for the use of M.O.D. inlays or large two surface inlays.

  4. Mutually-Antagonistic Interactions in Baseball Networks

    CERN Document Server

    Saavedra, Serguei; McCotter, Trent; Porter, Mason A; Mucha, Peter J


    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit interesting structural changes over time. We also find that these networks exhibit a significant network structure that is sensitive to baseball's rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to compare the performance of players who competed under different conditions. We find that a player's position in the network does not correlate with his success in the random walker ranking but instead has a substantial effect on its sensitivity to changes in his own aggregate performance.

  5. Mutually-antagonistic interactions in baseball networks (United States)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.


    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  6. Antagonists of IAP proteins as cancer therapeutics. (United States)

    Dynek, Jasmin N; Vucic, Domagoj


    Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking apoptosis, modulating signal transduction, and affecting cellular proliferation. Through their interactions with inducers and effectors of apoptosis IAP proteins can effectively suppress apoptosis triggered by diverse stimuli including death receptor signaling, irradiation, chemotherapeutic agents, or growth factor withdrawal. Evasion of apoptosis, in part due to the action of IAP proteins, enhances resistance of cancer cells to treatment with chemotherapeutic agents and contributes to tumor progression. Additionally, IAP genes are known to be subject to amplification, mutation, and chromosomal translocation in human malignancies and autoimmune diseases. In this review we will discuss the role of IAP proteins in cancer and the development of antagonists targeting IAP proteins for cancer treatment.

  7. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony


    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/ at which European health professionals can register online to receive copies of the quarterly publication.

  8. Antagonistic activity of marine sponges associated Actinobacteria

    Institute of Scientific and Technical Information of China (English)

    Selvakumar Dharmaraj; Dhevendaran Kandasamy


    Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology), nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance), physiological (pH, temperature) and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate), soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are universally well


    NARCIS (Netherlands)



    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or antagonist

  10. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology

    NARCIS (Netherlands)

    Al-Inany, Hesham G.; Youssef, Mohamed A.; Ayeleke, Reuben Olugbenga; Brown, Julie; Lam, Wai Sun; Broekmans, Frank J.


    Background: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists direct

  11. Antagonistic and Bargaining Games in Optimal Marketing Decisions (United States)

    Lipovetsky, S.


    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  12. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.


    This thesis focuses on the optimisation of controlled ovarian stimulation for IVF using exogenous FSH and GnRH antagonist co-treatment, by studying the timing of the initiation of GnRH antagonist co-medication and the role of ovarian reserve markers in optimising ovarian response and reproductive ou

  13. Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression. (United States)

    Raab-Graham, Kimberly F; Workman, Emily R; Namjoshi, Sanjeev; Niere, Farr


    Healthy neurons have an optimal operating range, coded globally by the frequency of action potentials or locally by calcium. The maintenance of this range is governed by homeostatic plasticity. Here, we discuss how new approaches to treat depression alter synaptic activity. These approaches induce the neuron to recruit homeostatic mechanisms to relieve depression. Homeostasis generally implies that the direction of activity necessary to restore the neuron's critical operating range is opposite in direction to its current activity pattern. Unconventional antidepressant therapies-deep brain stimulation and NMDAR antagonists-alter the neuron's "depressed" state by pushing the neuron's current activity in the same direction but to the extreme edge. These therapies rally the intrinsic drive of neurons in the opposite direction, thereby allowing the cell to return to baseline activity, form new synapses, and restore proper communication. In this review, we discuss seminal studies on protein synthesis dependent homeostatic plasticity and their contribution to our understanding of molecular mechanisms underlying the effectiveness of NMDAR antagonists as rapid antidepressants. Rapid antidepressant efficacy is likely to require a cascade of mRNA translational regulation. Emerging evidence suggests that changes in synaptic strength or intrinsic excitability converge on the same protein synthesis pathways, relieving depressive symptoms. Thus, we address the question: Are there multiple homeostatic mechanisms that induce the neuron and neuronal circuits to self-correct to regulate mood in vivo? Targeting alternative ways to induce homeostatic protein synthesis may provide, faster, safer, and longer lasting antidepressants. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease.

  14. Weed biocontrol in landscape restoration (United States)

    Weed biological control programs in natural areas are often undertaken with the goal of restoring native plant communities and/or ecosystem services to a pre-invasion level. These objectives may be achieved in some areas with biological control alone; however, in other sites integration of biologica...

  15. Origins of the Restoration Playhouse. (United States)

    Wilson, Dennis D.

    Contrary to the popular theory that the proscenium type of playhouse was imported from France by the Court of Charles II in 1660, the Restoration playhouse in fact developed from Elizabethan theatres and court masques. These Elizabethan theatres were the private theatres, and were generally small, rectangular, roofed structures where aristocratic…

  16. Zirconia-reinforced dental restorations

    NARCIS (Netherlands)

    C. Chen


    The series of studies conducted in this thesis showed that there are several ways to enhance the performance of fixed restorations regarding the application of zirconia. One possible way is to change the sintering procedure of zirconia, so that the physical properties of zirconia such BFS, density o

  17. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis

    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for salt and pepper noise. The inference in the model is discussed...

  18. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis Linda


    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for the salt and pepper noise. The inference in the model is discussed...

  19. A review on anterior teeth restorations

    Directory of Open Access Journals (Sweden)

    Gaurav Solanki


    Full Text Available Restorations of teeth have been a need of time since very long. As the time have passed, there have been different advances in the field of restorative materials and tooth restorations. Many newer restorative materials are now available to us for the purpose of tooth restorations still some of the older materials are materials of choice for a sector of society. This article focuses on few such restorative materials and also tells us about a few patents granted in such field.

  20. IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model. (United States)

    Pilat, Dominika; Rojewska, Ewelina; Jurga, Agnieszka M; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna


    An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. In CCI-exposed rats, spinal levels of IL-1alpha mRNA were slightly downregulated on the 7th day, and protein levels were not changed on the 7th and 14th days. Levels of IL-1 receptor antagonist and IL-1 receptor type I were slightly upregulated in the ipsilateral part of the spinal cord on the 7th and 14th days; however, protein levels were not changed at those time points. Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.

  1. Phonemic restoration in developmental dyslexia

    Directory of Open Access Journals (Sweden)

    Stephanie N. Del Tufo


    Full Text Available The comprehension of fluent speech in one’s native language requires that listeners integrate the detailed acoustic-phonetic information available in the sound signal with linguistic knowledge. This interplay is especially apparent in the phoneme restoration effect, a phenomenon in which a missing phoneme is ‘restored’ via the influence of top-down information from the lexicon and through bottom-up acoustic processing. Developmental dyslexia is a disorder characterized by an inability to read at the level of one’s peers without any clear failure due to environmental influences. In the current study we utilized the phonemic restoration illusion paradigm, to examine individual differences in phonemic restoration across a range of reading ability, from very good to dyslexic readers. Results demonstrate that restoration occurs less in those who have high scores on measures of phonological processing. Based on these results, we suggest that the processing or representation of acoustic detail may not be as reliable in poor and dyslexic readers, with the result that lexical information is more likely to override acoustic properties of the stimuli. This pattern of increased restoration could result from a failure of perceptual tuning, in which unstable representations of speech sounds result in the acceptance of non-speech sounds as speech. An additional or alternative theory is that degraded or impaired phonological processing at the speech sound level may reflect architecture that is overly plastic and consequently fails to stabilize appropriately for speech sound representations. Therefore the inability to separate speech and noise may result as a deficit in separating noise from the acoustic signal.

  2. Efficient restoration of variable area soundtracks:


    Abdelâali Hassaïne; Etienne Decencière; Bernard Besserer


    The restoration of motion picture films using digital image processing has been an active research field for many years. The restoration of the soundtrack however, has mainly been performed in the sound domain, using signal processing methods, in spite of the fact that it is recorded as a continuous image between the images of the film and the perforations. In this paper a restoration method for variable area soundtrack restoration at the image level is presented. First, a novel method is pro...

  3. Fine Tuning of a Type 1 Interferon Antagonist.

    Directory of Open Access Journals (Sweden)

    Victoria Urin

    Full Text Available Type I interferons are multi-potent cytokines that serve as first line of defense against viruses and other pathogens, posses immunomudolatory functions and elicit a growth inhibitory response. In recent years it has been shown that interferons are also detrimental, for example in lupus, AIDS, tuberculosis and cognitive decline, highlighted the need to develop interferon antagonists. We have previously developed the antagonist IFN-1ant, with much reduced binding to the IFNAR1 receptor and enhanced binding to IFNAR2. Here, we further tune the IFN-1ant by producing three additional antagonists based on IFN-1ant but with altered activity profiles. We show that in all three cases the antiproliferative activity of interferons is blocked and the induction of gene transcription of immunomudolatory and antiproliferative associated genes are substantially decreased. Conversely, each of the new antagonists elicits a different degree of antiviral response, STAT phosphorylation and related gene induction. Two of the new antagonists promote decreased activity in relation to the original IFN-1ant, while one of them promotes increased activity. As we do not know the exact causes of the detrimental effects of IFNs, the four antagonists that were produced and analyzed provide the opportunity to investigate the extent of antagonistic and agonistic activity optimal for a given condition.

  4. Nalmefene: radioimmunoassay for a new opioid antagonist. (United States)

    Dixon, R; Hsiao, J; Taaffe, W; Hahn, E; Tuttle, R


    A specific radioimmunoassay (RIA) has been developed for the quantitation of a new opioid antagonist, nalmefene, in human plasma. The method employs a rabbit antiserum to an albumin conjugate of naltrexone-6-(O-carboxymethyl)oxime and [3H]naltrexone as the radioligand. Assay specificity was achieved by extraction of nalmefene from plasma at pH 9 into ether prior to RIA. The procedure has a limit of sensitivity of 0.2 ng/mL of nalmefene using a 0.5-mL sample of plasma for analysis. The intra- and interassay coefficients of variation did not exceed 5.6 and 11%, respectively. The specificity of the RIA was established by demonstrating excellent agreement (r = 0.99) with a less sensitive and more time consuming HPLC procedure in the analysis of clinical plasma samples. The use of the RIA for the pharmacokinetic evaluation of nalmefene is illustrated with plasma concentration profiles of the drug in humans following intravenous and oral administration.

  5. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis


    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  6. Digital color restoration of old paintings. (United States)

    Pappas, M; Pitas, I


    Physical and chemical changes can degrade the visual color appearance of old paintings. Five digital color restoration techniques, which can be used to simulate the original appearance of paintings, are presented. Although a small number of color samples is employed in the restoration procedure, simulation results indicate that good restoration quality can be attained.

  7. 5 CFR 353.301 - Restoration rights. (United States)


    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Restoration rights. 353.301 Section 353... DUTY FROM UNIFORMED SERVICE OR COMPENSABLE INJURY Compensable Injury § 353.301 Restoration rights. (a.... Although these restoration rights are agencywide, the employee's basic entitlement is to the...

  8. Image Restoration with New Technology

    DEFF Research Database (Denmark)

    Bülow-Møller, Anne Marie

    The article examines the role played by the corporate website while a company - Arla - attempted to restore an image tarnished by unethical behaviour. The company's strategy focussed on dialogue: it introduced a large number of authentic employees in their natural role as cook, dairy farmer, etc...... their image as a faceless monopoly with a humanized, personalised version. However, it should also be questioned if, in the long run, it was the image campaign rather than the visible efforts of the company to behave with consideration that brought about the desired change. Keywords: Image restoration......., and made them available to readers as experts providing inspiration and advice, or as writers blogging about the world of company, or as responsible people answering readers' frank questions about their practices in an open forum. It is argued that the electronic platform allowed the company to substitute...

  9. Resilience and Restoration of Lakes

    Directory of Open Access Journals (Sweden)

    Kathryn L. Cottingham


    Full Text Available Lake water quality and ecosystem services are normally maintained by several feedbacks. Among these are nutrient retention and humic production by wetlands, nutrient retention and woody habitat production by riparian forests, food web structures that cha nnel phosphorus to consumers rather than phytoplankton, and biogeochemical mechanisms that inhibit phosphorus recycling from sediments. In degraded lakes, these resilience mechanisms are replaced by new ones that connect lakes to larger, regional economi c and social systems. New controls that maintain degraded lakes include runoff from agricultural and urban areas, absence of wetlands and riparian forests, and changes in lake food webs and biogeochemistry that channel phosphorus to blooms of nuisance al gae. Economic analyses show that degraded lakes are significantly less valuable than normal lakes. Because of this difference in value, the economic benefits of restoring lakes could be used to create incentives for lake restoration.

  10. Procedures for restoring vestibular disorders



    This paper will discuss therapeutic possibilities for disorders of the vestibular organs and the neurons involved, which confront ENT clinicians in everyday practice. Treatment of such disorders can be tackled either symptomatically or causally. The possible strategies for restoring the body's vestibular sense, visual function and co-ordination include medication, as well as physical and surgical procedures. Prophylactic or preventive measures are possible in some disorders which involve vert...

  11. Articulator selection for restorative dentistry. (United States)

    Hobo, S; Shillingburg, H T; Whitsett, L D


    There are many types of articulators that can be used for making fixed restorations. While unquestionably the most accurate, the fully adjustable instrument is not feasible or necessary for many forms of simple occlusal treatment. The effects of tooth-hinge axis radius, intercondylar distance, and condylar inclination on occlusal morphology have been discussed. Guidelines have been proposed for matching the type of articulator with the extent of treatment anticipated. The use of small, nonadjustable hinge articulators is not recommended.

  12. Minimum thickness anterior porcelain restorations. (United States)

    Radz, Gary M


    Porcelain laminate veneers (PLVs) provide the dentist and the patient with an opportunity to enhance the patient's smile in a minimally to virtually noninvasive manner. Today's PLV demonstrates excellent clinical performance and as materials and techniques have evolved, the PLV has become one of the most predictable, most esthetic, and least invasive modalities of treatment. This article explores the latest porcelain materials and their use in minimum thickness restoration.

  13. Image Restoration And Resolution Enhancement (United States)

    Byrne, Charles L.; Fitzgerald, Raymond M.


    We consider mathematical algorithms for the restoration of object information from finitely many measurements of the object's spectrum, with particular emphasis on the development of linear and nonlinear non-iterative methods that can incorporate prior information about object extent and shape. The linear method presented here generalizes the minimum energy bandlimited extrapolation procedure, which is the closed form limit of Gerchberg-Papoulis iteration in this case. The nonlinear method generalizes the maximum entropy method (MEM) of Burg.

  14. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists. (United States)

    Khanfar, Mohammad A; Affini, Anna; Lutsenko, Kiril; Nikolic, Katarina; Butini, Stefania; Stark, Holger


    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  15. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar


    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  16. Identification of a novel conformationally constrained glucagon receptor antagonist. (United States)

    Lee, Esther C Y; Tu, Meihua; Stevens, Benjamin D; Bian, Jianwei; Aspnes, Gary; Perreault, Christian; Sammons, Matthew F; Wright, Stephen W; Litchfield, John; Kalgutkar, Amit S; Sharma, Raman; Didiuk, Mary T; Ebner, David C; Filipski, Kevin J; Brown, Janice; Atkinson, Karen; Pfefferkorn, Jeffrey A; Guzman-Perez, Angel


    Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences.

  17. New potential uroselective NO-donor alpha1-antagonists. (United States)

    Boschi, Donatella; Tron, Gian Cesare; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto; Poggesi, Elena; Motta, Gianni; Leonardi, Amedeo


    A recent uroselective alpha(1)-adrenoceptor antagonist, REC15/2739, has been joined with nitrooxy and furoxan NO-donor moieties to give new NO-donor alpha(1)-antagonists. All the compounds studied proved to be potent and selective ligands of human cloned alpha(1a)-receptor subtype. Derivatives 6 and 7 were able to relax the prostatic portion of rat vas deferens contracted by (-)-noradrenaline because of both their alpha(1A)-antagonist and their NO-donor properties.

  18. Methodology for ranking restoration options

    Energy Technology Data Exchange (ETDEWEB)

    Hedemann Jensen, Per


    The work described in this report has been performed as a part of the RESTRAT Project FI4P-CT95-0021a (PL 950128) co-funded by the Nuclear Fission Safety Programme of the European Commission. The RESTRAT project has the overall objective of developing generic methodologies for ranking restoration techniques as a function of contamination and site characteristics. The project includes analyses of existing remediation methodologies and contaminated sites, and is structured in the following steps: characterisation of relevant contaminated sites; identification and characterisation of relevant restoration techniques; assessment of the radiological impact; development and application of a selection methodology for restoration options; formulation of generic conclusions and development of a manual. The project is intended to apply to situations in which sites with nuclear installations have been contaminated with radioactive materials as a result of the operation of these installations. The areas considered for remedial measures include contaminated land areas, rivers and sediments in rivers, lakes, and sea areas. Five contaminated European sites have been studied. Various remedial measures have been envisaged with respect to the optimisation of the protection of the populations being exposed to the radionuclides at the sites. Cost-benefit analysis and multi-attribute utility analysis have been applied for optimisation. Health, economic and social attributes have been included and weighting factors for the different attributes have been determined by the use of scaling constants. (au)

  19. Materials for chairside CAD/CAM restorations. (United States)

    Fasbinder, Dennis J


    Chairside computer-aided design/computer-aided manufacturing (CAD/CAM) systems have become considerably more accurate, efficient, and prevalent as the technology has evolved in the past 25 years. The initial restorative material option for chairside CAD/CAM restorations was limited to ceramic blocks. Restorative material options have multiplied and now include esthetic ceramics, high-strength ceramics, and composite materials for both definitive and temporary restoration applications. This article will review current materials available for chairside CAD/CAM restorations.

  20. The pharmacological properties of lipophilic calcium antagonists. (United States)

    van Zwieten, P A


    Several types of calcium antagonists (CA) (verapamil, diltiazem, nifedipine and related drugs) may be used as antihypertensives. In practice, the dihydropyridines (nifedipine and related drugs) are the CA used most frequently as antihypertensives. Apart from the lowering of blood pressure CA may lead to other, theoretically beneficial, effects: regression of left ventricular and vascular hypertrophy, renal protection, weak natriuretic, weak antiplatelet, anti-ischaemic and antiatherogenic activity. Several new dihydropyridine CA have been introduced in recent years. The advantages of the newer compounds, such as amlodipine, felodipine, isradipine, lacidipine and lercanidipine, may include: vasoselectivity, hence little or no cardiodepressant activity; an improved kinetic profile, resulting in a slow onset and long duration of action, fewer side-effects such as reflex tachycardia and headache, owing to the slow onset of the antihypertensive action. For a few newer CA a predominant effect on specialized circulatory beds (renal, coronary and cerebral) has been claimed. The new CA, which are clearly lipophilic, deserve special attention. Owing to the lipophilic character of such compounds considerable concentration occurs in lipid-containing membrane depots. The CA thus concentrated are slowly released from these depots and, subsequently, reach their targets, the L-type calcium channels. This phenomenon explains both the slow onset and the long duration of action of these CA. Owing to the slow onset of action reflex tachycardia is virtually absent. The long duration of action allows satisfactory control of blood pressure in hypertensives by means of a single daily dose. A few lipophilic dihydropyridine CA are vasoselective. This property implies that at therapeutic, vasodilatory dosages no cardiodepressant activity occurs. Lercanidipine is a recently introduced example of a lipophilic and vasoselective dihydropyridine CA. It is an effective vasodilator

  1. The science and practice of river restoration (United States)

    Wohl, Ellen; Lane, Stuart N.; Wilcox, Andrew C.


    River restoration is one of the most prominent areas of applied water-resources science. From an initial focus on enhancing fish habitat or river appearance, primarily through structural modification of channel form, restoration has expanded to incorporate a wide variety of management activities designed to enhance river process and form. Restoration is conducted on headwater streams, large lowland rivers, and entire river networks in urban, agricultural, and less intensively human-altered environments. We critically examine how contemporary practitioners approach river restoration and challenges for implementing restoration, which include clearly identified objectives, holistic understanding of rivers as ecosystems, and the role of restoration as a social process. We also examine challenges for scientific understanding in river restoration. These include: how physical complexity supports biogeochemical function, stream metabolism, and stream ecosystem productivity; characterizing response curves of different river components; understanding sediment dynamics; and increasing appreciation of the importance of incorporating climate change considerations and resiliency into restoration planning. Finally, we examine changes in river restoration within the past decade, such as increasing use of stream mitigation banking; development of new tools and technologies; different types of process-based restoration; growing recognition of the importance of biological-physical feedbacks in rivers; increasing expectations of water quality improvements from restoration; and more effective communication between practitioners and river scientists.


    Directory of Open Access Journals (Sweden)

    B. B. Gegenava


    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  3. Structure-based drug design identifies novel LPA3 antagonists. (United States)

    Fells, James I; Tsukahara, Ryoko; Liu, Jianxiong; Tigyi, Gabor; Parrill, Abby L


    Compound 5 ([5-(3-nitrophenoxy)-1,3-dioxo-1,3-dihydro-2-isoindol-2-yl]acetic acid) was identified as a weak selective LPA(3) antagonist (IC(50)=4504 nM) in a virtual screening effort to optimize a dual LPA(2 and 3) antagonist. Structure-based drug design techniques were used to prioritize similarity search matches of compound 5. This strategy rapidly identified 10 novel antagonists. The two most efficacious compounds identified inhibit activation of the LPA(3) receptor by 200 nM LPA with IC(50) values of 752 nM and 2992 nM. These compounds additionally define changes to our previously reported pharmacophore that will improve its ability to identify more potent and selective LPA(3) receptor antagonists. The results of the combined computational and experimental screening are reported.

  4. Secondary prevention with calcium antagonists after acute myocardial infarction

    DEFF Research Database (Denmark)

    Hansen, J F


    Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival...

  5. Perampanel: A Selective AMPA Antagonist for Treating Seizures


    Krauss, Gregory L.


    Perampanel is a selective, noncompetitive AMPA receptor antagonist that has recently been approved for treating localization-related epilepsy. This article reviews the pharmacology, clinical development, efficacy, and safety/tolerability of perampanel.

  6. Complications of TNF-α antagonists and iron homeostasis (United States)

    TNF-α is a central regulator of inflammation and its blockade downregulates other proinflammatory cytokines, chemokines, and growth factors. Subsequently, TNF-α antagonists are currently used in treatment regimens directed toward several inflammatory diseases. Despite a beneficia...

  7. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen


    from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  8. Structure-activity relationships of benzothiazole GPR35 antagonists. (United States)

    Abdalhameed, Manahil M; Zhao, Pingwei; Hurst, Dow P; Reggio, Patricia H; Abood, Mary E; Croatt, Mitchell P


    The first structure-activity relationships for a benzothiazole scaffold acting as an antagonist at GPR35 is presented. Analogues were designed based on a lead compound that was previously determined to have selective activity as a GPR35 antagonist. The synthetic route was modular in nature to independently explore the role of the middle and both ends of the scaffold. The activities of the analogues illustrate the importance of all three segments of the compound.

  9. Deficiency of interleukin-1 receptor antagonist responsive to anakinra. (United States)

    Schnellbacher, Charlotte; Ciocca, Giovanna; Menendez, Roxanna; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Duarte, Ana M; Rivas-Chacon, Rafael


    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acute-phase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.

  10. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists


    Mohammad eKhanfar; Anna eAffini; Kiril eLutsenko; Katarina eNikolic; Stefania eButini; Holger eStark


    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex...

  11. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian;


    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras.......About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  12. Wear characteristics of trimethylolpropane trimethacrylate filler-containing resins for the full crown restoration of primary molars. (United States)

    Wada, Kanae; Ikeda, Eri; Wada, Junichiro; Inoue, Go; Miyasaka, Munenaga; Miyashin, Michiyo


    Although the demand for aesthetic restoration of primary molars has increased, the full-crown restorations using resin and the details of the wear characteristics of trimethylolpropane trimethacrylate (TMPT) filler containing resins for primary molars are not well understood. This study was conducted to determine whether new light-cured composite resin (Fantasista) and 4-META/MMATBB resin (Bondfill SB) are appropriate for full crown restoration of primary molars by evaluating their wear characteristics. Both resins products contain TMPT filler. The properties of the resins were evaluated through in vitro impacting-sliding wear tests; the wear properties of the opposing enamel specimens used in the tests were also studied. The properties of the resins were compared with those of Litefill, MetafilC, and Clearfil FII, which had been evaluated previously. Fantasista exhibited simple shape of wear that was suggestive of a higher wear resistance than that of Litefill. Fantasista caused the least damage to the antagonistic primary enamel.

  13. Fracture resistance of endodontically treated teeth restored with indirect composite inlay and onlay restorations – An in vitro study

    Directory of Open Access Journals (Sweden)

    Ibraheem F. Alshiddi


    Conclusion: Within the limitations of this study, endodontically treated teeth were successfully restored with indirect composite inlay and onlay restorations. However, the fractures that accompanied the inlay restorations were more severe and were unable to be restored.

  14. Long-term evaluation of extensive restorations in permanent teeth

    DEFF Research Database (Denmark)

    Nieuwenhuysen, J.-P. van; D'hoore, W.D.; Carvalho, J.;


    Biostatistics, cast crowns, complex restorations, composite resins, decision making, dental amalgam, metal ceramic crowns, multi-surfaced restorations, prosthodontics, restorative dentistry......Biostatistics, cast crowns, complex restorations, composite resins, decision making, dental amalgam, metal ceramic crowns, multi-surfaced restorations, prosthodontics, restorative dentistry...

  15. Factors influencing bonding fixed restorations

    Directory of Open Access Journals (Sweden)

    Medić Vesna


    Full Text Available INTRODUCTION Crown displacement often occurs because the features of tooth preparations do not counteract the forces directed against restorations. OBJECTIVE The purpose of this study was to evaluate the effect of preparation designs on retention and resistance of fixed restorations. METHOD The study was performed on 64 differently sized stainless steel dies. Also, caps which were used for evaluated retention were made of stainless steel for each die. After cementing the caps on experimental dies, measuring of necessary tensile forces to separate cemented caps from dies was done. Caps, which were made of a silver-palladium alloy with a slope of 60° to the longitudinal axis formed on the occlusal surface, were used for evaluating resistance. A sudden drop in load pressure recorded by the test machine indicated failure for that cap. RESULTS A significant difference was found between the tensile force required to remove the caps from the dies with different length (p<0.05 and different taper (p<0.01. The greatest retentive strengths (2579.2 N and 2989.8 N were noticed in experimental dies with the greatest length and smallest taper. No statistically significant (p>0.05 differences were found between tensile loads for caps cemented on dies with different diameter. Although there was an apparent slight increase in resistance values for caps on dies with smaller tapers, the increase in resistance for those preparation designs was not statistically significant. There was a significant difference among the resistance values for caps on dies with different length (p<0.01 and diameter (p<0.05. CONCLUSION In the light of the results obtained, it could be reasonably concluded that retention and resistance of the restoration is in inverse proportion to convergence angle of the prepared teeth. But, at a constant convergence angle, retention and resistance increase with rising length and diameter.

  16. β-Adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signalling. (United States)

    Sharifpanah, Fatemeh; Saliu, Fatjon; Bekhite, Mohamed M; Wartenberg, Maria; Sauer, Heinrich


    The β-adrenoceptor antagonist Propranolol has been successfully used to treat infantile hemangioma. However, its mechanism of action is so far unknown. The hypothesis of this research was that β-adrenoceptor antagonists may interfere with endothelial cell differentiation of stem cells. Specifically, the effects of the non-specific β-adrenergic receptor (β-adrenoceptor) antagonist Propranolol, the β1-adrenoceptor-specific antagonist Atenolol and the β2-adrenoceptor-specific antagonist ICI118,551 on vasculogenesis of mouse embryonic stem (ES) cells were investigated. All three β-blockers dose-dependently downregulated formation of capillary structures in ES cell-derived embryoid bodies and decreased the expression of the vascular cell markers CD31 and VE-cadherin. Furthermore, β-blockers downregulated the expression of fibroblast growth factor-2 (FGF-2), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor 165 (VEGF165), VEGF receptor 2 (VEGF-R2) and phospho VEGF-R2, as well as neuropilin 1 (NRP1) and plexin-B1 which are essential modulators of embryonic angiogenesis with additional roles in vessel remodelling and arteriogenesis. Under conditions of β-adrenoceptor inhibition, the endogenous generation of nitric oxide (NO) as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) was decreased in embryoid bodies, whereas an increase in NO generation was observed with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Consequently, vasculogenesis of ES cells was restored upon treatment of differentiating ES cells with β-adrenoceptor antagonists in the presence of NO donor. In summary, our data suggest that β-blockers impair vasculogenesis of ES cells by interfering with NO generation which could be the explanation for their anti-angiogenic effects in infantile hemangioma.

  17. Contribution of genetics to ecological restoration. (United States)

    Mijangos, Jose Luis; Pacioni, Carlo; Spencer, Peter B S; Craig, Michael D


    Ecological restoration of degraded ecosystems has emerged as a critical tool in the fight to reverse and ameliorate the current loss of biodiversity and ecosystem services. Approaches derived from different genetic disciplines are extending the theoretical and applied frameworks on which ecological restoration is based. We performed a search of scientific articles and identified 160 articles that employed a genetic approach within a restoration context to shed light on the links between genetics and restoration. These articles were then classified on whether they examined association between genetics and fitness or the application of genetics in demographic studies, and on the way the studies informed restoration practice. Although genetic research in restoration is rapidly growing, we found that studies could make better use of the extensive toolbox developed by applied fields in genetics. Overall, 41% of reviewed studies used genetic information to evaluate or monitor restoration, and 59% provided genetic information to guide prerestoration decision-making processes. Reviewed studies suggest that restoration practitioners often overlook the importance of including genetic aspects within their restoration goals. Even though there is a genetic basis influencing the provision of ecosystem services, few studies explored this relationship. We provide a view of research gaps, future directions and challenges in the genetics of restoration.

  18. Restoring fish ecological quality in estuaries: Implication of interactive and cumulative effects among anthropogenic stressors. (United States)

    Teichert, Nils; Borja, Angel; Chust, Guillem; Uriarte, Ainhize; Lepage, Mario


    Estuaries are subjected to multiple anthropogenic stressors, which have additive, antagonistic or synergistic effects. Current challenges include the use of large databases of biological monitoring surveys (e.g. the European Water Framework Directive) to help environmental managers prioritizing restoration measures. This study investigated the impact of nine stressor categories on the fish ecological status derived from 90 estuaries of the North East Atlantic countries. We used a random forest model to: 1) detect the dominant stressors and their non-linear effects; 2) evaluate the ecological benefits expected from reducing pressure from stressors; and 3) investigate the interactions among stressors. Results showed that largest restoration benefits were expected when mitigating water pollution and oxygen depletion. Non-additive effects represented half of pairwise interactions among stressors, and antagonisms were the most common. Dredged sediments, flow changes and oxygen depletion were predominantly implicated in non-additive interactions, whereas the remainder stressors often showed additive impacts. The prevalence of interactive impacts reflects a complex scenario for estuaries management; hence, we proposed a step-by-step restoration scheme focusing on the mitigation of stressors providing the maximum of restoration benefits under a multi-stress context.

  19. Mitochondrial DNA, restoring Beethovens music. (United States)

    Merheb, Maxime; Vaiedelich, Stéphane; Maniguet, Thiérry; Hänni, Catherine


    Great ancient composers have endured many obstacles and constraints which are very difficult to understand unless we perform the restoration process of ancient music. Species identification in leather used during manufacturing is the key step to start such a restoration process in order to produce a facsimile of a museum piano. Our study reveals the species identification in the leather covering the hammer head in a piano created by Erard in 1802. This is the last existing piano similar to the piano that Beethoven used with its leather preserved in its original state. The leather sample was not present in a homogeneous piece, yet combined with glue. Using a DNA extraction method that avoids PCR inhibitors; we discovered that sheep and cattle are the origin of the combination. To identify the species in the leather, we focused on the amounts of mitochondrial DNA in both leather and glue and results have led us to the conclusion that the leather used to cover the hammer head in this piano was made of cattle hide.

  20. Guidelines for Direct Adhesive Composite Restoration. (United States)

    Society Of Cariology And Endodontology, Chinese Stomatological Association Csa


    Direct adhesive composite restoration, a technique to restore tooth defects by bonding composite resin materials, has been widely used in the restoration of dental caries or other tooth defects. Retention of composite resin restoration mainly relies on bonding strength between the materials and dental tissue. The clinical outcomes rely greatly on the regulated clinical practice of dentists. In 2011, the Society of Cariology and Endodontology of Chinese Stomatological Association (CSA) published the 'Practices and evaluation criteria of composite resin bonded restoration (Discussion Version)'. Since then, opinions and comments regarding the 'Discussion Version' have been widely circulated within the Society. The final version of the guideline was based on systematic reviews of scientific literature and requirements for the edit of technical guidelines, and through several rounds of discussions, revisions and supplements. The society recommends this guideline for clinicians to use in their practices, when conducting direct composite restorations.

  1. Shame and Guilt in Restorative Justice

    DEFF Research Database (Denmark)

    Rodogno, Raffaele


    In this article, I examine the relevance and desirability of shame and guilt to restorative justice conferences. I argue that a careful study of the psychology of shame and guilt reveals that both emotions possess traits that can be desirable and traits that can be undesirable for restoration. More...... in particular, having presented the aims of restorative justice, the importance of face-to-face conferences in reaching these aims, the emotional dynamics that take place within such conferences, and the relevant parts of the empirical psychology of shame and guilt, I argue that restorative justice...... practitioners have to take account of a rather more complex picture than it had hitherto been thought. Restorative conferences are not simply about "shame management," though practitioners must certainly avoid shaming and humiliation. Given the nature of shame, guilt, and restorative conferences...

  2. [Odontogenic maxillary sinusitis caused by dental restoration]. (United States)

    Sato, Kiminori


    We report herein on 5 patients with odontogenic maxillary sinusitis caused by a dental restoration (caries cutting, cavity preparation, inlay restoration). Odontogenic maxillary sinusitis was noted following dental restoration. Even though the pulp cavity and dental pulp were intact, the odontogenic maxillary sinusitis occurred caused by an apical lesion. Infection by way of the dentinal tubules was suggested to be a cause of the pathophysiology. Endoscopic sinus surgery was indicated in patients with intractable odontogenic maxillary sinusitis caused by the dental restoration. Cone-beam x-ray CT was useful for the accurate diagnosis of odontogenic maxillary sinusitis caused by a dental restoration. Physicians should thus be aware of the possibility that a tooth, which has undergone dental restoration, may cause odontogenic maxillary sinusitis.

  3. Biological restoration: A 4/5 crown

    Directory of Open Access Journals (Sweden)

    Monize Ferreira Figueiredo de Carvalho


    Full Text Available Dental caries is one of the most prevalent conditions in humans; the purpose of restorative dentistry is to recreate the anatomy of the affected tooth thus the use of fragments from natural teeth as an effective restorative method. A maxillary first premolar left was prepared for an inverted 4/5 crown due to involvement of the vestibular face, after prepared received an allogeneic collage with similar color and dimension. Follow-up after 12 months indicated a stable restoration. Clinically, the site was without signs of caries, migration of the fragment or marginal infiltration. Biological restoration is a viable alternative for reestablishing function and esthetics to damaged/decayed teeth and therefore, biological restoration as an alternative to other restorative options.

  4. Architectural restoration: different conceptions during centuries

    Directory of Open Access Journals (Sweden)

    Salvatore Lorusso


    Full Text Available The work reassumes the fundamental phases, in reference to the historical changes, of the conceptions related to the restoration and to the maintenance of the architectural works of art. It is opportune to reassume the evolution of the methods and the techniques applied to the restoration of the aforesaid manufactured articles, also in relationship to the theoretical conceptions. The explication of the routine of restoration has concerned particularly the actual applications. Close to the theory and to the routine of the restoration it has been set in evidence the development of the concept of "maintenance", understood as preliminary and complementary to the restoration itself: such concept has been express referring to the Charters of restoration from the beginning of the last century to today. It is intended, therefore, to follow a historical-critical path conceived in the different, and also complementary, phases of historical, aesthetical and technological development.

  5. Evaluating the process of ecological restoration

    Directory of Open Access Journals (Sweden)

    Christer Nilsson


    Full Text Available We developed a conceptual framework for evaluating the process of ecological restoration and applied it to 10 examples of restoration projects in the northern hemisphere. We identified three major phases, planning, implementation, and monitoring, in the restoration process. We found that evaluation occurred both within and between the three phases, that it included both formal and informal components, and that it often had an impact on the performance of the projects. Most evaluations were short-term and only some parts of them were properly documented. Poor or short-term evaluation of the restoration process creates a risk that inefficient methods will continue to be used, which reduces the efficiency and effectiveness of restoration. To improve the restoration process and to transfer the knowledge to future projects, we argue for more formal, sustained evaluation procedures, involving all relevant stakeholders, and increased and improved documentation and dissemination of the results.

  6. The Management of Dissonance in Nature Restoration

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel


    by the Skjern River Restoration Project (1999-2003), one interpretation of the landscape sometimes suppresses other valid interpretations, neglecting its diverse history. Landscape architecture might, however, provide an alternative approach to nature restoration that is more site-specific, allowing...... for multiple interpretations to coexist. Indications can be found in the Re-naturalization of River Aire (2002-2015)—a restoration project, which reveals approaches that could be labelled landscape architecture specific....

  7. Can Viral Videos Help Beaver Restore Streams? (United States)

    Castro, J. M.; Pollock, M. M.; Lewallen, G.; Jordan, C.; Woodruff, K.


    Have you watched YouTube lately? Did you notice the plethora of cute animal videos? Researchers, including members of our Beaver Restoration Research team, have been studying the restoration potential of beaver for decades, yet in the past few years, beaver have gained broad acclaim and some much deserved credit for restoration of aquatic systems in North America. Is it because people can now see these charismatic critters in action from the comfort of their laptops? While the newly released Beaver Restoration Guidebook attempts to answer many questions, sadly, this is not one of them. We do, however, address the use of beaver (Castor canadensis) in stream, wetland, and floodplain restoration and discuss the many positive effects of beaver on fluvial ecosystems. Our team, composed of researchers from NOAA National Marine Fisheries Service, US Fish and Wildlife Service, US Forest Service, and Portland State University, has developed a scientifically rigorous, yet accessible, practitioner's guide that provides a synthesis of the best available science for using beaver to improve ecosystem functions. Divided into two broad sections -- Beaver Ecology and Beaver Restoration and Management -- the guidebook focuses on the many ways in which beaver improve habitat, primarily through the construction of dams that impound water and retain sediment. In Beaver Ecology, we open with a discussion of the general effects that beaver dams have on physical and biological processes, and we close with "Frequently Asked Questions" and "Myth Busters". In Restoration and Management, we discuss common emerging restoration techniques and methods for mitigating unwanted beaver effects, followed by case studies from pioneering practitioners who have used many of these beaver restoration techniques in the field. The lessons they have learned will help guide future restoration efforts. We have also included a comprehensive beaver ecology library of over 1400 references from scientific journals

  8. Restoration of variable density film soundtracks


    Besserer, Bernard; Etienne, Decencière; Hassaïne, Abdelâali


    Full text available at; International audience; The restoration of motion picture films has been an active research field for many years. The restoration of the soundtrack however has mainly been performed at the audio domain in spite of the fast that it is recorded as a continuous image on the film stock. In this paper, we propose a new restoration method for variable density soundtracks. The method first d...

  9. Governing Forest Landscape Restoration: Cases from Indonesia

    Directory of Open Access Journals (Sweden)

    Cora van Oosten


    Full Text Available Forest landscape restoration includes both the planning and implementation of measures to restore degraded forests within the perspective of the wider landscape. Governing forest landscape restoration requires fundamental considerations about the conceptualisation of forested landscapes and the types of restoration measures to be taken, and about who should be engaged in the governance process. A variety of governance approaches to forest landscape restoration exist, differing in both the nature of the object to be governed and the mode of governance. This paper analyses the nature and governance of restoration in three cases of forest landscape restoration in Indonesia. In each of these cases, both the original aim for restoration and the initiators of the process differ. The cases also differ in how deeply embedded they are in formal spatial planning mechanisms at the various political scales. Nonetheless, the cases show similar trends. All cases show a dynamic process of mobilising the landscape’s stakeholders, plus a flexible process of crafting institutional space for conflict management, negotiation and decision making at the landscape level. As a result, the landscape focus changed over time from reserved forests to forested mosaic lands. The cases illustrate that the governance of forest landscape restoration should not be based on strict design criteria, but rather on a flexible governance approach that stimulates the creation of novel public-private institutional arrangements at the landscape level.

  10. Clinical guidelines for indirect resin restorations. (United States)

    Shannon, A


    Ongoing advances in adhesive dentistry have made it possible to successfully and predictably bond tooth-supporting restorations using conservative preparation techniques. Improvements in the durability and esthetic properties of tooth-colored restorative materials have also increased the range of available treatment options. However, dentists have been slow to accept both direct and indirect posterior esthetics. This article provides a step-by-step technique for practitioners who choose to treat their patients with indirect resin esthetic restorations. It will not discuss other posterior restorative treatment techniques or materials (i.e. gold, porcelain, amalgam, bonded amalgam, or direct resin).

  11. Esthetic restoration of discolored primary incisors. (United States)

    Margolis, Fred S


    Restoring primary teeth can be a strenuous task for many dentists who would like to have an esthetic, easy-to-use and relatively quick restoration for children. But, the restoration of carious, fractured or discolored primary incisors gives the dentist the satisfaction of knowing that he/she has restored the smile and self-confidence of a growing child. This article describes a technique which is relatively easy and produces a beautiful outcome in a relatively short time. The author has used the technique in hundreds of children for over twenty-five years. Modifications in the technique have been made as newer materials and techniques have evolved.

  12. Composite veneering of complex amalgam restorations. (United States)

    Demarco, Flávio Fernando; Zanchi, César Henrique; Bueno, Márcia; Piva, Evandro


    In large posterior cavities, indirect restorations could provide improved performance when compared to direct restorations, but with higher cost and removal of sound tooth structure. Improved mechanical properties have resulted in good clinical performance for amalgam in large cavities but without an esthetic appearance. Resin composites have become popular for posterior restorations, mainly because of good esthetic results. A restorative technique is presented that combines the esthetic properties of directly bonded resin composite and the wide range of indications for amalgam in stress-bearing areas.

  13. Ecological feasibility studies in restoration decision making. (United States)

    Hopfensperger, Kristine N; Engelhardt, Katharina A M; Seagle, Steven W


    The restoration of degraded systems is essential for maintaining the provision of valuable ecosystem services, including the maintenance of aesthetic values. However, restoration projects often fail to reach desired goals for a variety of ecologic, financial, and social reasons. Feasibility studies that evaluate whether a restoration effort should even be attempted can enhance restoration success by highlighting potential pitfalls and gaps in knowledge before the design phase of a restoration. Feasibility studies also can bring stakeholders together before a restoration project is designed to discuss potential disagreements. For these reasons, a feasibility study was conducted to evaluate the efficacy of restoring a tidal freshwater marsh in the Potomac River near Alexandria, Virginia. The study focused on science rather than engineering questions, and thus differed in approach from other feasibility studies that are mostly engineering driven. The authors report the framework they used to conduct a feasibility study to inform other potential restoration projects with similar goals. The seven steps of the framework encompass (1) initiation of a feasibility study, (2) compilation of existing data, (3) collection of current site information, (4) examination of case studies, (5) synthesis of information in a handbook, (6) meeting with selected stakeholders, and (7) evaluation of meeting outcomes. By conducting a feasibility study using the seven-step framework, the authors set the stage for conducting future compliance studies and enhancing the chance of a successful restoration.


    Institute of Scientific and Technical Information of China (English)

    WANG Xu-gao; LI Xiu-zhen; HE Hong S; HU Yuan-man


    Ecological restoration is widely employed from tens to millions of hectares in space, and from tens of days to thousands of years in time, which forces consideration of it thoroughly. We argue that three questions are the most important among the contents relevant of ecological restoration, including why, what and how to restore degraded systems. Why to restore determines whether or not the degraded ecological systems should be restored. What to restore is the goal of ecological restoration. The explicit goal of ecological restoration is necessary to guide ecological restoration workers in pursuit of excellence and prevent restoration from being swamped by purely technological activities. And how to restore means the methods and steps we should apply. To ensure the final success of ecological restoration, restored sites should be monitored and managed for long time to determine whether the selected methods are appropriate, and can be remedy better. Only to deal with these effectively, ecological restoration would be the hope for the future.

  15. A pharmacophore model for dopamine D4 receptor antagonists (United States)

    Boström, Jonas; Gundertofte, Klaus; Liljefors, Tommy


    A pharmacophore model for dopamine D4 antagonists has been developed on the basis of a previously reported dopamine D2 model. By using exhaustive conformational analyses (MM3* force field and the GB/SA hydration model) and least-squares molecular superimposition studies, a set of eighteen structurally diverse high affinity D4 antagonists have successfully been accommodated in the D4 pharmacophore model. Enantioselectivities may be rationalized by conformational energies required for the enantiomers to adopt their proposed bioactive conformations. The pharmacophore models for antagonists at the D4 and D2 receptor subtypes have been compared in order to get insight into molecular properties of importance for D2/D4 receptor selectivity. It is concluded that the bioactive conformations of antagonists at the two receptor subtypes are essentially identical. Receptor essential volumes previously identified for the D2 receptor are shown to be present also in the D4 receptor. In addition, a novel receptor essential volume in the D4 receptor, not present in the D2 receptor, has been identified. This feature may be exploited for the design of D4 selective antagonists. However, it is concluded that the major determinant for D2/D4 selectivity is the nature of the interactions between the receptor and aromatic ring systems. The effects of the electronic properties of these ring systems on the affinities for the two receptor subtypes differ substantially.

  16. Anterior provisional restorations used to determine form, function, and esthetics for complex restorative situations, using all-ceramic restorative systems. (United States)

    Reshad, Mamaly; Cascione, Domenico; Kim, Tae


    A technique is proposed for the restoration of a large and visible maxillary anterior defect. The importance of proper diagnosis, treatment planning, and communication is emphasized. Irreversible treatment should only be rendered once patient approval has been obtained through objective evaluation with provisional restorations. The techniques presented in this article use a combination of ceramic systems currently available to satisfy functional demands while achieving acceptable esthetics. A controlled series of steps, where the provisional restorative components are being replaced by the definitive ones is planned. The only difference between the provisional and definitive restorative components is the material used. The definitive restorations consisted of an implant-supported zirconium oxide framework. Individual pressed porcelain restorations were luted to the framework and a natural tooth. CLINICAL SIGNIFICANCE Provisional restorations allow an objective form of communication. Vertical and horizontal transitional lines can be effectively masked with appropriate treatment planning and a skilled ceramist. Many traditional dental laboratory steps may be eliminated or simplified without compromising the definitive restorations.

  17. Dileptons and Chiral Symmetry Restoration

    CERN Document Server

    Hohler, P M


    We report on recent work relating the medium effects observed in dilepton spectra in heavy-ion collisions to potential signals of chiral symmetry restoration. The key connection remains the approach to spectral function degeneracy between the vector-isovector channel with its chiral partner, the axialvector-isovector channel. Several approaches are discussed to elaborate this connection, namely QCD and Weinberg sum rules with input for chiral order parameters from lattice QCD, and chiral hadronic theory to directly evaluate the medium effects of the axialvector channel and the pertinent pion decay constant as function of temperature. A pattern emerges where the chiral mass splitting between rho and a_1 burns off and is accompanied by a strong broadening of the spectral distributions.

  18. Image restoration using spectrum estimation (United States)

    Na, Ki-Woon; Paik, Joon-Ki


    A stochastic approach to image restoration is proposed by using various spectrum estimation techniques. In order to estimate the original image from the knowledge of observed image, the minimum mean square error filter or Wiener filter is known to be optimum in the sense of minimizing the mean square error. The optimality of Wiener filter, however, holds only when the power spectra of the original image and noise are given in addition to the transfer function of the imaging system. In practice, the information of the original image is generally not available. In the present paper additive noise is assumed to be white with known variance and the Wiener filter is implemented using various estimation techniques for the original spectrum. The proposed method shows significant improvement over the conventional methods, such as the Wiener filter using constant signal-to-noise power ratio, particularly for images with low signal-to-noise ratio.

  19. Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep. (United States)

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit


    Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30-90 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2α were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level.

  20. Optimal load shedding and restoration (United States)

    Xu, Ding

    Load shedding is an emergency control action in power systems that can save systems from a wide-area blackout. Underfrequency load shedding, steady state load shedding, and voltage load shedding are widely used in power systems. These methods utilize either the steady state model or a simplified dynamic model to represent a power systems. In this dissertation, a general optimal load shedding method that considers both the dynamic process and load distribution is proposed. The unfavorable load shedding is then formulated as an optimization problem with the objective function of cost minimization. This objective function is subjected to system, security, and operation constraints. The entire problem becomes a question of optimization with differential and nonlinear equations as constraints. To solve this problem, discretization is used to change the differential equations into algebraic equations. The original problem is thus reformulated as an optimization problem and can be solved by a standard mathematical program. The general idea is then applied to traditional power systems, deregulated power systems, power systems with distributed generation, and load restoration. In the traditional power system, the method shows that governor action, generation dynamic, disturbance location, and economic factors can be taken into consideration. In the deregulated power system, two power market models are developed and incorporated into the load shedding scheme. In power systems with multiple distributed generations, the different cases of disturbances are analyzed and models of different distributed generation developed. The general idea is then applied. Finally, the load restoration problem is studied, and it is proposed that an optimization method be applied to it. This dissertation provides a comprehensive solution for load shedding problem in power systems. The models developed in this research can also be used to study other power system problems.

  1. Megasessions for Robotic Hair Restoration. (United States)

    Pereira, Joa O Carlos; Pereira Filho, Joa O Carlos; Cabrera Pereira, Joa O Pedro


    A robotic system can select and remove individual hair follicles from the donor area with great precision and without fatigue. This report describes the use of the robotic system in a megasession for hair restoration. Patients were instructed to cut their hair to 1.0 to 1.2 mm before surgery. The robot selected and removed 600 to 800 grafts per hour so the follicular units (FU)s could be transplanted manually to recipient sites. The robot arm consists of a sharp inner punch and a blunt outer punch which together separate FUs from the sur- rounding tissue. Stereoscopic cameras controlled by image processing software allow the system to identify the angle and direction of hair growth. The physician and one assistant control the harvesting with a hand-held remote control and computer monitor while the patient is positioned in an adjustable chair. When the robot has harvested all the FUs they are removed by technicians with small forceps. Hairline design, creation of recipient sites, and graft placement are performed manually by the physician. Clinical photographs before and after surgery show that patients experience excellent outcomes with the robotic megasession. Phy- sician fatigue during graft extraction is reduced because the robot performs the repetitive movements without fatigue. Variability of graft extraction is minimized because the robot's optical system can be programmed to choose the best FUs. The transection rate is reduced because the robot's graft extraction system uses two needles, a sharp one to piece the skin and a blunt needle to dissect the root without trauma. A robotic megasession for hair restoration is minimally invasive, does not result in linear scars in the donor area, and is associated with minimal fatigue and discomfort for both patient and physician. Healing is rapid and patients experience a high level of satisfaction with the results. J Drugs Dermatol. 2016;15(11):1407-1412..

  2. Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone. (United States)

    Hughes, Sam; Hickey, Louise; Donaldson, Lucy F; Lumb, Bridget M; Pickering, Anthony E


    The descending noradrenergic (NAergic) projection to the spinal cord forms part of an endogenous analgesic system. After nerve injury, a localised failure in this compensatory system has been implicated as a permissive factor in the development of neuropathic sensitisation. We investigated whether restoring descending NAergic tone with intrathecal reboxetine can oppose the development of the neuropathic pain phenotype after tibial nerve transection (TNT). Rats had a lumbar intrathecal catheter implanted at the time of nerve injury for administration of reboxetine (10 μg) in both acute and chronic dosing experiments. In acute dosing experiments, both intrathecal and systemic (30 mg/kg) reboxetine partially reversed mechanical allodynia. This antiallodynic effect of intrathecal reboxetine was blocked by prior administration of yohimbine (α2-adrenoceptor antagonist, 30 μg) but not by prazosin (α1-adrenoceptor antagonist, 30 μg) or propranolol (β-adrenoceptor antagonist, 100 μg). Chronic intrathecal reboxetine (10 μg, intrathecally, twice daily for 2 weeks) suppressed the development of cold and mechanical allodynia. Nerve-injured animals demonstrated a place preference for intrathecal reboxetine, suggesting that it also reduced spontaneous pain. In contrast, an equivalent antiallodynic dose of systemic reboxetine (30 mg/kg) was aversive in both naive and TNT rats. On cessation of chronic intrathecal reboxetine, there was a gradual development of allodynic sensitisation that was indistinguishable from control TNT animals by 7 days after the end of dosing. Our results suggest that pharmacological restoration of spinal NAergic tone with intrathecal reboxetine can suppress both allodynia and spontaneous pain in the TNT model.

  3. Survival of ART restorations assessed using selected FDI and modified ART restoration criteria

    NARCIS (Netherlands)

    Farag, A.; Sanden, W.J.M. van der; Abdelwahab, H.; Frencken, J.E.F.M.


    A new set of criteria for assessing the quality of restorations using modern restorative materials, named FDI criteria, was recently introduced. This study tested the null hypothesis that there is no significant difference in survival estimate percentages of ART restorations assessed using selected

  4. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Tuminello


    Full Text Available Research on apolipoprotein E (APOE has consistently revealed a relationship between the gene's ε4 allele and risk for development of Alzheimer's disease (AD. However, research with younger populations of ε4 carriers has suggested that the APOE ε4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.

  5. Discovery of the improved antagonistic prolactin variants by library screening. (United States)

    Liu, Yun; Gong, Wei; Breinholt, Jens; Nørskov-Lauritsen, Leif; Zhang, Jinchao; Ma, Qinhong; Chen, Jianhe; Panina, Svetlana; Guo, Wei; Li, Tengkun; Zhang, Jingyuan; Kong, Meng; Liu, Zibing; Mao, Jingjing; Christensen, Leif; Hu, Sean; Wang, Lingyun


    Prolactin (PRL), a potent growth stimulator of the mammary epithelium, has been suggested to be a factor contributing to the development and progression of breast and prostate cancer. Several PRL receptor (PRLR) antagonists have been identified in the past decades, but their in vivo growth inhibitory potency was restricted by low receptor affinity, rendering them pharmacologically unattractive for clinical treatment. Thus, higher receptor affinity is essential for the development of improved PRLR antagonistic variants with improved in vivo potency. In this study, we generated Site 1 focused protein libraries of human G129R-PRL mutants and screened for those with increased affinity to the human PRLR. By combining the mutations with enhanced affinities for PRLR, we identified a novel G129R-PRL variant with mutations at Site 1 that render nearly 50-fold increase in the antagonistic potency in vitro.


    Directory of Open Access Journals (Sweden)



    Full Text Available Schizophyllum commune Fr., is one of the important fungi, causes brown germ and seed rot of oil palm. Biodiversity of antagonistic bacteria from oil palm plantations in Peninsular Malaysia is expected to support in development of biopesticide. Isolation with liquid assay and screening antagonistic bacteria using dual culture assay were carried out in the bioexploration. A total of 265 bacterial isolates from plant parts of oil palm screened 52 antagonistic bacterial isolates against 5. commune. Bacterial isolates were identified by using Biolog* Identification System i.e. Bacillus macroccanus, B. thermoglucosidasius, Burkholderia cepacia, B. gladioli, B. multivorans, B pyrrocinia, B. spinosa, Corynebacterium agropyri, C. misitidis, Enterobacter aerogenes, Microbacterium testaceum, Pseudomonas aeruginosa, P. citronellolis, Rhodococcus rhodochrous, Serratia ficaria, Serratia sp., S. marcescens, Staphylococcus sciuri, Sternotrophomonas maltophilia.

  7. Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity (United States)

    Kaku, David A.; Giffard, Rona G.; Choi, Dennis W.


    Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.

  8. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V


    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  9. Development and characterization of high affinity leptins and leptin antagonists. (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh


    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin.

  10. Development and Characterization of High Affinity Leptins and Leptin Antagonists* (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh


    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin. PMID:21119198

  11. Restoration of the endodontically treated posterior tooth

    Directory of Open Access Journals (Sweden)

    Andrea Polesel


    Results and conclusions: Direct adhesive restorations, indirect bonded restorations and traditional full crown are three therapeutic options for the single posterior endodontically treated teeth. The amount of remaining sound tooth structure is the most significant factor influencing the therapeutic approach. The clinician's operative skill is a determining aspect for long-term success of adhesive inlays.

  12. The Teacher's Guide to Restorative Classroom Discipline (United States)

    Meyer, Luanna H.; Evans, Ian M.


    With restorative discipline, schools move beyond punitive approaches to shared expectations for learning and behavior. Used together with "The School Leader's Guide to Restorative Discipline," this teacher's guide shows how to create a welcoming and responsible community within your classroom, contributing to a consistent, schoolwide approach to…

  13. Changing trends in hair restoration surgery

    Directory of Open Access Journals (Sweden)

    Venkataram Mysore


    Full Text Available Androgenetic alopecia is an important and common cause for baldness. Despite recent advances, the drug therapy of this condition remains unsatisfactory. Surgical hair restoration is the only permanent method of treating this condition. Introduction of recent techniques such as follicular unit transplantation have improved the cosmetic results and patient satisfaction. This article discusses the latest trends in hair restoration surgery.

  14. Restoration of missing or misplaced canines. (United States)

    Bower, C F; Reinhardt, R A


    Restorative treatments for canines were discussed to correct three clinical abnormalities: (1) fully erupted permanent canine in the lateral incisor position, (2) missing permanent canines, and (3) partially exposed canines in normal arch position. The primary concerns are the development of esthetics, anterior guidance, and adequate support for fixed restorations.

  15. Restoration of a fractured primary incisor. (United States)

    Romero, M; Saez, M; Cabrerizo, C


    Esthetic restoration on primary teeth has been a special challenge to pediatric dentists. Composite restorations are the most often used treatment for decay and fractures of primary teeth, however, there are other possible alternatives. We present a case in which we have used an acrylic crown to treat a fractured primary incisor in a 1.8 years old child.

  16. Restoring primary anterior teeth: updated for 2014. (United States)

    Waggoner, William F


    The purpose of this paper was to review the current literature associated with the techniques and materials for the restoration of primary anterior teeth and make clinical recommendations based upon the available literature. A variety of esthetic restorative materials are available to utilize for restoring primary incisors. Awareness of the specific strengths, weakness, and properties of each material can enhance the clinician's ability to make the best choice of selection for each individual situation. Intracoronal restorations of primary teeth may utilize resin composites, glass ionomer cements, resin-modified ionomers, or polyacid-modified resins. Full coronal restoration of primary incisors may be indicated for a number of reasons. Crowns available for restoration of primary incisors include those that are directly bonded onto the tooth, which generally are a resin material, and crowns that are luted onto the tooth and are either some type of stainless steel or zirconia crown. There is insufficient controlled, clinical data to suggest that one type of restoration is superior to another. Operator preferences, esthetic demands by parents, the child's behavior, the amount of tooth structure remaining, and moisture and hemorrhage control are all variables that affect the decision and ultimate outcome of whatever restorative solution is chosen.

  17. 76 FR 47055 - Emergency Restoration Plan (ERP) (United States)


    ... 7 CFR Part 1730 RIN 0572-AC16 Emergency Restoration Plan (ERP) AGENCY: Rural Utilities Service, USDA... maintain an Emergency Response Plan (ERP) that details how the borrower will restore its system in the... ERP requirement was not entirely new to the borrowers, as RUS had recommended similar ``plans'' in...

  18. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan


    BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...... proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive...

  19. Barnidipine, a long-acting slow onset calcium antagonist. (United States)

    Korstanje, C


    Barnidipine is a stereochemically pure dihydropyridine calcium antagonist with a high potency. The drug showed a slow onset and long-lasting vasorelaxating effect in vitro, and strong antihypertensive activity in hypertension models. Barnidipine was shown to have a high vasoselectivity and offered protection in cardiac and renal ischaemia models. The in vitro drug:drug interaction profile suggests a low potential for clinically relevant interactions with concomitant medication. It can be anticipated that barnidipine is an attractive calcium antagonist, offering good blood pressure control without compensatory baroreflex activity.

  20. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist (United States)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev


    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  1. [Esthetic restorations of primary anterior teeth]. (United States)

    Elqadir, A Jamil; Shapira, J; Ziskind, K; Ram, D


    Esthetic treatment of primary teeth is one of the greatest challenges to pediatric dentists. A variety of restorative options using full coverage are available for anterior primary teeth. In the last half century the emphasis on treatment of severely decayed primary teeth shifted from extraction to restoration. In the past, restorations consisted of placement of stainless steel crowns on severely decayed teeth. However, they are esthetically unacceptable today. Over the last decade parents expect a higher esthetic standard for their children's primary teeth. Thus, the restoration should provide esthetic appearance and durability in addition to restoring function. The purpose of this review is to describe the types of full coverage options for anterior primary teeth currently available.

  2. Techniques of forest restoration in restingas

    Directory of Open Access Journals (Sweden)

    Liliane Garcia da Silva Morais Rodrigues


    Full Text Available Restinga is an ecosystem of the Atlantic Forest Biome vegetation which has ecological functions and is undergoing anthropogenic occupations that result in the disturbance and its suppression of these environments. But to be the restoration of degraded restinga is necessary to know the different formations of the ecosystem and their respective characteristics. From this diagnosis, one can choose the most appropriate techniques to apply for its restoration. Thus, this study aims to conduct a literature on restoration techniques in restinga environments. It was found that forest restoration on restinga, in most cases there is use of natural regeneration techniques nucleation, and these studies highlight the successional advances and establishments of life forms preserved features of the area, thus making the restoration in these environments.

  3. Crown lengthening surgery: a restorative-driven periodontal procedure. (United States)

    Levine, D F; Handelsman, M; Ravon, N A


    Improper management of the periodontal tissues during restorative procedures is a common, but often overlooked, cause of failure. When a restoration is placed, the preservation of an intact, healthy periodontium is necessary to maintain the tooth or teeth being restored. Predictable long-term restorative success requires a combination of restorative principles with the correct management of the periodontal tissues.

  4. An in vitro study of dental enamel wear by restorative materials using radiometric method; Estudo in vitro do desgaste do esmalte dental pelos materiais restauradores utilizando metodo radiometrico

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Lena Katekawa


    There is an increasing demand and interest to study the dental materials wear as well as about the abrasion effect on antagonistic teeth. Due to the fact that the existent restorative materials have no specifications about their abrasiveness, it is necessary the establishment of degrees of comparison among them to support clinical application. In this work, the radiometric method was applied to study the enamel wear caused by another enamel and by restorative materials (Ceramco II, Noritake and Finesse porcelains, Artglass and Targis). The dental enamel made radioactive by irradiation at the IEA-R1m nuclear research reactor under a thermal neutron flux was submitted to wear in a machine which allows sliding motion of an antagonistic surface in contact with this radioactive enamel. The enamel wear was evaluated by measuring beta activity of {sup 32}P transferred to water from this irradiated tooth. Results obtained indicated that dental porcelains cause pronounced enamel wear when compared with that provoked by another enamel or by resin materials. Resin materials caused less enamel wear than another enamel. Vickers microhardness data obtained for antagonistic materials showed a correlation with the wear caused to the enamel. This study allowed to conclude that the radiometric method proposed can be used satisfactorily in the evaluation of enamel wear by restorative materials. This method presents advantages due to quick responses and ease of analyses There is (author)

  5. Error image aware content restoration (United States)

    Choi, Sungwoo; Lee, Moonsik; Jung, Byunghee


    As the resolution of TV significantly increased, content consumers have become increasingly sensitive to the subtlest defect in TV contents. This rising standard in quality demanded by consumers has posed a new challenge in today's context where the tape-based process has transitioned to the file-based process: the transition necessitated digitalizing old archives, a process which inevitably produces errors such as disordered pixel blocks, scattered white noise, or totally missing pixels. Unsurprisingly, detecting and fixing such errors require a substantial amount of time and human labor to meet the standard demanded by today's consumers. In this paper, we introduce a novel, automated error restoration algorithm which can be applied to different types of classic errors by utilizing adjacent images while preserving the undamaged parts of an error image as much as possible. We tested our method to error images detected from our quality check system in KBS(Korean Broadcasting System) video archive. We are also implementing the algorithm as a plugin of well-known NLE(Non-linear editing system), which is a familiar tool for quality control agent.

  6. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    DEFF Research Database (Denmark)

    Brygger, Louise; Herrstedt, Jørn


    INTRODUCTION: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients. AREAS COVERED: The purpose of this article is to outline the risk of cardiac adverse events...

  7. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  8. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Bruce Lyeth


    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.

  9. How Hybrid Organizations Turn Antagonistic Assets into Complementarities

    DEFF Research Database (Denmark)

    Hockerts, Kai


    This article focuses on people excluded from traditional markets as employees, producers, or consumers on the grounds that they lack the appropriate skills. It describes the processes through which these perceived liabilities can be overcome by so-called hybrid organizations. Hybrids pursue expli...... for complementarities, and by creating demands for antagonistic assets, or by using partnerships....

  10. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn;


    Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered: Preclin......Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered...... receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...... antagonists appear to assume an intermediate position by being marginally superior to placebo but inferior to conventional antipsychotic drugs. Three previous 5-HT2A receptor antagonists have been discontinued after Phase II or III trials, and available Phase IIa data on the remaining 5-HT2A receptor...

  11. Facilitative and antagonistic interactions between plant viruses in mixed infections. (United States)

    Syller, Jerzy


    Mixed infections of plant viruses are common in nature, and a number of important virus diseases of plants are the outcomes of interactions between causative agents. Multiple infections lead to a variety of intrahost virus-virus interactions, many of which may result in the generation of variants showing novel genetic features, and thus change the genetic structure of the viral population. Hence, virus-virus interactions in plants may be of crucial significance for the understanding of viral pathogenesis and evolution, and consequently for the development of efficient and stable control strategies. The interactions between plant viruses in mixed infections are generally categorized as synergistic or antagonistic. Moreover, mixtures of synergistic and antagonistic interactions, creating usually unpredictable biological and epidemiological consequences, are likely to occur in plants. The mechanisms of some of these are still unknown. This review aims to bring together the current knowledge on the most commonly occurring facilitative and antagonistic interactions between related or unrelated viruses infecting the same host plant. The best characterized implications of these interactions for virus-vector-host relationships are included. The terms 'synergism' and 'helper dependence' for facilitative virus-virus interactions, and 'cross-protection' and 'mutual exclusion' for antagonistic interactions, are applied in this article.

  12. Determinants of effective, safe and convenient vitamin K antagonist use

    NARCIS (Netherlands)

    Kooistra, Hilde Afra Margaretha


    Vitamin K antagonists (VKA) are frequently used anticoagulants. They are very effective in preventing atrial fibrillation related strokes and recurrent venous thrombosis. However, it can be difficult to achieve an optimal balance between the efficacy and side effects (bleeding), as the dose response

  13. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)


    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  14. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, A.R.; Napoli, M. Di; Goldstein, J.N.; Schreuder, F.H.; Tetri, S.; Tatlisumak, T.; Yan, B.; Nieuwenhuizen, K.M.; Dequatre-Ponchelle, N.; Lee-Archer, M.; Horstmann, S.; Wilson, D.; Pomero, F.; Masotti, L.; Lerpiniere, C.; Godoy, D.A.; Cohen, A.S.; Houben, R.; Al-Shahi Salman, R.; Pennati, P.; Fenoglio, L.; Werring, D.; Veltkamp, R.; Wood, E.; Dewey, H.M.; Cordonnier, C.; Klijn, C.J.M.; Meligeni, F.; Davis, S.M.; Huhtakangas, J.; Staals, J.; Rosand, J.; Meretoja, A.


    OBJECTIVE: There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  15. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, Adrian R.; Di Napoli, Mario; Goldstein, Joshua N.; Schreuder, Floris H B M; Tetri, Sami; Tatlisumak, Turgut; Yan, Bernard; Van Nieuwenhuizen, Koen M.; Dequatre-Ponchelle, Nelly; Lee-Archer, Matthew; Horstmann, Solveig; Wilson, Duncan; Pomero, Fulvio; Masotti, Luca; Lerpiniere, Christine; Godoy, Daniel Agustin; Cohen, Abigail S.; Houben, Rik; Al-Shahi Salman, Rustam; Pennati, Paolo; Fenoglio, Luigi; Werring, David; Veltkamp, Roland; Wood, Edith; Dewey, Helen M.; Cordonnier, Charlotte; Klijn, Catharina J M; Meligeni, Fabrizio; Davis, Stephen M.; Huhtakangas, Juha; Staals, Julie; Rosand, Jonathan; Meretoja, Atte


    Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  16. Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists. (United States)

    Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung; Yeom, Miyoung; Moon, Bongjin; Huang, Xi-Ping; Roth, Bryan L; Lee, Kangho; Rhim, Hyewhon; Choo, Il Han; Chong, Youhoon; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah


    The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1-([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R, 5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.

  17. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G


    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  18. Does intergenerational social mobility affect antagonistic attitudes towards ethnic minorities?

    NARCIS (Netherlands)

    Tolsma, J.; Graaf, N.D. de; Quillian, L.


    Up till now, no study satisfactorily addressed the effect of social mobility on antagonistic attitudes toward ethnic minorities. In this contribution, we investigate the effect of educational and class intergenerational mobility on ethnic stereotypes, ethnic threat, and opposition to ethnic intermar

  19. Komplikationer til langtidsbehandling med vitamin K-antagonister

    DEFF Research Database (Denmark)

    May, O; Garne, E; Mickley, H


    Long-term treatment with vitamin K antagonists (vKA) frequently involves complications. The commonest complication is haemorrhage and cases of serious haemorrhage are stated in the literature to occur with a frequency per 1,000 treatment years of 12-108, of which 2-17 are fatal. The majority...

  20. Myofascial force transmission via extramuscular pathways occurs between antagonistic muscles. (United States)

    Huijing, Peter A; Baan, Guus C


    Most often muscles (as organs) are viewed as independent actuators. To test if this is true for antagonistic muscles, force was measured simultaneously at: (1) the proximal and distal tendons of the extensor digitorum muscle (EDL) to quantify any proximo-distal force differences, as an indicator of myofascial force transmission, (2) at the distal tendons of the whole antagonistic peroneal muscle group (PER) to test if effects of EDL length changes are present and (3) at the proximal end of the tibia to test if myofascially transmitted force is exerted there. EDL length was manipulated either at the proximal or distal tendons. This way equal EDL lengths are attained at two different positions of the muscle with respect to the tibia and antagonistic muscles. Despite its relatively small size, lengthening of the EDL changed forces exerted on the tibia and forces exerted by its antagonistic muscle group. Apart from its extramuscular myofascial connections, EDL has no connections to either the tibia or these antagonistic muscles. Proximal EDL lengthening increased distal muscular forces (active PER DeltaF approximately +1.7%), but decreased tibial forces (passive from 0.3 to 0 N; active DeltaF approximately -5%). Therefore, it is concluded that these antagonistic muscles do not act independently, because of myofascial force transmission between them. Such a decrease in tibial force indicates release of pre-strained connections. Distal EDL lengthening had opposite effects (tripling passive force exerted on tibia; active PER force DeltaF approximately -3.6%). It is concluded that the length and relative position of the EDL is a co-determinant of passive and active force exerted at tendons of nearby antagonistic muscle groups. These results necessitate a new view of the locomotor apparatus, which needs to take into account the high interdependence of muscles and muscle fibres as force generators, as well as proximo-distal force differences and serial and parallel

  1. Hydrological classification, a practical tool for mangrove restoration

    NARCIS (Netherlands)

    Loon, van Anne F.; Brake, te Bram; Huijgevoort, Van Marjolein H.J.; Dijksma, Roel


    Mangrove restoration projects, aimed at restoring important values of mangrove forests after degradation, often fail because hydrological conditions are disregarded. We present a simple, but robust methodology to determine hydrological suitability for mangrove species, which can guide restoration

  2. Atraumatic restorative treatment in atypical cavities

    Directory of Open Access Journals (Sweden)

    Letícia Simino Carvalho


    Full Text Available The atraumatic restorative treatment has been widely divulged among professionals in the area of Pediatric Dentistry. This restorative technique is included in the philosophy of Minimal Intervention and is considered one of the most conservative treatments, because only the layer of infected dentin caries is removed. Moreover, the atraumatic restorative treatment has been shown to be less painful than conventional approaches, and local anesthesia is rarely required. After the removal of the infected dentin, the cavities are filled with glass ionomer cement, a material that has antimicrobial capacity, good marginal sealing and constant fluorine release and recharge. In spite of the increasing number of studies about atraumatic restorative treatment, only studies related to restorations in occlusal cavities have shown scientific evidences about the technique. The aim of this study was to evaluate the feasibility of atraumatic restorative treatment in cavities with 3 or more surfaces involved, by means of a clinical case report of a patient with extensive dstruction in primary teeth, who was submitted to atraumatic restorative treatment, and observe the result of the treatment after one year of clinical and radiographic control.


    Latarjet, Raymond; Caldas, Luis Renato


    1. E. coli, strain K-12, and B. megatherium 899, irradiated in strict but still undefined physiological conditions with certain heavy doses of ultraviolet light, are efficiently restored by catalase, which acts on or fixes itself upon the bacteria in a few minutes. This restoration (C. R.), different from photorestoration, is aided by a little visible light. 2. At 37° the restorability lasts for about 2 hours after UV irradiation; the restored cells begin to divide at the same time as the normal survivors. 3. C. R. is not produced after x-irradiation. 4. B. megatherium Mox and E. coli, strain B/r show little C. R.; E. coli strain B shows none. None of these three strains is lysogenic, whereas the two preceding catalase-restorable strains are. 5. Phage production in the system "K-12 infected with T2 phage" is restored by catalase after UV irradiation, whereas phage production in the system "infected B" is not. 6. With K-12, catalase does not prevent the growth of phage and the lysis induced by UV irradiation (Lwoff's phenomenon). 7. Hypotheses are discussed concerning: (a) the chemical nature of this action of catalase; (b) a possible relation between C. R. and lysogenicity of the sensitive bacteria; (c) the consequences of such chemical restorations on the general problem of cell radiosensitivity. PMID:14898028

  4. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vikram, Ajit [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India); Jena, Gopabandhu, E-mail: [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India)


    Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  5. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model

    Directory of Open Access Journals (Sweden)

    Maria Gomis-González


    Full Text Available Fragile X syndrome (FXS is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1 knockout (KO mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1 receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD. In addition, low doses of rimonabant (from 0.01 mg/kg equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS.

  6. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model (United States)

    Gomis-González, Maria; Busquets-Garcia, Arnau; Matute, Carlos; Maldonado, Rafael; Mato, Susana; Ozaita, Andrés


    Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS. PMID:27589806

  7. The Significance of Freedom of Expression in an Antagonistic Society: Critical Understanding of Fascist Discourses and Linguistic Vulnerability

    Directory of Open Access Journals (Sweden)

    Alen Toplišek


    Full Text Available In this article I will address the complex relations between linguistic vulnerability as it is understood and construed by Judith Butler, and the freedom of expression in an antagonistic society that was conceptualized by Chantal Mouffe. The purpose of this article is to move away from the dominant moralizing discourse which tackles the emergence of fascistic and hateful discursive practices uncritically and in a politically neutral manner, and then offer an alternative view of the paradox between the freedom of expression and the regulation of hate speech. First, I concentrate on the performative functioning of words that injure and the question of how to subvert this discursive subjection that the hate speaker is seeking to constitute in a way that will enable the critical agency of the one injured. Butler’s post-structuralist view on the performance of discursive acts reveals potential sites and possibilities for critical agency. With her critical analysis of moderate consensus politics, Mouffe identifies the narrowing of the political space for articulation of antagonistic relations in society as the effect of the dominant post-political rationality. At the end I come to the conclusion that generating open discursive spaces is of crucial importance for the facilitation of critical subversion of hateful contents and restoring a state of normality.

  8. Accumulation of Deleterious Mutations Near Sexually Antagonistic Genes

    Directory of Open Access Journals (Sweden)

    Tim Connallon


    Full Text Available Mutation generates a steady supply of genetic variation that, while occasionally useful for adaptation, is more often deleterious for fitness. Recent research has emphasized that the fitness effects of mutations often differ between the sexes, leading to important evolutionary consequences for the maintenance of genetic variation and long-term population viability. Some forms of sex-specific selection—i.e., stronger purifying selection in males than females—can help purge a population’s load of female-harming mutations and promote population growth. Other scenarios—e.g., sexually antagonistic selection, in which mutations that harm females are beneficial for males—inflate genetic loads and potentially dampen population viability. Evolutionary processes of sexual antagonism and purifying selection are likely to impact the evolutionary dynamics of different loci within a genome, yet theory has mostly ignored the potential for interactions between such loci to jointly shape the evolutionary genetic basis of female and male fitness variation. Here, we show that sexually antagonistic selection at a locus tends to elevate the frequencies of deleterious alleles at tightly linked loci that evolve under purifying selection. Moreover, haplotypes that segregate for different sexually antagonistic alleles accumulate different types of deleterious mutations. Haplotypes that carry female-benefit sexually antagonistic alleles preferentially accumulate mutations that are primarily male harming, whereas male-benefit haplotypes accumulate mutations that are primarily female harming. The theory predicts that sexually antagonistic selection should shape the genomic organization of genetic variation that differentially impacts female and male fitness, and contribute to sexual dimorphism in the genetic basis of fitness variation.

  9. Ubiquitination profiling identifies sensitivity factors for IAP antagonist treatment. (United States)

    Varfolomeev, Eugene; Izrael-Tomasevic, Anita; Yu, Kebing; Bustos, Daisy; Goncharov, Tatiana; Belmont, Lisa D; Masselot, Alexandre; Bakalarski, Corey E; Kirkpatrick, Donald S; Vucic, Domagoj


    Evasion of cell death is one crucial capability acquired by tumour cells to ward-off anti-tumour therapies and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote cancer cell survival by mediating proliferative signalling and blocking cell death in response to diverse stimuli. Using immunoaffinity enrichment and MS, ubiquitination sites on thousands of proteins were profiled upon initiation of cell death by IAP antagonists in IAP antagonist-sensitive and -resistant breast cancer cell lines. Our analyses identified hundreds of proteins with elevated levels of ubiquitin-remnant [K-GG (Lys-Gly-Gly)] peptides upon activation of cell death by the IAP antagonist BV6. The majority of these were observed in BV6-sensitive, but not-resistant, cells. Among these were known pro-apoptotic regulators, including CYC (cytochrome c), RIP1 (receptor-interacting protein 1) and a selection of proteins known to reside in the mitochondria or regulate NF-κB (nuclear factor κB) signalling. Analysis of early time-points revealed that IAP antagonist treatment stimulated rapid ubiquitination of NF-κB signalling proteins, including TRAF2 [TNF (tumour necrosis factor) receptor-associated factor 2], HOIL-1 (haem-oxidized iron-regulatory protein 2 ubiquitin ligase-1), NEMO (NF-κB essential modifier), as well as c-IAP1 (cellular IAP1) auto-ubiquitination. Knockdown of several NF-κB pathway members reduced BV6-induced cell death and TNF production in sensitive cell lines. Importantly, RIP1 was found to be constitutively ubiquitinated in sensitive breast-cancer cell lines at higher basal level than in resistant cell lines. Together, these data show the diverse and temporally defined roles of protein ubiquitination following IAP-antagonist treatment and provide critical insights into predictive diagnostics that may enhance clinical efficacy.

  10. Development of Restorative Justice in China: Theory and Practice


    Yinzhi Shen


    Restorative justice has become a global social movement for criminal justice reform, with over eighty countries adopting some form of restorative justice program to tackle their crime problems. The theory of restorative justice was introduced to the Chinese academia in 2002. So far, various restorative justice programs have been developed in China. This paper aims to systematically review the development of restorative justice in China by analyzing academic literature on restorative justice a...

  11. Maximum entropy signal restoration with linear programming

    Energy Technology Data Exchange (ETDEWEB)

    Mastin, G.A.; Hanson, R.J.


    Dantzig's bounded-variable method is used to express the maximum entropy restoration problem as a linear programming problem. This is done by approximating the nonlinear objective function with piecewise linear segments, then bounding the variables as a function of the number of segments used. The use of a linear programming approach allows equality constraints found in the traditional Lagrange multiplier method to be relaxed. A robust revised simplex algorithm is used to implement the restoration. Experimental results from 128- and 512-point signal restorations are presented.

  12. Current Concepts in Restorative Implant Dentistry

    Institute of Scientific and Technical Information of China (English)



    Patients today are incteasingly aware of dental implants.and their expectations are for esthetically and functionally pleasingimplant restorations that mimic natural teeth.This presentation will give both the experienced and novice practitioner a better understand-ing of how restorative implant dentistry has evolved.Treatment planning and restorative options for single implants.multiple implants andfully edentulons arches will be discussed,and the use of modern materials and CADCAM technology in fabricating the most contemporaryfixed implant supported prostheses will be demonstrated.

  13. The digital restoration of film

    Directory of Open Access Journals (Sweden)

    Catanese, Rossella


    Full Text Available Aquest article tracta sobre la conservació i la restauració de pel·lícules amb tecnologies digitals. Les pel·lícules, com a expressió de la memòria col·lectiva, formen part del patrimoni comú de la humanitat, i mereixen ser preservades i difoses. Per això, la qüestió de la preservació dels materials cinematogràfics està guanyant pes, sobretot si tenim en compte la fragilitat estructural i la curta durada de l'estoc de pel·lícules. L'estat actual del mitjà audiovisual és de transició: a poc a poc l'element analògic i fotoquímic és substituït pel sistema digital. I això influeix molt en les pràctiques de producció i distribució del cinema, i també en els debats teòrics sobre el mitjà: els criteris d'arxivament i els processos de restauració no són una excepció a aquesta lògica.Este artículo trata sobre la conservación y la restauración de películas con tecnologías digitales. Las películas, como expresión de la memoria colectiva, forman parte del patrimonio común de la humanidad, y merecen ser preservadas y difundidas. Por eso, la cuestión de la preservación de los materiales cinematográficos está ganando peso, sobre todo si tenemos en cuenta la fragilidad estructural y la corta duración del stock de películas. El estado actual del medio audiovisual es de transición: poco a poco el elemento analógico y fotoquímico es sustituido por el sistema digital. Lo cual influye mucho en las prácticas de producción y distribución del cine, y también en los debates teóricos sobre el medio: los criterios de archivo y los procesos de restauración no son una excepción a esta lógica.This article focuses on the issues of conservation and restoration of films through digital technologies. Films, as an expression of collective memory, become part of the common heritage of humankind, which deserves to be safeguarded and disseminated. As a consequence of this awareness, the issue of preserving cinematic

  14. Water Awareness Through Environmental Restoration (United States)

    Davis-Caldwell, K.


    and negative effects of human presence on the local and global water supply. Student research scientifically tested ways to slow down the effects of run-off contaminants. Students also revisit water analysis and plant trees as buffers as part of their stream preservation efforts in a culminating activity. Oyster Reef Restoration Project: As a result of changes in climate, pollution and human consumption, the oyster population in the Chesapeake Bay had previously been on a rapid decline. The Oyster Reef Restoration Project allows students to understand the creatures of the bay and the cause of this decline. They explore the domino effect this has had on the quality of the water in the bay and future implications on the environment when the oyster population fluctuates significantly. Students construct concrete reefs and study the components of its contents and the reef's impact on the bay. Students are responsible for mixing, pouring and preparing the reef for its eventual drop in the bay. Wetlands Recovery: Following the elimination of a substantial amount of the natural wetlands behind the elementary and middle schools, a wetlands area was erected on the school grounds. This pond has been used to learn about habitats and the role humans, plants and organisms play in the preservation of the earth soil and water supply. This wetland is used by both the elementary and middle schools as a place for hands-on inquiry based learning. Students maintain the upkeep of the pond and teach other students at lower grades.

  15. Procedures for restoring vestibular disorders

    Directory of Open Access Journals (Sweden)

    Walther, Leif Erik


    Full Text Available This paper will discuss therapeutic possibilities for disorders of the vestibular organs and the neurons involved, which confront ENT clinicians in everyday practice. Treatment of such disorders can be tackled either symptomatically or causally. The possible strategies for restoring the body's vestibular sense, visual function and co-ordination include medication, as well as physical and surgical procedures. Prophylactic or preventive measures are possible in some disorders which involve vertigo (bilateral vestibulopathy, kinetosis, height vertigo, vestibular disorders when diving (Tables 1 and 2. Glucocorticoid and training therapy encourage the compensation of unilateral vestibular loss. In the case of a bilateral vestibular loss, it is important to treat the underlying disease (e.g. Cogan's disease. Although balance training does improve the patient's sense of balance, it will not restore it completely.In the case of Meniere's disease, there are a number of medications available to either treat bouts or to act as a prophylactic (e.g. dimenhydrinate or betahistine. In addition, there are non-ablative (sacculotomy as well as ablative surgical procedures (e.g. labyrinthectomy, neurectomy of the vestibular nerve. In everyday practice, it has become common to proceed with low risk therapies initially. The physical treatment of mild postural vertigo can be carried out quickly and easily in outpatients (repositioning or liberatory maneuvers. In very rare cases it may be necessary to carry out a semicircular canal occlusion. Isolated disturbances of the otolith function or an involvement of the otolith can be found in roughly 50% of labyrinth disturbances. A specific surgical procedure to selectively block the otolith organs is currently being studied. When an external perilymph fistula involving loss of perilymph is suspected, an exploratory tympanotomy involving also the round and oval window niches must be carried out. A traumatic rupture of the

  16. Terrorism, Forgiveness and Restorative Justice

    Directory of Open Access Journals (Sweden)

    Antony Pemberton


    Full Text Available This paper is intended to enhance understanding of the complexities of restorative justice in cases of terrorism from a victimological perspective. It does so first by analysing what separates terrorism from other forms of crime. The author argues that the main distinction concerns the peculiarly public nature of terrorism, in which the attack on the direct victims is intended to influence a (far larger group of so-called vicarious victims. This means that the public is likely to experience terrorist attacks as attacks on themselves. As a consequence the public can feel entitled to processes of forgiveness which in turn can conflict with the direct victims’ own experience. To illuminate this issue the paper proposes a novel distinction in third party forgiveness processes: between public forgiveness, i.e. forgiveness relating to the public wrongfulness inherent in crime, and vicarious forgiveness, i.e. the public’s experience of forgiveness itself. The complexities for restorative justice after terrorism can be then be viewed in terms of the tensions between the direct victims’ private and the publics’ vicarious forgiveness processes. Este artículo pretende facilitar la comprensión de las complejidades de la justicia restaurativa en casos de terrorismo desde una perspectiva victimológica. Lo hace primero mediante el análisis de lo que separa el terrorismo de otras formas de delincuencia. El autor sostiene que la distinción principal se refiere a la naturaleza pública específica del terrorismo, ya que mediante el ataque a las víctimas directas se pretende influir en el grupo (mucho más grande de las llamadas víctimas vicarias. Esto significa que es probable que el público sienta los ataques terroristas como ataques contra ellos mismos. De esta forma, el público puede sentirse con derecho sobre los procesos de perdón, lo que, a su vez, puede entrar en conflicto con la propia experiencia de las víctimas directas. Para iluminar

  17. Design, synthesis, and structure-activity relationship of novel CCR2 antagonists. (United States)

    Kothandaraman, Shankaran; Donnely, Karla L; Butora, Gabor; Jiao, Richard; Pasternak, Alexander; Morriello, Gregori J; Goble, Stephen D; Zhou, Changyou; Mills, Sander G; Maccoss, Malcolm; Vicario, Pasquale P; Ayala, Julia M; Demartino, Julie A; Struthers, Mary; Cascieri, Margaret A; Yang, Lihu


    A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog 59 was found to posses potent antagonistic activity.

  18. Smooth coronal surface, resin restoration and microleakage. (United States)

    Yanikoğlu, F; Türkmen, C; Kartal, N; Başaran, B


    The space between the resin and the cavity walls has always become interesting to search. The aim of this study was to evaluate any differences on leakage values of Class 5 type resin restorations prepared on surrounding surfaces of the tooth crown. Ninety human teeth were prepared as Class 5 cavities on buccal, lingual, mesial and distal surfaces and were randomly divided into groups for bevelling, groove preparation and as control. The subgroups were arranged as fluoride gel and/or sealant applications. Fluoride gel was applied following the cavity preparations. Sealant was applied over composite resin restorations. Treated teeth were thermocycled and immersed into dye solution for 96 hours. The restorations were evaluated in a stereo-microscope following the sectioning. Bevelling of the cavosurfaces and/or preparation of a groove addition to cavity procedures did not make any difference on the microleakage scores of the restorations done on either surfaces statistically.

  19. Geomorphic Analysis - Trinity River Restoration Potential (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The goal of the Trinity River project is to identify the potential positive effects of large-scale restoration actions in a 63 kilometer reach of the Trinity River...

  20. Habitat Analysis - Trinity River Restoration Potential (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The goal of the Trinity River project is to identify the potential positive effects of large-scale restoration actions in a 63 kilometer reach of the Trinity River...

  1. Commentary: Jail-based competency restoration. (United States)

    Kapoor, Reena


    Many factors influence restoration of competence to stand trial: age, IQ, severity of mental illness, criminal history, treatment history, and others. This commentary poses the question of whether competency to stand trial is also influenced by the setting in which restoration treatment occurs. Jail-based competency-restoration programs, which are in their infancy and have yet to produce large-scale data demonstrating their efficacy, are examined. Several factors related to jail-based restoration are considered: choosing the right candidates for the program, impact of treatment in a punitive setting, ability to maintain separation between treaters and forensic evaluators, procedures for involuntary medication, aggregation of incompetent defendants in regional jails, effect on malingering, and cost savings.

  2. Connecting River Systems Restoration Assessment Composite Model (United States)

    U.S. Geological Survey, Department of the Interior — Well-established conservation planning principles and techniques framed by geodesign were used to assess the restorability of areas that historically supported...

  3. Western Lake Erie Restoration Assessment Degree Flowlines (United States)

    U.S. Geological Survey, Department of the Interior — This represents the flowline network in Western Lale Erie Restoration Assessment (WLERA). It is attributed with the number of disconnections between the reach and...

  4. Saginaw Bay Restoration Assessment Degree Flowlines (United States)

    U.S. Geological Survey, Department of the Interior — This represents the flowline network in Sagina Bay Restoration Assessment (SBRA). It is attributed with the number of disconnections between the reach and the...

  5. Connecting River Systems Restoration Assessment Degree Flowlines (United States)

    U.S. Geological Survey, Department of the Interior — This represents the flowline network in Connecting River Systems Restoration Assessment (CRSRA). It is attributed with the number of disconnections between the reach...

  6. Fisheries Restoration Grant Program Projects [ds168 (United States)

    California Department of Resources — This shapefile (FRGP_All_020209.shp) represents the locations of all ongoing and completed salmonid restoration projects in California with existing records in the...

  7. US Forest Service Integrated Resource Restoration (IRR) (United States)

    US Forest Service, Department of Agriculture — A map service on the www depicting activities funded through the Integrated Resource Restoration (IRR) NFRR Budget Line Item and reported through the U.S. Forest...

  8. A dual method for maximum entropy restoration (United States)

    Smith, C. B.


    A simple iterative dual algorithm for maximum entropy image restoration is presented. The dual algorithm involves fewer parameters than conventional minimization in the image space. Minicomputer test results for Fourier synthesis with inadequate phantom data are given.

  9. Saginaw Bay Restoration Assessment Composite Model (United States)

    U.S. Geological Survey, Department of the Interior — Well-established conservation planning principles and techniques framed by geodesign were used to assess the restorability of areas that historically supported...

  10. Restoration of multichannel microwave radiometric images (United States)

    Chin, R. T.; Yeh, C.-L.; Olson, W. S.


    A constrained iterative image restoration method is applied to multichannel diffraction-limited imagery. This method is based on the Gerchberg-Papoulis algorithm utilizing incomplete information and partial constraints. The procedure is described using the orthogonal projection operators which project onto two prescribed subspaces iteratively. Its properties and limitations are presented. The effect of noise was investigated and a better understanding of the performance of the algorithm with noisy data has been achieved. The restoration scheme with the selection of appropriate constraints was applied to a practical problem. The 6.6, 10.7, 18, and 21 GHz satellite images obtained by the scanning multichannel microwave radiometer (SMMR), each having different spatial resolution, were restored to a common, high resolution (that of the 37 GHz channels) to demonstrate the effectiveness of the method. Both simulated data and real data were used in this study. The restored multichannel images may be utilized to retrieve rainfall distributions.

  11. ROV Based Underwater Blurred Image Restoration

    Institute of Scientific and Technical Information of China (English)

    LIU Zhishen; DING Tianfu; WANG Gang


    In this paper, we present a method of ROV based image processing to restore underwater blurry images from the theory of light and image transmission in the sea. Computer is used to simulate the maximum detection range of the ROV under different water body conditions. The receiving irradiance of the video camera at different detection ranges is also calculated. The ROV's detection performance under different water body conditions is given by simulation. We restore the underwater blurry images using the Wiener filter based on the simulation. The Wiener filter is shown to be a simple useful method for underwater image restoration in the ROV underwater experiments. We also present examples of restored images of an underwater standard target taken by the video camera in these experiments.

  12. Ceramics as biomaterials for dental restoration. (United States)

    Höland, Wolfram; Schweiger, Marcel; Watzke, Ronny; Peschke, Arnd; Kappert, Heinrich


    Sintered ceramics and glass-ceramics are widely used as biomaterials for dental restoration, especially as dental inlays, onlays, veneers, crowns or bridges. Biomaterials were developed either to veneer metal frameworks or to produce metal-free dental restorations. Different types of glass-ceramics and ceramics are available and necessary today to fulfill customers' needs (patients, dentists and dental technicians) regarding the properties of the biomaterials and the processing of the products. All of these different types of biomaterials already cover the entire range of indications of dental restorations. Today, patients are increasingly interested in metal-free restoration. Glass-ceramics are particularly suitable for fabricating inlays, crowns and small bridges, as these materials achieve very strong, esthetic results. High-strength ceramics are preferred in situations where the material is exposed to high masticatory forces.

  13. Western Lake Erie Restoration Assessment Composite Model (United States)

    U.S. Geological Survey, Department of the Interior — Well-established conservation planning principles and techniques framed by geodesign were used to assess the restorability of areas that historically supported...


    Directory of Open Access Journals (Sweden)

    Abdelâali Hassaïne


    Full Text Available The restoration of motion picture films using digital image processing has been an active research field for many years. The restoration of the soundtrack however, has mainly been performed in the sound domain, using signal processing methods, in spite of the fact that it is recorded as a continuous image between the images of the film and the perforations. In this paper a restoration method for variable area soundtrack restoration at the image level is presented. First, a novel method is proposed for the detection of the symmetry axis of the scanned soundtrack. Then, a comparison between the watershed and the region growing segmentation of the soundtrack is developed. Another algorithm aiming to enforce the symmetry and to correct the edges of the segmented image is presented. A last step aiming to smooth the edges of the obtained image is performed. Finally, experimental results are reported and possible future improvements are discussed.

  15. Forest restoration, biodiversity and ecosystem functioning

    Directory of Open Access Journals (Sweden)

    Aerts Raf


    Full Text Available Abstract Globally, forests cover nearly one third of the land area and they contain over 80% of terrestrial biodiversity. Both the extent and quality of forest habitat continue to decrease and the associated loss of biodiversity jeopardizes forest ecosystem functioning and the ability of forests to provide ecosystem services. In the light of the increasing population pressure, it is of major importance not only to conserve, but also to restore forest ecosystems. Ecological restoration has recently started to adopt insights from the biodiversity-ecosystem functioning (BEF perspective. Central is the focus on restoring the relation between biodiversity and ecosystem functioning. Here we provide an overview of important considerations related to forest restoration that can be inferred from this BEF-perspective. Restoring multiple forest functions requires multiple species. It is highly unlikely that species-poor plantations, which may be optimal for above-ground biomass production, will outperform species diverse assemblages for a combination of functions, including overall carbon storage and control over water and nutrient flows. Restoring stable forest functions also requires multiple species. In particular in the light of global climatic change scenarios, which predict more frequent extreme disturbances and climatic events, it is important to incorporate insights from the relation between biodiversity and stability of ecosystem functioning into forest restoration projects. Rather than focussing on species per se, focussing on functional diversity of tree species assemblages seems appropriate when selecting tree species for restoration. Finally, also plant genetic diversity and above - below-ground linkages should be considered during the restoration process, as these likely have prominent but until now poorly understood effects at the level of the ecosystem. The BEF-approach provides a useful framework to evaluate forest restoration in an

  16. Restoration of the endodontically treated posterior tooth


    Andrea Polesel


    Objectives: To analyse the key factors of the restoration in the posterior endodontically treated teeth, through a literature review and clinical cases presentation. To focus on the clinical advantages of the adhesive indirect restorations, describing the basic principles for long-term success. Materials and methods: The biomechanical changes due to the root canal therapy and the degree of healthy dental tissue lost because of pathology and iatrogenic factors are the critical points leadin...

  17. Leadership success within disaster restoration projects. (United States)

    Rapp, Randy R; Baroudi, Bassam


    Successful project managers draw their performance from essential leadership traits, as guided by their core values.Within disaster recovery, contractors who mitigate, repair, and reconstruct the built environment are often faced with challenges exceeding the norm. The effective leader is commonly expected to consider stakeholder motivations within distressing situations as well as other external and environmental factors when seeking to lead the project team to successful outcomes. This research is most concerned with leadership within the context of disaster restoration of the built environment. Its stimulus comes from the Restoration Industry Association (RIA)'s efforts to highlight leadership traits and core values for its Certified Restorer Body of Knowledge but would be of value to others associated with disaster recovery operations. Among organizations whose membership includes thousands of practitioners who restore and reconstruct the built environment after disasters, the RIA is the only one yet to formally and substantially research which core values and leader traits are deemed critical for the success of efforts to manage the means and methods applied on recovery job sites. Forty-six seasoned disaster restoration industry project professionals voluntarily responded to a survey questionnaire that sought their opinions about the traits and core values that they consider most important for successful disaster restoration project leadership. The most important leader traits were effective communication, professional competence, and leadership by example. The most important restoration industry values were integrity, compassion, and trustworthiness. The recognized imperative of compassion was unexpected in light of stereotypes often associated with construction-related contractors. This and other findings permit disaster response and recovery stakeholders to better understand qualities they should wish to see in leaders of contractor organizations, which

  18. Alternatives to testosterone replacement: testosterone restoration. (United States)

    McCullough, Andrew


    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.

  19. [Dental restoration materials in pediatric dentistry]. (United States)

    Davidson, C L


    Restorative materials in pediatric dentistry have to fulfill special requirements. They should be easy to handle and applicable in a not always dry mouth. They should potentially be adhesive in order to avoid too much mechanical preparation. They do not have to be extremely wear resistant as the dwell time of the restorations is relatively short. Glass-ionomer cements and in particular the resin modified types possess properties which make them almost ideal for the required purpose.

  20. Laser application in otology for hearing restoration (United States)

    Lombardo, Igino


    Prior to the development of the stapes replacement prosthesis in the early 1950s, loss of hearing due to otosclerosis remained an untreatable disease. Today, loss of hearing due to otosclerosis can be restored in the majority of cases to near normal levels. Since 1980 the laser has played a major and important role in otosclerosis surgery. This paper explores the use of lasers for hearing restoration and compares the results of laser surgery to non-laser surgery.

  1. Marginal microfiltration in amalgam restorations. Review


    Lahoud Salem, Víctor; Departamento Académico de Estomatología Rehabilitadora. Facultad de Odontología, Universidad Nacional Mayor de San Marcos, Lima. Perú.


    The present articule is review references from phenomenon of microfiltration in restorations with amalgam and yours consecuents in changes of color in the interface tooth-restorations, margin deterioted , sensitivity dentinarea postoperate, caries secondary and pulp inflamation. Besides naming the mechanicals for to reduce microfiltration, and yours effects for use of sealers dentinaries representation for the varnish cavitys and adhesive systens Conclusive indicate wath the amalgam is the ma...

  2. Resin composites : Sandwich restorations and curing techniques


    Lindberg, Anders


    Since the mid-1990s resin composite has been used for Class II restorations in stress-bearing areas as an alternative to amalgam. Reasons for this were the patients’ fear of mercury in dental amalgam and a growing demand for aesthetic restorations. During the last decades, the use of new resin composites with more optimized filler loading have resulted in reduced clinical wear. Improved and simplified amphiphilic bonding systems have been introduced. However, one of the main problems with res...

  3. Design and discovery of 1,3-benzodiazepines as novel dopamine antagonists. (United States)

    Zhu, Zhaoning; Sun, Zhong-Yue; Ye, Yuanzan; McKittrick, Brian; Greenlee, William; Czarniecki, Michael; Fawzi, Ahmad; Zhang, Hongtao; Lachowicz, Jean E


    A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR development of the novel dopamine antagonists.

  4. Remote sensing for restoration ecology: Application for restoring degraded, damaged, transformed, or destroyed ecosystems. (United States)

    Reif, Molly K; Theel, Heather J


    Restoration monitoring is generally perceived as costly and time consuming, given the assumptions of successfully restoring ecological functions and services of a particular ecosystem or habitat. Opportunities exist for remote sensing to bolster the restoration science associated with a wide variety of injured resources, including resources affected by fire, hydropower operations, chemical releases, and oil spills, among others. In the last decade, the role of remote sensing to support restoration monitoring has increased, in part due to the advent of high-resolution satellite sensors as well as other sensor technology, such as lidar. Restoration practitioners in federal agencies require monitoring standards to assess restoration performance of injured resources. This review attempts to address a technical need and provides an introductory overview of spatial data and restoration metric considerations, as well as an in-depth review of optical (e.g., spaceborne, airborne, unmanned aerial vehicles) and active (e.g., radar, lidar) sensors and examples of restoration metrics that can be measured with remotely sensed data (e.g., land cover, species or habitat type, change detection, quality, degradation, diversity, and pressures or threats). To that end, the present article helps restoration practitioners assemble information not only about essential restoration metrics but also about the evolving technological approaches that can be used to best assess them. Given the need for monitoring standards to assess restoration success of injured resources, a universal monitoring framework should include a range of remote sensing options with which to measure common restoration metrics. Integr Environ Assess Manag 2016;X:000-000. Published 2016. This article is a US Government work and is in the public domain in the USA. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.

  5. A Policy Analysis Perspective on Ecological Restoration

    Directory of Open Access Journals (Sweden)

    Susan Baker


    Full Text Available Using a simple stages model of the policy process, we explore the politics of ecological restoration using an array of examples drawn across sector, different size and scale, and from different countries. A policy analysis perspective reveals how, at both the program and project levels, ecological restoration operates within a complex and dynamic interplay between technical decision making, ideologies, and interest politics. Viewed through the stages model, restoration policy involves negotiating nature across stages in the policy making process, including agenda setting, policy formulation, implementation, and evaluation. The stages model is a useful heuristic devise; however, this linear model assumes that policy makers approach the issue rationally. In practice, ecological restoration policy takes place in the context of different distributions of power between the various public and private actors involved at the different stages of restoration policy making. This allows us to reiterate the point that ecological restoration is best seen not only as a technical task but as a social and political project.


    Directory of Open Access Journals (Sweden)



    Full Text Available ABSTRACT: Dental restoration is the most commonly administered dental treatment. These restorations are subjected to dynamic conditions in oral cavity, are likely to fail and need replacement. Ideal restorative material should pass two tests - Longitivity and Esthetics. Longitivity of the restorative material depends on three major factors - first is Patient’s factors, second is Operator`s skills and last is the Restorative material itself. Dentists today have a plethora of materials to choose from. Materials like Silver Amalgam being tested over a century, other nubile but promising materials, developed recently and yet to be tested in long run. This puts a dentist in dilemma so as which material to select to ensure durable clinical p erformance after placement. Amalgam has been tested over 165 years and has fulfilled almost all desired qualities of a restorative material except esthetics. On the other hand composites have advantage in cases where esthetics is of prime importance; howev er Recent studies conclude them at par with amalgam 1 . Performance of these two materials is assessed on following criterions - Longevity, wear resistance, cost effectiveness, marginal leakage and predisposal to secondary decay, biocompatibility, pulp irri tation, tooth preparation, technique sensitivity and esthetics

  7. Survival of ART restorations assessed using selected FDI and modified ART restoration criteria. (United States)

    Farag, Abeer; van der Sanden, Wil J M; Abdelwahab, Hisran; Frencken, Jo E


    A new set of criteria for assessing the quality of restorations using modern restorative materials, named FDI criteria, was recently introduced. This study tested the null hypothesis that there is no significant difference in survival estimate percentages of ART restorations assessed using selected FDI and modified ART criteria after 1 and 5 years. One operator placed a total of 60 class I and 30 Class II high-viscosity glass-ionomer ART restorations in ninety 14- to 15-year-olds. Two calibrated and independent evaluators using both criteria evaluated restorations on diestone replicas at baseline and after 1 and 5 years. Statistical analyses were done using the Kaplan-Meier method and log-rank test. The survival results of ART restorations assessed using both sets of criteria after 1 and 5 years (p = 0.27) did not differ significantly. Three ART restorations were assessed as failures according to the ART criteria, while they were assessed as survived using the FDI criteria. We conclude that the modified ART criteria enable reliable assessment of ART restorations in permanent teeth from diestone replicas and that there was no significant difference in survival estimates of ART restorations assessed using both sets of criteria. The null hypothesis was accepted.

  8. Drivers of Ecological Restoration: Lessons from a Century of Restoration in Iceland

    Directory of Open Access Journals (Sweden)

    Ása L. Aradóttir


    Full Text Available We analyzed the main drivers for ecological restoration in Iceland from 1907 to 2010 and assessed whether the drivers have changed over time and what factors might explain the changes, if any. Our study was based on a catalogue of 100 restoration projects, programs, and areas, representing 75% to 85% of all restoration activities in Iceland. Catastrophic erosion was an early driver for soil conservation and restoration efforts that still ranked high in the 2000s, reflecting the immense scale of soil erosion and desertification in Iceland. Socioeconomic drivers such as farming and the provision of wood products were strong motivators of ecological restoration over most of the 20th century, although their relative importance decreased with time as the number and diversity of drivers increased. In the 1960s and 1970s, the construction of hard infrastructure, and moral values such as improving the aesthetics of the countryside and "repaying the debt to the land" emerged as motivations for restoration actions. In the late 1990s, the United Nations Climate Change Convention became a driver for restoration, and the importance of nature conservation and recreation increased. Technological development and financial incentives did not show up as drivers of ecological restoration in our study, although there are some indications of their influence. Furthermore, policy was a minor driver, which might reflect weak policy instruments for ecological restoration and some counteractive policies.

  9. Lead optimization studies of cinnamic amide EP2 antagonists. (United States)

    Ganesh, Thota; Jiang, Jianxiong; Yang, Myung-Soon; Dingledine, Ray


    Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (∼10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role.

  10. Anti-antimicrobial peptides: folding-mediated host defense antagonists. (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G


    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance.

  11. Churg-Strauss syndrome associated with leukotriene receptor antagonists (LTRA). (United States)

    Cuchacovich, R; Justiniano, M; Espinoza, L R


    Churg-Strauss syndrome (CSS) is a rare vasculitic disorder that generally occurs in patients with bronchial asthma. CSS is being increasingly recognized in asthmatic patients treated with leukotriene receptor antagonists. However, the nature of this relationship remains to be elucidated. The present report describes three asthmatic patients who developed clinical manifestations highly suggestive of CSS, although one patient lacked the presence of eosinophilia. The patient, however, exhibited biopsy-proven cutaneous necrotizing vasculitis, which improved after withdrawal of montelukast. The second patient presented with systemic constitutional signs including fever, malaise, arthralgias, clinical jaundice, peripheral blood eosinophilia, and biopsy-proven eosinophilic hepatitis. The third patient also had circulating eosinophilia, scleritis, and arthritis. All patients improved after discontinuation of the leukotriene receptor antagonist (montelukast).

  12. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane


    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  13. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen


    Considerable evidence has emerged to suggest that histamine participates in the regulation of the inflammatory response, immune reaction, coagulation cascade, and cardiovascular function. Furthermore, histamine may play a major role in the growth of normal and malignant tissue as a regulator...... of proliferation and angiogenesis. Specific histamine receptors have been identified on the surface of bone marrow cells, immune competent cells, endothelial cells, fibroblasts, and also on malignant cells. This has prompted research in regulation by specific histamine receptor agonists and antagonists. Results...... from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...

  14. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J


    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  15. Non-imidazole histamine NO-donor H3-antagonists. (United States)

    Tosco, Paolo; Bertinaria, Massimo; Di Stilo, Antonella; Cena, Clara; Fruttero, Roberta; Gasco, Alberto


    Recently a series of H3-antagonists related to Imoproxifan was realised (I); in these products the oxime substructure of the lead was constrained in NO-donor furoxan systems and in the corresponding furazan derivatives. In this paper, a new series of compounds derived from I by substituting the imidazole ring with the ethoxycarbonylpiperazino moiety present in the non-imidazole H3-ligand A-923 is described. For all the products synthesis and preliminary pharmacological characterisation, as well as their hydrophilic-lipophilic balance, are reported. The imidazole ring replacement generally results in a decreased H3-antagonist activity with respect to the analogues of series I and, in some cases, induces relaxing effects on the electrically contracted guinea-pig ileum, probably due to increased affinity for other receptor systems.

  16. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists (United States)


    Center for Substance Abuse Research Lewis Katz School of Medicine at Temple University 3500 N, Broad Street Philadelphia, PA 19140 AND ADDRESS(ES) 8...processes), affect the ability of opioid drugs to counteract pain. We predicted that one way of increasing the effectiveness of the pain-relieving... drugs would be to eliminate or reduce the activity of the chemokines by administering chemokine receptor antagonists (CRAs). The blockade of one or

  17. Potent and orally efficacious benzothiazole amides as TRPV1 antagonists. (United States)

    Besidski, Yevgeni; Brown, William; Bylund, Johan; Dabrowski, Michael; Dautrey, Sophie; Harter, Magali; Horoszok, Lucy; Hu, Yin; Johnson, Dean; Johnstone, Shawn; Jones, Paul; Leclerc, Sandrine; Kolmodin, Karin; Kers, Inger; Labarre, Maryse; Labrecque, Denis; Laird, Jennifer; Lundström, Therese; Martino, John; Maudet, Mickaël; Munro, Alexander; Nylöf, Martin; Penwell, Andrea; Rotticci, Didier; Slaitas, Andis; Sundgren-Andersson, Anna; Svensson, Mats; Terp, Gitte; Villanueva, Huascar; Walpole, Christopher; Zemribo, Ronald; Griffin, Andrew M


    Benzothiazole amides were identified as TRPV1 antagonists from high throughput screening using recombinant human TRPV1 receptor and structure-activity relationships were explored to pinpoint key pharmacophore interactions. By increasing aqueous solubility, through the attachment of polar groups to the benzothiazole core, and enhancing metabolic stability, by blocking metabolic sites, the drug-like properties and pharmokinetic profiles of benzothiazole compounds were sufficiently optimized such that their therapeutic potential could be verified in rat pharmacological models of pain.

  18. Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists

    DEFF Research Database (Denmark)

    Henderson, Alan J; Guzzo, Peter R; Ghosh, Animesh;


    A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found...... to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography....

  19. Exploration of a new series of PAR1 antagonists. (United States)

    Planty, Bruno; Pujol, Chantal; Lamothe, Marie; Maraval, Catherine; Horn, Clemens; Le Grand, Bruno; Perez, Michel


    Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.

  20. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine


    Funder JW


    John W FunderPrince Henry's Institute, Clayton, Victoria, AustraliaAbstract: Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor (MR) antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more MR-specific. From a marginal role as a potassium-sparing diuretic, spironolactone was shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure, as ...

  1. Approaches to the rational design of selective melanocortin receptor antagonists (United States)

    Hruby, Victor J; Cai, Minying; Nyberg, Joel; Muthu, Dhanasekaran


    Introduction When establishing the physiological roles of specific receptors in normal and disease states, it is critical to have selective antagonist ligands for each receptor in a receptor system with several subtypes. The melanocortin receptors have five subtypes referred to as the melanocortin 1 receptor, melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and melanocortin 5 receptor, and they are of critical importance for many aspects of human health and disease. Areas covered This article reviews the current efforts to design selective antagonistic ligands for the five human melanocortin receptors summarizing the currently published orthosteric and allosteric antagonists for each of these receptors. Expert opinion Though there has been progress, there are still few drugs available that address the many significant biological activities and diseases that are associated with these receptors, which is possibly due to the lack of receptor selectivity that these designed ligands are currently showing. The authors believe that further studies into the antagonists’ 3D conformational and topographical properties in addition to future mutagenesis studies will provide greater insight into these ligands which could play a role in the treatment of various diseases in the future. PMID:22646078

  2. Synergistic and antagonistic drug combinations depend on network topology. (United States)

    Yin, Ning; Ma, Wenzhe; Pei, Jianfeng; Ouyang, Qi; Tang, Chao; Lai, Luhua


    Drug combinations may exhibit synergistic or antagonistic effects. Rational design of synergistic drug combinations remains a challenge despite active experimental and computational efforts. Because drugs manifest their action via their targets, the effects of drug combinations should depend on the interaction of their targets in a network manner. We therefore modeled the effects of drug combinations along with their targets interacting in a network, trying to elucidate the relationships between the network topology involving drug targets and drug combination effects. We used three-node enzymatic networks with various topologies and parameters to study two-drug combinations. These networks can be simplifications of more complex networks involving drug targets, or closely connected target networks themselves. We found that the effects of most of the combinations were not sensitive to parameter variation, indicating that drug combinational effects largely depend on network topology. We then identified and analyzed consistent synergistic or antagonistic drug combination motifs. Synergistic motifs encompass a diverse range of patterns, including both serial and parallel combinations, while antagonistic combinations are relatively less common and homogenous, mostly composed of a positive feedback loop and a downstream link. Overall our study indicated that designing novel synergistic drug combinations based on network topology could be promising, and the motifs we identified could be a useful catalog for rational drug combination design in enzymatic systems.

  3. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  4. IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα (United States)

    Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J.


    Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activity of IAP antagonists (also known as Smac mimetics) using cells from primary and metastatic osteosarcomas that arose spontaneously in mice engineered to lack p53 and Rb expression in osteoblast-derived cells. The IAP antagonists SM-164, GDC-0152 and LCL161, which efficiently target XIAP and cIAPs, sensitized cells from most osteosarcomas to killing by low levels of TNFα but not TRAIL. RIPK1 expression levels and activity correlated with sensitivity. RIPK3 levels varied considerably between tumors and RIPK3 was not required for IAP antagonism to sensitize osteosarcoma cells to TNFα. IAP antagonists, including SM-164, lacked mutagenic activity. These data suggest that drugs targeting XIAP and cIAP1/2 may be effective for osteosarcoma patients whose tumors express abundant RIPK1 and contain high levels of TNFα, and would be unlikely to provoke therapy-induced cancers in osteosarcoma survivors. PMID:27129149

  5. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Directory of Open Access Journals (Sweden)

    Zolaly MA


    Full Text Available Mohammed A ZolalyDepartment of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaBackground: The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures.Methods: The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever.Results: Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine.Conclusion: Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.Keywords: antihistamine, nonantihistamine, histamine H1 antagonist, febrile seizures

  6. Receptor discrimination and control of agonist-antagonist binding. (United States)

    Tallarida, R J


    The law of mass action is the common model for the interaction of agonist and antagonist compounds with cellular receptors. Parameters of the interaction, obtained from functional and radioligand-binding studies, allow discrimination and subtyping of receptors and aid in understanding specific mechanisms. This article reviews the theory and associated mathematical models and graphical transformations of data that underlie the determination of receptor parameters. The main theory assumes that agonist and antagonist compounds bind to cells that have a fixed number of receptors and provides the framework for obtaining drug-receptor parameters from data and their graphical transformations. Conditions that produce a change in receptor number, a newer concept in pharmacology, can have an important effect on the parameter values derived in the usual way. This review concludes with a discussion of the quantitative study of receptor-mediated feedback control of endogenous ligands, a very new topic with potentially important implications for understanding antagonist effectiveness, loss of control, and chaos in regulated mass action binding.

  7. μ Opioid receptor: novel antagonists and structural modeling (United States)

    Kaserer, Teresa; Lantero, Aquilino; Schmidhammer, Helmut; Spetea, Mariana; Schuster, Daniela


    The μ opioid receptor (MOR) is a prominent member of the G protein-coupled receptor family and the molecular target of morphine and other opioid drugs. Despite the long tradition of MOR-targeting drugs, still little is known about the ligand-receptor interactions and structure-function relationships underlying the distinct biological effects upon receptor activation or inhibition. With the resolved crystal structure of the β-funaltrexamine-MOR complex, we aimed at the discovery of novel agonists and antagonists using virtual screening tools, i.e. docking, pharmacophore- and shape-based modeling. We suggest important molecular interactions, which active molecules share and distinguish agonists and antagonists. These results allowed for the generation of theoretically validated in silico workflows that were employed for prospective virtual screening. Out of 18 virtual hits evaluated in in vitro pharmacological assays, three displayed antagonist activity and the most active compound significantly inhibited morphine-induced antinociception. The new identified chemotypes hold promise for further development into neurochemical tools for studying the MOR or as potential therapeutic lead candidates.

  8. Newer calcium channel antagonists and the treatment of hypertension. (United States)

    Cummins, D F


    Calcium channel antagonists have become popular medications for the management of hypertension. These agents belong to the diphenylalkylamine, benzothiazepine, dihydropyridine, or tetralol chemical classes. Although the medications share a common pharmacological mechanism in reducing peripheral vascular resistance, clinical differences between the sub-classes can be linked to structural profiles. This heterogeneity is manifested by differences in vascular selectivity, effects on cardiac conduction and adverse events. The lack of differentiation between calcium channel antagonists in clinical trials has contributed to uncertainty associated with their impact on morbidity and mortality. Data from more recent studies in specific patient populations underscores the importance of investigating these antihypertensives as individual agents. A proposed therapeutic classification system suggests that newer agents should share the slow onset and long-acting antihypertensive effect of amlodipine. Additionally, a favourable trough-to-peak ratio has been recommended as an objective measurement of efficacy. The newer drugs, barnidipine and lacidipine, have a therapeutic profile similar to amlodipine, but trough-to-peak ratios are not substantially greater than the recommended minimum of 0.50. Aranidipine, cilnidipine and efonidipine have unique pharmacological properties that distinguish them from traditional dihydropyridines. Although clinical significance is unconfirmed, these newer options may be beneficial for patients with co-morbid conditions that preclude use of older antagonists.

  9. Role of dorsal hippocampal orexin-1 receptors in memory restoration induced by morphine sensitization phenomenon. (United States)

    Alijanpour, S; Tirgar, F; Zarrindast, M-R


    The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of the dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using the Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in the retrieval session (probe trial) this treatment decreased the time spent in the target quadrant. Moreover, morphine-induced sensitization (15 or 20mg/kg, s.c.; once daily for 3days and followed by 5days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40nmol/rat), 5min before morphine (20mg/kg/day×3days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by the morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40nmol/rat) into the CA1 region in the training session, 5min prior to morphine (5mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization.

  10. Arbuscular mycorrhizal colonization of giant sequoia (Sequoiadendron giganteum) in response to restoration practices. (United States)

    Fahey, Catherine; York, Robert A; Pawlowska, Teresa E


    Interactions with soil microbiota determine the success of restoring plants to their native habitats. The goal of our study was to understand the effects of restoration practices on interactions of giant sequoia Sequoiadendron giganteum with arbuscular mycorrhizal (AM) fungi (Glomeromycota). Natural regeneration of Sequoiadendron is threatened by the absence of severe fires that create forest canopy gaps. Generating artificial canopy gaps offers an alternative tool for giant sequoia restoration. We investigated the effect of regeneration practices, including (i) sapling location within gaps, (ii) gap size and (iii) soil substrate, on AM fungal colonization of giant sequoia sapling roots in a native giant sequoia grove of the Sierra Nevada, California. We found that the extent of AM fungal root colonization was positively correlated with sapling height and light availability, which were related to the location of the sapling within the gap and the gap size. While colonization frequency by arbuscules in saplings on ash substrate was higher relative to saplings in mineral soil, the total AM fungal root colonization was similar between the substrates. A negative correlation between root colonization by Glomeromycota and non-AM fungal species indicated antagonistic interactions between different classes of root-associated fungi. Using DNA genotyping, we identified six AM fungal taxa representing genera Glomus and Ambispora present in Sequoiadendron roots. Overall, we found that AM fungal colonization of giant sequoia roots was associated with availability of plant-assimilated carbon to the fungus rather than with the AM fungal supply of mineral nutrients to the roots. We conclude that restoration practices affecting light availability and carbon assimilation alter feedbacks between sapling growth and activity of AM fungi in the roots.

  11. 7 CFR 1410.10 - Restoration of wetlands. (United States)


    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Restoration of wetlands. 1410.10 Section 1410.10... Restoration of wetlands. (a) An owner or operator who entered into a CRP contract on land that is suitable for restoration to wetlands or that was restored to wetlands while under such contract, may, if approved by...

  12. [Key points in anterior esthetic restorations with all ceramic]. (United States)

    Luo, Xiaoping; Qian, Dongdong; Yuan, Yu; Meng, Xiangfeng


    This paper introduced the key points in fabricating anterior esthetic restorations with all ceramic materials, including pre-operative smile design, standard tooth preparation, provisional restoration fabrication, all ceramic materials selection, all ceramic restoration bonding, ceramic crack and fracture prevention. And then, the authors summarized and reviewed the clinical common problems in anterior esthetic restorations.

  13. Effective River Restoration in the 21st Century

    NARCIS (Netherlands)

    Friberg, N.; Angelopoulos, N.V.; Buijse, A.D.; Cowx, I.G.; Kail, J.; Moe, T.F.; Moir, H.; O'Hare, M.T.; Verdonschot, P.F.M.; Wolter, C.


    This paper is a comprehensive and updated overview of river restoration and covers all relevant aspects from drivers of restoration, linkages between hydromorphology and biota, the current restoration paradigm, effects of restorations to future directions and ways forward in the way we conduct ri

  14. Transforming ecosystems: When, where, and how to restore contaminated sites. (United States)

    Rohr, Jason R; Farag, Aïda M; Cadotte, Marc W; Clements, William H; Smith, James R; Ulrich, Cheryl P; Woods, Richard


    Chemical contamination has impaired ecosystems, reducing biodiversity and the provisioning of functions and services. This has spurred a movement to restore contaminated ecosystems and develop and implement national and international regulations that require it. Nevertheless, ecological restoration remains a young and rapidly growing discipline and its intersection with toxicology is even more nascent and underdeveloped. Consequently, we provide guidance to scientists and practitioners on when, where, and how to restore contaminated ecosystems. Although restoration has many benefits, it also can be expensive, and in many cases systems can recover without human intervention. Hence, the first question we address is: "When should we restore contaminated ecosystems?" Second, we provide suggestions on what to restore-biodiversity, functions, services, all 3, or something else--and where to restore given expected changes to habitats driven by global climate change. Finally, we provide guidance on how to restore contaminated ecosystems. To do this, we analyze critical aspects of the literature dealing with the ecology of restoring contaminated ecosystems. Additionally, we review approaches for translating the science of restoration to on-the-ground actions, which includes discussions of market incentives and the finances of restoration, stakeholder outreach and governance models for ecosystem restoration, and working with contractors to implement restoration plans. By explicitly considering the mechanisms and strategies that maximize the success of the restoration of contaminated sites, we hope that our synthesis serves to increase and improve collaborations between restoration ecologists and ecotoxicologists and set a roadmap for the restoration of contaminated ecosystems.

  15. 30 CFR 874.14 - Water supply restoration. (United States)


    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Water supply restoration. 874.14 Section 874.14... ABANDONED MINE LAND RECLAMATION GENERAL RECLAMATION REQUIREMENTS § 874.14 Water supply restoration. (a) Any... supply restoration projects. For purposes of this section, “water supply restoration projects” are...

  16. River restoration: separating myths from reality (United States)

    Friberg, N.; Woodward, G.


    River restorations are a social construct where degraded systems are physically modified to obtain a pre-disturbance set of attributes. These can be purely esthetic but are often linked to some kind of biotic recovery or the provision of important ecosystem services such as flood control or self-purification. The social setting of restoration projects, with a range of potential conflicts, significantly reduces scale of most interventions to a size with little room, or wish, for natural processes. We show that projects sizes are still very small and that the restoration target is not to recover natural geomorphic processes but rather to fulfil human perception of what a nice stream looks like. One case from Danish lowland streams, using a space-for-time substitution approach, shows excess use of pebble and gravel when restoring channelized sandy bottom streams, de-coupling the link between energy and substrate characteristics that are found in natural lowland systems. This has implication for both the biological structure and functioning of these systems as a direct link between substrate heterogeneity and macroinvertebrate diversity was not found in restored streams, while the density of grazer increased indicating an increased use of periphyton as a basal resource. Another case of adding woody debris to UK lowland streams, using a BACI study design, showed very little effect on the macroinvertebrate community even after a 100-year flood, which indicate that added tree trunks did not provide additional flow refugia. We suggest that restoration schemes should aim at restoring the natural physical structural complexity in the streams and at the same time enhance the possibility of re-generating the natural geomorphological processes sustaining the habitats in streams and rivers.

  17. Benefits of investing in ecosystem restoration. (United States)

    DE Groot, Rudolf S; Blignaut, James; VAN DER Ploeg, Sander; Aronson, James; Elmqvist, Thomas; Farley, Joshua


    Measures aimed at conservation or restoration of ecosystems are often seen as net-cost projects by governments and businesses because they are based on incomplete and often faulty cost-benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) of ecosystem restoration projects that had sufficient reliable data in 9 different biomes ranging from coral reefs to tropical forests. Costs included capital investment and maintenance of the restoration project, and benefits were based on the monetary value of the total bundle of ecosystem services provided by the restored ecosystem. Assuming restoration is always imperfect and benefits attain only 75% of the maximum value of the reference systems over 20 years, we calculated the net present value at the social discount rates of 2% and 8%. We also conducted 2 threshold cum sensitivity analyses. Benefit-cost ratios ranged from about 0.05:1 (coral reefs and coastal systems, worst-case scenario) to as much as 35:1 (grasslands, best-case scenario). Our results provide only partial estimates of benefits at one point in time and reflect the lower limit of the welfare benefits of ecosystem restoration because both scarcity of and demand for ecosystem services is increasing and new benefits of natural ecosystems and biological diversity are being discovered. Nonetheless, when accounting for even the incomplete range of known benefits through the use of static estimates that fail to capture rising values, the majority of the restoration projects we analyzed provided net benefits and should be considered not only as profitable but also as high-yielding investments. Beneficios de Invertir en la Restauración de Ecosistemas.

  18. Kappa opioid receptor antagonist and N-methyl-D- aspartate receptor antagonist affect dynorphin- induced spinal cord electrophysiologic impairment

    Institute of Scientific and Technical Information of China (English)

    Yu Chen; Liangbi Xiang; Jun Liu; Dapeng Zhou; Hailong Yu; Qi Wang; Wenfeng Han; Weijian Ren


    The latencies of motor- and somatosensory-evoked potentials were prolonged to different degrees, and wave amplitude was obviously decreased, after injection of dynorphin into the rat subarachnoid cavity.The wave amplitude and latencies of motor- and somatosensory-evoked potentials were significantly recovered at 7 and 14 days after combined injection of dynorphin and either the kappa opioid receptor antagonist nor-binaltorphimine or the N-methyl-D-aspartate receptor antagonist MK-801.The wave amplitude and latency were similar in rats after combined injection of dynorphin and nor-binaltorphimine or MK-801.These results suggest that intrathecal injection of dynorphin causes damage to spinal cord function.Prevention of N-methyl-D-aspartate receptor or kappa receptor activation lessened the injury to spinal cord function induced by dynorphin.

  19. Development of Restorative Justice in China: Theory and Practice

    Directory of Open Access Journals (Sweden)

    Yinzhi Shen


    Full Text Available Restorative justice has become a global social movement for criminal justice reform, with over eighty countries adopting some form of restorative justice program to tackle their crime problems. The theory of restorative justice was introduced to the Chinese academia in 2002. So far, various restorative justice programs have been developed in China. This paper aims to systematically review the development of restorative justice in China by analyzing academic literature on restorative justice and key legislative documentations. Major debates in restorative justice among Chinese scholars and a review of the indigenous restorative justice practice, criminal reconciliation (Xingshi Hejie, are provided. The study also analyzes the impetus of this soaring popularity of restorative justice in China, considering the macro social, political and legal background. Last but not least, a review of the major evaluation studies of current programs reveals that little is known about the process of various restorative justice programs from the parties’ own perspective.

  20. Anti free radical action of calcium antagonists and H1 and H2 receptors antagonists in neoplastic disease. (United States)

    della Rovere, F; Broccio, M; Granata, A; Zirilli, A; Brugnano, L; Artemisia, A; Broccio, G


    The blood of the subjects suffering from Neoplastic Disease (ND) shows phenomena of membrane peroxidation due to the presence of Free Radicals (FRs), in a quantity much greater than the one observed in the blood of healthy subjects. This can be detected either by calculating the time necessary for the formation of "Heinz bodies" (Hbs), (p < 0.00001) after oxidative stress of the blood in vitro with acetylphenylidrazine (APH), or by calculating the methemoglobin (metHb) quantity that forms after the same treatment (P < 0.00001). The statistical analyses we carried out showed that metHb formation was not affected by age, sex, smoking habits, red blood cell number, Hb, Ht or tumor staging. In this study, by using equal parameters of investigation, we noted that the blood of the subjects with ND who were previously treated with calcium-antagonists drugs and with antagonists of H1 and H2 receptors, gave results completely superimposable on the results obtained from healthy subjects, implying that the treatment had avoided the increase of FRs. Therefore we concluded that calcium-antagonists and the antagonists of the H1 and H2 receptors behave as antioxidant substances, having decreased the FRs damaging activity on the cellular membranes, thus controlling, although to a limited degree, the pejorative evolution of the disease. It is also important to remember that investigations into the ND, even possible screenings, must take into account the above said data, submitting the subjects under investigation to a pharmacological wash out, particularly with those substances which, are considered to be scavengers of FRs. Some of these substances are investigated in this work.

  1. Conformational studies of 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists leading to new spirocyclic antagonists. (United States)

    Pasternak, Alexander; Goble, Stephen D; Doss, George A; Tsou, Nancy N; Butora, Gabor; Vicario, Pasquale P; Ayala, Julia Marie; Struthers, Mary; Demartino, Julie A; Mills, Sander G; Yang, Lihu


    In an effort to shed light on the active binding conformation of our 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists, we prepared several conformationally constrained analogs resulting from backbone cyclization. Evaluation of CCR2 binding affinities for these analogs gave insight into the optimal relative positions of the piperidine and benzylamide moieties while simultaneously leading to the discovery of a new, potent lead type based upon a spirocyclic acetal scaffold.

  2. Prioritization of Forest Restoration Projects: Tradeoffs between Wildfire Protection, Ecological Restoration and Economic Objectives

    Directory of Open Access Journals (Sweden)

    Kevin C. Vogler


    Full Text Available The implementation of US federal forest restoration programs on national forests is a complex process that requires balancing diverse socioecological goals with project economics. Despite both the large geographic scope and substantial investments in restoration projects, a quantitative decision support framework to locate optimal project areas and examine tradeoffs among alternative restoration strategies is lacking. We developed and demonstrated a new prioritization approach for restoration projects using optimization and the framework of production possibility frontiers. The study area was a 914,657 ha national forest in eastern Oregon, US that was identified as a national priority for restoration with the goal of increasing fire resiliency and sustaining ecosystem services. The results illustrated sharp tradeoffs among the various restoration goals due to weak spatial correlation of forest stressors and provisional ecosystem services. The sharpest tradeoffs were found in simulated projects that addressed either wildfire risk to the urban interface or wildfire hazard, highlighting the challenges associated with meeting both economic and fire protection goals. Understanding the nature of tradeoffs between restoration objectives and communicating them to forest stakeholders will allow forest managers to more effectively design and implement economically feasible restoration projects.

  3. Plant invaders, global change and landscape restoration (United States)

    Pyke, D.A.; Knick, S.T.


    Modifications in land uses, technology, transportation and biogeochemical cycles currently influence the spread of organisms by reducing the barriers that once restricted their movements. We provide an overview of the spatial and temporal extent for agents of environmental change (land and disturbance transformations, biogeochemical modifications, biotic additions and losses) and highlight those that strongly influence rangeland ecosystems. Restoration may provide a mechanism for ameliorating the impacts of invasive species, but applications of restoration practices over large scales, e.g. ecoregions, will yield benefits earlier when the landscape is prioritised by criteria that identify locations where critical restoration species can grow and where success will be high. We used the Great Basin, USA as our region of interest where the invasive annual grass, cheatgrass (Bromus tectorum), dominates millions of hectares. A landscape-level restoration model for sagebrush (Artemisia tridentata ssp. tridentata and ssp. wyomingensis) was developed to meet the goal of establishing priority habitat for wildlife. This approach could be used in long-range planning of rangeland ecosystems where funds and labour for restoration projects may vary annually. Copyright ?? NISC Pty Ltd.

  4. Radiopacity of restorative materials using digital images. (United States)

    Salzedas, Leda Maria Pescinini; Louzada, Mário Jefferson Quirino; de Oliveira Filho, Antonio Braz


    The radiopacity of esthetic restorative materials has been established as an important requirement, improving the radiographic diagnosis. The aim of this study was to evaluate the radiopacity of six restorative materials using a direct digital image system, comparing them to the dental tissues (enamel-dentin), expressed as equivalent thickness of aluminum (millimeters of aluminum). Five specimens of each material were made. Three 2-mm thick longitudinal sections were cut from an intact extracted permanent molar tooth (including enamel and dentin). An aluminum step wedge with 9 steps was used. The samples of different materials were placed on a phosphor plate together with a tooth section, aluminum step wedge and metal code letter, and were exposed using a dental x-ray unit. Five measurements of radiographic density were obtained from each image of each item assessed (restorative material, enamel, dentin, each step of the aluminum step wedge) and the mean of these values was calculated. Radiopacity values were subsequently calculated as equivalents of aluminum thickness. Analysis of variance (ANOVA) indicated significant differences in radiopacity values among the materials (Pcomposite restorations it is important that the restorative material to be used has enough radiopacity, in order to be easily distinguished from the tooth structure in the radiographic image. Knowledge on the radiopacity of different materials helps professionals to select the most suitable material, along with other properties such as biocompatibility, adhesion and esthetic.

  5. What constitutes an ideal dental restorative material? (United States)

    Rekow, E D; Bayne, S C; Carvalho, R M; Steele, J G


    Intense environmental concerns recently have prompted dentistry to evaluate the performance and environmental impact of existing restoration materials. Doing so entices us to explore the 'what if?' innovation in materials science to create more ideal restorative materials. Articulating a specification for our design and evaluation methods is proving to be more complicated than originally anticipated. Challenges exist not only in specifying how the material should be manipulated and perform clinically but also in understanding and incorporating implications of the skill of the operator placing the restoration, economic considerations, expectations patients have for their investment, cost-effectiveness, influences of the health care system on how and for whom restorations are to be placed, and global challenges that limit the types of materials available in different areas of the world. The quandary is to find ways to actively engage multiple stakeholders to agree on priorities and future actions to focus future directions on the creation of more ideal restorative materials that can be available throughout the world.

  6. Spatially Adaptive Intensity Bounds for Image Restoration

    Directory of Open Access Journals (Sweden)

    Kaaren L. May


    Full Text Available Spatially-adaptive intensity bounds on the image estimate are shown to be an effective means of regularising the ill-posed image restoration problem. For blind restoration, the local intensity constraints also help to further define the solution, thereby reducing the number of multiple solutions and local minima. The bounds are defined in terms of the local statistics of the image estimate and a control parameter which determines the scale of the bounds. Guidelines for choosing this parameter are developed in the context of classical (nonblind image restoration. The intensity bounds are applied by means of the gradient projection method, and conditions for convergence are derived when the bounds are refined using the current image estimate. Based on this method, a new alternating constrained minimisation approach is proposed for blind image restoration. On the basis of the experimental results provided, it is found that local intensity bounds offer a simple, flexible method of constraining both the nonblind and blind restoration problems.

  7. Smooth surface glass ionomer restoration for primary teeth. (United States)

    Killian, C M; Croll, T P


    Glass ionomer restorative cement offers the clinician an alternative to bonded composite resin for restoration of certain lesions in primary teeth. This article details a step-by-step procedure for restoration of a smooth surface carious lesion in a primary incisor using an encapsulated glass ionomer restorative material and reviews advantages and limitations of the cement. A light-hardened glass ionomer liner/base that has proven useful as an enamel and dentin restorative is also described.

  8. Restorative culture in school. Continuation of discussion

    Directory of Open Access Journals (Sweden)

    A.A. Pentin


    Full Text Available The article deals with the lack of effective ways of building relationships, parenting responsibility and conflict solving in the school community. It is addressed to the whole school community – to the administration, psychologists and social workers, to the faculty, parents and students. We discuss the key concepts and principles of “restorative culture” and the reasons for its introduction in educational institutions. The restorative culture refers to activities on formation and spread of interpersonal relations value in the aspect of its understanding, trust, acceptance of active responsibility, separation of problems and subjects, and focus on the successful experience. We briefly discuss the theory of restorative justice and narrative practice. Particular attention is paid to the typical methods of school response to conflicts, and to zero-tolerance policy. We propose that the school community needs a number of specific technologies that would optimally suit for different types of situations and would constitute a part of the system

  9. Pardon in the light of restorative justice

    Directory of Open Access Journals (Sweden)

    Miladinović Dušica


    Full Text Available The main aim of this paper is to consider pardon in the restorative justice context. Beginning from the basic standpoint that restorative justice imposes request for interests-balancing of different subjects connected by criminal act, the author tries to examine the articulation of the aforementioned standpoint through the pardon concept, accepted in domestic positive law. There is no doubt that the institute is designed in favour of the crime perpetrator, which is confirmed by the analysis of different legal effects produced by its content, while the victim- and society interests remained, at least, insufficiently protected. Therefore, the author points to some positive examples from comparative law and poses certain suggestions, that can be of use for eventual reforming of the institute, in order to achieve values of restorative justice. .

  10. Design for Restoration: beyond the survey

    Directory of Open Access Journals (Sweden)

    Giovanni Carbonara


    Full Text Available  This new issue, that we can define special, marks an important change for DISEGNARECON (its transfer from the University of Bologna to the University of L’Aquila facing the topic of the Design for the Restoration in a way that is special too. Treated in fact - beside the outgoing editor in chief, Roberto Mingucci - by Mario Centofanti, who now assumes the responsibility for the magazine, and Giovanni Carbonara, which is definitely authoritative reference in the field. Sharing a strong interest for communicating the Restoration Project, they intended to indicate the substantial union of methods and objectives between the disciplines of architectural survey and of restoration, which makes the meaning of an aggregation now also institutionally formalized and particularly significant for the project on the existing architecture. 

  11. Restoring gingival harmony around single tooth implants. (United States)

    Reikie, D F


    One of the biggest challenges to restoring a single tooth implant in the esthetic zone of the mouth is the creation of harmonious gingival contour around the restoration. Soft- or hard-tissue deficiencies of the edentulous space are the most common obstacles to achieving gingival symmetry around the proposed restoration. Numerous gingival and osseous grafting and regeneration techniques are available but may complicate treatment by increasing the number of surgical procedures and sites necessary. This article describes a technique for treating mild-to-moderate ridge defects without the required additional surgical procedures or a surgical donor site. Soft-tissue overcontouring is provided around the healing abutment by modification of the surgical flap at second-stage implant surgery. Subsequent gingivoplasty allows establishment of anatomic gingival architecture that surrounds the single implant prosthesis.

  12. Application of Laser Irradiation for Restorative Treatments (United States)

    Davoudi, Amin; Sanei, Maryam; Badrian, Hamid


    Nowadays, lasers are widely used in many fields of medicine. Also, they can be applied at many branches of dental practice such as diagnosis, preventive procedures, restorative treatments, and endodontic therapies. Procedures like caries removal, re-mineralization, and vital pulp therapy are the most noticeable effects of laser irradiation which has gained much attention among clinicians. With controlled and appropriate wavelength, they can help stimulating dentinogenesis, controlling pulpal hemorrhage, sterilization, healing of collagenic proteins, formation of a fibrous matrix, and inducing hard tissue barrier. Nevertheless, there are many controversies in literatures regarding their effects on the quality of bonded restorations. It hampered a wide application of lasers in some aspects of restorative dentistry and requirements to identify the best way to use this technology. The aim of this mini review is to explain special characteristics of laser therapy and to introduce the possible applications of laser devices for dental purposes. PMID:27990188

  13. Restorative and Invisalign: a new approach. (United States)

    Norris, Robert A; Brandt, Douglas J; Crawford, Craig H; Fallah, Mohamed


    This case report describes an interdisciplinary treatment approach using the Invisalign System (Align Technology, Inc., Santa Clara, California) for orthodontics in combination with restorative dentistry. This combined approach was selected for an optimum esthetic and functional result. This case report demonstrates how a restorative case can be improved with prerestorative orthodontic alignment. The Invisalign System was used for opening the bite anteriorly, space distribution, and midline correction. The restorative dentistry procedures involved veneering to enhance the maxillary incisor length-to-width ratio and provide anterior guidance. The cosmetic alternative treatment modality to conventional fixed orthodontics allowed the clinician to accomplish the prerestorative orthodontic goals to help meet the desires of an esthetically conscientious patient.

  14. Predictions of in vivo prolactin levels from in vitro k I values of d 2 receptor antagonists using an agonist-antagonist interaction model

    NARCIS (Netherlands)

    Petersson, K.J.; Vermeulen, A.M.J.; Friberg, L.E.


    Prolactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess th

  15. Angiotensin II type 1 receptor blockade restores angiotensin-(1-7)-induced coronary vasodilation in hypertrophic rat hearts. (United States)

    Souza, Álvaro P S; Sobrinho, Deny B S; Almeida, Jônathas F Q; Alves, Gisele M M; Macedo, Larissa M; Porto, Juliana E; Vêncio, Eneida F; Colugnati, Diego B; Santos, Robson A S; Ferreira, Anderson J; Mendes, Elizabeth P; Castro, Carlos H


    The aim of the present study was to investigate the coronary effects of Ang-(1-7) [angiotensin-(1-7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1-7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (N(G)-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1-7) in control hearts. The coronary vasodilation produced by Ang-(1-7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1-7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1-7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1-7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas

  16. Nerve Transfers to Restore Shoulder Function. (United States)

    Leechavengvongs, Somsak; Malungpaishorpe, Kanchai; Uerpairojkit, Chairoj; Ng, Chye Yew; Witoonchart, Kiat


    The restoration of shoulder function after brachial plexus injury represents a significant challenge facing the peripheral nerve surgeons. This is owing to a combination of the complex biomechanics of the shoulder girdle, the multitude of muscles and nerves that could be potentially injured, and a limited number of donor options. In general, nerve transfer is favored over tendon transfer, because the biomechanics of the musculotendinous units are not altered. This article summarizes the surgical techniques and clinical results of nerve transfers for restoration of shoulder function.

  17. Matrix Krylov subspace methods for image restoration

    Directory of Open Access Journals (Sweden)

    khalide jbilou


    Full Text Available In the present paper, we consider some matrix Krylov subspace methods for solving ill-posed linear matrix equations and in those problems coming from the restoration of blurred and noisy images. Applying the well known Tikhonov regularization procedure leads to a Sylvester matrix equation depending the Tikhonov regularized parameter. We apply the matrix versions of the well known Krylov subspace methods, namely the Least Squared (LSQR and the conjugate gradient (CG methods to get approximate solutions representing the restored images. Some numerical tests are presented to show the effectiveness of the proposed methods.

  18. Symmetry Non-restoration at High Temperature

    CERN Document Server

    Rius, N


    We discuss the (non)-restoration of global and local symmetries at high temperature. First, we analyze a two-scalar model with $Z_2 \\times Z_2$ symmetry using the exact renormalization group. We conclude that inverse symmetry breaking is possible in this kind of models within the perturbative regime. Regarding local symmetries, we consider the $SU(2) \\otimes U(1)$ gauge symmetry and focus on the case of a strongly interacting scalar sector. Employing a model-independent chiral Lagrangian we find indications of symmetry restoration.

  19. Alternatives to testosterone replacement: testosterone restoration

    Directory of Open Access Journals (Sweden)

    Andrew McCullough


    Full Text Available The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.

  20. The Management of Dissonance in Nature Restoration

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel


    Nature restoration is far from a neural undertaking. Just like any other type of heritage production, it can be the source of dissonance—‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particularly sensitive to site-specificity. As exemplified...... for multiple interpretations to coexist. Indications can be found in the Re-naturalization of River Aire (2002-2015)—a restoration project, which reveals approaches that could be labelled landscape architecture specific....

  1. The Management of Dissonance in Nature Restoration

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel


    Nature restoration is far from a neural undertaking. Just like any other type of heritage production, it can be the source of dissonance—‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particularly sensitive to site-specificity. As exemplified...... for multiple interpretations to coexist. Indications can be found in the Re-naturalization of River Aire (2002-2015)—a restoration project, which reveals approaches that could be labelled landscape architecture specific....

  2. Combination restoration in full mouth rehabilitation

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar


    Full Text Available Successful restoration of the dentition requires plenty of contemporary and conventional treatment techniques and planning and attachment retained partial dentures are one such kind of treatment modality in prosthodontics. Satisfactory restoration in a patient with a partially edentulous situation can be challenging especially when unilateral or bilateral posterior segment of teeth is missing. One such treatment modality is attachment-retained cast partial dentures. The purpose of this article is to provide an overview of a case with maxillary complete denture and opposing cast partial denture with precision attachment.

  3. Criteria for the replacement of restorations

    DEFF Research Database (Denmark)

    Wilson, Nairn; Lynch, Christopher; Brunton, Paul Brunton


    The replacement of a restoration is one of the most common procedures in dentistry. However, the criteria for such intervention, excluding catastrophic failure and persistent discomfort and pain, continue to be the subject of considerable debate. The decision-making process remains subjective...... on the part of the treating clinician, while the evidence base for refurbishment and repair rather than replacement for the management of defective and failing restorations continues to grow and strengthen. This article, prepared as an Academy of Operative Dentistry European Section consensus publication...

  4. Environmental Restoration Program Control Management System

    Energy Technology Data Exchange (ETDEWEB)

    Duke, R.T.


    Environmental Restoration managers need to demonstrate that their programs are under control. Unlike most industrial programs, the public is heavily involved in Environmental Restoration activities. The public is demanding that the country prove that real progress is being made towards cleaning up the environment. A Program Control Management System can fill this need. It provides a structure for planning, work authorization, data accumulation, data analysis and change control. But it takes time to implement a control system and the public is losing its patience. This paper describes critical items essential to the quick development and implementation of a successful control system.

  5. Iterative restoration algorithms for nonlinear constraint computing (United States)

    Szu, Harold

    A general iterative-restoration principle is introduced to facilitate the implementation of nonlinear optical processors. The von Neumann convergence theorem is generalized to include nonorthogonal subspaces which can be reduced to a special orthogonal projection operator by applying an orthogonality condition. This principle is shown to permit derivation of the Jacobi algorithm, the recursive principle, the van Cittert (1931) deconvolution method, the iteration schemes of Gerchberg (1974) and Papoulis (1975), and iteration schemes using two Fourier conjugate domains (e.g., Fienup, 1981). Applications to restoring the image of a double star and division by hard and soft zeros are discussed, and sample results are presented graphically.

  6. Environmental Restoration Information Resource Management Program Plan

    Energy Technology Data Exchange (ETDEWEB)


    The Environmental Restoration Information Resources Management (ER IRM) Program Plan defines program requirements, organizational structures and responsibilities, and work breakdown structure and to establish an approved baseline against which overall progress of the program as well as the effectiveness of its management will be measured. This plan will guide ER IRM Program execution and define the program`s essential elements. This plan will be routinely updated to incorporate key decisions and programmatic changes and will serve as the project baseline document. Environmental Restoration Waste Management Program intersite procedures and work instructions will be developed to facilitate the implementation of this plan.

  7. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard


    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  8. Classification and virtual screening of androgen receptor antagonists. (United States)

    Li, Jiazhong; Gramatica, Paola


    Computational tools, such as quantitative structure-activity relationship (QSAR), are highly useful as screening support for prioritization of substances of very high concern (SVHC). From the practical point of view, QSAR models should be effective to pick out more active rather than inactive compounds, expressed as sensitivity in classification works. This research investigates the classification of a big data set of endocrine-disrupting chemicals (EDCs)-androgen receptor (AR) antagonists, mainly aiming to improve the external sensitivity and to screen for potential AR binders. The kNN, lazy IB1, and ADTree methods and the consensus approach were used to build different models, which improve the sensitivity on external chemicals from 57.1% (literature) to 76.4%. Additionally, the models' predictive abilities were further validated on a blind collected data set (sensitivity: 85.7%). Then the proposed classifiers were used: (i) to distinguish a set of AR binders into antagonists and agonists; (ii) to screen a combined estrogen receptor binder database to find out possible chemicals that can bind to both AR and ER; and (iii) to virtually screen our in-house environmental chemical database. The in silico screening results suggest: (i) that some compounds can affect the normal endocrine system through a complex mechanism binding both to ER and AR; (ii) new EDCs, which are nonER binders, but can in silico bind to AR, are recognized; and (iii) about 20% of compounds in a big data set of environmental chemicals are predicted as new AR antagonists. The priority should be given to them to experimentally test the binding activities with AR.

  9. Sexually antagonistic "zygotic drive" of the sex chromosomes.

    Directory of Open Access Journals (Sweden)

    William R Rice


    Full Text Available Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive", because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race" between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.

  10. Discovery of dopamine D₄ receptor antagonists with planar chirality. (United States)

    Sanna, Fabrizio; Ortner, Birgit; Hübner, Harald; Löber, Stefan; Tschammer, Nuska; Gmeiner, Peter


    Employing the D4 selective phenylpiperazine 2 as a lead compound, planar chiral analogs with paracyclophane substructure were synthesized and evaluated for their ability to bind and activate dopamine receptors. The study revealed that the introduction of a [2.2]paracyclophane moiety is tolerated by dopamine receptors of the D2 family. Subtype selectivity for D4 and ligand efficacy depend on the absolute configuration of the test compounds. Whereas the achiral single-layered lead 2 and the double-layered paracyclophane (R)-3 showed partial agonist properties, the enantiomer (S)-3 behaved as a neutral antagonist.

  11. Lymphocyte homing antagonists in the treatment of inflammatory bowel diseases. (United States)

    Saruta, Masayuki; Papadakis, Konstantinos A


    Lymphocyte homing antagonists represent promising therapeutic agents for the treatment of idiopathic inflammatory bowel disease (IBD). Several critical molecules involved in the recruitment of inflammatory cells in the intestine, including integrins and chemokine receptors, have been successfully targeted for the treatment of IBD. These agents have shown great promise for the induction and maintenance of remission for both Crohn disease and ulcerative colitis. This article discusses currently approved prototypic agents for the treatment of IBD (natalizumab, anti-α4 integrin; vedolizumab, anti-α4β7 integrin), and several other agents in the same class currently under development.

  12. The opiate antagonist, naltrexone, in the treatment of trichotillomania

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N;


    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were...... improved with naltrexone (P = 0.026). Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant. Future studies will have to examine whether pharmacological modulation of the opiate system may...

  13. Estrogen Receptor Agonists and Antagonists in the Yeast Estrogen Bioassay. (United States)

    Wang, Si; Bovee, Toine F H


    Cell-based bioassays can be used to predict the eventual biological activity of a substance on a living organism. In vitro reporter gene bioassays are based on recombinant vertebrate cell lines or yeast strains and especially the latter are easy-to-handle, cheap, and fast. Moreover, yeast cells do not express estrogen, androgen, progesterone or glucocorticoid receptors, and are thus powerful tools in the development of specific reporter gene systems that are devoid of crosstalk from other hormone pathways. This chapter describes our experience with an in-house developed RIKILT yeast estrogen bioassay for testing estrogen receptor agonists and antagonists, focusing on the applicability of the latter.

  14. Antagonistic action of pitrazepin on human and rat GABAA receptors (United States)

    Demuro, Angelo; Martinez-Torres, Ataulfo; Francesconi, Walter; Miledi, Ricardo


    Pitrazepin, 3-(piperazinyl-1)-9H-dibenz(c,f) triazolo(4,5-a)azepin is a piperazine antagonist of GABA in a variety of electrophysiological and in vitro binding studies involving GABA and glycine receptors. In the present study we have investigated the effects of pitrazepin, and the GABAA antagonist bicuculline, on membrane currents elicited by GABA in Xenopus oocytes injected with rat cerebral cortex mRNA or cDNAs encoding α1β2 or α1β2γ2S human GABAA receptor subunits.The three types of GABAA receptors expressed were reversibly antagonized by bicuculline and pitrazepin in a concentration-dependent manner. GABA dose-current response curves for the three types of receptors were shifted to the right, in a parallel manner, by increasing concentrations of pitrazepin.Schild analyses gave pA2 values of 6.42±0.62, n=4, 6.41±1.2, n=5 and 6.21±1.24, n=6, in oocytes expressing rat cerebral cortex, α1β2 or α1β2γ2S human GABAA receptors respectively (values are given as means±s.e.mean), and the Hill coefficients were all close to unity. All this is consistent with the notion that pitrazepin acts as a competitive antagonist of these GABAA receptors; and that their antagonism by pitrazepin is not strongly dependent on the subunit composition of the receptors here studied.Since pitrazepin has been reported to act also at the benzodiazepine binding site, we studied the effect of the benzodiazepine antagonist Ro 15-1788 (flumazenil) on the inhibition of α1β2γ2S receptors by pitrazepin. Co-application of Ro 15-1788 did not alter the inhibiting effect of pitrazepin. Moreover, pitrazepin did not antagonize the potentiation of GABA-currents by flunitrazepam. All this suggests that pitrazepin does not affect the GABA receptor-chloride channel by interacting with the benzodiazepine receptor site. PMID:10369456

  15. Restorative dentistry for the older patient cohort. (United States)

    Jablonski, R Y; Barber, M W


    The ageing UK population presents a number of challenges to the restorative dentist as a result of complex treatment needs and a significant maintenance burden. This paper discusses how ageing may influence the provision of dental treatment and outlines a variety of conservative, periodontal, endodontic and prosthodontic considerations that are important in the management of the older patient cohort.

  16. Ghost suppression in image restoration filtering (United States)

    Riemer, T. E.; Mcgillem, C. D.


    An optimum image restoration filter is described in which provision is made to constrain the spatial extent of the restoration function, the noise level of the filter output and the rate of falloff of the composite system point-spread away from the origin. Experimental results show that sidelobes on the composite system point-spread function produce ghosts in the restored image near discontinuities in intensity level. By redetermining the filter using a penalty function that is zero over the main lobe of the composite point-spread function of the optimum filter and nonzero where the point-spread function departs from a smoothly decaying function in the sidelobe region, a great reduction in sidelobe level is obtained. Almost no loss in resolving power of the composite system results from this procedure. By iteratively carrying out the same procedure even further reductions in sidelobe level are obtained. Examples of original and iterated restoration functions are shown along with their effects on a test image.

  17. Benefits of investing in ecosystem restoration

    NARCIS (Netherlands)

    Groot, de R.S.; Blignaut, J.; Ploeg, van der S.; Aronson, J.; Elmqvist, T.; Farley, J.


    Measures aimed at conservation or restoration of ecosystems are often seen as net-cost projects by governments and businesses because they are based on incomplete and often faulty cost-benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) o

  18. Comparison of active and passive stream restoration

    DEFF Research Database (Denmark)

    Kristensen, Esben Astrup; Thodsen, Hans; Dehli, Bjarke


    Modification and channelization of streams and rivers have been conducted extensively throughout the world during the past century. Subsequently, much effort has been directed at re-creating the lost habitats and thereby improving living conditions for aquatic organisms. However, as restoration m...

  19. Restorative Justice: Pedagogy, Praxis, and Discipline (United States)

    Morrison, Brenda E.; Vaandering, Dorothy


    In the ongoing effort of designing school contexts in support of proactive discipline, a range of practices and theoretical frameworks have been advanced, from behaviorist approaches to social and emotional learning. This article describes the theory and practice of restorative justice with the aim of defining this distinctive paradigm, in…

  20. Setting targets in strategies for river restoration

    NARCIS (Netherlands)

    Pedroli, G.B.M.; Blust, de G.; Looy, van K.; Rooij, van S.A.M.


    Since about 90% of the natural floodplain area of rivers in Europe has been reclaimed and now lacks river dynamics, nature rehabilitation along rivers is of crucial importance for the restoration of their natural function. Flood protection, self-purification of surface water, groundwater recharge, s

  1. Relativity restored: Dirac anisotropy in QED3. (United States)

    Vafek, O; Tesanović, Z; Franz, M


    We show that, at long length scales and low energies and to leading order in 1/N expansion, the anisotropic QED in 2+1 dimensions renormalizes to an isotropic limit. Consequently, the (Euclidean) relativistic invariance of the theory is spontaneously restored at the isotropic critical point.

  2. The importance of demonstratively restoring order.

    Directory of Open Access Journals (Sweden)

    Kees Keizer

    Full Text Available Contrary to what is often assumed, order is not the strongest context for encouraging normative behavior. The strongest context effect on normative behavior comes from cues that clearly convey other people's respect for norms. Ironically, this show of respect necessitates some contrasting disrespect that is being restored. Using civic virtues (such as helping behavior as a prototype of normative behavior, the three field experiments described in this paper reveal the impact of normative cues on civic virtues. Results show that the strongest effect on making people follow prosocial norms in public places emanates from seeing order being restored, rather than just order being present. The robust and surprisingly large effects show that observing other people's respect for one particular norm (as evidenced in their restoring physical order makes it more likely that the onlooker follows other norms as well. This implies that prosocial behavior has the highest chance of spreading when people observe order being restored. There are clear policy implications: create low cost "normative respect cues" wherever it is desirable to increase conformity to norms.

  3. Stimulating nitrate removal processes of restored wetlands. (United States)

    Ballantine, Kate A; Groffman, Peter M; Lehmann, Johannes; Schneider, Rebecca L


    The environmental and health effects caused by nitrate contamination of aquatic systems are a serious problem throughout the world. A strategy proposed to address nitrate pollution is the restoration of wetlands. However, although natural wetlands often remove nitrate via high rates of denitrification, wetlands restored for water quality functions often fall below expectations. This may be in part because key drivers for denitrification, in particular soil carbon, are slow to develop in restored wetlands. We added organic soil amendments that range along a gradient of carbon lability to four newly restored wetlands in western New York to investigate the effect of carbon additions on denitrification and other processes of the nitrogen cycle. Soil carbon increased by 12.67-63.30% with the use of soil amendments (p ≤ 0.0001). Soil nitrate, the carbon to nitrogen ratio, and microbial biomass nitrogen were the most significant predictors of denitrification potential. Denitrification potential, potential net nitrogen nitrification and mineralization, and soil nitrate and ammonium, were highest in topsoil-amended plots, with increases in denitrification potential of 161.27% over control plots. While amendment with topsoil more than doubled several key nitrogen cycling processes, more research is required to determine what type and level of amendment application are most effective for stimulating removal of exogenous nitrate and meeting functional goals within an acceptable time frame.

  4. Clinical performance of machined titanium restorations. (United States)

    Walter, M; Böning, K; Reppel, P D


    In 37 patients 88 titanium restorations were placed during a 1-year period 1990-91. The 69 crowns and 19 fixed partial dentures comprised 147 prosthodontic units. All restorations were fabricated by duplication milling and electrical discharge machining of pure titanium (Procera Technology, Nobelpharma, Gothenburg, Sweden). Based on the results of clinical follow-up, Kaplan-Meier survivor functions were calculated. The survivor rate of 40 metal crowns and pontics was 100%. In 107 porcelain-fused-to-metal units the 3-year survivor rate concerning removal was 95%. When relating the survival to an intact ceramic veneer, the 3-year survivor rate of porcelain-fused-to-metal units was 84%. The quality of the restorations evaluated by the rating system of the California Dental Association was found to be satisfactory in the vast majority of cases. It can be concluded that machined titanium restorations are suitable for clinical use, although not all problems, especially in the field of metal-ceramics have yet been completely solved.

  5. Super-Kamiokande worth full restoration

    CERN Multimedia

    Mishima, I


    While prospects are good that the SuperKamiokande facility will be partially repaired after an accident last November, the government has yet to confirm whether it will spend the estimated 2.5 billion yen needed for a full-scale restoration (1 page).

  6. 78 FR 56202 - Ecological Restoration Policy (United States)


    ..., and science-based restoration policy to guide achievement of sustainable management and ecological... conservation and rehabilitation of wildlife, fish, and game species. Such programs include specific habitat..., geologic, fish and wildlife, historic, cultural, or other similar values. Streams eligible for inclusion...

  7. Nerve Transfers to Restore Elbow Function. (United States)

    Bulstra, Liselotte F; Shin, Alexander Y


    The purpose of this article is to provide an overview of the various nerve transfer options for restoration of elbow function. This article describes nerve transfer strategies for elbow flexion and extension including the indications, limitations, and expected outcomes based on current literature.

  8. Restor pakub kileseina asemele moodulaeda / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-


    Tüli ehitusfirma Restor ja Tallinna linna vahel linnamüüriäärse maa täisehitamise pärast. Restori nõue ehitusloa taastamiseks jäi rahuldamata muinsuskaitsealal omavoliliselt lammutatud 18. sajandi hoonete pärast. Restoril on valminud ridaelamuboksid Plate ja Eppingi tornide vahel

  9. My Non-Restorative Sleep Syndrome

    Directory of Open Access Journals (Sweden)

    Chakravarthy Ambar


    Full Text Available Personal experience of systemic effects of late night sleep deprivation and non-restorative sleep-a common experience amongst doctors, has been described. Results of some simple self-experimentations have been mentioned to highlight the possible pathogenetic mechanisms.

  10. Restoring faith in politics from deliberation

    Directory of Open Access Journals (Sweden)

    Quim Brugué


    Full Text Available Politics is in difficulties. It is constantly blamed by people, who also require it to respond. The world is increasingly complex and diverse, and politics is needed to facilitate the continuity of a civilized community. The article defines the conceptual and operative bases of deliberative democracy, which is interpreted as the way to restore faith in politics.

  11. Oral environment control before restorative treatment

    Directory of Open Access Journals (Sweden)

    Ian Matos Vieira


    Full Text Available The aim of the present study was to describe caries disease treatment, by means of a clinical case report, with a view to promoting the patient’s health before definitive restorative treatments, considering that treatment should include changes in the patient’s dietary and hygiene habits, and not be restricted only to restoring lesions, as well as the establishment of an individualized treatment plan for each patient. Iodine-based antimicrobial solution was applied, instructions about oral hygiene and dietary habit changes were provided. The stepwise excavation technique was performed in tooth 15, mass excavation followed by the application of glass ionomer cement in the other teeth that presented carious lesions. White stain lesions were remineralized, and cicatrizes and fissures in the posterior teeth were sealed. After health was reestablished, the temporary restorations were replaced by definitive restorations. Changes in the treatment philosophy of caries disease, based on changes in the patient’s habits and removal of foci of infection have been presented with the object of producing an effective change in this paradigm, in order to increase the longevity of teeth with less operative intervention.

  12. 75 FR 71625 - System Restoration Reliability Standards (United States)


    ... Energy Regulatory Commission 18 CFR Part 40 System Restoration Reliability Standards November 18, 2010... to approve Reliability Standards EOP-001-1 (Emergency Operations Planning), EOP- 005-2 (System... modifications to proposed EOP-005-2 and EOP-006-2. The proposed Reliability Standards require that...

  13. Synthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease. (United States)

    Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin


    Graves' disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus-pituitary-thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies.

  14. Wind River Watershed Restoration: 1999 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Connolly, Patrick J.


    This document represents work conducted as part of the Wind River Watershed Restoration Project during its first year of funding through the Bonneville Power Administration (BPA). The project is a comprehensive effort involving public and private entities seeking to restore water quality and fishery resources in the basin through cooperative actions. Project elements include coordination, watershed assessment, restoration, monitoring, and education. Entities involved with implementing project components are the Underwood Conservation District (UCD), USDA Forest Service (USFS), U.S. Geological Survey--Columbia River Research Lab (USGS-CRRL), and WA Department of Fish & Wildlife (WDFW). Following categories given in the FY1999 Statement of Work, the broad categories, the related objectives, and the entities associated with each objective (lead entity in boldface) were as follows: Coordination--Objective 1: Coordinate the Wind River watershed Action Committee (AC) and Technical Advisory Committee (TAC) to develop a prioritized list of watershed enhancement projects. Monitoring--Objective 2: Monitor natural production of juvenile, smolt, and adult steelhead in the Wind River subbasin. Objective 3: Evaluate physical habitat conditions in the Wind River subbasin. Assessment--Objective 4: Assess watershed health using an ecosystem-based diagnostic model that will provide the technical basis to prioritize out-year restoration projects. Restoration--Objective 5: Reduce road related sediment sources by reducing road densities to less than 2 miles per square mile. Objective 6: Rehabilitate riparian corridors, flood plains, and channel morphology to reduce maximum water temperatures to less than 61 F, to increase bank stability to greater than 90%, to reduce bankfull width to depth ratios to less than 30, and to provide natural levels of pools and cover for fish. Objective 7: Maintain and evaluate passage for adult and juvenile steelhead at artificial barriers. Education

  15. Wetland Microbial Community Response to Restoration (United States)

    Theroux, S.; Hartman, W.; Tringe, S. G.


    Wetland restoration has been proposed as a potential long-term carbon storage solution, with a goal of engineering geochemical dynamics to accelerate peat accretion and encourage greenhouse gas (GHG) sequestration. However, wetland microbial community composition and metabolic rates are poorly understood and their predicted response to wetland restoration is a veritable unknown. In an effort to better understand the underlying factors that shape the balance of carbon flux in wetland soils, we targeted the microbial communities along a salinity gradient ranging from freshwater tidal marshes to hypersaline ponds in the San Francisco Bay-Delta region. Using 16S rRNA gene sequencing and shotgun metagenomics, coupled with greenhouse gas measurements, we sampled sixteen sites capturing a range in salinity and restoration status. Seawater delivers sulfate to wetland ecosystems, encouraging sulfate reduction and discouraging methane production. As expected, we observed the highest rates of methane production in the freshwater wetlands. Recently restored wetlands had significantly higher rates of methane production compared to their historic counterparts that could be attributed to variations in trace metal and organic carbon content in younger wetlands. In contrast, our sequencing results revealed an almost immediate return of the indigenous microbial communities following seasonal flooding and full tidal restoration in saline and hypersaline wetlands and managed ponds. Notably, we found elevated methane production rates in hypersaline ponds, the result of methylotrophic methane production confirmed by sequence data and lab incubations. Our study links belowground microbial communities and their aboveground greenhouse gas production and highlights the inherent complexity in predicting wetland microbial response in the face of both natural and unnatural disturbances.

  16. Cost Estimating Handbook for Environmental Restoration

    Energy Technology Data Exchange (ETDEWEB)



    Environmental restoration (ER) projects have presented the DOE and cost estimators with a number of properties that are not comparable to the normal estimating climate within DOE. These properties include: An entirely new set of specialized expressions and terminology. A higher than normal exposure to cost and schedule risk, as compared to most other DOE projects, due to changing regulations, public involvement, resource shortages, and scope of work. A higher than normal percentage of indirect costs to the total estimated cost due primarily to record keeping, special training, liability, and indemnification. More than one estimate for a project, particularly in the assessment phase, in order to provide input into the evaluation of alternatives for the cleanup action. While some aspects of existing guidance for cost estimators will be applicable to environmental restoration projects, some components of the present guidelines will have to be modified to reflect the unique elements of these projects. The purpose of this Handbook is to assist cost estimators in the preparation of environmental restoration estimates for Environmental Restoration and Waste Management (EM) projects undertaken by DOE. The DOE has, in recent years, seen a significant increase in the number, size, and frequency of environmental restoration projects that must be costed by the various DOE offices. The coming years will show the EM program to be the largest non-weapons program undertaken by DOE. These projects create new and unique estimating requirements since historical cost and estimating precedents are meager at best. It is anticipated that this Handbook will enhance the quality of cost data within DOE in several ways by providing: The basis for accurate, consistent, and traceable baselines. Sound methodologies, guidelines, and estimating formats. Sources of cost data/databases and estimating tools and techniques available at DOE cost professionals.

  17. Assessing the carbon benefit of saltmarsh restoration (United States)

    Taylor, Benjamin; Paterson, David; Hanley, Nicholas


    The quantification of carbon sequestration rates in coastal ecosystems is required to better realise their potential role in climate change mitigation. Through accurate valuation this service can be fully appreciated and perhaps help facilitate efforts to restore vulnerable ecosystems such as saltmarshes. Vegetated coastal ecosystems are suggested to account for approximately 50% of oceanic sedimentary carbon despite their 2% areal extent. Saltmarshes, conservatively estimated to store 430 ± 30 Tg C in surface sediment deposits, have experienced extensive decline in the recent past; through processes such as land use change and coastal squeeze. Saltmarsh habitats offer a range of services that benefit society and the natural world, making their conservation meaningful and beneficial. The associated costs of restoration projects could, in part, be subsidised through payment for ecosystem services, specifically Blue carbon. Additional storage is generated through the (re)vegetation of mudflat areas leading to an altered ecosystem state and function; providing similar benefits to natural saltmarsh areas. The Eden Estuary, Fife, Scotland has been a site of saltmarsh restoration since 2000; providing a temporal and spatial scale to evaluate these additional benefits. The study is being conducted to quantify the carbon benefit of restoration efforts and provide an insight into the evolution of this benefit through sites of different ages. Seasonal sediment deposition and settlement rates are measured across the estuary in: mudflat, young planted saltmarsh, old planted saltmarsh and extant high marsh areas. Carbon values being derived from loss on ignition organic content values. Samples are taken across a tidal cycle on a seasonal basis; providing data on tidal influence, vegetation condition effects and climatic factors on sedimentation and carbon sequestration rates. These data will inform on the annual characteristics of sedimentary processes in the estuary and be

  18. Effects of clonidine and alpha-adrenoceptor antagonists on motor activity in DSP4-treated mice II: interactions with apomorphine. (United States)

    Fredriksson, A; Archer, T


    Adult mice were administered either the noradrenaline (NA) neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or distilled water (control), 10-12 days before motor activity testing, and 6 h before testing all the mice were administered reserpine (10 mg/kg), the monoamine-depleting agent. The interactive effects of (I) clonidine, the alpha(2)-adrenoceptor agonist, with the dopamine (DA) agonist, apomorphine, and the alpha(2)-antagonist, yohimbine, and (II) with either yohimbine or the alpha(1)-antagonist, prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that apomorphine (3 mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the DSP4 mice. Co-administration of clonidine (3 mg/kg) with apomorphine potentiated the effects of apomorphine on motor activity and this effect was enhanced markedly by DSP4 pretreatment. Yohimbine (10 mg/kg) antagonized the motor activity-stimulating effects of apomorphine in both DSP4-treated and control mice. Co-administration of clonidine with apomorphine, following yohimbine, restored motor activity levels to those obtained in the absence of yohimbine and this effect upon locomotor activity was enhanced by DSP4 pretreatment. The effects of clonidine on motor activity were enhanced by NA-denervation. Prazzosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-min period but was not affected by DSP4 treatment. Analysis of post-decapitation convulsions (PDCs) indicated loss of the reflex by DSP4 pretreatment. Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to neurologic disorders such as parkinsonism.

  19. The evolution of histamine H₃ antagonists/inverse agonists. (United States)

    Lebois, Evan P; Jones, Carrie K; Lindsley, Craig W


    This article describes our efforts along with recent advances in the development, biological evaluation and clinical proof of concept of small molecule histamine H₃ antagonists/inverse agonists. The H3 receptor is a presynaptic autoreceptor within the Class A GPCR family, but also functions as a heteroreceptor modulating levels of neurotransmitters such as dopamine, acetylcholine, norepinephrine, serotonin, GABA and glutamate. Thus, H₃R has garnered a great deal of interest from the pharmaceutical industry for the possible treatment of obesity, epilepsy, sleep/wake, schizophrenia, Alzheimer's disease, neuropathic pain and ADHD. Within the two main classes of H₃ ligands, both imidazole and non-imidazole derived, have shown sufficient potency and specificity which culminated with efficacy in preclinical models for various CNS disorders. Importantly, conserved elements have been identified within the small molecule H₃ ligand scaffolds that resulted in a highly predictive pharmacophore model. Understanding of the pharmacophore model has allowed several groups to dial H₃R activity into scaffolds designed for other CNS targets, and engender directed polypharmacology. Moreover, Abbott, GSK, Pfizer and several others have reported positive Phase I and/or Phase II data with structurally diverse H₃R antagonists/inverse agonists.

  20. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hui [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Laboratory Medicine, The Affiliated Tenth People' s Hospital, Tongji University, Shanghai 200072 (China); Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Wang, Zhanli [College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014 (China); Liang, Huaping, E-mail: [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)


    Research highlights: {yields} Evodiamine interacted with the AhR. {yields} Evodiamine inhibited the specific binding of [{sup 3}H]-TCDD to the AhR. {yields} Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K{sub i} value of 28.4 {+-} 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  1. CCR9 Antagonists in the Treatment of Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Pirow Bekker


    Full Text Available While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.

  2. Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda


    Full Text Available Aldosterone, a specific mineralocorticoid receptor (MR agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is or angiotensin II type 1 receptor antagonists (ARBs. However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS inhibitors gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+ channel blockers (CCBs have inhibitory actions on aldosterone production in in vitro and in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

  3. CGRP antagonists and antibodies for the treatment of migraine. (United States)

    Vécsei, László; Szok, Délia; Csáti, Anett; Tajti, János


    Introduction: Migraine is a highly devastating neurovascular disorder that affects up to 16% of the population worldwide. In spite of intensive research, its origin remains enigmatic with no therapeutic option appropriate for all migraine patients. One of the leading hypotheses is related to the function of the calcitonin gene-related peptide (CGRP). Regardless, the pharmaceutical options currently applied for the acute and prophylactic treatment of migraine are not appropriate for all migraine patients. Areas covered: This article is based on a literature review using the PubMed database and highlights the CGRP theory of the pathomechanism of migraine. Expert opinion: Since migraine is a CGRP-related disorder, it appeared obvious to develop CGRP receptor antagonists that exert high efficacy, both intravenously and orally. Unfortunately, the frequent use of these antagonists results in an elevated liver transaminase level. In an attempt to bypass these harmful side effects, efforts should be made to modify these pharmacons. The use of fully humanized monoclonal antibodies (mAbs) that target CGRP and its receptors may also be possible. However, while Phase I and II clinical trials are promising, a long-term follow-up of these therapies is still needed.

  4. Implications of hedgehog signaling antagonists for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jingwu Xie


    The hedgehog(Hh)pathway,initially discovered inDrosophila by two Nobel laureates,Dr.Eric Wieschaus and Dr.Christiane Nusslein-Volhard,is a major regulator for cell differentiation,tissue polarity and cell proliferation.Studies from many laboratories,including ours,reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers,including medulloblastomas,gastrointestinal,lung,breast and prostate cancers.Thus,it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers.Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway,which have significant clinical implications in novel cancer therapeutics.This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers,the molecular basis of Hh signaling activation,the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.

  5. Rogue sperm indicate sexually antagonistic coevolution in nematodes.

    Directory of Open Access Journals (Sweden)

    Ronald E Ellis


    Full Text Available Intense reproductive competition often continues long after animals finish mating. In many species, sperm from one male compete with those from others to find and fertilize oocytes. Since this competition occurs inside the female reproductive tract, she often influences the outcome through physical or chemical factors, leading to cryptic female choice. Finally, traits that help males compete with each other are sometimes harmful to females, and female countermeasures may thwart the interests of males, which can lead to an arms race between the sexes known as sexually antagonistic coevolution. New studies from Caenorhabditis nematodes suggest that males compete with each other by producing sperm that migrate aggressively and that these sperm may be more likely to win access to oocytes. However, one byproduct of this competition appears to be an increased probability that these sperm will go astray, invading the ovary, prematurely activating oocytes, and sometimes crossing basement membranes and leaving the gonad altogether. These harmful effects are sometimes observed in crosses between animals of the same species but are most easily detected in interspecies crosses, leading to dramatically lowered fitness, presumably because the competitiveness of the sperm and the associated female countermeasures are not precisely matched. This mismatch is most obvious in crosses involving individuals from androdioecious species (which have both hermaphrodites and males, as predicted by the lower levels of sperm competition these species experience. These results suggest a striking example of sexually antagonistic coevolution and dramatically expand the value of nematodes as a laboratory system for studying postcopulatory interactions.

  6. Human homosexuality: a paradigmatic arena for sexually antagonistic selection? (United States)

    Camperio Ciani, Andrea; Battaglia, Umberto; Zanzotto, Giovanni


    Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait.

  7. Comparative proteome analysis of two antagonist Bacillus subtilis strains. (United States)

    Zhang, C X; Zhao, X; Han, F; Yang, M F; Chen, H; Chida, T; Shen, S H


    Natural wild-type strains of Bacillus subtilis are extensively used in agriculture as biocontrol agents for plants. This study examined two antagonist B. subtilis strains, KB-1111 and KB-1122, and the results illustrated that KB-1122 was a more potent inhibitor of the indicator pathogen than KB- 1111. Thus, to investigate the intrinsic differences between the two antagonist strains under normal culture conditions, samples of KB-1111 and KB-1122 were analyzed using MALDI-TOF-MS. The main differences were related to 20 abundant intracellular and 17 extracellular proteins. When searching the NCBI database, a number of the differentially expressed proteins were identified, including 11 cellular proteins and 10 secretory proteins. Among these proteins, class III stress-response-related ATPase, aconitate hydratase, alpha-amylase precursor, and a secretory protein, endo-1, 4-beta-glucanase, were differentially expressed by the two strains. These results are useful to comprehend the intrinsic differences between the antagonism of KB-1111 and KB-1122.

  8. mGluR5 positive modulators both potentiate activation and restore inhibition in NMDA receptors by PKC dependent pathway

    Directory of Open Access Journals (Sweden)

    Liao Pei-Fei


    Full Text Available Abstract Background In order to understand the interaction between the metabotropic glutamate subtype 5 (mGluR5 and N-methyl-D-aspartate (NMDA receptors, the influence of mGluR5 positive modulators in the inhibition of NMDA receptors by the noncompetitive antagonist ketamine, the competitive antagonist D-APV and the selective NR2B inhibitor ifenprodil was investigated. Methods This study used the multi-electrode dish (MED system to observe field potentials in hippocampal slices of mice. Results Data showed that the mGluR5 agonist (RS-2-chloro-5-hydroxyphenylglycine (CHPG, as well as the positive allosteric modulators 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl benzamide (CDPPB and 3,3'-difluorobenzaldazine (DFB alone did not alter the basal field potentials, but enhanced the amplitude of field potentials induced by NMDA. The inhibitory action of ketamine on NMDA-induced response was reversed by CHPG, DFB, and CDPPB, whereas the blockade of NMDA receptor by D-APV was restored by CHPG and CDPPB, but not by DFB. Alternatively, activation of NMDA receptors prior to the application of mGluR5 modulators, CHPG was able to enhance NMDA-induced field potentials and reverse the suppressive effect of ketamine and D-APV, but not ifenprodil. In addition, chelerythrine chloride (CTC, a protein kinase C (PKC inhibitor, blocked the regulation of mGluR5 positive modulators in enhancing NMDA receptor activation and recovering NMDA receptor inhibition. The PKC activator (PMA mimicked the effects of mGluR5 positive modulators on enhancing NMDA receptor activation and reversing NMDA antagonist-evoked NMDA receptor suppression. Conclusion Our results demonstrate that the PKC-dependent pathway may be involved in the positive modulation of mGluR5 resulting in potentiating NMDA receptor activation and reversing NMDA receptor suppression induced by NMDA antagonists.

  9. The cost and feasibility of marine coastal restoration. (United States)

    Bayraktarov, Elisa; Saunders, Megan I; Abdullah, Sabah; Mills, Morena; Beher, Jutta; Possingham, Hugh P; Mumby, Peter J; Lovelock, Catherine E


    Land-use change in the coastal zone has led to worldwide degradation of marine coastal ecosystems and a loss of the goods and services they provide. Restoration is the process of assisting the recovery of an ecosystem that has been degraded, damaged, or destroyed and is critical for habitats where natural recovery is hindered. Uncertainties about restoration cost and feasibility can impede decisions on whether, what, how, where, and how much to restore. Here, we perform a synthesis of 235 studies with 954 observations from restoration or rehabilitation projects of coral reefs, seagrass, mangroves, salt-marshes, and oyster reefs worldwide, and evaluate cost, survival of restored organisms, project duration, area, and techniques applied. Findings showed that while the median and average reported costs for restoration of one hectare of marine coastal habitat were around US$80000 (2010) and US$1600000 (2010), respectively, the real total costs (median) are likely to be two to four times higher. Coral reefs and seagrass were among the most expensive ecosystems to restore. Mangrove restoration projects were typically the largest and the least expensive per hectare. Most marine coastal restoration projects were conducted in Australia, Europe, and USA, while total restoration costs were significantly (up to 30 times) cheaper in countries with developing economies. Community- or volunteer-based marine restoration projects usually have lower costs. Median survival of restored marine and coastal organisms, often assessed only within the first one to two years after restoration, was highest for saltmarshes (64.8%) and coral reefs (64.5%) and lowest for seagrass (38.0%). However, success rates reported in the scientific literature could be biased towards publishing successes rather than failures. The majority of restoration projects were short-lived and seldom reported monitoring costs. Restoration success depended primarily on the ecosystem, site selection, and techniques

  10. Incorporating climate change projections into riparian restoration planning and design (United States)

    Perry, Laura G.; Lindsay V. Reynolds,; Beechie, Timothy J.; Collins, Mathias J.; Shafroth, Patrick B.


    Climate change and associated changes in streamflow may alter riparian habitats substantially in coming decades. Riparian restoration provides opportunities to respond proactively to projected climate change effects, increase riparian ecosystem resilience to climate change, and simultaneously address effects of both climate change and other human disturbances. However, climate change may alter which restoration methods are most effective and which restoration goals can be achieved. Incorporating climate change into riparian restoration planning and design is critical to long-term restoration of desired community composition and ecosystem services. In this review, we discuss and provide examples of how climate change might be incorporated into restoration planning at the key stages of assessing the project context, establishing restoration goals and design criteria, evaluating design alternatives, and monitoring restoration outcomes. Restoration planners have access to numerous tools to predict future climate, streamflow, and riparian ecology at restoration sites. Planners can use those predictions to assess which species or ecosystem services will be most vulnerable under future conditions, and which sites will be most suitable for restoration. To accommodate future climate and streamflow change, planners may need to adjust methods for planting, invasive species control, channel and floodplain reconstruction, and water management. Given the considerable uncertainty in future climate and streamflow projections, riparian ecological responses, and effects on restoration outcomes, planners will need to consider multiple potential future scenarios, implement a variety of restoration methods, design projects with flexibility to adjust to future conditions, and plan to respond adaptively to unexpected change.

  11. Final Restoration and Mitigation Monitoring Plan for the Island Ponds Restoration Project (United States)

    US Fish and Wildlife Service, Department of the Interior — This Restoration and Mitigation Monitoring Plan (RMMP) presents the approaches necessary to satisfy mitigation and monitoring requirements described in the various...

  12. Actions of dopamine antagonists on stimulated striatal and limbic dopamine release: an in vivo voltammetric study.


    Stamford, J. A.; Kruk, Z L; Millar, J.


    1. Fast cyclic voltammetry at carbon fibre microelectrodes was used to study the effects of several dopamine antagonists upon stimulated dopamine release in the rat striatum and nucleus accumbens. 2. In both nuclei, stimulated dopamine release was increased by D2-receptor-selective and mixed D1/D2-receptor antagonists. The D1-selective antagonist SCH 23390 had no effect. 3. Striatal and limbic dopamine release were elevated by cis- but not trans-flupenthixol. 4. The 'atypical' neuroleptics (c...

  13. Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice


    Chung, Sanny S. W.; Wang, Xiangyuan; Roberts, Shelby S.; Stephen M Griffey; Reczek, Peter R.; Wolgemuth, Debra J.


    Meeting men's contraceptive needs, orally administered retinoic acid receptor antagonists represent new lead molecules in developing non-hormonal, reversible male contraceptives without adverse side effects.

  14. Synthesis and Dual Histamine H1 and H2 Receptor Antagonist Activity of Cyanoguanidine Derivatives



    Premedication with a combination of histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists has been suggested as a prophylactic principle, for instance, in anaesthesia and surgery. Aiming at pharmacological hybrids combining H1R and H2R antagonistic activity, a series of cyanoguanidines 14–35 was synthesized by linking mepyramine-type H1R antagonist substructures with roxatidine-, tiotidine-, or ranitidine-type H2R antagonist moieties. N-desmethylmepyramine was connected via a poly-met...

  15. Restoration of motion-blurred image based on border deformation detection: a traffic sign restoration model.

    Directory of Open Access Journals (Sweden)

    Yiliang Zeng

    Full Text Available Due to the rapid development of motor vehicle Driver Assistance Systems (DAS, the safety problems associated with automatic driving have become a hot issue in Intelligent Transportation. The traffic sign is one of the most important tools used to reinforce traffic rules. However, traffic sign image degradation based on computer vision is unavoidable during the vehicle movement process. In order to quickly and accurately recognize traffic signs in motion-blurred images in DAS, a new image restoration algorithm based on border deformation detection in the spatial domain is proposed in this paper. The border of a traffic sign is extracted using color information, and then the width of the border is measured in all directions. According to the width measured and the corresponding direction, both the motion direction and scale of the image can be confirmed, and this information can be used to restore the motion-blurred image. Finally, a gray mean grads (GMG ratio is presented to evaluate the image restoration quality. Compared to the traditional restoration approach which is based on the blind deconvolution method and Lucy-Richardson method, our method can greatly restore motion blurred images and improve the correct recognition rate. Our experiments show that the proposed method is able to restore traffic sign information accurately and efficiently.

  16. [Restoring esthetics and function of posterior teeth using direct composite restoration]. (United States)

    Samet, N


    The growing demand for esthetic restorations in the posterior segments and the reports from all over the world concerning the possibility of a toxic effect of amalgam brought to the development of the composite resin materials. These allow excellent esthetic results without compromising the quality and long-term stability of the restorations. Out of the various types of posterior esthetic restorations, the most available are the direct ones. There are several substantial differences between fabricating amalgam or posterior composite restorations. The most significant difference concerns bonding to the tooth structures. The key to success in these restorations is the understanding of the reasons for failure, and the ways to prevent them. The failures are divided into two groups: biological failures--namely secondary caries, and mechanical failures--namely fracture and abrasion. The other key is understanding the materials used and their proper handling. This article illustrates in detail a step-by-step procedure the sequence of fabricating a posterior composite restoration in a posterior mandibular tooth, describing both techniques and materials used.

  17. Restoration in Its Natural Context: How Ecological Momentary Assessment Can Advance Restoration Research

    Directory of Open Access Journals (Sweden)

    Femke Beute


    Full Text Available More and more people use self-tracking technologies to track their psychological states, physiology, and behaviors to gain a better understanding of themselves or to achieve a certain goal. Ecological Momentary Assessment (EMA also offers an excellent opportunity for restorative environments research, which examines how our physical environment (especially nature can positively influence health and wellbeing. It enables investigating restorative health effects in everyday life, providing not only high ecological validity but also opportunities to study in more detail the dynamic processes playing out over time on recovery, thereby bridging the gap between laboratory (i.e., short-term effects and epidemiological (long-term effects research. We have identified four main areas in which self-tracking could help advance restoration research: (1 capturing a rich set of environment types and restorative characteristics; (2 distinguishing intra-individual from inter-individual effects; (3 bridging the gap between laboratory and epidemiological research; and (4 advancing theoretical insights by measuring a more broad range of effects in everyday life. This paper briefly introduces restorative environments research, then reviews the state of the art of self-tracking technologies and methodologies, discusses how these can be implemented to advance restoration research, and presents some examples of pioneering work in this area.

  18. US Forest Service Collaborative Forest Landscape Restoration Program (United States)

    US Forest Service, Department of Agriculture — A map service on the www that depicts Collaborative Forest Landscape Restoration (CFLR) and High Priority Restoration (HRP) project accomplishments. These are ten...

  19. Non-monetary benefit indicators for prioritizing wetlands restoration projects (United States)

    Ecological restoration of wetlands can reestablish ecosystem services that provide valuable social and environmental benefits. Explicitly characterizing these benefits can help managers better allocate scarce resources among potential restoration projects. Economic valuation stud...

  20. Rocky Mountain Arsenal National Wildlife Refuge : Restoration Site Histories (United States)

    US Fish and Wildlife Service, Department of the Interior — This project contains a collection of restoration site histories for the cleanup restoration at Rocky Mountain Arsenal National Wildlife Refuge. This project...

  1. South Bay Salt Pond Restoration Project : Phase 1 monitoring plan (United States)

    US Fish and Wildlife Service, Department of the Interior — This SBSP Restoration Project Monitoring Plan provides methods to document the effect of restoration on important elements such as mercury uptake, and water and...

  2. Selecting cost-effective areas for restoration of ecosystem services. (United States)

    Adame, M F; Hermoso, V; Perhans, K; Lovelock, C E; Herrera-Silveira, J A


    Selection of areas for restoration should be based on cost-effectiveness analysis to attain the maximum benefit with a limited budget and overcome the traditional ad hoc allocation of funds for restoration projects. Restoration projects need to be planned on the basis of ecological knowledge and economic and social constraints. We devised a novel approach for selecting cost-effective areas for restoration on the basis of biodiversity and potential provision of 3 ecosystem services: carbon storage, water depuration, and coastal protection. We used Marxan, a spatial prioritization tool, to balance the provision of ecosystem services against the cost of restoration. We tested this approach in a mangrove ecosystem in the Caribbean. Our approach efficiently selected restoration areas that at low cost were compatible with biodiversity targets and that maximized the provision of one or more ecosystem services. Choosing areas for restoration of mangroves on the basis carbon storage potential, largely guaranteed the restoration of biodiversity and other ecosystem services.

  3. Use of Amphibian Communities as Indicators of Restoration Success (United States)

    U.S. Geological Survey, Department of the Interior — The Comprehensive Everglades Restoration Plan (CERP) requires the use of ecological indicators to measure the success of restoration efforts. The Everglades...

  4. A modeling framework for system restoration from cascading failures. (United States)

    Liu, Chaoran; Li, Daqing; Zio, Enrico; Kang, Rui


    System restoration from cascading failures is an integral part of the overall defense against catastrophic breakdown in networked critical infrastructures. From the outbreak of cascading failures to the system complete breakdown, actions can be taken to prevent failure propagation through the entire network. While most analysis efforts have been carried out before or after cascading failures, restoration during cascading failures has been rarely studied. In this paper, we present a modeling framework to investigate the effects of in-process restoration, which depends strongly on the timing and strength of the restoration actions. Furthermore, in the model we also consider additional disturbances to the system due to restoration actions themselves. We demonstrate that the effect of restoration is also influenced by the combination of system loading level and restoration disturbance. Our modeling framework will help to provide insights on practical restoration from cascading failures and guide improvements of reliability and resilience of actual network systems.

  5. Effects of histamine and its antagonists on murine T-cells and bone marrow-derived dendritic cells. (United States)

    Hu, Xiufen; Zafar, Mohammad Ishraq; Gao, Feng


    We determined the effects of histamine and its antagonists on the surface marker expression of dendritic cells (DCs) and the influence of lipopolysaccharide (LPS), histamine, and histamine receptor antagonists on DCs and T-cells. The bone marrow was extracted from the femurs and tibiae of 6- to 8-week-old female Balb/c mice and cultured in medium containing penicillin, streptomycin, L-glutamine, fetal calf serum, or granulocyte macrophage colony-stimulating factor (GM-CSF) alone or with interleukin (IL)-4. The cells received three different doses of LPS and histamine, plus three different doses of descarboethoxyloratadine (DCL). We assayed the supernatant for various cytokines. The spleen cells of DO11.10 mice were examined by flow cytometry, which included labeling and sorting CD4+ T-cells, as well as coculture of DCs and T-cells with ovalbumin (OVA)323-339 peptide. Histamine or histamine plus DCL did not affect the expression of major histocompatibility complex class II, CD11c, CD11b, CD86, and CD80. However, GM-CSF increased the expression of all markers except CD80. Histamine increased interferon-γ production in GM-CSF + IL-4-cultured cells; it also enhanced IL-10 production, but suppressed IL-12 production in LPS-stimulated DCs with no DCL. Cimetidine inhibited IL-10 production and restored IL-12 secretion in LPS-treated DCs. LPS increased IL-10 and decreased IL-12 levels. GM-CSF + IL-4-generated DCs had a stronger stimulatory effect on DO11.10 T-cell proliferation than GM-CSF-generated DCs. Inducible costimulator ligand expression was higher in GM-CSF + IL-4- than in GM-CSF-generated DC groups after 2 days of coculture, but decreased 4 days later. IL-13 production was higher in bone marrow DCs generated with GM-CSF than in those generated with GM-CSF + IL-4. OVA-pulsed DCs and OVA-plus-DCL DCs showed increased IL-12 levels. OVA plus LPS increased both IL-10 and interferon-α. Although histamine or histamine receptor-1 antagonists did not influence DC LPS

  6. [Progress and prospects on evaluation of ecological restoration: a review of the 5th World Conference on Ecological Restoration]. (United States)

    Ding, Jing-Yi; Zhao, Wen-Wu


    The 5th World Conference on Ecological Restoration was held in Madison, Wisconsin, USA on October 6-11, 2013. About 1200 delegates from more than 50 countries attended the conference, and discussed the latest developments in different thematic areas of ecological restoration. Discussions on evaluation of ecological restoration were mainly from three aspects: The construction for evaluation indicator system of ecological restoration; the evaluation methods of ecological restoration; monitoring and dynamic evaluation of ecological restoration. The meeting stressed the importance of evaluation in the process of ecological restoration and concerned the challenges in evaluation of ecological restoration. The conference had the following enlightenments for China' s research on evaluation of ecological restoration: 1) Strengthening the construction of comprehensive evaluation indicators system and focusing on the multi-participation in the evaluation process. 2) Paying more attentions on scale effect and scale transformation in the evaluation process of ecological restoration. 3) Expanding the application of 3S technology in assessing the success of ecological restoration and promoting the dynamic monitoring of ecological restoration. 4) Carrying out international exchanges and cooperation actively, and promoting China's international influence in ecological restoration research.


    Directory of Open Access Journals (Sweden)

    V. P. Ivanov


    Full Text Available The paper contains definitions for a process and a methodology for restoration of parts on the basis of the analysis of the known methods and their selection. Geometric parameters and operational properties that should be provided for restoration of parts have been determined in the paper. A process for selection of the required method for restoration parts has been improved and it makes it possible to synthesize an optimal process of the restoration according to a criterion of industrial resource consumption with due account of quality, productivity and security limits. A justification on measures that meet the required limits has been presented in the paper. The paper shows a direction of technical solutions that ensure complete use of residual life of repair fund parts. These solutions can be achieved through close application of all repair sizes of work-pieces with revision of their values, uniform removal of the allowance while cutting the work-pieces at optimum locating, application of coating processes only in technically justified cases, application of straightening with thermal fixing of its results or all-around compression of deformable elements. The paper proposes to limit a number of overhauls for the units together with restoration of basic and fundamental parts by two repairs for the whole period of their lifetime. Number of shaft journal building-up should be limited by one building-up operation throughout the whole life cycle of the part with the purpose to preserve its length within the prescribed limits. It has been recommended to expand an application area of volumetric plastic deformation of material in the form of thermoplastic distribution or reduction of repair work-pieces representing class of rotation bodies with holes that ensures an allowance to machine external and internal surfaces for nominal dimensions without coating. A structure of the coating material with fine inclusions of carbides or nitrides of metals and

  8. Research advance in forest restoration on the burned blanks

    Institute of Scientific and Technical Information of China (English)

    LIXiu-zhen; ZHAOShan-lun; YINHai-wei; KONGFan-hua


    How to restore the destroyed forest after forest fire is a key question that man must face. This paper reviewed the research situation and history on the forest restoration burned blanks and summed up the research methods used into four scales: seed-bank scale, community scale, ecosystem scale and landscape scale. The new technologies such as GIS & Remote Sensing used to vegetation restoration were also summarized. The strategies and developing trend of vegetation restoration research on burned blanks were discussed.

  9. Glassfiber Post: An Alternative for Restoring Grossly Decayed Primary Incisors


    Mehra, Manjul; Grover, Rashu


    ABSTRACT Restoration of primary incisors, which have been severely damaged by rampant caries or trauma, is a difficult task for the pediatric dentist. With the introduction of new adhesive systems and restorative materials, alternative approaches for treating these teeth have been proposed. This paper discusses the restoration of carious primary maxillary incisors using composite resin restoration reinforced with fiberglass post. Two case reports are presented here to describe the procedure. ...

  10. Guidelines for monitoring the success of peatland restoration


    Bonnett, S. A.; Linsted, R.; Ross, S; Maltby, E.; Natural England


    The aim of this guidance is to provide information to enable peatland restoration projects to develop appropriate monitoring programmes. Degraded peatlands are restored for a wide range of reasons. Restoration objectives can include protecting and enhancing biodiversity, improving water quality, reducing flood risk and protecting cultural heritage or carbon stores. Restoration projects need monitoring programmes to show whether these objectives are being met and to help them to adapt practice...

  11. Collarless metal ceramic restorations to obscure the umbrella effect

    Directory of Open Access Journals (Sweden)

    Afroz Shaista


    Full Text Available Esthetics with porcelain fused to metal restoration in the anterior region can be adversely affected due to the inadequate teeth preparations and design of the prosthesis. We presented here a case report where esthetics was compromised due to darkening of the interdental papilla and marginal gingival and overcontoured restorations in relation to porcelain fused to metal restorations. Good esthetic results were obtained by using basic principles of tooth preparation and using collarless metal ceramic restorations.

  12. Study on the Ecological Restoration Project of Dalian Lake

    Institute of Scientific and Technical Information of China (English)


    Choosing Dalian Lake as study area to implement ecological restoration project,the existing environmental problems in Dalian Lake were analyzed firstly,and then the project area in Dalian Lake was divided into wetland restoration and reconstruction area,forest wetland cultivation area and shallow wetland restoration and diversity conservation area,finally corresponding restoration measures were put forward according to various function areas,so as to improve the economic output of wetland and operability an...

  13. Clinical experience in Europe with uroselective alpha1-antagonists. (United States)

    Debruyne, F M; Van der Poel, H G


    alpha1-Adrenoreceptors are thought to be involved in prostate smooth muscle contractions and could hence play a role in the dynamic component of intravesical obstruction associated with symptomatic BPH. Consequently, since the mid-eighties alpha receptor blocking agents have been used for the treatment of BPH. Non-selective alpha blockers are usually associated with systemic side-effects which resulted in an exclusion or withdrawal of many patients from this form of treatment. With the availability of so-called uroselective alpha blockers the management picture has changed since it was anticipated that these compounds cause lesser side-effects with at least the same, or even better, efficacy. Comparative clinical studies are essential for determining the eventual advantages of the uroselective alpha1-antagonists and a large number of such studies have been performed worldwide studying the various available compounds. European studies with terazosin showed clear superiority of the drug over the placebo while causing only limited side-effects. Various other studies using alpha-blocking agents such as doxazosin, tamsulosin and alfuzosin yielded identical results. Especially with tamsulosin and alfuzosin, the side-effects were comparable with those encountered in the placebo group. About 7% of the patients using tamsulosin experienced retrograde ejaculation in one study which did not occur in the alfuzosin studies. Important studies in Europe have also investigated the value of a combination of an alpha blocker with a 5alpha-reductase inhibitor. Comparable studies in which both alfuzosin and doxazosin were combined with the 5alpha-reductase inhibitor Proscar have shown that a combination is not superior to a blocker monotherapy and especially in the ALFIN study the results show that alfuzosin monotherapy is superior to Proscar in the management of symptomatic BPH. European studies have evaluated Quality of Life, sexuality as well as socio-economical outcome of the

  14. Reinventing the Wheel: Teaching Restoration Ecology without the Ecology (United States)

    Speldewinde, Peter


    Restoration ecology is "the process of assisting the recovery of an ecosystem that has been degraded, damaged or destroyed." Restoration can range from returning the system to its "natural" state through to restoring some ecological functionality to a system. The University of Western Australia offers an undergraduate degree in Restoration…

  15. Power Grid Islands Service Restoration Based on Cloud Computing

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hao; HE Jinghan; YIN Hang; BO Zhiqian; B Kirby


    To reduce customer minutes loss (CML), service restoration is an increasingly important task for the power grid. The main objective in islands service restoration procedures is to restore as many loads as possible for healthy networks through the reconfiguration without violating the network operation constraints. The proposed method can be described by the following equation.

  16. 21 CFR 878.3800 - External aesthetic restoration prosthesis. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External aesthetic restoration prosthesis. 878... External aesthetic restoration prosthesis. (a) Identification. An external aesthetic restoration prosthesis... external prosthesis adhesive. The device is not intended to be implanted. (b) Classification. Class...

  17. 5 CFR 844.402 - Restoration of earning capacity. (United States)


    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Restoration of earning capacity. 844.402... Reinstatement of Disability Annuity § 844.402 Restoration of earning capacity. (a) Earning capacity... capacity is considered to be restored. The disability annuity will terminate on the June 30 after the...

  18. 12 CFR 325.104 - Capital restoration plans. (United States)


    ... under section 38(e)(2) of the FDI Act. A bank that is required to submit a capital restoration plan as a... FDI Act by each company that controls the bank. (c) Review of capital restoration plans. Within 60... restoration plan that does not contain the guarantee required under section 38(e)(2) of the FDI Act, the...

  19. Amalgam and ART restorations in children: a controlled clinical trial

    NARCIS (Netherlands)

    Amorim, R.G. de; Leal, S.C.; Mulder, J.; Creugers, N.H.J.; Frencken, J.E.F.M.


    OBJECTIVES: The aims of this study were to compare 2-year cumulative survival rates of amalgam and atraumatic restorative treatment (ART) restorations in primary molars and to investigate the determinants of the survival rate of restorations. MATERIALS AND METHODS: A controlled clinical trial using

  20. Coral restoration Bonaire : an evaluation of growth, regeneration and survival

    NARCIS (Netherlands)

    Meesters, H.W.G.; Boomstra, B.; Hurtado-Lopez, N.; Montbrun, A.; Virdis, F.


    The Coral restoration of Staghorn (Acropora cervicornis) and Elkhorn (A. palmata) as practiced by the Coral Restoration Foundation Bonaire (CRFB) is shown to be highly successful in terms of growth and survival of new colonies, in both nurseries and transplant locations. Coral restoration is expecte

  1. Refining cast implant-retained restorations by electrical discharge machining. (United States)

    Schmitt, S M; Chance, D A; Cronin, R J


    The UCLA abutment was developed to create implant-retained restorations with ideal contours, excellent esthetics, and minimal vertical space requirements for restorative materials. A major drawback of this abutment is that casting inaccuracies in the lost-wax process are difficult to control. This article describes a method of refining cast implant-retained restorations by use of electrical discharge machining.

  2. 44 CFR 206.226 - Restoration of damaged facilities. (United States)


    ... funding for and require restoration of a destroyed facility at a new location when: (i) The facility is... facilities. 206.226 Section 206.226 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... § 206.226 Restoration of damaged facilities. Work to restore eligible facilities on the basis of...

  3. Reinventing the Wheel: Teaching Restoration Ecology without the Ecology (United States)

    Speldewinde, Peter


    Restoration ecology is "the process of assisting the recovery of an ecosystem that has been degraded, damaged or destroyed." Restoration can range from returning the system to its "natural" state through to restoring some ecological functionality to a system. The University of Western Australia offers an undergraduate degree in…

  4. Marginal Integrity of Glass Ionomer and All Ceramic Restorations (United States)


    crowns and orthodontic bands (Croll & Helpin, 1994).Another useful application of GI is as a liner under direct restorations (Davidson, 1994). GI...effect adjacent to the margins of indirect restorations (Tantbirojn, 1997). Recurrent decay is a major cause of failure of dental restorations

  5. 5 CFR 353.303 - Restoration rights of TAPER employees. (United States)


    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Restoration rights of TAPER employees... Restoration rights of TAPER employees. An employee serving in the competitive service under a temporary... employee serving in a position classified above GS-15), is entitled to be restored to the position he...

  6. Glass ionomer restorative cement systems: an update. (United States)

    Berg, Joel H; Croll, Theodore P


    Glass ionomer cements have been used in pediatric restorative dentistry for more than two decades. Their usefulness in clinical dentistry is preferential to other materials because of fluoride release from the glass component, biocompatibility, chemical adhesion to dentin and enamel, coefficient of thermal expansion similar to that of tooth structure, and versatility. The purpose of this paper was to review the uses of glass ionomer materials in pediatric dentistry, specifically as pit and fissure sealants, dentin and enamel replacement repair materials, and luting cements, and for use in glass ionomer/resin-based composite stratification tooth restoration (the sandwich technique). This article can also be used as a guide to research and clinical references regarding specific aspects of the glass ionomer systems and how they are used for young patients.

  7. Integrating TQM into environmental restoration projects

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, J.A. [Jacobs Engineering Group, Inc., Lenexa, KS (United States)


    Responsible and cost-effective waste management and environmental restoration are best achieved when the principles and procedures of Total Quality Management are made an integral part of the process. By describing three case histories, we explore and explain techniques for using TQM in environmental projects. Key aspects considered include: quality measurement systems; establishing and maintaining standard operating procedures; management and technical peer review; the use of Quality Improvement Teams; Roadmapping (a new procedure that the US Department of Energy is incorporating into environmental restoration programs); and the role of audit teams in document production. The three case histories covered include: The Department of Energy`s Uranium Mill Tailings Remedial Action Project on which Roadmapping and Quality Improvement Teams have led to significant changes in procedures; the EPA ARCS program on which adoption of project management Standard Operating Procedures enhanced cost and schedule control; the Jacobs Engineering TQM program that emphasizes performance measurement and management and project technical peer review.

  8. Nonsurgical gingival displacement in restorative dentistry. (United States)

    Thomas, Manuel S; Joseph, Robin Mathai; Parolia, Abhishek


    Gingival displacement is critical for obtaining accurate impressions for the fabrication of fixed restorations, especially when the finish line is at or just within the gingival sulcus. Displacement of the gingival tissue is also important when dealing with the restoration of cervical lesions due to their proximity to the periodontal tissue. The methods of gingival tissue displacement can be broadly classified as nonsurgical and surgical techniques, with nonsurgical being the more commonly practiced method. Dentists must alter their armamentarium and gingival displacement techniques to meet specific demands and obtain predictable results. Hence, the purpose of this article is to describe the different means by which nonsurgical gingival displacement can be achieved effectively under a variety of clinical situations.

  9. Enamel hypoplasia: challenges of esthetic restorative treatment. (United States)

    Ruschel, Vanessa Carla; Araújo, Élito; Bernardon, Jussara Karina; Lopes, Guilherme Carpena


    Enamel defects, such as white or yellow-brown spots, usually cause problems that are more esthetic than functional. Enamel hypoplasia may be the result of hereditary, systemic, or local factors. Dental trauma is a local etiologic factor. It is relatively common in the primary dentition and can cause defects on the surface of permanent successors. Treatment for such defects can differ, depending on the depth of the spots. For deeper white-spot lesions, a composite resin restoration may be necessary. This is an excellent mode of treatment, due to both its low cost and its conservation of healthy tooth structure. The objective of this case report is to describe composite resin restoration of a maxillary central incisor affected by enamel hypoplasia.

  10. Big Canyon Creek Ecological Restoration Strategy.

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lynn; Richardson, Shannon


    He-yey, Nez Perce for steelhead or rainbow trout (Oncorhynchus mykiss), are a culturally and ecologically significant resource within the Big Canyon Creek watershed; they are also part of the federally listed Snake River Basin Steelhead DPS. The majority of the Big Canyon Creek drainage is considered critical habitat for that DPS as well as for the federally listed Snake River fall chinook (Oncorhynchus tshawytscha) ESU. The Nez Perce Soil and Water Conservation District (District) and the Nez Perce Tribe Department of Fisheries Resources Management-Watershed (Tribe), in an effort to support the continued existence of these and other aquatic species, have developed this document to direct funding toward priority restoration projects in priority areas for the Big Canyon Creek watershed. In order to achieve this, the District and the Tribe: (1) Developed a working group and technical team composed of managers from a variety of stakeholders within the basin; (2) Established geographically distinct sub-watershed areas called Assessment Units (AUs); (3) Created a prioritization framework for the AUs and prioritized them; and (4) Developed treatment strategies to utilize within the prioritized AUs. Assessment Units were delineated by significant shifts in sampled juvenile O. mykiss (steelhead/rainbow trout) densities, which were found to fall at fish passage barriers. The prioritization framework considered four aspects critical to determining the relative importance of performing restoration in a certain area: density of critical fish species, physical condition of the AU, water quantity, and water quality. It was established, through vigorous data analysis within these four areas, that the geographic priority areas for restoration within the Big Canyon Creek watershed are Big Canyon Creek from stream km 45.5 to the headwaters, Little Canyon from km 15 to 30, the mainstem corridors of Big Canyon (mouth to 7km) and Little Canyon (mouth to 7km). The District and the Tribe

  11. Hearing Restoration with Auditory Brainstem Implant (United States)

    NAKATOMI, Hirofumi; MIYAWAKI, Satoru; KIN, Taichi; SAITO, Nobuhito


    Auditory brainstem implant (ABI) technology attempts to restore hearing in deaf patients caused by bilateral cochlear nerve injury through the direct stimulation of the brainstem, but many aspects of the related mechanisms remain unknown. The unresolved issues can be grouped into three topics: which patients are the best candidates; which type of electrode should be used; and how to improve restored hearing. We evaluated our experience with 11 cases of ABI placement. We found that if at least seven of eleven electrodes of the MED-EL ABI are effectively placed in a patient with no deformation of the fourth ventricle, open set sentence recognition of approximately 20% and closed set word recognition of approximately 65% can be achieved only with the ABI. Appropriate selection of patients for ABI placement can lead to good outcomes. Further investigation is required regarding patient selection criteria and methods of surgery for effective ABI placement. PMID:27464470

  12. Electronic approaches to restoration of sight (United States)

    Goetz, G. A.; Palanker, D. V.


    Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.

  13. The precision problem in conservation and restoration (United States)

    Hiers, J. Kevin; Jackson, Stephen T.; Hobbs, Richard J.; Bernhardt, Emily S.; Valentine, Leonie E.


    Within the varied contexts of environmental policy, conservation of imperilled species populations, and restoration of damaged habitats, an emphasis on idealized optimal conditions has led to increasingly specific targets for management. Overly-precise conservation targets can reduce habitat variability at multiple scales, with unintended consequences for future ecological resilience. We describe this dilemma in the context of endangered species management, stream restoration, and climate-change adaptation. Inappropriate application of conservation targets can be expensive, with marginal conservation benefit. Reduced habitat variability can limit options for managers trying to balance competing objectives with limited resources. Conservation policies should embrace habitat variability, expand decision-space appropriately, and support adaptation to local circumstances to increase ecological resilience in a rapidly changing world.

  14. Restoring diesel engine camshafts by laser treatement (United States)

    Astashkevich, B. M.; Zinov'ev, G. S.; Voronin, I. N.


    The reliability of parts of the gas-distributing mechanism and drives of fuel pumps determines to a great degree the operating conditions of cylinder-piston parts and the economic characteristics of diesel engines. Intense wear of the camshaft pair disturbs the distribution phases and the lead angle of fuel supply to the diesel cylinders and increases the rigidity of the operation of the connecting rod-piston group. This causes incomplete combustion of fuel and fuming, a rise in the temperature of exhaust gases, sticking of the rings in the piston grooves and their premature failure, wear cracks, and chips and failure of the parts of the cylinder-piston unit, decreasing the efficiency of the diesel. Laser surface treatment is used to restore cams. It makes it possible to increase substantially the wear resistance of cams and restore their worn surfaces. This paper concerns the characteristics of the cams after such a treatment.

  15. Invisalign and porecelain: the contemporary restorative powerhouse. (United States)

    Smallwood, Trent W


    For years, restorative practices and traditional orthodontics stood largely separate from one another save for the most extreme instances. Orthodontics has evolved over the years, and a new breed of orthodontic technology appeared in the late 1990s. A clear alternative to traditional orthodontics emerged, and Invisalign (Align Technology, Inc., Santa Clara, CA) was born. Historically, orthodontics and restorative work, within a practice, rarely coincided on the same patient, but the advances within both disciplines have afforded a new and innovative way of considering conservative dentistry. No longer does there have to be aggressive preparation to attain a desired result. With patient understanding, a negligible amount of patience, and the desire to achieve the very best dentistry has to offer, the potential is limitless.

  16. Effects Due to Rhizospheric Soil Application of an Antagonistic Bacterial Endophyte on Native Bacterial Community and Its Survival in Soil: A Case Study with Pseudomonas aeruginosa from Banana (United States)

    Thomas, Pious; Sekhar, Aparna C.


    Effective translation of research findings from laboratory to agricultural fields is essential for the success of biocontrol or growth promotion trials employing beneficial microorganisms. The rhizosphere is to be viewed holistically as a dynamic ecological niche comprising of diverse microorganisms including competitors and noxious antagonists to the bio-inoculant. This study was undertaken to assess the effects due to the soil application of an endophytic bacterium with multiple pathogen antagonistic potential on native bacterial community and its sustenance in agricultural soil. Pseudomonas aeruginosa was employed as a model system considering its frequent isolation as an endophyte, wide antagonistic effects reported against different phytopathogens and soil pests, and that the species is a known human pathogen which makes its usage in agriculture precarious. Employing the strain ‘GNS.13.2a’ from banana, its survival in field soil and the effects upon soil inoculation were investigated by monitoring total culturable bacterial fraction as the representative indicator of soil microbial community. Serial dilution plating of uninoculated control versus P. aeruginosa inoculated soil from banana rhizosphere indicated a significant reduction in native bacterial cfu soon after inoculation compared with control soil as assessed on cetrimide- nalidixic acid selective medium against nutrient agar. Sampling on day-4 showed a significant reduction in P. aeruginosa cfu in inoculated soil and a continuous dip thereafter registering >99% reduction within 1 week while the native bacterial population resurged with cfu restoration on par with control. This was validated in contained trials with banana plants. Conversely, P. aeruginosa showed static cfu or proliferation in axenic-soil. Lateral introduction of soil microbiome in P. aeruginosa established soil under axenic conditions or its co-incubation with soil microbiota in suspension indicated significant adverse effects by

  17. Lost lake - restoration of a Carolina bay

    Energy Technology Data Exchange (ETDEWEB)

    Hanlin, H.G.; McLendon, J.P. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology; Wike, L.D. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology]|[Westinghouse Savannah River Co., Aiken, SC (United States). Savannah River Technology Center; Dietsch, B.M. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology]|[Univ. of Georgia, Aiken, SC (United States)


    Carolina bays are shallow wetland depressions found only on the Atlantic Coastal Plain. Although these isolated interstream wetlands support many types of communities, they share the common features of having a sandy margin, a fluctuating water level, an elliptical shape, and a northwest to southeast orientation. Lost Lake, an 11.3 hectare Carolina bay, was ditched and drained for agricultural production before establishment of the Savannah River Site in 1950. Later it received overflow from a seepage basin containing a variety of chemicals, primarily solvents and some heavy metals. In 1990 a plan was developed for the restoration of Lost Lake, and restoration activities were complete by mid-1991. Lost Lake is the first known project designed for the restoration and recovery of a Carolina bay. The bay was divided into eight soil treatment zones, allowing four treatments in duplicate. Each of the eight zones was planted with eight species of native wetland plants. Recolonization of the bay by amphibians and reptiles is being evaluated by using drift fences with pitfall traps and coverboard arrays in each of the treatment zones. Additional drift fences in five upland habitats were also established. Hoop turtle traps, funnel minnow traps, and dip nets were utilized for aquatic sampling. The presence of 43 species common to the region has been documented at Lost Lake. More than one-third of these species show evidence of breeding populations being established. Three species found prior to the restoration activity and a number of species common to undisturbed Carolina bays were not encountered. Colonization by additional species is anticipated as the wetland undergoes further succession.

  18. Construction of generic and adaptive restoration strategies


    Qin, Zhijun; 覃智君


    Electric power systems are among the most critical infrastructures of modern societies. The interruption of electric supply may cause great adverse impact on the economy of modern societies. For the sustainable development of modern societies, power systems have been undergoing a paradigm shift towards more environmentally-friendly, economic, reliable and resilient modern power grids. Power system restoration has been identified as one of the most important enabling technologies to achieve on...

  19. The advent of the restorative plastic surgeon. (United States)

    Carty, Matthew J; Pribaz, Julian J; Talbot, Simon G; Caterson, Edward J; Pomahac, Bohdan


    Plastic surgery is presently typified by the existence of discrete clinical identities, namely that of the cosmetic plastic surgeon and the reconstructive plastic surgeon. The emergence of vascularized composite allotransplantation has been accompanied by the development of a third distinct clinical identity, that of the restorative plastic surgeon. The authors describe the core competencies that characterize this new identity, and discuss the implications of the advent of this new professional paradigm.

  20. Chiral Symmetry restoration from the hadronic regime

    CERN Document Server

    Nicola, Angel Gomez; Morales, John; de Elvira, Jacobo Ruiz; Andres, Ricardo Torres


    We discuss recent advances on QCD chiral symmetry restoration at finite temperature, within the theoretical framework of Effective Theories. $U(3)$ Ward Identities are derived between pseudoscalar susceptibilities and quark condensates, allowing to explain the behaviour of lattice meson screening masses. Unitarized interactions and the generated $f_0(500)$ thermal state are showed to play an essential role in the description of the transition through the scalar susceptibility

  1. Alternatives to testosterone replacement: testosterone restoration


    Andrew McCullough


    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supp...

  2. Rapid Hydraulic Assessment for Stream Restoration (United States)


    account the hydraulic conditions of the stream being restored. This is true whether the project involves a few feet of bank stabilization or several...coefficient, α, expresses a correction for nonuniformity in the velocity distribution, and in most applications this value is assumed to be 1 or read from...a table (e.g., Chow 1959, p.28). The depth and slope angle terms can be replaced by a vertical expression of the depth, y, because in most rivers

  3. Upper anterior zone restoration with composites


    Lamas Lara, César; CD, Docente del Área de Operatoria Dental y Endodoncia de la Facultad de Odontología de la UNMSM.; Angulo de la Vega, Giselle; CD, Alumna de la Especialidad de Rehabilitación Oral de la Facultad de Odontología de la UNMSM.


    The anterior sector problems are very common in our professional practice and became vital importance to make a suitable rehabilitation in these cases; we can not do a good rehabilitation if we do not know the basic characteristics, both aesthetic and functional. Today the composites are a valid alternative for the restoration of the anterior sector, since they offer to us a conservative and aesthetic possibility, but independently of the material to use we have to based on certain rules or p...


    Directory of Open Access Journals (Sweden)



    Full Text Available ABASTRACT: Atraumatic Restorative Treatment (ART was origina lly developed in field settings in African subcontinent (Tanzania by Univ ersity of Dar el Salaam in 1980s; subsequently World Health Organization (WHO promote s the use of ART especially with children. As the name indicates Atraumatic Restorat ive Treatment (ART is basically a minimally invasive procedure that involves removing of softened carious dentine using hand instruments and then restoring the cavity with an a dhesive material usually the Glass Ionomer Cement [1]. ART is based on the maximum preservation of sound tooth tissue and the minimum feeling of discomfort and pain, since there is use o f hand instruments it perhaps also reduces pain due to reduced vibrations as occurs while use o f rotary dental instruments. This technique is gaining popularity and acceptability especially in c hildren, elderly and with those individuals who have fear and anxiety about dental treatment [2 , 3]. ART requires use of very minimal portable dental equipment and was designed to use in field/community settings. It was developed for use in less developed countries of the world, where art was seen as an affordable option for patents who can’t afford to pay for more s ophisticated treatments, but with improved technique and use of improved restorative materials its use has considerable expanded to developed countries as well [4-6]. This article give s a brief overview of ART and its uses in the present scenario. KEY WORDS: ART = Atraumatic Restorative Technique, GIC = Glas s Ionomer Cement

  5. Breast restoration decision making: enhancing the process. (United States)

    Reaby, L L


    The purpose of this study was to explore the breast restoration decision-making patterns used by women who opted to have their breast cancer treated by mastectomy. Sixty-four women wearing external breast prostheses and 31 women with breast reconstructions were interviewed. Modified versions of Simon's notion of "bounded rationality" and Janis and Mann's conflict model provided the conceptual scaffolding for the study. Five breast restoration decision-making patterns emerged from the analysis of the interview data: (a) Enlightened (actively seeks information, considers positive and negative aspects, and demonstrates deliberation on the alternatives), (b) Contented (passively accepts minimum information on alternatives because of a preference toward a particular type), (c) Sideliner (uncritically adopts any alternative that is easy and simple to implement), (d) Shifter (gives over the decision to others), and (e) Panic-stricken (can make no rational decision on alternatives). In the prosthesis group, the major pattern used was the Sideliner, and in the reconstruction group it was the Contented. None of the participants used the Enlightened pattern. The data indicated that there was no evidence of active information-seeking behavior or deliberation on the alternatives as part of the women's decision-making process. The findings suggest a need for a registered nurse oncology specialist to be accessible to women during the period when decisions regarding breast restoration are made. This professional has the knowledge to interact effectively with these women and serve as their advocate during the decision-making process. Implications for professional practice and a model for competent breast restoration decision making are presented.

  6. Creating a catchment perspective for river restoration (United States)

    Benda, L.; Miller, D.; Barquín, J.


    One of the major challenges in river restoration is to identify the natural fluvial landscape in catchments with a long history of river control. Intensive land use on valley floors often predates the earliest remote sensing: levees, dikes, dams, and other structures alter valley-floor morphology, river channels and flow regimes. Consequently, morphological patterns indicative of the fluvial landscape including multiple channels, extensive floodplains, wetlands, and fluvial-riparian and tributary-confluence dynamics can be obscured, and information to develop appropriate and cost effective river restoration strategies can be unavailable. This is the case in the Pas River catchment in northern Spain (650 km2), in which land use and development have obscured the natural fluvial landscape in many parts of the basin. To address this issue we coupled general principles of hydro-geomorphic processes with computer tools to characterize the fluvial landscape. Using a 5-m digital elevation model, valley-floor surfaces were mapped according to elevation above the channel and proximity to key geomorphic processes. The predicted fluvial landscape is patchily distributed according to topography, valley morphology, river network structure, and fan and terrace landforms. The vast majority of the fluvial landscape in the main segments of the Pas River catchment is presently masked by human infrastructure, with only 15% not impacted by river control structures and development. The reconstructed fluvial landscape provides a catchment scale context to support restoration planning, in which areas of potential ecological productivity and diversity could be targeted for in-channel, floodplain and riparian restoration projects.

  7. Creating a catchment perspective for river restoration

    Directory of Open Access Journals (Sweden)

    L. Benda


    Full Text Available One of the major challenges in river restoration is to identify the natural fluvial landscape in catchments with a long history of river control. Intensive land use on valley floors often predates the earliest remote sensing: levees, dikes, dams, and other structures alter valley-floor morphology, river channels and flow regimes. Consequently, morphological patterns indicative of the fluvial landscape including multiple channels, extensive floodplains, wetlands, and fluvial-riparian and tributary-confluence dynamics can be obscured, and information to develop appropriate and cost effective river restoration strategies can be unavailable. This is the case in the Pas River catchment in northern Spain (650 km2, in which land use and development have obscured the natural fluvial landscape in many parts of the basin. To address this issue we coupled general principles of hydro-geomorphic processes with computer tools to characterize the fluvial landscape. Using a 5-m digital elevation model, valley-floor surfaces were mapped according to elevation above the channel and proximity to key geomorphic processes. The predicted fluvial landscape is patchily distributed according to topography, valley morphology, river network structure, and fan and terrace landforms. The vast majority of the fluvial landscape in the main segments of the Pas River catchment is presently masked by human infrastructure, with only 15% not impacted by river control structures and development. The reconstructed fluvial landscape provides a catchment scale context to support restoration planning, in which areas of potential ecological productivity and diversity could be targeted for in-channel, floodplain and riparian restoration projects.

  8. Fracture Resistance of Pulpotomized Primary Molar Restored with Extensive Class II Amalgam Restorations

    Directory of Open Access Journals (Sweden)

    F. Mazhari


    Full Text Available Objective: The aim of the present study was to evaluate fracture resistance of pulpoto-mized primary molar teeth restored with extensive multisurface amalgam restorations.Materials and Methods: Eighty extracted carious human primary molar teeth were se-lected forpresent study. Teeth were divided in to eight groups of ten. Mesio- or disto-occlusal and Mesio-occluso-distal cavities with different cavity wall thickness (1.5 or 2.5mm were prepared in both first and second primary molar teeth. After restoring teeth with amalgam, all specimens were stored in distilled water at 37°C for 7 days. Then samples were thermocycled for 1000 cycles from 5°C to 55°C. The specimens then were subjected to a compressive load in a universal testing machine at a crosshead speed of 0.5 mm min-1. ANOVA and t-test were used for statistical analysis.Results: Mean fracture resistance of first and second molar teeth were 975.5 N (SD=368.8 and 1049.2 N (SD=540.1 respectively. In the first molar group, fracture resis-tance of two-surface cavities was significantly more than three-surface cavities (P<0.001, however this difference was not statistically significant in the second molar group. In both first and second molar group, fracture resistance incavities with 2.5 mm wall thickness, was significantly more than the group with 1.5 mm wall thickness.Conclusion: The mean fracture resistance in pulpotomized primary molar restored with amalgam restorations was higher than reported maximum bite force in primary teeth even in extensive multi-surface restorations. Therefore, the teeth with large proximal carious lesions in schoolchildren could be restored with amalgam.

  9. The need for complementary hydraulic analysis in post-restoration monitoring of river restoration projects

    Directory of Open Access Journals (Sweden)

    T. A. Endreny


    Full Text Available River restoration design methods are incrementally improved by studying and learning from monitoring data in previous projects. In this paper, we report post-restoration monitoring data for a Natural Channel Design (NCD restoration project along 1600 m (10 channel wavelengths of the Batavia Kill in the Catskill Mountains, NY, implemented in 2001 and 2002. The NCD project used a reference-reach to determine channel form, empirical relations between the project site and reference site bankfull dimensions to size channel geometry, and hydraulic and sediment computations to test channel capacity and sediment stability. In addition 12 cross-vanes and 48 j-hook vanes used in NCD for river training were installed to protect against bank erosion and maintain scour pools for fish habitat. Changes in pool depths were monitored with surveys from 2002–2004, and then after the channel-altering April 2005 flood. Aggradation in pools was attributed to cross-vane arms not concentrating flow in the center of the channel, which subsequently caused flow splitting and 4 partial point bar avulsions during the 2005 flood. Hydrodynamic simulation at the 18 m3s−1 bankfull flow suggested avulsions occurred where vanes allowed erosive bank scour to initiate the avulsion cut, and once the flow was split, the diminished in-channel flow caused more aggradation in the pools. In this project post-restoration monitoring had detected aggradation and considered it a problem. The lesson for the larger river restoration community is monitoring protocol should include complementary hydraulic and sediment analysis to comprehend potential consequences and develop preventative maintenance. River restoration and monitoring teams should be trained in robust hydraulic and sediment analytical methods that help them extend project restoration goals.

  10. 1/f scaling in heart rate requires antagonistic autonomic control (United States)

    Struzik, Zbigniew R.; Hayano, Junichiro; Sakata, Seiichiro; Kwak, Shin; Yamamoto, Yoshiharu


    We present systematic evidence for the origins of 1/f -type temporal scaling in human heart rate. The heart rate is regulated by the activity of two branches of the autonomic nervous system: the parasympathetic (PNS) and the sympathetic (SNS) nervous systems. We examine alterations in the scaling property when the balance between PNS and SNS activity is modified, and find that the relative PNS suppression by congestive heart failure results in a substantial increase in the Hurst exponent H towards random-walk scaling 1/f2 and a similar breakdown is observed with relative SNS suppression by primary autonomic failure. These results suggest that 1/f scaling in heart rate requires the intricate balance between the antagonistic activity of PNS and SNS.

  11. Pathological gambling induced by dopamine antagonists: a case report. (United States)

    Grötsch, Philipp; Lange, Claudia; Wiesbeck, Gerhard A; Lang, Undine


    Pathological gambling is defined as inappropriate, persistent, and maladaptive gambling behaviour. It is a non-pharmacological addiction classified as an impulse control disorder. However, pathological gambling has been associated with dopamine agonist use. Here we report of a 28-year-old man with a first major depressive episode and a post-traumatic stress disorder who has been treated with a combination of the serotonine/noradrenaline reuptake inhibitor duloxetine and the tricyclic antidepressant maprotiline. The administration of antipsychotic flupentixole (up to 7 mg) turned this slight online poker gambler into an excessive gambler. Only after the discontinuation of the antidopaminergic agents and the switch to bupropion did this gambling behaviour stop which suggests a causal relationship between dopamine antagonists and pathological gambling.

  12. Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists

    DEFF Research Database (Denmark)

    Pottegård, Anton; Christensen, R. D.; Wang, S. V.;


    PurposeWe present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. MethodsWe used...... a self-controlled case series to estimate the incidence rate ratio (IRR) comparing the rate of INR measurements of 4.0 in concomitant tramadol and VKA-exposed periods to VKA-only-exposed periods. Secondary analyses considered specific subgroups, alternative exposure criteria, alternative outcome...... definitions, and other drugs. ResultsWe identified 513 VKA users with at least 1 INR measurement 4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53-2.10), with a stronger association among users of phenprocoumon compared...

  13. Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists. (United States)

    Ganesh, Thota; Jiang, Jianxiong; Shashidharamurthy, Rangaiah; Dingledine, Ray


    Prostanoid receptor EP2 is emerging as a novel target for development of anti-inflammatory drugs for the treatment of chronic neurodegenerative and peripheral diseases; however, the availability of EP2 antagonist probes for exploration of peripheral disease models is very limited. We now report identification and characterization of a novel chemical class of compounds that show nanomolar potency and competitive antagonism of the EP2 receptor. A compound in this class, TG6-129, showed prolonged plasma half-life and did not cross the blood brain barrier. This compound also suppressed the induction of inflammatory mRNA markers in a macrophage cell line upon activation of EP2. Thus, this compound could be useful as a probe for a variety of peripheral chronic inflammatory diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease, in which EP2 appears to play a pathogenic role.

  14. [Antifibrillatory activity of dipeptide antagonist of nerve growth factor]. (United States)

    Kryzhanovskiĭ, S A; Stoliarchuk, V N; Vititnova, M B; Tsorin, I B; Pekel'dina, E S; Gudasheva, T A


    In experiments on anesthetized rats were assessed antifibrillatoty action of dipeptide GK-1. This compound is the fragment of fourth loop of nerve growth factor (NGF) and manifests antagonistic activity in respect to TrkA receptor, that specified for NGF. It is shown that this compound is able to significantly increase the threshold of electrical fibrillation of the heart and its effectiveness is not inferior to the reference antiarrhythmics I and III class on Vaughan Williams classification. However, unlike the latter, antifibrillatory action of dipeptide GK-1 was delayed and realized within 40-60 minutes after its administration. It is discussed possible mechanisms underlying antifibrillatory action of dipeptide GK-1, that, to some extent, may be associated with its ability to change the reactivity of beta-adrenergic structures of the heart.

  15. Suvorexant: The first orexin receptor antagonist to treat insomnia

    Directory of Open Access Journals (Sweden)

    Ashok K Dubey


    Full Text Available Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management.

  16. Are Urban Stream Restoration Plans Worth Implementing? (United States)

    Sarvilinna, Auri; Lehtoranta, Virpi; Hjerppe, Turo


    To manage and conserve ecosystems in a more sustainable way, it is important to identify the importance of the ecosystem services they provide and understand the connection between natural and socio-economic systems. Historically, streams have been an underrated part of the urban environment. Many of them have been straightened and often channelized under pressure of urbanization. However, little knowledge exists concerning the economic value of stream restoration or the value of the improved ecosystem services. We used the contingent valuation method to assess the social acceptability of a policy-level water management plan in the city of Helsinki, Finland, and the values placed on improvements in a set of ecosystem services, accounting for preference uncertainty. According to our study, the action plan would provide high returns on restoration investments, since the benefit-cost ratio was 15-37. Moreover, seventy-two percent of the respondents willing to pay for stream restoration chose "I want to conserve streams as a part of urban nature for future generations" as the most motivating reason. Our study indicates that the water management plan for urban streams in Helsinki has strong public support. If better marketed to the population within the watershed, the future projects could be partly funded by the local residents, making the projects easier to accomplish. The results of this study can be used in planning, management and decision making related to small urban watercourses.

  17. Advanced Protection & Service Restoration for FREEDM Systems (United States)

    Singh, Urvir

    A smart electric power distribution system (FREEDM system) that incorporates DERs (Distributed Energy Resources), SSTs (Solid State Transformers - that can limit the fault current to two times of the rated current) & RSC (Reliable & Secure Communication) capabilities has been studied in this work in order to develop its appropriate protection & service restoration techniques. First, a solution is proposed that can make conventional protective devices be able to provide effective protection for FREEDM systems. Results show that although this scheme can provide required protection but it can be quite slow. Using the FREEDM system's communication capabilities, a communication assisted Overcurrent (O/C) protection scheme is proposed & results show that by using communication (blocking signals) very fast operating times are achieved thereby, mitigating the problem of conventional O/C scheme. Using the FREEDM System's DGI (Distributed Grid Intelligence) capability, an automated FLISR (Fault Location, Isolation & Service Restoration) scheme is proposed that is based on the concept of 'software agents' & uses lesser data (than conventional centralized approaches). Test results illustrated that this scheme is able to provide a global optimal system reconfiguration for service restoration.

  18. Restorative effects of virtual nature settings. (United States)

    Valtchanov, Deltcho; Barton, Kevin R; Ellard, Colin


    Previous research regarding the potential benefits of exposing individuals to surrogate nature (photographs and videos) has found that such immersion results in restorative effects such as increased positive affect, decreased negative affect, and decreased stress. In the current experiment, we examined whether immersion in a virtual computer-generated nature setting could produce restorative effects. Twenty-two participants were equally divided between two conditions, while controlling for gender. In each condition, participants performed a stress-induction task, and were then immersed in virtual reality (VR) for 10 minutes. The control condition featured a slide show in VR, and the nature experimental condition featured an active exploration of a virtual forest. Participants in the nature condition were found to exhibit increased positive affect and decreased stress after immersion in VR when compared to those in the control condition. The results suggest that immersion in virtual nature settings has similar beneficial effects as exposure to surrogate nature. These results also suggest that VR can be used as a tool to study and understand restorative effects.

  19. Strategic planning for power system restorations

    Energy Technology Data Exchange (ETDEWEB)

    Bent, Russell W [Los Alamos National Laboratory; Van Hententyck, Pascal [BROWN UNIV.; Coffrin, Carleton [BROWN UNIV.


    This paper considers the power system restoration planning problem (PSRPP) for disaster recovery, a fundamental problem faced by all populated areas. PSRPPs are complex stochastic optimization problems that combine resource allocation, warehouse location, and vehicle routing considerations. Furthermore, electrical power systems are complex systems whose behavior can only be determined by physics simulations. Moreover, these problems must be solved under tight runtime constraints to be practical in real-world disaster situations. This work is three fold: (1) it formalizes the specification of PSRPPs; (2) introduces a simple optimization-simulation hybridization necessary for solving PSRPPs; and (3) presents a complete restoration algorithm that utilizes the strengths of mixed integer programming, constraint programming, and large neighborhood search. This paper studied a novel problem in the field of humanitarian logistics, the Power System Restoration Problem (PSRPP). The PSRPP models the strategic planning process for post disaster power system recovery. The paper proposed a multi-stage stochastic hybrid optimization algorithm that yields high quality solutions to real-world benchmarks provided by Los Alamos National Laboratory (LANL). The algorithm uses a variety of technologies, including MIP, constraint programming, and large neighborhood search, to exploit the structure of each individual optimization subproblem. The experimental results on hurricane disaster benchmarks indicate that the algorithm is practical from a computational standpoint and produce significant improvements over existing relief delivery procedures.


    Johnston, Colin


    Aldosterone's deleterious pathophysiological effects on the cardiovascular system if blocked by mineralcorticord antagonists (MRAs) logically should lead to improvement in heart function and outcomes in heart failure (HF). The first trial to test this hypothesis was tthe RALES trial in 1999 which treated patients with class III-IV HF with spironolactone. It showed significant reduction in mortality and cardiovascular hospitalzation rates. This was confirmed & extended in EMHASIS-HF RCT with classs II-III being treated with ACEIs & BB who received placebo or elperinone (a MRA) with again a statistically significant fall in mortality & hospitalization.The possible cardioprotective effects of MRA post acute myocardial infarct (MI) is less clear. The EPHESUS RCT in 2003 demostrated that elperinone given 3-14 days AMI in patients with early signs of HF reduced mortality & morbidity. However in the ALBTROSS trial using spironolactone 2 days after AMI showed no benfit in patients without HF but in a subgroup with ST elevation there was a 80% reduction in mortality after 6 months. However a recent meta-analysis from 25 RCT with data invovling 19,333 patients with either HF or post MI assigned aldosterone antagonists (AA)or placebo showed a 18% reduction in mortality including a 20% fall in CV mortality and a 19% reduction in SCD.The role of AA in HFPEF is even even more contraversial. The TOPCAT RCT of 3445 patients with symptomatc HFPEF randomised to spironolactone failed to meet the primary composite end point of death, aborted cardiac arrest or hospitalization although there was a reduction in hospitalization for HF (HR 0.83 P = 0.04).The differences between selective or non-selective MRAs, their ADRs & off target effects will also be discussed.

  1. Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra). (United States)

    Simons, Rudy; Vincken, Jean-Paul; Mol, Loes A M; The, Susan A M; Bovee, Toine F H; Luijendijk, Teus J C; Verbruggen, Marian A; Gruppen, Harry


    The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography-mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E(2)). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20-60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E(2), not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.

  2. Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists. (United States)

    Sadek, Bassem; Kuder, Kamil; Subramanian, Dhanasekaran; Shafiullah, Mohamed; Stark, Holger; Lażewska, Dorota; Adem, Abdu; Kieć-Kononowicz, Katarzyna


    To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic drugs (AEDs), aromatic ether, and diether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in the maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in rats. The anticonvulsive effects of a systemic injection of 1-12 on MES-induced and PTZ-kindled seizures were evaluated against the reference AED phenytoin (PHT) and the structurally related H3R antagonist/inverse agonist pitolisant (PIT). Among the most promising ligands 2, 4, 5, and 11, there was a significant and dose-dependent reduction in the duration of tonic hind limb extension (THLE) in MES-induced seizure subsequent to administration of 4 and 5 [(5, 10, and 15 mg/kg, intraperitoneally (i.p.)]. The protective effects observed for the 1-(3-(3-(4-chlorophenyl)propoxy)propyl)-3-methylpiperidine derivative 11 at 10 mg/kg, i.p. were significantly greater than those of PIT, and were reversed by pretreatment with the central nervous system penetrant H1R antagonist pyrilamine (PYR) (10 mg/kg). Moreover, the protective action of the reference AED PHT, at a dose of 5 mg/kg (without considerable protection in the MES model), was significantly augmented when coadministered with derivative 11 (5 mg/kg, i.p.). Surprisingly, pretreatment with derivative 7 (10 mg/kg, i.p.), an ethylphenoxyhexyl-piperidine derivative without considerable protection in the MES model, potently altered PTZ-kindled seizure, significantly prolonged myoclonic latency time, and clearly shortened the total seizure time when compared with control, PHT, and PIT. These interesting results highlight the potential of H3R ligands as new AEDs or as adjuvants to available AED therapeutics.

  3. Alpha antagonists and intraoperative floppy iris syndrome: A spectrum

    Directory of Open Access Journals (Sweden)

    Sharif A Issa


    Full Text Available Sharif A Issa, Omar H Hadid, Oliver Baylis, Margaret DayanDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, UKBackground: To determine occurrence of features of intraoperative floppy iris syndrome (IFIS during cataract surgery in patients taking systemic alpha-antagonists (AA.Methods: We prospectively studied patients on AA and who underwent phacoemulsification. The following were recorded: pupil diameter preoperatively, iris flaccidity, iris prolapse and peroperative miosis.Results: We studied 40 eyes of 31 subjects. Mean age was 78 years. Overall, 14 eyes (13 patients showed signs of IFIS: 9/13 (69% eyes of patients on tamsulosin, 1/18 (6% eyes in the doxazosin group, 2/2 prazosin patients, 1/4 eyes in the indoramin group, and 1/2 eyes in two patients on a combination of doxazosin and tamsulosin. Most cases (92% had only one or two signs of IFIS. Bilateral cataract surgery was undertaken in 9 patients but only one patient (on tamsulosin had features of IFIS in both eyes, while 4 patients (2 on tamsulosin and 2 on other AA showed signs of IFIS in one eye only, and 4 patients did not show IFIS in either eye.Conclusion: Most AA were associated with IFIS, but it tends to present as a spectrum of signs rather than full triad originally described. Tamsulosin was most likely to be associated with IFIS; however, its intake does not necessarily mean that IFIS will occur. For patients on AA, the behavior of the iris intraoperatively in one eye is a poor predictor of the other eye. Surgeons should anticipate the occurrence of IFIS in any patient on AA.Keywords: alpha blocker, alpha antagonist, cataract surgery, intraoperative floppy iris syndrome, tamsulosin.

  4. Effect of composite/amalgam thickness on fracture resistance of maxillary premolar teeth, restored with combined amalgam-composite restorations (United States)

    Firouzmandi, Maryam; Doozandeh, Maryam; Abbasi, Sanaz


    Background Combined amalgam-composite restorations have been used through many years to benefit from the advantages of both dental amalgam and composite resin. Two variations have been mentioned for this technique, this study investigated the fracture resistance of maxillary premolar teeth with extended mesio-occluso-distal (MOD) cavities, restored with the two variations of combined amalgam-composite restorations. Material and Methods Sixty intact extracted premolar teeth were randomly divided into 6 groups (G1-G6) of 10 teeth. G1; consisted of intact teeth and G2; consisted of teeth with MOD preparations were assigned as the positive and negative control groups respectively. Other experimental groups after MOD preparations were as follows: G3, amalgam restoration; G4, composite restoration; G5 combined amalgam-composite restoration with amalgam placement only on 1mm of the gingival floor of the proximal boxes; G6, combined amalgam-composite restoration with amalgam placement to the height of contact area of the proximal surface of the tooth. Fracture strength of the specimens was measured and the data were analyzed using one-way analysis of variance (ANOVA). The level of significance was Pamalgam-composite restoration was similar to that achieved with composite restoration alone and more than that of amalgam restoration alone. It can be concluded that the thickness of amalgam in combined amalgam-composite restorations did not affect fracture resistance of the teeth. Key words:Amalgam, composite, fracture resistance, restoration. PMID:27398176

  5. Comparison of GnRH Agonist, GnRH Antagonist, and GnRH Antagonist Mild Protocol of Controlled Ovarian Hyperstimulation in Good Prognosis Patients

    Directory of Open Access Journals (Sweden)

    Martin Stimpfel


    Full Text Available The reports on how to stimulate the ovaries for oocyte retrieval in good prognosis patients are contradictory and often favor one type of controlled ovarian hyperstimulation (COH. For this reason, we retrospectively analyzed data from IVF/ICSI cycles carried out at our IVF Unit in good prognosis patients (aged <38 years, first and second attempts of IVF/ICSI, more than 3 oocytes retrieved to elucidate which type of COH is optimal at our condition. The included patients were undergoing COH using GnRH agonist, GnRH antagonist or GnRH antagonist mild protocol in combination with gonadotrophins. We found significant differences in the average number of retrieved oocytes, immature oocytes, fertilized oocytes, embryos, transferred embryos, embryos frozen per cycle, and cycles with embryo freezing between studied COH protocols. Although there were no differences in live birth rate (LBR, miscarriages, and ectopic pregnancies between compared protocols, pregnancy rate was significantly higher in GnRH antagonist mild protocol in comparison with both GnRH antagonist and GnRH agonist protocols and cumulative LBR per cycle was significantly higher in GnRH antagonist mild protocol in comparison to GnRH agonist protocol. Our data show that GnRH antagonist mild protocol of COH could be the best method of choice in good prognosis patients.

  6. Palila restoration research, 1996−2012 (United States)

    Banko, Paul C.; Farmer, Chris; Atkinson, Carter T.; Brinck, Kevin W.; Camp, Richad; Cole, Colleen; Canner, Raymond; Dougill, Steve; Goltz, Daniel; Gray, Elizabeth; Hess, Steven C.; Higashino, Jennifer; Jarvi, Susan I.; Johnson, Luanne; Laniawe, Leona; Laut, Megan; Miller, Linda; Murray, Christopher J.; Nelson, Daniel; Leonard, David L.; Oboyshi, Peter; Patch-Highfill, Leanne; Pollock, David D.; Rapozo, Kalei; Schwarzfeld, Marla; Slotterback, John; Stephens, Robert M.; Banko, Paul C.; Farmer, Chris


    The Palila Restoration Project was initiated in 1996 by the U.S. Geological Survey to assist government agencies mitigate the effects of realigning Saddle Road (Highway 200) through Palila Critical Habitat (U.S. Fish and Wildlife Service 1998, Federal Highway Administration 1999). Ecological research on the palila (Loxioides bailleui), an endangered Hawaiian forest bird, carried out by the U.S. Geological Survey (formerly organized as the Research Division of U.S. Fish and Wildlife Service) since 1987 and research conducted by the Palila Restoration Project provided the scientific bases for developing a recovery strategy (U.S. Fish and Wildlife Service 2006) and its adaptive implementation. The main objectives of the Palila Restoration Project were to develop techniques for reintroducing the palila to a portion of its former range, investigate the biological threats to the palila and its habitat, and synthesize the existing body of ecological knowledge concerning the palila. Five broad study themes formed the research framework: 1. Population reintroduction and restoration 2. Demography and breeding ecology 3. Habitat use and food ecology 4. Vegetation ecology 5. Predator ecology and management An element that was not included in the research program of the project was the ecology and management of introduced ungulates, which has historically constituted the single greatest threat to Palila Critical Habitat (Banko et al. 2009). The absence of ungulate studies should not be interpreted to mean that we believe ungulates no longer damage palila habitat. Other research has already established that removing alien browsers and grazers from Mauna Kea is essential for the recovery of the subalpine forest on which palila now depend (Scowcroft and Giffin 1983; Scowcroft and Sakai 1983; Scowcroft and Conrad 1988, 1992; Hess et al. 1999). Moreover, the Federal District Court of Hawai‘i has ordered the state of Hawai‘i to remove browsing ungulates from Palila Critical

  7. Glassfiber post: an alternative for restoring grossly decayed primary incisors. (United States)

    Mehra, Manjul; Grover, Rashu


    Restoration of primary incisors, which have been severely damaged by rampant caries or trauma, is a difficult task for the pediatric dentist. With the introduction of new adhesive systems and restorative materials, alternative approaches for treating these teeth have been proposed. This paper discusses the restoration of carious primary maxillary incisors using composite resin restoration reinforced with fiberglass post. Two case reports are presented here to describe the procedure. Over a 1 year period, the crowns have demonstrated good retention and esthetic results. How to cite this article: Mehra M, Grover R. Glassfiber Post: An Alternative for Restoring Grossly Decayed Primary Incisors. Int J Clin Pediatr Dent 2012;5(2):159-162.

  8. Columbia Estuary Ecosystem Restoration Program: Restoration Design Challenges for Topographic Mounds, Channel Outlets, and Reed Canarygrass

    Energy Technology Data Exchange (ETDEWEB)

    Diefenderfer, Heida L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Borde, Amy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sinks, Ian A. [Columbia Land Trust, Vancouver, WA (United States); Cullinan, Valerie I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zimmerman, Shon A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)


    The purpose of this study was to provide science-based information to practitioners and managers of restoration projects in the Columbia Estuary Ecosystem Restoration Program (CEERP) regarding aspects of restoration techniques that currently pose known challenges and uncertainties. The CEERP is a program of the Bonneville Power Administration (BPA) and the U.S. Army Corps of Engineers (Corps), Portland District, in collaboration with the National Marine Fisheries Service and five estuary sponsors implementing restoration. The estuary sponsors are Columbia Land Trust, Columbia River Estuary Study Taskforce, Cowlitz Tribe, Lower Columbia Estuary Partnership, and Washington Department of Fish and Wildlife. The scope of the research conducted during federal fiscal year 2015 included three aspects of hydrologic reconnection that were selected based on available scientific information and feedback from restoration practitioners during project reviews: the design of mounds (also called hummocks, peninsulas, or berms); the control of reed canarygrass (Phalaris arundinaceae); and aspects of channel network design related to habitat connectivity for juvenile salmonids.

  9. A restorative approach for class II resin composite restorations: a two-year follow-up. (United States)

    Santos, M J M C


    This clinical report describes a restorative technique used to replace two Class II resin composite restorations on the upper premolars. A sectional matrix band was used in conjunction with an elastic ring (Composi-Tight) to obtain tight proximal contact. A nanofilled resin composite (Filtek Supreme Ultra) was incrementally applied using oblique layers to reduce the C-factor, each layer being no more than 2 mm thick, and then light cured for 20 seconds with a light-emitting diode lamp (EliparFreeLight 2 LED Curing Light) with a power density of 660 mW/cm(2). A centripetal technique was used to restore the lost tooth structure from the periphery toward the center of the cavity in order to achieve a better contour and anatomy with less excess, thereby minimizing the use of rotary instruments during the finishing procedures. Finally, the resin composite restorations were finished and polished, and a surface sealer (Perma Seal) was applied to fill small gaps and defects that may have been present on the surfaces and margins of the restorations after the finishing and polishing procedures.

  10. Agar composition affects in vitro screening of biocontrol activity of antagonistic microorganisms. (United States)

    Bosmans, L; De Bruijn, I; De Mot, R; Rediers, H; Lievens, B


    Agar-based screening assays are the method of choice when evaluating antagonistic potential of bacterial biocontrol-candidates against pathogens. We showed that when using the same medium, but different agar compositions, the activity of a bacterial antagonist against Agrobacterium was strongly affected. Consequently, results from in vitro screenings should be interpreted cautiously.

  11. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview. (United States)

    Soltani, Hoda; Pardakhty, Abbas


    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of "new drug delivery systems" is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  12. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview


    Soltani, Hoda; Pardakhty, Abbas


    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of “new drug delivery systems” is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  13. Screening of Fungus Antagonists against Six Main Disease Pathogens in Crops

    Institute of Scientific and Technical Information of China (English)


    28 soil samples were collected from the rhizosphere of 16 plant species in six different districts in Hunan. As a result of isolation and purification, 122 fungus strains were obtained of which the antagonistic activity was tested against six fungus pathogens in tomato, cotton, cucumber, chilli, rice and rape, and 17 strains were found antagonistic to one or more pathogenic fungi.

  14. Agar composition affects in vitro screening of biocontrol activity of antagonistic microorganisms

    NARCIS (Netherlands)

    Bosmans, Lien; De Bruijn, I.; de Mot, Rene; Readers, Hans; Lievens, Bart


    Agar-based screening assays are the method of choice when evaluating antagonistic potential of bacterial biocontrol-candidates against pathogens.Weshowed thatwhen using the samemedium, but different agar compositions, the activity of a bacterial antagonist against Agrobacteriumwas strongly affected.

  15. Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist

    DEFF Research Database (Denmark)

    Klementiev, Boris; Li, Shizhong; Korshunova, Irina


    Interleukin 1 (IL-1) is implicated in neuroinflammation, an essential component of neurodegeneration. We evaluated the potential anti-inflammatory effect of a novel peptide antagonist of IL-1 signaling, Ilantide.......Interleukin 1 (IL-1) is implicated in neuroinflammation, an essential component of neurodegeneration. We evaluated the potential anti-inflammatory effect of a novel peptide antagonist of IL-1 signaling, Ilantide....

  16. Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis. (United States)

    Santella, Joseph B; Gardner, Daniel S; Duncia, John V; Wu, Hong; Dhar, Murali; Cavallaro, Cullen; Tebben, Andrew J; Carter, Percy H; Barrish, Joel C; Yarde, Melissa; Briceno, Stephanie W; Cvijic, Mary Ellen; Grafstrom, R Robert; Liu, Richard; Patel, Sima R; Watson, Andrew J; Yang, Guchen; Rose, Anne V; Vickery, Rodney D; Caceres-Cortes, Janet; Caporuscio, Christian; Camac, Daniel M; Khan, Javed A; An, Yongmi; Foster, William R; Davies, Paul; Hynes, John


    High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.

  17. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists. (United States)

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling


    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  18. Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

    DEFF Research Database (Denmark)

    Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund;


    synergistic effect when combining the mRNA antagonists against Survivin with the chemotherapeutic Taxol. This effect was demonstrated at concentrations of antagonists far lower than any previously demonstrated, indicating the high potential of locked nucleic acid for therapeutic use. Further characterisations...

  19. Transitions between male and female heterogamety caused by sex-antagonistic selection

    NARCIS (Netherlands)

    van Doorn, G. Sander; Kirkpatrick, Mark


    Many animal taxa show frequent and rapid transitions between male heterogamety (XY) and female heterogamety (ZW). We develop a model showing how these transitions can be driven by sex-antagonistic selection. Sex-antagonistic selection acting on loci linked to a new sex-determination mutation can cau

  20. Draft genome sequence of the antagonistic rhizosphere bacterium Serratia plymuthica strain PRI-2C. (United States)

    Garbeva, P; van Elsas, J D; de Boer, W


    Serratia plymuthica strain PRI-2C is a rhizosphere bacterial strain with antagonistic activity against different plant pathogens. Here we present the 5.39-Mb (G+C content, 55.67%) draft genome sequence of S. plymuthica strain PRI-2C with the aim of providing insight into the genomic basis of its antagonistic activity.

  1. Thatcher Bay, Washington, Nearshore Restoration Assessment (United States)

    Breems, Joel; Wyllie-Echeverria, Sandy; Grossman, Eric E.; Elliott, Joel


    The San Juan Archipelago, located at the confluence of the Puget Sound, the Straits of Juan de Fuca in Washington State, and the Straits of Georgia, British Columbia, Canada, provides essential nearshore habitat for diverse salmonid, forage fish, and bird populations. With 408 miles of coastline, the San Juan Islands provide a significant portion of the available nearshore habitat for the greater Puget Sound and are an essential part of the regional efforts to restore Puget Sound (Puget Sound Shared Strategy 2005). The nearshore areas of the San Juan Islands provide a critical link between the terrestrial and marine environments. For this reason the focus on restoration and conservation of nearshore habitat in the San Juan Islands is of paramount importance. Wood-waste was a common by-product of historical lumber-milling operations. To date, relatively little attention has been given to the impact of historical lumber-milling operations in the San Juan Archipelago. Thatcher Bay, on Blakely Island, located near the east edge of the archipelago, is presented here as a case study on the restoration potential for a wood-waste contaminated nearshore area. Case study components include (1) a brief discussion of the history of milling operations. (2) an estimate of the location and amount of the current distribution of wood-waste at the site, (3) a preliminary examination of the impacts of wood-waste on benthic flora and fauna at the site, and (4) the presentation of several restoration alternatives for the site. The history of milling activity in Thatcher Bay began in 1879 with the construction of a mill in the southeastern part of the bay. Milling activity continued for more than 60 years, until the mill closed in 1942. Currently, the primary evidence of the historical milling operations is the presence of approximately 5,000 yd3 of wood-waste contaminated sediments. The distribution and thickness of residual wood-waste at the site was determined by using sediment

  2. Shifting paradigms in coastal restoration: Six decades' lessons from China. (United States)

    Liu, Zezheng; Cui, Baoshan; He, Qiang


    With accelerating degradation of coastal environment worldwide, restoration has been elevated as a global strategy to enhance the functioning and social services of coastal ecosystems. While many developing countries suffer from intense coastal degradation, current understanding of the science and practice of their coastal restorations is extremely limited. Based on analysis of >1000 restoration projects, we provide the first synthesis of China's coastal restorations. We show that China's coastal restoration has recently entered a rapidly developing stage, with an increasing number of restoration projects carried out in multiple types of coastal ecosystems. While long-term, national-level restorations enforced by the government appear promising for some coastal ecosystems, especially mangroves, restorations of many other coastal ecosystems, such as salt marshes, seagrasses and coral reefs, have been much less implemented, likely due to under-appreciation of their ecosystem services values. Furthermore, the planning, techniques, research/assessment, and participation models underlying current restorations remain largely inadequate for restoration to effectively halt rapid coastal degradation. To promote success, we propose a framework where paradigms in current restorations from planning to implementation and assessment are transformed in multiple ways. Our study has broad implications for coastal environmental management policies and practices, and should inform sustainable development of coupled human-ocean systems in many countries.

  3. Designing regional pattern for ecosystem restoration: A case study

    Institute of Scientific and Technical Information of China (English)

    LI Guoqiang; MA Keming; FU Bojie; LIU Shiling


    Designing regional pattern is challenging for ecosystem restoration both in theory and in practice. The present study proposed a new approach to design regional pattern for ecosystem restoration with a case in the arid valley of Upper Minjiang River, SW China. The procedures are: (1) Determine the regional pattern of main environmental factors based on the relationships between the important environmental factors and the main geographical factors generated from DEM data. (2) Overlay the maps of the main environmental factors. (3) Generate a lookup table according to the species selection rule we proposed to link the candidate restoration species to the main environmental factors.(4) Determine the regional pattern of ecosystem restoration by positioning the restoration species in the map of environmental factors according to the lookup table. The regional restoration pattern designed in this way would be applicable not only to restoring a region, but also to predicting the future landscape change.

  4. Effective Image Restorations Using a Novel Spatial Adaptive Prior

    Directory of Open Access Journals (Sweden)

    Limin Luo


    Full Text Available Bayesian or Maximum a posteriori (MAP approaches can effectively overcome the ill-posed problems of image restoration or deconvolution through incorporating a priori image information. Many restoration methods, such as nonquadratic prior Bayesian restoration and total variation regularization, have been proposed with edge-preserving and noise-removing properties. However, these methods are often inefficient in restoring continuous variation region and suppressing block artifacts. To handle this, this paper proposes a Bayesian restoration approach with a novel spatial adaptive (SA prior. Through selectively and adaptively incorporating the nonlocal image information into the SA prior model, the proposed method effectively suppress the negative disturbance from irrelevant neighbor pixels, and utilizes the positive regularization from the relevant ones. A two-step restoration algorithm for the proposed approach is also given. Comparative experimentation and analysis demonstrate that, bearing high-quality edge-preserving and noise-removing properties, the proposed restoration also has good deblocking property.

  5. Guidelines for managing the orthodontic-restorative patient. (United States)

    Kokich, V G; Spear, F M


    Occasionally, patients require restorative treatment during or after orthodontic therapy. Patients with worn or abraded teeth, peg-shaped lateral incisors, fractured teeth, multiple edentulous spaces, or other restorative needs may require tooth positioning that is slightly different from a nonrestored, nonabraded, completely dentulous adolescent. Generally, orthodontists are not accustomed to dealing with patients who require restorative intervention. Should the objectives of orthodontic treatment differ for the restorative patient compared with the nonrestorative patient? How should the teeth be positioned during orthodontic therapy to facilitate specific restorations? Should teeth be restored before, during, or perhaps after orthodontics? The answers to these and other important questions are vital to the successful treatment of some orthodontic patients. This article will provide a series of eight guidelines to help the interdisciplinary team manage treatment for the orthodontic-restorative patient.

  6. Antagonistic activity of autosimbionts А. viridans, B. subtilis and their probiotic association to conditionally microflora

    Directory of Open Access Journals (Sweden)

    Stepansky D.A.


    Full Text Available In this research the data on examination of antagonist qualities of bioassotiantes A. viridans and strain B. subtilis 3 towards pathogenic and opportunistic pathogenic microflora isolated from oropharynx and nasopharynx of children who were in contact with patients with pulmonary tuberculosis (MBT + are submitted. The expressed antagonist activity of autosimbionts A. viridans towards pathogenic and opportunistic pathogenic microflora was shown. Common antagonist activity of A. viridans (k N 1 and B. subtilis 3 towards diverse strains of test-cultures is 1,5-2 times higher, than separate antagonist activity of A. viridans (k №1 and B. subtilis 3. Received research data showed the possibility of continuing work on development of probiotic associations, that contain representatives of normal microflora - bioassociants A. viridans and probiotic strains B. subtilis 3 with broadspectrum of antagonistic activity in relation to the various groups of bacterium.

  7. Screening of antagonistic bacteria for biological control of nursery wilt of black pepper (Piper nigrum). (United States)

    Anith, K N; Radhakrishnan, N V; Manomohandas, T P


    Bacterial antagonists of Phytophthora capsici were isolated from underground shoot portions of rooted cuttings of black pepper. Initially isolates were screened by dual culture on potato dextrose agar and carrot agar. Further, a screening was done on black pepper shoots for supression of lesion caused by the pathogen. Most of the antagonists showed varying levels of antagonism in the dual culture and the shoot assay. Isolate PN-026, showing the highest suppression of lesion development in the shoot assay was found to be the most efficient antagonist in reducing Phytophthora capsici induced nursery wilt of black pepper. This screening involving the host, pathogen, and the antagonist, performed on black pepper shoot (the planting material for this vegetatively propagated crop), could be used as a rapid and reliable method for the isolation of efficient bacterial antagonists of P. capsici.

  8. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. (United States)

    Westby, Mike; Smith-Burchnell, Caroline; Mori, Julie; Lewis, Marilyn; Mosley, Michael; Stockdale, Mark; Dorr, Patrick; Ciaramella, Giuseppe; Perros, Manos


    Maraviroc is a CCR5 antagonist in clinical development as one of a new class of antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor binding. We investigated the mechanism of HIV resistance to maraviroc by using in vitro sequential passage and site-directed mutagenesis. Serial passage through increasing maraviroc concentrations failed to select maraviroc-resistant variants from some laboratory-adapted and clinical isolates of HIV-1. However, high-level resistance to maraviroc was selected from three of six primary isolates passaged in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to maraviroc in both treated and control cultures; all resistant variants were able to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an inability to replicate in CCR5 Delta32/Delta32 PBL. Strain-specific mutations were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3 background. This recombinant virus was completely resistant to maraviroc but retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and 323 in the V3 loop (numbering from HXB2) to their original sequence restored wild-type susceptibility to maraviroc, while reversion of either mutation resulted in a partially sensitive virus with reduced maximal inhibition (plateau). The plateaus are consistent with the virus having acquired the ability to utilize maraviroc-bound receptor for entry. This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus.

  9. Evaluation of periodontal status adjacent to interproximal surfaces restored with composite resin, in comparison with non-restored interproximal surfaces

    Directory of Open Access Journals (Sweden)

    Elvia Christina Barros de Almeida


    Full Text Available Objective: The purpose of this study was to evaluate the periodontal status of interproximal surfaces restored with composite resin, in comparison with non-restored interproximal surfaces. Methods: In 65 patients, we analyzed 145 restored surfaces and 145 non-restored surfaces. Results: Most of the restored surfaces (54.3% showed radiographic alterations, which was shown to be higher among restorations with clinically detected proximal excess (56.8% x 52.8%; with lack of restorative material (64.5% x 51.4%; in restorations with proximal overhang (67.7% x 44.4%; in teeth with gingival inflammation?/bleeding (55.1% x 40.0% and in teeth with probing depth exceeding 3 mm (64.3% x 52.9%. However, there were no significant associations for these variables. Of the non-restored surfaces, 24.4% showed radiographic alterations, however there were no significant associations. Conclusion: The results showed a statistical significance for radiographic alterations in restored and non-restored surfaces.

  10. Clinical Investigation of a New Bulk Fill Composite Resin in the Restoration of Posterior Teeth (United States)


    Dental Restoration Failure of Marginal Integrity; Dental Caries; Unrepairable Overhanging of Dental Restorative Materials; Poor Aesthetics of Existing Restoration; Secondary Dental Caries Associated With Failed or Defective Dental Restorations; Fractured Dental Restorative Materials Without Loss of Materials; Fracture of Dental Restorative Materials With Loss of Material

  11. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B


    , in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-ylpropoxyphenylmethanol, and its (S-enantiomer (4 significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R-enantiomer (3 in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats. Keywords: histamine, H3 receptor, isomeric antagonists, anticonvulsant activity, stereo­selectivity

  12. Dopamine D(3) receptor antagonists: The quest for a potentially selective PET ligand. Part two: Lead optimization. (United States)

    Micheli, Fabrizio; Holmes, Ian; Arista, Luca; Bonanomi, Giorgio; Braggio, Simone; Cardullo, Francesca; Di Fabio, Romano; Donati, Daniele; Gentile, Gabriella; Hamprecht, Dieter; Terreni, Silvia; Heidbreder, Christian; Savoia, Chiara; Griffante, Cristiana; Worby, Angela


    The lead optimization process to identify new selective dopamine D(3) receptor antagonists is reported. DMPK parameters and binding data suggest that selective D(3) receptor antagonists as potential PET ligands might have been identified.

  13. Identifying sites for elk restoration in Arkansas (United States)

    Telesco, R.L.; Van Manen, F.T.; Clark, J.D.; Cartwright, Michael E.


    We used spatial data to identify potential areas for elk (Cervus elaphus) restoration in Arkansas. To assess habitat, we used locations of 239 elk groups collected from helicopter surveys in the Buffalo National River area of northwestern Arkansas, USA, from 1992 to 2002. We calculated the Mahalanobis distance (D2) statistic based on the relationship between those elk-group locations and a suite of 9 landscape variables to evaluate winter habitat in Arkansas. We tested model performance in the Buffalo National River area by comparing the D2 values of pixels representing areas with and without elk pellets along 19 fixed-width transects surveyed in March 2002. Pixels with elk scat had lower D2 values than pixels in which we found no pellets (logistic regression: Wald χ2 = 24.37, P cover, gently sloping ridge tops and valleys, low human population density, and low road densities. To assess the potential for elk–human conflicts in Arkansas, we used the analytical hierarchy process to rank the importance of 8 criteria based on expert opinion from biologists involved in elk management. The biologists ranked availability of forage on public lands as having the strongest influence on the potential for elk–human conflict (33%), followed by human population growth rate (22%) and the amount of private land in row crops (18%). We then applied those rankings in a weighted linear summation to map the relative potential for elk–human conflict. Finally, we used white-tailed deer (Odocoileus virginianus) densities to identify areas where success of elk restoration may be hampered due to meningeal worm (Parelaphostrongylus tenuis) transmission. By combining results of the 3 spatial data layers (i.e., habitat model, elk–human conflict model, deer density), our model indicated that restoration sites located in west-central and north-central Arkansas were most favorable for reintroduction.

  14. Shape Restoration by Active Self-Assembly

    Directory of Open Access Journals (Sweden)

    D. Arbuckle


    Full Text Available Shape restoration is defined as the problem of constructing a desired, or goal, solid shape Sg by growing an initial solid Si, which is a subset of the goal but is otherwise unknown. This definition attempts to capture abstractly a situation that often arises in the physical world when a solid object loses its desired shape due to wear and tear, corrosion or other phenomena. For example, if the top of the femur becomes distorted, the hip joint no longer functions properly and may have to be replaced surgically. Growing it in place back to its original shape would be an attractive alternative to replacement. This paper presents a solution to the shape restoration problem by using autonomous assembly agents (robots that self-assemble to fill the volume between Sg and Si. If the robots have very small dimension (micro or nano, the desired shape is approximated with high accuracy. The assembly agents initially execute a random walk. When two robots meet, they may exchange a small number of messages. The robot behavior is controlled by a finite state machine with a small number of states. Communication contact models chemical communication, which is likely to be the medium of choice for robots at the nanoscale, while small state and small messages are limitations that also are expected of nanorobots. Simulations presented here show that swarms of such robots organize themselves to achieve shape restoration by using distributed algorithms. This is one more example of an interesting geometric problem that can be solved by the Active Self-Assembly paradigm introduced in previous papers by the authors.

  15. Proximal Contact Repair of Complex Amalgam Restorations. (United States)

    Zguri, M N; Casey, J A; Jessup, J P; Vandewalle, K S


    The carving of a complex amalgam restoration may occasionally result in light proximal contact with the adjacent tooth. The purpose of this study was to investigate the strength of complex amalgam restorations repaired with a proximal slot amalgam preparation. Extracted human third molars of similar coronal size were sectioned 1 mm apical to the height of the contour using a saw and were randomly distributed into 9 groups of 10 teeth each. One pin was placed at each line angle of the flattened dentinal tooth surface. A metal matrix band was placed and an admixed alloy was condensed and carved to create a full crown contour but with a flat occlusal surface. A proximal slot was prepared with or without a retention groove and repaired using a single-composition spherical amalgam 15 minutes, 24 hours, one week, or six months after the initial crown condensation. The specimens were stored for 24 hours in 37°C water before fracture at the marginal ridge using a round-ended blade in a universal testing machine. The control group was not repaired. The mean maximum force in newtons and standard deviation were determined per group. Data were analyzed with a 2-way analysis of variance as well as Tukey and Dunnett tests (α=0.05). Significant differences were found between groups based on type of slot preparation (p=0.017) but not on time (p=0.327), with no significant interaction (p=0.152). No significant difference in the strength of the marginal ridge was found between any repair group and the unrepaired control group (p>0.076). The proximal repair strength of a complex amalgam restoration was not significantly different from an unrepaired amalgam crown. Placing a retention groove in the proximal slot preparation resulted in significantly greater fracture strength than a slot with no retention grooves. Time of repair had no significant effect on the strength of the repair.

  16. Restoring Soil Quality to Mitigate Soil Degradation

    Directory of Open Access Journals (Sweden)

    Rattan Lal


    Full Text Available Feeding the world population, 7.3 billion in 2015 and projected to increase to 9.5 billion by 2050, necessitates an increase in agricultural production of ~70% between 2005 and 2050. Soil degradation, characterized by decline in quality and decrease in ecosystem goods and services, is a major constraint to achieving the required increase in agricultural production. Soil is a non-renewable resource on human time scales with its vulnerability to degradation depending on complex interactions between processes, factors and causes occurring at a range of spatial and temporal scales. Among the major soil degradation processes are accelerated erosion, depletion of the soil organic carbon (SOC pool and loss in biodiversity, loss of soil fertility and elemental imbalance, acidification and salinization. Soil degradation trends can be reversed by conversion to a restorative land use and adoption of recommended management practices. The strategy is to minimize soil erosion, create positive SOC and N budgets, enhance activity and species diversity of soil biota (micro, meso, and macro, and improve structural stability and pore geometry. Improving soil quality (i.e., increasing SOC pool, improving soil structure, enhancing soil fertility can reduce risks of soil degradation (physical, chemical, biological and ecological while improving the environment. Increasing the SOC pool to above the critical level (10 to 15 g/kg is essential to set-in-motion the restorative trends. Site-specific techniques of restoring soil quality include conservation agriculture, integrated nutrient management, continuous vegetative cover such as residue mulch and cover cropping, and controlled grazing at appropriate stocking rates. The strategy is to produce “more from less” by reducing losses and increasing soil, water, and nutrient use efficiency.

  17. Soil disturbance as a grassland restoration measure

    DEFF Research Database (Denmark)

    Schnoor, Tim; Bruun, Hans Henrik; Olsson, Pål Axel


    Soil disturbance is recognized as an important driver of biodiversity in dry grasslands, and can therefore be implemented as a restoration measure. However, because community re-assembly following disturbance includes stochastic processes, a focus only on species richness or establishment success...... target. Species richness and functional diversity both increased in response to soil disturbance, and rotavation, but not ploughing, had a persistent positive effect on the occurrence of specialist species of calcareous sandy grassland. However, no type of soil disturbance caused the plant species...

  18. Occlusal considerations for dental implant restorations. (United States)

    Bergmann, Ranier H


    When placed, dental implants are put into an ever-changing oral environment in which teeth can continue to migrate. Yet, the implants themselves are ankylosed. This can lead to occlusal instability. Teeth may continue to erupt, leaving the implants in infraocclusion. Teeth may move mesially away from an implant, requiring modification to close an open contact point. Friction in the connection between teeth and implants can lead to intrusion of teeth and damage to the periodontal attachment apparatus. Implant occlusion with shallow incisal guidance minimizes lateral and tipping forces. Cross-arch stabilization allows the best distribution of occlusal forces. The choice of restorative materials influences long-term occlusal stability.

  19. Minimally invasive restorative dentistry: a biomimetic approach. (United States)

    Malterud, Mark I


    When providing dental treatment for a given patient, the practitioner should use a minimally invasive technique that conserves sound tooth structure as a clinical imperative. Biomimetics is a tenet that guides the author's practice and is generally described as the mimicking of natural life. This can be accomplished in many cases using contemporary composite resins and adhesive dental procedures. Both provide clinical benefits and support the biomimetic philosophy for treatment. This article illustrates a minimally invasive approach for the restoration of carious cervical defects created by poor hygiene exacerbated by the presence of orthodontic brackets.

  20. Flouride release from various restorative materials. (United States)

    Bala, O; Uçtaşli, M; Can, H; Türköz, E; Can, M


    Fluoride release from six light-activated restorative materials, including two resinmodified glass-ionomers, two composites, and two compomers, was evaluated and compared with one conventional acid-based glass-ionomer cement. The amount and rate of release varied among the tested materials. Both resin-modified glass-ionomers and the conventional acid-base glass-ionomer cements released more fluoride then the composites and compomers (p < 0.05). Additionally, composite materials released less fluoride than compomer materials (p < 0.05). Release of fluoride by the tested materials showed a significant decrease after all the tested time intervals.

  1. Big Canyon Creek Ecological Restoration Strategy.

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, Lynn; Richardson, Shannon


    He-yey, Nez Perce for steelhead or rainbow trout (Oncorhynchus mykiss), are a culturally and ecologically significant resource within the Big Canyon Creek watershed; they are also part of the federally listed Snake River Basin Steelhead DPS. The majority of the Big Canyon Creek drainage is considered critical habitat for that DPS as well as for the federally listed Snake River fall chinook (Oncorhynchus tshawytscha) ESU. The Nez Perce Soil and Water Conservation District (District) and the Nez Perce Tribe Department of Fisheries Resources Management-Watershed (Tribe), in an effort to support the continued existence of these and other aquatic species, have developed this document to direct funding toward priority restoration projects in priority areas for the Big Canyon Creek watershed. In order to achieve this, the District and the Tribe: (1) Developed a working group and technical team composed of managers from a variety of stakeholders within the basin; (2) Established geographically distinct sub-watershed areas called Assessment Units (AUs); (3) Created a prioritization framework for the AUs and prioritized them; and (4) Developed treatment strategies to utilize within the prioritized AUs. Assessment Units were delineated by significant shifts in sampled juvenile O. mykiss (steelhead/rainbow trout) densities, which were found to fall at fish passage barriers. The prioritization framework considered four aspects critical to determining the relative importance of performing restoration in a certain area: density of critical fish species, physical condition of the AU, water quantity, and water quality. It was established, through vigorous data analysis within these four areas, that the geographic priority areas for restoration within the Big Canyon Creek watershed are Big Canyon Creek from stream km 45.5 to the headwaters, Little Canyon from km 15 to 30, the mainstem corridors of Big Canyon (mouth to 7km) and Little Canyon (mouth to 7km). The District and the Tribe

  2. Planning aquatic ecosystem restoration monitoring programs

    Energy Technology Data Exchange (ETDEWEB)

    Thom, R.M.; Wellman, K.F.


    This study was conducted as part of the Evaluation of Environmental Investments Research Program (EEIRP). The EEIRP is sponsored by the US Army Corps of Engineers. The objectives of this work are to (1) identify relevant approaches and features for environmental investment measures to be applied throughout the project life; (2) develop methods to access the effectiveness of the approach or feature for providing the intended environmental output; (3) develop and provide guidance for formulating environmental projects; and (4) provide guidance for formulating and identifying relevant cost components of alternate restoration plans.

  3. Esthetics: the orthodontic-periodontic restorative connection. (United States)

    Kokich, V G


    As we complete the 20th and progress into the 21st century, orthodontists worldwide are experiencing a gradual but significant change in their practices. The number of adult patients has increased substantially. Although adults cooperate better than adolescents, they present a different set of challenges for the orthodontist. Adults may have worn or abraded teeth, uneven gingival margins, missing papillae, and periodontal bone loss, all of which can jeopardize the esthetic appearance of the teeth after bracket removal. This article will discuss the solutions for managing these challenging orthodontic-periodontic-restorative situations to produce a more ideal esthetic result.

  4. Microeconomic analysis of military aircraft bearing restoration (United States)

    Hein, G. F.


    The risk and cost of a bearing restoration by grinding program was analyzed. A microeconomic impact analysis was performed. The annual cost savings to U.S. Army aviation is approximately $950,000.00 for three engines and three transmissions. The capital value over an indefinite life is approximately ten million dollars. The annual cost savings for U.S. Air Force engines is approximately $313,000.00 with a capital value of approximately 3.1 million dollars. The program will result in the government obtaining bearings at lower costs at equivalent reliability. The bearing industry can recover lost profits during a period of reduced demand and higher costs.

  5. Audit of fuel processing restoration property

    Energy Technology Data Exchange (ETDEWEB)



    In April, 1992, due to a diminished need for reprocessed uranium, the Secretary of Energy terminated the Fuel Processing Restoration (FPR) project. The termination left management and operating (M&O) contractors at the Idaho National Engineering Laboratory (Laboratory) with over $54 million in tools, equipment and material to be retained, utilized or disposed of. The objectives of the audit were to determine whether FPR property was adequately accounted for and whether the property was properly redistributed or excessed when the FPR project was terminated.

  6. Power to the people? Restoring citizen participation. (United States)

    Morone, James A; Kilbreth, Elizabeth H


    This article investigates a lost ideal--citizen participation in health policy. We begin by mapping the different types of participation. We then suggest what direct citizen action has achieved in the past, why it ought to be restored today, and how we might go about reviving it. A changing social environment--marked by globalization, immigration, a culture war, and managed care--could be addressed by robust, local, democratic health reforms. Finally, we contrast the top-down health sector with education and crime policies that take communities far more seriously.

  7. Restoring interventions: eco-sustainable weed control

    Directory of Open Access Journals (Sweden)

    Facciotto G


    Full Text Available The creation and enlargement of ecological networks is paramount to conserve plant biodiversity, to offer refuge to the local fauna and to improve the environment in general. Such networks intend to conserve areas of great natural value, to restore degraded areas and to link them physically through the creation of ecological corridors. The work described was carried out in order to improve and enlarge an ecological corridor within the experimental farm “Mezzi” of CRA-ISP at Casale Monferrato (AL - Italy. One of its bigger problems, weed control, was solved by increasing the planting density, by sowing herbaceous crops and mulching with woody chips.

  8. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists. (United States)

    Sadek, Bassem; Saad, Ali; Schwed, Johannes Stephan; Weizel, Lilia; Walter, Miriam; Stark, Holger


    Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%-80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide (1). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide (2) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S-enantiomer (1), the results show that animals pretreated intraperitoneally (ip) with the R-enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R)-enantiomer (3), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its (S)-enantiomer (4) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R)-enantiomer (3) in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and

  9. The NK1 receptor antagonist L822429 reduces heroin reinforcement. (United States)

    Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus


    Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1 h: ShA) or long (12 h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects.

  10. Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats. (United States)

    Wen, Di; Zang, Guoqing; Sun, DongLei; Yu, Feng; Mei, Dong; Ma, Chunling; Cong, Bin


    Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

  11. Estimating the Size and Impact of the Ecological Restoration Economy.

    Directory of Open Access Journals (Sweden)

    Todd BenDor

    Full Text Available Domestic public debate continues over the economic impacts of environmental regulations that require environmental restoration. This debate has occurred in the absence of broad-scale empirical research on economic output and employment resulting from environmental restoration, restoration-related conservation, and mitigation actions - the activities that are part of what we term the "restoration economy." In this article, we provide a high-level accounting of the size and scope of the restoration economy in terms of employment, value added, and overall economic output on a national scale. We conducted a national survey of businesses that participate in restoration work in order to estimate the total sales and number of jobs directly associated with the restoration economy, and to provide a profile of this nascent sector in terms of type of restoration work, industrial classification, workforce needs, and growth potential. We use survey results as inputs into a national input-output model (IMPLAN 3.1 in order to estimate the indirect and induced economic impacts of restoration activities. Based on this analysis we conclude that the domestic ecological restoration sector directly employs ~ 126,000 workers and generates ~ $9.5 billion in economic output (sales annually. This activity supports an additional 95,000 jobs and $15 billion in economic output through indirect (business-to-business linkages and increased household spending.

  12. Estimating the Size and Impact of the Ecological Restoration Economy. (United States)

    BenDor, Todd; Lester, T William; Livengood, Avery; Davis, Adam; Yonavjak, Logan


    Domestic public debate continues over the economic impacts of environmental regulations that require environmental restoration. This debate has occurred in the absence of broad-scale empirical research on economic output and employment resulting from environmental restoration, restoration-related conservation, and mitigation actions - the activities that are part of what we term the "restoration economy." In this article, we provide a high-level accounting of the size and scope of the restoration economy in terms of employment, value added, and overall economic output on a national scale. We conducted a national survey of businesses that participate in restoration work in order to estimate the total sales and number of jobs directly associated with the restoration economy, and to provide a profile of this nascent sector in terms of type of restoration work, industrial classification, workforce needs, and growth potential. We use survey results as inputs into a national input-output model (IMPLAN 3.1) in order to estimate the indirect and induced economic impacts of restoration activities. Based on this analysis we conclude that the domestic ecological restoration sector directly employs ~ 126,000 workers and generates ~ $9.5 billion in economic output (sales) annually. This activity supports an additional 95,000 jobs and $15 billion in economic output through indirect (business-to-business) linkages and increased household spending.

  13. Macroinvertebrate community assembly in pools created during peatland restoration. (United States)

    Brown, Lee E; Ramchunder, Sorain J; Beadle, Jeannie M; Holden, Joseph


    Many degraded ecosystems are subject to restoration attempts, providing new opportunities to unravel the processes of ecological community assembly. Restoration of previously drained northern peatlands, primarily to promote peat and carbon accumulation, has created hundreds of thousands of new open water pools. We assessed the potential benefits of this wetland restoration for aquatic biodiversity, and how communities reassemble, by comparing pool ecosystems in regions of the UK Pennines on intact (never drained) versus restored (blocked drainage-ditches) peatland. We also evaluated the conceptual idea that comparing reference ecosystems in terms of their compositional similarity to null assemblages (and thus the relative importance of stochastic versus deterministic assembly) can guide evaluations of restoration success better than analyses of community composition or diversity. Community composition data highlighted some differences in the macroinvertebrate composition of restored pools compared to undisturbed peatland pools, which could be used to suggest that alternative end-points to restoration were influenced by stochastic processes. However, widely used diversity metrics indicated no differences between undisturbed and restored pools. Novel evaluations of restoration using null models confirmed the similarity of deterministic assembly processes from the national species pool across all pools. Stochastic elements were important drivers of between-pool differences at the regional-scale but the scale of these effects was also similar across most of the pools studied. The amalgamation of assembly theory into ecosystem restoration monitoring allows us to conclude with more certainty that restoration has been successful from an ecological perspective in these systems. Evaluation of these UK findings compared to those from peatlands across Europe and North America further suggests that restoring peatland pools delivers significant benefits for aquatic fauna by

  14. The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

    Directory of Open Access Journals (Sweden)

    Mallory Batty


    Full Text Available This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa. Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.

  15. Survey of H2-antagonist usage in acute upper gastrointestinal hemorrhage. (United States)

    Bhatt, B D; Meriano, F V; Phipps, T L; Ho, H; Zuckerman, M J


    H2-antagonists are frequently used in the management of upper gastrointestinal (UGI) hemorrhage despite their lack of proven efficacy. In order to determine the pattern of H2-antagonist usage for this indication, we retrospectively reviewed the charts of 137 patients admitted with acute UGI bleeding over a 1-year period at two teaching hospitals in West Texas. An H2-antagonist was ordered in 89% of patients (77%) intravenous, 12% oral). It was administered within 2 h of admission in 25% of these patients, within 4 h in 54%, and within 8 h in 78%. An H2-antagonist was ordered among the initial six orders in 49% and among the initial 10 orders in 77% of patients. Considering orders for specific therapies, an H2-antagonist was in the initial three orders in 60% of patients and among the initial six orders in 97%. Of the patients who were prescribed an H2-antagonist and who also had upper endoscopy, the drug was ordered prior to endoscopy in 86%. This review of H2-antagonist usage in the management of acute UGI bleeding has identified a prescribing pattern of writing for these drugs early in the sequence of order writing, with the drugs being given early in the course of hospitalization.

  16. Seven-year clinical evaluation of painful cracked teeth restored with a direct composite restoration.

    NARCIS (Netherlands)

    Opdam, N.J.M.; Roeters, J.J.; Loomans, B.A.C.; Bronkhorst, E.M.


    The purpose of this study was to investigate long-term clinical effectiveness of treating painful cracked teeth with a direct bonded composite resin restoration. The hypothesis tested was that cracked teeth treated with or without cuspal coverage showed the same performance. Forty-one patients atten

  17. Fracture resistance of teeth restored with different resin-based restorative systems

    Directory of Open Access Journals (Sweden)

    Willian Yoshio Kikuti


    Full Text Available The aim of the present study was to evaluate the fracture resistance of teeth restored with resin composite. Forty-eight maxillary premolar teeth were chosen and randomly divided to six groups: G1 (control: sound teeth; G2: MOD preparation, unrestored; G3: MOD + Adper Single Bond 2/P60; G4: MOD + Adper Easy One/P60; G5: MOD + P90 restorative system; G6: MOD + Adper Easy One/P90 Bond/P90. Specimens were subjected to compressive axial loading (0.5 mm/min. Flexural strength and the modulus of elasticity were also tested (n = 7. The only statistical equivalence with sound teeth was noted for G3 (p < 0.05. Flexural strength and the modulus of elasticity varied among the composites tested (n = 10. The reestablishment of the resistance to fracture in premolars subjected to Class II MOD preparations is restorative-system-dependent. The silorane restorative system is not able to recover the resistance to fracture.

  18. Agonists and Antagonists of TGF-β Family Ligands. (United States)

    Chang, Chenbei


    The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

  19. Antagonistic evolution in an aposematic predator-prey signaling system. (United States)

    Speed, Michael P; Franks, Daniel W


    Warning signals within species, such as the bright colors of chemically defended animals, are usually considered mutualistic, monomorphic traits. Such a view is however increasingly at odds with the growing empirical literature, showing nontrivial levels of signal variation within prey populations. Key to understanding this variation, we argue, could be a recognition that toxicity levels frequently vary within populations because of environmental heterogeneity. Inequalities in defense may undermine mutualistic monomorphic signaling, causing evolutionary antagonism between loci that determine appearance of less well-defended and better defended prey forms within species. In this article, we apply a stochastic model of evolved phenotypic plasticity to the evolution of prey signals. We show that when toxicity levels vary, then antagonistic interactions can lead to evolutionary conflict between alleles at different signaling loci, causing signal evolution, "red queen-like" evolutionary chase, and one or more forms of signaling equilibria. A key prediction is that variation in the way that predators use information about toxicity levels in their attack behaviors profoundly affects the evolutionary characteristics of the prey signaling systems. Environmental variation is known to cause variation in many qualities that organisms signal; our approach may therefore have application to other signaling systems.

  20. Preliminary investigations into triazole derived androgen receptor antagonists. (United States)

    Altimari, Jarrad M; Niranjan, Birunthi; Risbridger, Gail P; Schweiker, Stephanie S; Lohning, Anna E; Henderson, Luke C


    A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3h. After preliminary biological screening at 20 and 40 μM, the most promising three compounds were found to display IC50 values of 40-50 μM against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue.

  1. Iontophoresis of endothelin receptor antagonists in rats and men.

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    Matthieu Roustit

    Full Text Available INTRODUCTION: The treatment of scleroderma-related digital ulcers is challenging. The oral endothelin receptor antagonist (ERA bosentan has been approved but it may induce liver toxicity. The objective of this study was to test whether ERAs bosentan and sitaxentan could be locally delivered using iontophoresis. METHODS: Cathodal and anodal iontophoresis of bosentan and sitaxentan were performed on anaesthetized rat hindquarters without and during endothelin-1 infusion. Skin blood flow was quantified using laser-Doppler imaging and cutaneous tolerability was assessed. Iontophoresis of sitaxentan (20 min, 20 or 100 µA was subsequently performed on the forearm skin of healthy men (n = 5. RESULTS: In rats neither bosentan nor sitaxentan increased skin blood flux compared to NaCl. When simultaneously infusing endothelin-1, cathodal iontophoresis of sitaxentan increased skin blood flux compared to NaCl (AUC(0-20 were 44032.2 ± 12277 and 14957.5 ± 23818.8 %BL.s, respectively; P = 0.01. In humans, sitaxentan did not significantly increase skin blood flux as compared to NaCl. Iontophoresis of ERAs was well tolerated both in animals and humans. CONCLUSIONS: This study shows that cathodal iontophoresis of sitaxentan but not bosentan partially reverses endothelin-induced skin vasoconstriction in rats, suggesting that sitaxentan diffuses into the dermis. However, sitaxentan does not influence basal skin microvascular tone in rats or in humans.

  2. Discovery and Characterization of an Endogenous CXCR4 Antagonist

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    Onofrio Zirafi


    Full Text Available CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

  3. Nalmefene: intravenous safety and kinetics of a new opioid antagonist. (United States)

    Dixon, R; Howes, J; Gentile, J; Hsu, H B; Hsiao, J; Garg, D; Weidler, D; Meyer, M; Tuttle, R


    In a placebo-controlled, double-blind study we evaluated the safety and kinetics of a new narcotic antagonist, nalmefene, after 2, 6, 12, and 24 mg intravenous doses to healthy men. At each dose level four subjects received active drug and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness. The plasma concentration-time data were best fit with a triexponential equation, and the terminal elimination phase had a harmonic mean t1/2 of 8 to 9 hours. Only about 5% of the dose was excreted in the urine as intact nalmefene, with up to 60% excreted as nalmefene glucuronide. Although intersubject differences were noted, mean or dose-normalized mean kinetic parameters such as clearance, steady-state volume of distribution, terminal t1/2, and AUC showed no consistent trends related to increasing doses, indicating that nalmefene has linear pharmacokinetics.

  4. Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists. (United States)

    Hong, Seoung-Soo; Bavadekar, Supriya A; Lee, Sang-Il; Patil, Popat N; Lalchandani, S G; Feller, Dennis R; Miller, Duane D


    The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.

  5. Blood flow distribution with adrenergic and histaminergic antagonists

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    Baker, C.H.; Davis, D.L.; Sutton, E.T.


    Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects.

  6. Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?

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    Gregory R. Tintinger


    Full Text Available The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotrien–independent mechanisms of action of montelukast and their potential clinical relevance.

  7. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton. (United States)

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P


    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.

  8. [Vascular calcifications, the hidden side effects of vitamin K antagonists]. (United States)

    Bennis, Youssef; Vengadessane, Subashini; Bodeau, Sandra; Gras, Valérie; Bricca, Giampiero; Kamel, Saïd; Liabeuf, Sophie


    Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA. This is the case of matrix Gla-protein (MGP), a protein that plays a major inhibitory role in the development of vascular calcifications. Several experimental and epidemiological results suggest that the use of the VKA could promote the development of vascular calcifications increasing thus the cardiovascular risk. This risk seems to be higher in patients with chronic kidney disease or mellitus diabetes who are more likely to develop vascular calcifications, and may be due to a decrease of the MGP activity. This review aims at summarizing the data currently available making vascular calcifications the probably underestimated side effects of VKA.

  9. Effect of antagonist muscle fatigue on knee extension torque. (United States)

    Beltman, J G M; Sargeant, A J; Ball, D; Maganaris, C N; de Haan, A


    The effect of hamstring fatigue on knee extension torque was examined at different knee angles for seven male subjects. Before and after a dynamic flexion fatigue protocol (180 degrees s(-1), until dynamic torque had declined by 50%), maximal voluntary contraction extension torque was measured at four knee flexion angles (90 degrees, 70 degrees, 50 degrees and 30 degrees ). Maximal torque generating capacity and voluntary activation of the quadriceps muscle were determined using electrical stimulation. Average rectified EMG of the biceps femoris was determined. Mean dynamic flexion torque declined by 48+/-11%. Extensor maximal voluntary contraction torque, maximal torque generating capacity, voluntary activation and average rectified EMG at the four knee angles were unaffected by the hamstring fatigue protocol. Only at 50 degrees knee angle was voluntary activation significantly lower (15.7%) after fatigue ( P<0.05). In addition, average rectified EMG before fatigue was not significantly influenced by knee angle. It was concluded that a fatigued hamstring muscle did not increase the maximal voluntary contraction extension torque and knee angle did not change coactivation. Three possible mechanisms may explain the results: a potential difference in recruited fibre populations in antagonist activity compared with the fibres which were fatigued in the protocol, a smaller loss in isometric torque generating capacity of the hamstring muscle than was expected from the dynamic measurements and/or a reduction in voluntary activation.

  10. Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure. (United States)

    Sica, Domenic A


    Spironolactone and eplerenone are both mineralocorticoid-receptor antagonists. These compounds block both the epithelial and nonepithelial actions of aldosterone, with the latter assuming increasing clinical relevance. Spironolactone and eplerenone both affect reductions in blood pressure either as mono- or add-on therapy; moreover, they each afford survival benefits in diverse circumstances of heart failure and the probability of renal protection in proteinuric chronic kidney disease. However, as use of mineralocorticoid-blocking agents has expanded, the hazards inherent in taking such drugs have become more apparent. Whereas the endocrine side effects of spironolactone are in most cases little more than a cosmetic annoyance, the potassium-sparing effects of both spironolactone and eplerenone can prove disastrous, even fatal, if sufficient degrees of hyperkalemia emerge. For most patients, however, the risk of developing hyperkalemia in and of itself should not discourage the sensible clinician from bringing these compounds into play. Hyperkalemia should always be considered a possibility in patients receiving either of these medications; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered.

  11. Spatial working memory in rats: effects of monoaminergic antagonists. (United States)

    Beatty, W W; Rush, J R


    To assess the possible involvement of the monoaminergic neurotransmitters norepinephrine, dopamine and serotonin in the maintenance of spatial working memory rats were treated with antagonists 0 or 2 hr after completing the first 4 choices in an 8 arm maze. Haloperidol (0.25-1 mg/kg), when administered 2 hr after Choice 4, produced a small but consistent impairment in performance on retention tests given 5 hr after the first 4 choices. This deficit closely resembled natural forgetting in terms of the type of errors committed. By contrast, haloperidol in the same doses given 0 hr after Choice 4 or 3 hr before the first 4 choices did not affect retention. Likewise treatment with propranolol (10-20 mg/kg), phentolamine (5-20 mg/kg) or methysergide (5-15 mg/kg) did not impair spatial memory, regardless of when these drugs were injected within the session. Evidently dopaminergic neuronal systems are important in the maintenance of normal spatial working memory.

  12. Antagonistic functions of two stardust isoforms in Drosophila photoreceptor cells. (United States)

    Bulgakova, Natalia A; Rentsch, Michaela; Knust, Elisabeth


    Membrane-associated guanylate kinases (MAGUKs) are scaffolding proteins that organize supramolecular protein complexes, thereby partitioning the plasma membrane into spatially and functionally distinct subdomains. Their modular organization is ideally suited to organize protein complexes with cell type- or stage-specific composition, or both. Often more than one MAGUK isoform is expressed by one gene in the same cell, yet very little is known about their individual in vivo functions. Here, we show that two isoforms of Drosophila stardust, Sdt-H (formerly called Sdt-B2) and Sdt-D, which differ in their N terminus, are expressed in adult photoreceptors. Both isoforms associate with Crumbs and PATJ, constituents of the conserved Crumbs-Stardust complex. However, they form distinct complexes, localized at the stalk, a restricted region of the apical plasma membrane. Strikingly, Sdt-H and Sdt-D have antagonistic functions. While Sdt-H overexpression increases stalk membrane length and prevents light-dependent retinal degeneration, Sdt-D overexpression reduces stalk length and enhances light-dependent retinal degeneration. These results suggest that a fine-tuned balance of different Crumbs complexes regulates photoreceptor homeostasis.

  13. Histamine and histamine receptor antagonists in cancer biology. (United States)

    Blaya, Bruno; Nicolau-Galmés, Francesca; Jangi, Shawkat M; Ortega-Martínez, Idoia; Alonso-Tejerina, Erika; Burgos-Bretones, Juan; Pérez-Yarza, Gorka; Asumendi, Aintzane; Boyano, María D


    Histamine has been demonstrated to be involved in cell proliferation, embryonic development, and tumour growth. These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3, and H4) that differ in their tissue expression patterns and functions. Although many in vitro and in vivo studies of the modulatory roles of histamine in tumour development and metastasis have been reported, the effect of histamine in the progression of some types of tumours remains controversial; however, recent findings on the role of histamine in the immune system have shed new light on this question. This review focuses on the recent advances in understanding the roles of histamine and its receptors in tumour biology. We report our recent observations of the anti-tumoural effect of H1 histamine antagonists on experimental and human melanomas. We have found that in spite of exogenous histamine stimulated human melanoma cell proliferation, clonogenic ability and migration activity in a dose-dependent manner, the melanoma tumour growth was not modulated by in vivo histamine treatment. On the contrary, terfenadine-treatment in vitro induced melanoma cell death by apoptosis and in vivo terfenadine treatment significantly inhibited tumour growth in murine models. These observations increase our understanding of cancer biology and may inspire novel anticancer therapeutic strategies.

  14. Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

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    A. Rodriguez-Barbero


    Full Text Available To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-β-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.

  15. A new class of NO-donor H3-antagonists. (United States)

    Tosco, Paolo; Bertinaria, Massimo; Di Stilo, Antonella; Marini, Elisabetta; Rolando, Barbara; Sorba, Giovanni; Fruttero, Roberta; Gasco, Alberto


    Synthesis and pharmacological characterisation of a series of compounds obtained by joining, through appropriate spacers, NO-donor furoxan and nitrooxy moieties to the imidazole ring, as well as their structurally related analogues devoid of NO-donating properties are described. All the products were studied for their capacity to interact with H3-receptors present on the guinea-pig ileum and with H2-receptors present on guinea-pig right atrium. The whole series of products displayed reversible H3-antagonistic activity. No activity on H2-receptors was observed when the products were tested at 10 microM concentration. Many of the products were also able to induce partial relaxation when added to the bath after electrical contraction of the guinea-pig ileum during the study of their H3-antagonism. This phenomenon seems to be dependent on various factors; for some compounds it proved to be dependent on NO-mediated sGC activation, for other products it could be due to their weak M3-antagonism. The investigation of the lipophilic-hydrophilic balance of all the products indicates, for many of them, an ideal value to cross the blood-brain barrier.

  16. Interactions of liposomes with dental restorative materials. (United States)

    Nguyen, Sanko; Adamczak, Malgorzata; Hiorth, Marianne; Smistad, Gro; Kopperud, Hilde Molvig


    The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an intermediate initial level of adsorption was found for the pectin coated liposomes, at least 70% high methoxylated-pectin coated liposomes still remained on the conventional resin composite after 60 min flow exposure. This indicates significant contribution of hydrophobic interactions in the prolonged binding of liposomes to resin composites. Based on these results, the present paper suggests two new possible applications of liposomes in the preservation of dental restorations.


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    Robério Anastácio Ferreira


    Full Text Available The direct sowing to tropical forest restoration can be viable when the ecological and silvicultural aspects of species areknown. This work evaluated the effect of breaking seed dormancy and a physical protector on the initial growth of riparian treespecies. The experiment was carried out in a randomized blocks design, in a factorial (2x2, with four blocks and four plots for eachtreatment. The treatment to break seed dormancy used were: immersion in sulphuric acid for 20 minutes and washing in water for 1hour plus soaking for 24 hours for Trema micrantha; immersion in boiling water (100oC with following soaking until refreshing for24 hours to Senna multijuga and Senna macranthera and pre-soaking in water for 2 hours for Solanum granuloso-leprosum. Thephysical protector used was a transparent plastic cup (500mL. The breaking seed dormancy used was efficient in laboratory, exceptfor S. macranthera. In field conditions, it was efficient only for S. multijuga and S. macranthera. The physical protector did notpresented any benefit for the studied tree species regarding seedlings emergence and survival, but it provided significant differencesin height and base diameter for S. multijuga and in height for S. macranthera after three months. After 24 months, T. micranthapresented the highest values for height and basal diameter. S. macranthera presented the height relative growth and T. micrantha thehighest basal diameter. The studied species can be recommended for ecological forest restoration, using direct sowing.

  18. Economic Valuation of Mangrove Restoration in Indonesia

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    Djoko Suprapto


    Full Text Available Mangrove forest is one of the important ecosystems in Karimunjawa, Indonesia. It provides a variety of services both ecologically and economically. However, over-exploited activity, such as timber theft, can be threatening the sustainability of mangrove forest in Karimunjawa now and in the future. Thus, the improved management for mangrove forest is necessary to ensure its sustainability, and it is depending on how people value the conservation from economic and environment consideration. This study examines the factors influencing on the willingness to pay (WTP of respondents for mangrove restoration in Karimunjawa. A total of 502 respondents were interviewed using census method. The method employed is Contingent Valuation Method (CVMSingle Bounded. In CVM, the logit model was defined based on dichotomous choice method to estimate the willingness-to-pay (WTP randomly with three different starting bid value. Findings showed that local awareness of the importance of the values given by mangroves was popularized among local communities. The findings also indicated that respondents who are higher education and have more income were more likely to pay for the mangrove restoration.

  19. Restoration of sea eagle population: A review

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    Josef RAJCHARD


    Full Text Available The population density of the white-tailed sea eagle Haliaeetus albicilla is very low in many countries. In last twenty years, the sea eagle population in South Bohemia was restored by strict protection subsidized by reintroduction. The active help consisted of feeding during winter and building of artificial nests. A new sea eagle breeding population arose in the Třeboň basin area in the early 1980’s. Until this time sea eagles had used former breeding places only for wintering, probably coming from the Baltic. The South Bohemian sea eagle population is very unique: it exists in a densely man-occupied landscape, mainly in areas with very intensive carp breeding in artificial fishponds and was partly artficially (help to wintering birds and reintroduction of some individuals restored. The experience from South Bohemia may have importance for populations of the sea eagle in other areas of its occurence, primarily in the continental conditions [Current Zoology 55 (5:–2009].

  20. Restoration of sea eagle population: A review

    Institute of Scientific and Technical Information of China (English)



    The population density of the white-tailed sea eagle Haliaeetus albicilla is very low in many countries. In last twenty years, the sea eagle population in South Bohemia was restored by strict protection subsidized by reintroduction. The active help consisted of feeding during winter and building of artificial nests. A new sea eagle breeding population arose in the T(r)ebo(n) basin area in the early 1980' s. Until this time sea eagles had used former breeding places only for wintering, probably coming from the Baltic. The South Bohemian sea eagle population is very unique: it exists in a densely man-occupied landscape, mainly in areas with very intensive carp breeding in artificial fishponds and was partly artficially (help to wintering birds and reintroduction of some individuals) restored. The experience from South Bohemia may have importance for populations of the sea eagle in other areas of its occurence, primarily in the continental conditions [Current Zoology 55 (5):315-318,2009].