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  • 1
    Online Resource
    Online Resource
    Cham :Springer International Publishing :
    Keywords: Pharmacology. ; Bioinformatics. ; Oncology. ; Medicine Philosophy. ; Pharmacology. ; Computational and Systems Biology. ; Oncology. ; Philosophy of Medicine.
    Description / Table of Contents: Chapter 1. Revisiting the concept of human disease (Mariano Bizzarri, Mirko Minini, and Noemi Monti) -- Chapter 2. Dynamical aspects of pharmacokinetic/pharmacodynamics and quantitative systems pharmacology models (Ioannis Loisios-Konstantinidis, Panteleimon D. Mavroudis, Panos Macheras) -- Chapter 3. The efficiency of multi-target drugs: a network approach (Lucas N. Alberca, Alan Talevi) -- Chapter 4. Mining Complex Biomedical Literature for Actionable Knowledge on Rare Diseases (Vinicius M. Alvesa, Stephen J. Capuzzia, Nancy Baker, Eugene N. Muratov, Alexander Trospsha, and Anthony J. Hickey) -- Chapter 5. Big Data, Personalized Medicine and Network Pharmacology: beyond the current paradigms (Alessandro Giuliani and Virginia Todde) -- Chapter 6. Epigenetic Control Using Small Molecules in Cancer (Tomohiro Kozako, Yukihiro Itoh, Shinichiro Honda, Takayoshi Suzuki) -- Chapter 7. Multiscale Modelling of Cancer: Micro-, Meso- and Macro-scales of Growth and Spread (Mark AJ Chaplain) -- Chapter 8. Precision Oncology vs Phenotypic approaches in the management of cancer: a case for the postmitotic state (Armando Aranda-Anzaldo and Myrna A.R. Dent) -- Chapter 9. Migrastatics - anti-metastatic drugs targeting cancer cell invasion (Aneta Gandalovičová , Daniel Rosel , Jan Brábek) -- Chapter 10. Critical steps in Epithelial-Mesenchymal transition as target for cancer treatment (Evgeny V. Denisov, Mohit Kumar Jolly, Vitaly P. Shubin, Alexey S. Tsukanov, Nadezhda V. Cherdyntseva) -- Chapter 11. Targeting the tumor-associated macrophages for ‘normalizing’ cancer (Julia Kzhyshkowska) -- Chapter 12. Tumor Reversion induced by embryo and oocyte extracts (Sara Proietti, Andrea Pensotti and Alessandra Cucina) -- Chapter 13. Trabectedin, a drug acting on both cancer cells and the tumor microenvironment (Paola Allavena, Manuela Liguori, Cristina Belgiovine) -- Chapter 14. Advances in Characterizing Recently-identified Molecular Actions of Melatonin: Clinical Implications (Russel J. Reiter, Ramaswamy Sharma, Sergio A. Rosales-Corral, Ana Coto-Montes, Jose Antonio Boga, Jerry Vriend) -- Chapter 15. Multitarget activities of Inositol and Inositol Hexakisphosphate (Ivana Vucenik) -- Chapter 16. Integration of Phytochemicals and Phytotherapy into Cancer Precision Medicine (Nadire Özenver and Thomas Efferth) -- Chapter 17. Synergistic Effects of Chinese Herbal Medicine and Biological Networks (Deep Jyoti Bhuyan, Saumya Perera1, Kirandeep Kaur, Muhammad A. Alsherbiny, Mitchell Low, Sai-Wang Seto, Chun-Guang Li, Xian Zhou) -- Chapter 18. Medicinal herbs: its therapeutic use in obstetrics and gynaecology (Irene Orbe, Daniel Paz, Leyre Pejenaute, Andrea Puente, Laura Diaz de Alda, Sandra Yague, Iñaki Lete) -- Chapter 19. Overcoming Antibiotic Resistance: New Perspectives (Matteo Bassetti, Elda Righi).
    Abstract: This volume – for pharmacologists, systems biologists, philosophers and historians of medicine – points to investigate new avenues in pharmacology research, by providing a full assessment of the premises underlying a radical shift in the pharmacology paradigm. The pharmaceutical industry is currently facing unparalleled challenges in developing innovative drugs. While drug-developing scientists in the 1990s mostly welcomed the transformation into a target-based approach, two decades of experience shows that this model is failing to boost both drug discovery and efficiency. Selected targets were often not druggable and with poor disease linkage, leading to either high toxicity or poor efficacy. Therefore, a profound rethinking of the current paradigm is needed. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggest that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development, efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets.
    Type of Medium: Online Resource
    Pages: XVI, 483 p. 49 illus., 41 illus. in color. , online resource.
    Edition: 1st ed. 2020.
    ISBN: 9783030328573
    Series Statement: Human Perspectives in Health Sciences and Technology, 2
    DDC: 615
    Language: English
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  • 2
    Call number: MOP 46074 / Mitte
    In: Special publications
    Type of Medium: Monograph available for loan
    Pages: 314 S.
    Series Statement: ESA SP 159
    Location: MOP - must be ordered
    Branch Library: GFZ Library
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European biophysics journal 22 (1993), S. 259-267 
    ISSN: 1432-1017
    Keywords: Myoglobin ; Conformational substates ; Electron paramagnetic resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract High spin FeIII myoglobin samples in solutions with different solvent composition have been investigated at low temperature by Electron Paramagnetic Resonance spectroscopy. The g = 6 line of the spectrum has been analyzed in terms of a distribution of the two crystal field parameters Δ1 and Δ2. By means of the Angular Overlap Method, it has been shown that these distributions entail, in turn, a distribution in the iron-heme displacement along the normal to the heme-plane. The spread in this iron-heme distance, which can be connected with the binding action of the proximal histidine, has been proposed as a quantitative measurement of the structural heterogeneity (conformational substate landscape) displayed by the protein molecules. The results point out, moreover, that the solvent composition can affect the structural heterogeneity of the protein system. In particular, addition of glycerol, ethylene glycol and sucrose yields a significant reduction in the spread of the ironheme displacement, while the presence of ammonium sulfate induces a change in the average position of the iron in the heme-plane. The role played by the solvent in the structure and dynamics of the protein, in connection also with the conformational substate distribution, is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1017
    Keywords: Key words Protein dynamics ; Hydration water ; Glassy dynamics ; Boson peak
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract The low-frequency dynamics of copper azurin has been studied at different temperatures for a dry and deuterium hydrated sample by incoherent neutron scattering and the experimental results have been compared with molecular dynamics (MD) simulations carried out in the same temperature range. Experimental Debye-Waller factors are consistent with a dynamical transition at approximately 200 K which appears partially suppressed in the dry sample. Inelastic and quasielastic scattering indicate that hydration water modulates both vibrational and diffusive motions. The low-temperature experimental dynamical structure factor of the hydrated protein shows an excess of inelastic scattering peaking at about 3 meV and whose position is slightly shifted downwards in the dry sample. Such an excess is reminiscent of the “boson peak” observed in glass-like materials. This vibrational peak is quite well reproduced by MD simulations, although at a lower energy. The experimental quasielastic scattering of the two samples at 300 K shows a two-step relaxation behaviour with similar characteristic times, while the corresponding intensities differ only by a scale factor. Also, MD simulations confirm the two-step diffusive trend, but the slow process seems to be characterized by a decay faster than the experimental one. Comparison with incoherent neutron scattering studies carried out on proteins having different structure indicates that globular proteins display common elastic, quasielastic and inelastic features, with an almost similar hydration dependence, irrespective of their secondary and tertiary structure.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1017
    Keywords: Key words Superoxide dismutase ; Conformational substates ; Electronic paramagnetic resonance ; Solvent effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Native and azide reacted Cu, Zn superoxide dismutase in aqueous and mixed water-glycerol solution have been investigated by EPR spectroscopy at low temperature. An accurate computer simulation, based on a well established theoretical model which has been reformulated for rhombic symmetry, has shown that the EPR spectrum of the copper ion in the native protein shows a significant g and A strain in the parallel region. The strain arises from a distribution of the ligand field strengths onto the metal ion and this could be traced back to the existence of a multiplicity of conformational states in the protein molecule. The strain is reduced in the presence of azide which is known to bind directly to the copper atom and to give rise to a more relaxed configuration corresponding to a square pyramidal geometry in which the apical ligand occupies an elongated position. In both samples, addition of glycerol further reduces the strain, indicating that the solvent is directly coupled to the protein matrix, thereby modulating the structural heterogeneity displayed by the protein molecule.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0550-3213
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Nuclear Physics, Section B 69 (1974), S. 298-306 
    ISSN: 0550-3213
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0550-3213
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0550-3213
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0550-3213
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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