The Experts below are selected from a list of 3039 Experts worldwide ranked by ideXlab platform
Gary B Evans - One of the best experts on this subject based on the ideXlab platform.
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neutron structures of the helicobacter pylori 5 methylthioadenosine nucleosidase highlight proton sharing and protonation states
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Michael T Banco, Gary B Evans, Vidhi Mishra, Andreas Ostermann, Tobias E Schrader, Andrey Kovalevsky, Donald R RonningAbstract:MTAN (5′-methylthioadenosine nucleosidase) catalyzes the hydrolysis of the N-ribosidic bond of a variety of adenosine-containing metabolites. The Helicobacter pylori MTAN (HpMTAN) hydrolyzes 6-amino-6-deoxyfutalosine in the second step of the alternative menaquinone biosynthetic pathway. Substrate binding of the adenine moiety is mediated almost exclusively by hydrogen bonds, and the proposed catalytic mechanism requires multiple proton-transfer events. Of particular interest is the protonation state of residue D198, which possesses a pKa above 8 and functions as a general acid to initiate the enzymatic reaction. In this study we present three corefined neutron/X-ray crystal structures of wild-type HpMTAN cocrystallized with S-adenosylhomocysteine (SAH), Formycin A (FMA), and (3R,4S)-4-(4-Chlorophenylthiomethyl)-1-[(9-deaza-adenin-9-yl)methyl]-3-hydroxypyrrolidine (p-ClPh-Thio-DADMe-Imma) as well as one neutron/X-ray crystal structure of an inactive variant (HpMTAN-D198N) cocrystallized with SAH. These results support a mechanism of D198 pKa elevation through the unexpected sharing of a proton with atom N7 of the adenine moiety possessing unconventional hydrogen-bond geometry. Additionally, the neutron structures also highlight active site features that promote the stabilization of the transition state and slight variations in these interactions that result in 100-fold difference in binding affinities between the DADMe-Imma and Imma analogs.
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RESEARCH ARTICLE Immucillins Impair Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis Multiplication In Vitro
2016Co-Authors: Elisangela Oliveira De Freitas, Gary B Evans, Peter C Tyler, Dirlei Nico, Keith Clinch, Vern L Schramm, Rong Guan, José Roberto Meyer-fern, Clarisa B. Palatnik-de-sousaAbstract:Chemotherapy against visceral leishmaniasis is associated with high toxicity and drug resis-tance. Leishmania parasites are purine auxotrophs that obtain their purines from exogenous sources. Nucleoside hydrolases release purines from nucleosides and are drug targets for anti-leishmanial drugs, absent in mammal cells. We investigated the substrate specificity of the Leishmania (L.) donovani recombinant nucleoside hydrolase NH36 and the inhibitory ef-fect of the immucillins IA (Imma), DIA (DADMe-Imma), DIH (DADMe-ImmH), SMIH (SerMe-ImmH), IH (ImmH), DIG (DADMe-ImmG), SMIG (SerMe-ImmG) and SMIA (SerME-Imma) on its enzymatic activity. The inhibitory effects of immucillins on the in vitromultipli-cation of L. (L.) infantum chagasi and L. (L.) amazonensis promastigotes were determined using 0.05–500 μM and, when needed, 0.01–50 nM of each drug. The inhibition on multipli-cation of L. (L.) infantum chagasi intracellular amastigotes in vitro was assayed using 0.5, 1, 5 and 10 μM of IA, IH and SMIH. The NH36 shows specificity for inosine, guanosine, adeno-sine, uridine and cytidine with preference for adenosine and inosine. IA, IH, DIH, DIG, SMIH and SMIG immucillins inhibited L. (L.) infantum chagasi and L. (L.) amazonensis promasti
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immucillins Imma and immh are effective and non toxic in the treatment of experimental visceral leishmaniasis
PLOS Neglected Tropical Diseases, 2015Co-Authors: Elisangela Oliveira De Freitas, Gary B Evans, Peter C Tyler, Dirlei Nico, Marcus Vinicius Alvessilva, Alexandre Morrot, Keith Clinch, Vern L Schramm, Clarisa B PalatnikdesousaAbstract:Background Immucillins Imma (IA), ImmH (IH) and SerMe-ImmH (SMIH) are synthetic deazapurine nucleoside analogues that inhibit Leishmania (L.) infantum chagasi and Leishmania (L.) amazonensis multiplication in vitro without macrophage toxicity. Immucillins are compared to the Glucantime standard drug in the chemotherapy of Leishmania (L.) infantum chagasi infection in mice and hamsters. These agents are tested for toxicity and immune system response. Methodology/Principal Findings BALB/c mice were infected with 107 amastigotes, treated with IA, IH, SMIH or Glucantime (2.5mg/kg/day) and monitored for clinical variables, parasite load, antibody levels and splenocyte IFN-γ, TNF-α, and IL-10 expression. Cytokines and CD4+, CD8+ and CD19+ lymphocyte frequencies were assessed in uninfected controls and in response to immucillins. Urea, creatinine, GOT and GPT levels were monitored in sera. Anti-Leishmania-specific IgG1 antibodies (anti-NH36) increased in untreated animals. IgG2a response, high levels of IFN-γ, TNF-α and lower levels of IL-10 were detected in mice treated with the immucillins and Glucantime. Immucillins permitted normal weight gain, prevented hepato-splenomegaly and cleared the parasite infection (85–89%) without renal and hepatic toxicity. Immucillins promoted 35% lower secretion of IFN-γ in uninfected controls than in infected mice. IA and IH increased the CD4+ T and CD19+ B cell frequencies. SMIH increased only the proportion of CD-19 B cells. IA and IH also cured infected hamsters with lower toxicity than Glucantime. Conclusions/Significance Immucillins IA, IH and SMIH were effective in treating leishmaniasis in mice. In hamsters, IA and IH were also effective. The highest therapeutic efficacy was obtained with IA, possibly due to its induction of a TH1 immune response. Low immucillin doses were required and showed no toxicity. Our results disclose the potential use of IA and IH in the therapy of visceral leishmaniasis.
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inhibition and structure of trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues
Biochemistry, 2007Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Corin Wing, Mahmoud Ghanem, Hua Deng, Peng Wu, Arti Gupta, Steven C AlmoAbstract:Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (Imma) and DADMe-Immucillin-A (DADMe-Imma) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. Imma demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-Imma resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300. The tight binding of DADMe-Imma supports a late SN1 transition state. Despite...
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inhibition and structure of trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues
Biochemistry, 2007Co-Authors: Agnes Rinaldomatthis, Gary B Evans, Richard H Furneaux, Peter C Tyler, Steven C Almo, Corin Wing, Mahmoud Ghanem, Hua Deng, Arti Gupta, Ching C WangAbstract:Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (Imma) and DADMe-Immucillin-A (DADMe-Imma) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. Imma demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-Imma resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300. The tight binding of DADMe-Imma supports a late SN1 transition state. Despite their tight binding to TvPNP, Imma and DADMe-Imma are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP x Imma x PO4 and TvPNP x DADMe-Imma x PO4 ternary complexes differ from previous structures with substrate analogues. The tight binding with DADMe-Imma is in part due to a 2.7 A ionic interaction between a PO4 oxygen and the N1' cation of the hydroxypyrrolidine and is weaker in the TvPNP x Imma x PO4 structure at 3.5 A. However, the TvPNP x Imma x PO4 structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP x DADMe-Imma x PO4. These structures explain why DADMe-Imma binds tighter than Imma. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an unfavorable leaving-group interaction.
Kazunari Domen - One of the best experts on this subject based on the ideXlab platform.
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Imma perovskite type oxynitride latio2n structure and electron density
ChemInform, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:A highly crystalline and high-purity LaTiO2N sample is synthesized from the corresponding oxides by ammonolysis (1.
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Imma perovskite type oxynitride latio2n structure and electron density
Chemical Communications, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:We present the first example of Imma perovskite-type oxynitride. LaTiO2N was found to have an Imma perovskite-type structure with a0b−b− tilt system. The Ti–(O,N) covalent bonding and existence of N atoms are responsible for the reduced band gap of LaTiO2N photocatalyst.
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Imma perovskite type oxynitride latio n structure and electron density
Chemical Communications, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:We present the first example of Imma perovskite-type oxynitride. LaTiO₂N was found to have an Imma perovskite-type structure with a⁰b⁻b⁻ tilt system. The Ti–(O,N) covalent bonding and existence of N atoms are responsible for the reduced band gap of LaTiO₂N photocatalyst.
Lars Hanson - One of the best experts on this subject based on the ideXlab platform.
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ips Imma for designing human robot collaboration workstations
5th International Digital Human Modeling Symposium Bonn Germany June 26-28 2017, 2017Co-Authors: Pamela Ruiz Castro, Dan Högberg, Nafise Mahdavian, Erik Brolin, Lars HansonAbstract:The global competition has forced manufacturing companies to further increase their productivity. This, together with technology development and changes in regulations, have led to the introduction ...
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creating and shaping the dhm tool Imma for ergonomic product and production design
International Journal of the Digital Human, 2016Co-Authors: Dan Högberg, Lars Hanson, Robert Bohlin, Johan S CarlsonAbstract:The history, status and outlook of the research and development actions associated with the creation of the digital human modelling tool intelligently moving manikins (Imma) are described. The underlying fundamental concepts are described and research and development results so far are illustrated or referred to. Two case studies illustrating use of Imma on industry-based problems are described. The paper also covers reflections on conceptions for prospective DHM tool developments from a general perspective, relating to areas of ergonomics and design methodology, as well as describing some of the plans for further developments and applications of the Imma tool. These may be of assistance when identifying challenges for future research and development of DHM tools that are used in product and production design processes in industry.
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digital test assembly of truck parts with the Imma tool an illustrative case
Work-a Journal of Prevention Assessment & Rehabilitation, 2012Co-Authors: Lars Hanson, Dan Högberg, M SoderholmAbstract:Several digital human modelling (DHM) tools have been developed for simulation and visualisation of human postures and motions. In 2010 the DHM tool Imma (Intelligently Moving Manikins) was introduced as a DHM tool that uses advanced path planning techniques to generate collision free and biomechanically acceptable motions for digital human models (as well as parts) in complex assembly situations. The aim of the paper is to illustrate how the IPS/Imma tool is used at Scania CV AB in a digital test assembly process, and to compare the tool with other DHM tools on the market. The illustrated case of using the Imma tool, here combined with the path planner tool IPS, indicates that the tool is promising. The major strengths of the tool are its user friendly interface, the motion generation algorithms, the batch simulation of manikins and the ergonomics assessment methods that consider time.
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assessment of manikin motions in Imma
Advances in Applied Human Modeling and Simulation, 2012Co-Authors: Erik Bertilsson, Dan Högberg, Ali Keyvani, Lars HansonAbstract:When evaluating human-machine interaction in a virtual environment using Digital human modelling (DHM) it is important to ensure that the predicted motions lie within the range of behavioural diversity for different people within a population. This paper presents a study in which a comparison is made between motions predicted by the DHM tool Imma (Intelligently Moving Manikin) and motions from real humans stored in a motion database. Results show similar motions but the predicted motions were in total statistically significantly different compared to the motions performed by real persons. The differences are most likely due to the balance function and joint constraints that the Imma tool uses for predicting motions. Differences can also be due to other factors, aside of body size, such as age, gender or strength that affects the movement behaviour.
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Imma - Intelligently Moving Manikins : Project Status 2011
2011Co-Authors: Lars Hanson, Robert Bohlin, Dan Högberg, J.s. CarlssonAbstract:The overall rationale and assumption for the research project presented is this paper is that a fast, easy to use, and reliable procedure to predict and validate manual assembly tasks is of major importance in product and production development processes to ensure high and robust product quality and process performance. A basic condition for the research is the belief that tools with such functionality are currently not available for companies to utilise in their development processes. Hence more research and development is needed in the area. This paper describes the status of the project Imma – Intelligently Moving Manikins and discusses coming initiatives. The project status is portrayed by a conceivable simulation task of a digital test assembly of a centre console.
Masatomo Yashima - One of the best experts on this subject based on the ideXlab platform.
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Imma perovskite type oxynitride latio2n structure and electron density
ChemInform, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:A highly crystalline and high-purity LaTiO2N sample is synthesized from the corresponding oxides by ammonolysis (1.
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Imma perovskite type oxynitride latio2n structure and electron density
Chemical Communications, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:We present the first example of Imma perovskite-type oxynitride. LaTiO2N was found to have an Imma perovskite-type structure with a0b−b− tilt system. The Ti–(O,N) covalent bonding and existence of N atoms are responsible for the reduced band gap of LaTiO2N photocatalyst.
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Imma perovskite type oxynitride latio n structure and electron density
Chemical Communications, 2010Co-Authors: Masatomo Yashima, Mio Saito, Hiromi Nakano, Tsuyoshi Takata, Kiyonori Ogisu, Kazunari DomenAbstract:We present the first example of Imma perovskite-type oxynitride. LaTiO₂N was found to have an Imma perovskite-type structure with a⁰b⁻b⁻ tilt system. The Ti–(O,N) covalent bonding and existence of N atoms are responsible for the reduced band gap of LaTiO₂N photocatalyst.
Dan Högberg - One of the best experts on this subject based on the ideXlab platform.
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ips Imma for designing human robot collaboration workstations
5th International Digital Human Modeling Symposium Bonn Germany June 26-28 2017, 2017Co-Authors: Pamela Ruiz Castro, Dan Högberg, Nafise Mahdavian, Erik Brolin, Lars HansonAbstract:The global competition has forced manufacturing companies to further increase their productivity. This, together with technology development and changes in regulations, have led to the introduction ...
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creating and shaping the dhm tool Imma for ergonomic product and production design
International Journal of the Digital Human, 2016Co-Authors: Dan Högberg, Lars Hanson, Robert Bohlin, Johan S CarlsonAbstract:The history, status and outlook of the research and development actions associated with the creation of the digital human modelling tool intelligently moving manikins (Imma) are described. The underlying fundamental concepts are described and research and development results so far are illustrated or referred to. Two case studies illustrating use of Imma on industry-based problems are described. The paper also covers reflections on conceptions for prospective DHM tool developments from a general perspective, relating to areas of ergonomics and design methodology, as well as describing some of the plans for further developments and applications of the Imma tool. These may be of assistance when identifying challenges for future research and development of DHM tools that are used in product and production design processes in industry.
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digital test assembly of truck parts with the Imma tool an illustrative case
Work-a Journal of Prevention Assessment & Rehabilitation, 2012Co-Authors: Lars Hanson, Dan Högberg, M SoderholmAbstract:Several digital human modelling (DHM) tools have been developed for simulation and visualisation of human postures and motions. In 2010 the DHM tool Imma (Intelligently Moving Manikins) was introduced as a DHM tool that uses advanced path planning techniques to generate collision free and biomechanically acceptable motions for digital human models (as well as parts) in complex assembly situations. The aim of the paper is to illustrate how the IPS/Imma tool is used at Scania CV AB in a digital test assembly process, and to compare the tool with other DHM tools on the market. The illustrated case of using the Imma tool, here combined with the path planner tool IPS, indicates that the tool is promising. The major strengths of the tool are its user friendly interface, the motion generation algorithms, the batch simulation of manikins and the ergonomics assessment methods that consider time.
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assessment of manikin motions in Imma
Advances in Applied Human Modeling and Simulation, 2012Co-Authors: Erik Bertilsson, Dan Högberg, Ali Keyvani, Lars HansonAbstract:When evaluating human-machine interaction in a virtual environment using Digital human modelling (DHM) it is important to ensure that the predicted motions lie within the range of behavioural diversity for different people within a population. This paper presents a study in which a comparison is made between motions predicted by the DHM tool Imma (Intelligently Moving Manikin) and motions from real humans stored in a motion database. Results show similar motions but the predicted motions were in total statistically significantly different compared to the motions performed by real persons. The differences are most likely due to the balance function and joint constraints that the Imma tool uses for predicting motions. Differences can also be due to other factors, aside of body size, such as age, gender or strength that affects the movement behaviour.
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Imma - Intelligently Moving Manikins : Project Status 2011
2011Co-Authors: Lars Hanson, Robert Bohlin, Dan Högberg, J.s. CarlssonAbstract:The overall rationale and assumption for the research project presented is this paper is that a fast, easy to use, and reliable procedure to predict and validate manual assembly tasks is of major importance in product and production development processes to ensure high and robust product quality and process performance. A basic condition for the research is the belief that tools with such functionality are currently not available for companies to utilise in their development processes. Hence more research and development is needed in the area. This paper describes the status of the project Imma – Intelligently Moving Manikins and discusses coming initiatives. The project status is portrayed by a conceivable simulation task of a digital test assembly of a centre console.
