magnetic resonance spectroscopy

Summary

Summary: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).

Top Publications

  1. Bustillo J, Chen H, Jones T, Lemke N, Abbott C, Qualls C, et al. Increased glutamine in patients undergoing long-term treatment for schizophrenia: a proton magnetic resonance spectroscopy study at 3 T. JAMA Psychiatry. 2014;71:265-72 pubmed publisher
    ..but glutamine, the principal metabolite of synaptic glutamate, can be quantified with proton magnetic resonance spectroscopy (1H-MRS)...
  2. Dean P, Otaduy M, Harris L, McNamara A, Seiss E, Sterr A. Monitoring long-term effects of mild traumatic brain injury with magnetic resonance spectroscopy: a pilot study. Neuroreport. 2013;24:677-81 pubmed publisher
    ..syndrome (PCS) after mild traumatic brain injury (mTBI; >12 months after injury) using magnetic resonance spectroscopy. We hypothesized that those mTBI participants with PCS will have larger metabolic differences than ..
  3. Mora S, Buring J, Ridker P. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014;129:553-61 pubmed publisher
    ..NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events)...
  4. Spur E, Decelle E, Cheng L. Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry. Eur J Nucl Med Mol Imaging. 2013;40 Suppl 1:S60-71 pubmed publisher
    ..At present, PCa metabolomics is mainly studied by magnetic resonance spectroscopy (MRS) and mass spectrometry (MS)...
  5. Communie G, Crepin T, Maurin D, Jensen M, Blackledge M, Ruigrok R. Structure of the tetramerization domain of measles virus phosphoprotein. J Virol. 2013;87:7166-9 pubmed publisher
  6. Hammer S, de Vries A, de Heer P, Bizino M, Wolterbeek R, Rabelink T, et al. Metabolic imaging of human kidney triglyceride content: reproducibility of proton magnetic resonance spectroscopy. PLoS ONE. 2013;8:e62209 pubmed publisher
    To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory motion compensation in vivo...
  7. Jensen P, Karlsson M, Lerche M, Meier S. Real-time DNP NMR observations of acetic acid uptake, intracellular acidification, and of consequences for glycolysis and alcoholic fermentation in yeast. Chemistry. 2013;19:13288-93 pubmed publisher
    ..Herein, dynamic nuclear polarization (DNP) NMR is used to observe acetate influx, ensuing intracellular acidification and the metabolic consequences on alcoholic fermentation and glycolysis in living cells...
  8. Jansen D, Zerbi V, Janssen C, Dederen P, Mutsaers M, Hafkemeijer A, et al. A longitudinal study of cognition, proton MR spectroscopy and synaptic and neuronal pathology in aging wild-type and A?PPswe-PS1dE9 mice. PLoS ONE. 2013;8:e63643 pubmed publisher
    Proton magnetic resonance spectroscopy ((1)H MRS) is a valuable tool in Alzheimer's disease research, investigating the functional integrity of the brain...
  9. Iorio E, Ricci A, Pisanu M, Bagnoli M, Podo F, Canevari S. Choline metabolic profiling by magnetic resonance spectroscopy. Methods Mol Biol. 2013;1049:255-70 pubmed publisher
    ..High-resolution multinuclear magnetic resonance spectroscopy (MRS) provides noninvasive means of monitoring metabolites that play a central role in several ..

More Information

Publications62

  1. Hingorani D, Gonzalez S, Li J, Pagel M. Sensing lanthanide metal content in biological tissues with magnetic resonance spectroscopy. Sensors (Basel). 2013;13:13732-43 pubmed publisher
    ..Improved sample handling methods are needed to improve measurement accuracy for samples with lower concentrations. ..
  2. Holmes M, Britton R. Total synthesis and structural revision of laurefurenynes A and B. Chemistry. 2013;19:12649-52 pubmed publisher
    ..Analysis of incongruities between the (1) H NMR spectra of synthetic and natural material led to a configurational reassignment for the natural product, which was also confirmed by total synthesis...
  3. Bowen S, Ardenkjaer Larsen J. Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization. J Magn Reson. 2013;236:26-30 pubmed publisher
  4. Targosz Gajniak M, Siuda J, Wicher M, Banasik T, Bujak M, Auguściak Duma A, et al. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci. 2013;335:58-63 pubmed publisher
    Proton magnetic resonance spectroscopy ((1)H-MRS) is one of the imaging techniques that could be potentially useful for identification of patients with mild cognitive impairment (MCI) who are at increased risk of developing dementia...
  5. Zhang Y, Chen X, Wen G, Wu G, Zhang X. Proton magnetic resonance spectroscopy ((1)H-MRS) reveals geniculocalcarine and striate area degeneration in primary glaucoma. PLoS ONE. 2013;8:e73197 pubmed publisher
    ..changed in the geniculocalcarine (GCT) and the striate area of occipital lobe by proton magnetic resonance spectroscopy ((1)H-MRS), suggesting neurodegeneration of the central visual pathway in primary glaucoma...
  6. Tumati S, Martens S, Aleman A. Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis. Neurosci Biobehav Rev. 2013;37:2571-86 pubmed publisher
    Research using proton magnetic resonance spectroscopy (MRS) can potentially elucidate metabolite changes representing early degeneration in Mild Cognitive Impairment (MCI), an early stage of dementia...
  7. Chitty K, Lagopoulos J, Lee R, Hickie I, Hermens D. A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder. Eur Neuropsychopharmacol. 2013;23:1348-63 pubmed publisher
    ..Studies utilizing proton-magnetic resonance spectroscopy ((1)H-MRS) have reported increased levels of combined glutamate and glutamine ("Glx"), ..
  8. Sahin N, Melhem E, Wang S, Krejza J, Poptani H, Chawla S, et al. Advanced MR imaging techniques in the evaluation of nonenhancing gliomas: perfusion-weighted imaging compared with proton magnetic resonance spectroscopy and tumor grade. Neuroradiol J. 2013;26:531-41 pubmed
    ..MR imaging techniques, including T2*-dynamic susceptibility contrast PWI (DSC-PWI) and proton magnetic resonance spectroscopy ((1)HMRS) in the evaluation of NE gliomas...
  9. Chen H, Hilty C. Hyperpolarized Hadamard spectroscopy using flow NMR. Anal Chem. 2013;85:7385-90 pubmed publisher
    ..In a broader sense, the multiscan NMR as described here is amenable to various correlation NMR experiments, and increases the versatility of D-DNP in small-molecule characterization. ..
  10. Tandon N, Bolo N, Sanghavi K, Mathew I, Francis A, Stanley J, et al. Brain metabolite alterations in young adults at familial high risk for schizophrenia using proton magnetic resonance spectroscopy. Schizophr Res. 2013;148:59-66 pubmed publisher
    Proton magnetic resonance spectroscopy ((1)H MRS) enables in-vivo measurement of several relevant brain metabolites and has provided evidence of a range of neurochemical abnormalities in schizophrenia, especially in glutamate and N-..
  11. Cabella C, Karlsson M, Canapè C, Catanzaro G, Colombo Serra S, Miragoli L, et al. In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-(13)C]glutamine. J Magn Reson. 2013;232:45-52 pubmed publisher
    ..These examples of [5-(13)C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid. ..
  12. Mustafi S, Chen H, Li H, LeMaster D, HERNANDEZ G. Analysing the visible conformational substates of the FK506-binding protein FKBP12. Biochem J. 2013;453:371-80 pubmed publisher
    ..The K44V mutation selectively reduces the line-broadening in the 40's loop, verifying that at least three distinct conformational transitions underlie the line-broadening processes of FKBP12. ..
  13. Hospenthal M, Freund S, Komander D. Assembly, analysis and architecture of atypical ubiquitin chains. Nat Struct Mol Biol. 2013;20:555-65 pubmed publisher
    ..Interactions via the Ile36 patch can displace Leu8 from the Ile44 patch, leading to marked structural perturbations of Ub. ..
  14. Harris T, Degani H, Frydman L. Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell cultures. NMR Biomed. 2013;26:1831-43 pubmed publisher
  15. Williamson M. Using chemical shift perturbation to characterise ligand binding. Prog Nucl Magn Reson Spectrosc. 2013;73:1-16 pubmed publisher
    ..By use of quantitative calculations of ligand-induced chemical shift changes, it is becoming possible to determine not just the position but also the orientation of ligands. ..
  16. Hill D, Orton M, Mariotti E, Boult J, Panek R, Jafar M, et al. Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic resonance spectroscopy data. PLoS ONE. 2013;8:e71996 pubmed publisher
  17. Kantarci K. Magnetic resonance spectroscopy in common dementias. Neuroimaging Clin N Am. 2013;23:393-406 pubmed publisher
    ..Proton magnetic resonance spectroscopy ((1)H MRS) is sensitive to the pathophysiologic processes associated with the risk of dementia in ..
  18. Millerioux Y, Ebikeme C, Biran M, Morand P, Bouyssou G, Vincent I, et al. The threonine degradation pathway of the Trypanosoma brucei procyclic form: the main carbon source for lipid biosynthesis is under metabolic control. Mol Microbiol. 2013;90:114-29 pubmed publisher
    ..We conclude that TDH expression is under control and can be downregulated in response to metabolic perturbations, such as in the PEPCK mutant in which the glycolytic metabolic flux was redirected towards acetate production. ..
  19. Ratai E, Zhang Z, Snyder B, Boxerman J, Safriel Y, McKinstry R, et al. Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677. Neuro Oncol. 2013;15:936-44 pubmed publisher
    ..Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment. ..
  20. Kotecha M, Klatt D, Magin R. Monitoring cartilage tissue engineering using magnetic resonance spectroscopy, imaging, and elastography. Tissue Eng Part B Rev. 2013;19:470-84 pubmed publisher
    ..b>Magnetic resonance spectroscopy can identify the changing molecular structure and alternations in the conformation of major ..
  21. Freed R, Hollenhorst C, Weiduschat N, Mao X, Kang G, Shungu D, et al. A pilot study of cortical glutathione in youth with depression. Psychiatry Res Neuroimaging. 2017;270:54-60 pubmed publisher
    This study used proton magnetic resonance spectroscopy (1H MRS) to measure in vivo brain glutathione (GSH) in adolescents with major depressive disorder (MDD), and explored the relationship between GSH and illness severity and ..
  22. Song Z, Pan J, Xie L, Gong G, Han S, Zhang W, et al. Expression, Purification, and Activity of ActhiS, a Thiazole Biosynthesis Enzyme from Acremonium chrysogenum. Biochemistry (Mosc). 2017;82:852-860 pubmed publisher
    ..These observations confirm that ActhiS is a thiazole biosynthesis enzyme in A. chrysogenum, and it serves as a sulfur source for the thiazole moiety. ..
  23. Chou H, Pathmasiri W, Deese Spruill J, Sumner S, Buchwalter D. Metabolomics reveal physiological changes in mayfly larvae (Neocloeon triangulifer) at ecological upper thermal limits. J Insect Physiol. 2017;101:107-112 pubmed publisher
    ..Limited evidence of anaerobic metabolism was observed in the heat treated larvae at 30°C, a temperature that is chronically lethal to larvae. ..
  24. Chen W, Lu S, Ou J, Wang G, Zu Y, Chen F, et al. Metabonomic characteristics and biomarker research of human lung cancer tissues by HR1H NMR spectroscopy. Cancer Biomark. 2016;16:653-64 pubmed publisher
    ..MVDA in combination with1H NMR spectra highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for future lung cancer biomarker research or identification. ..
  25. Tamrazi B, Shiroishi M, Liu C. Advanced Imaging of Intracranial Meningiomas. Neurosurg Clin N Am. 2016;27:137-43 pubmed publisher
    ..Although no advanced imaging technique has been able to definitively subclassify meningiomas, current results are encouraging and may be helpful in surgical planning. ..
  26. Baeken C, Lefaucheur J, Van Schuerbeek P. The impact of accelerated high frequency rTMS on brain neurochemicals in treatment-resistant depression: Insights from 1H MR spectroscopy. Clin Neurophysiol. 2017;128:1664-1672 pubmed publisher
    ..Although more statistical power is needed for reaching firm conclusions, aHF-rTMS does not appear to negatively influence neural integrity. ..
  27. Söder J, Hagman R, Dicksved J, Lindåse S, Malmlöf K, Agback P, et al. The urine metabolome differs between lean and overweight Labrador Retriever dogs during a feed-challenge. PLoS ONE. 2017;12:e0180086 pubmed publisher
    ..The lowered urinary taurine concentration in overweight dogs could indicate alterations in lipid metabolism and merits further investigation. ..
  28. Son S, Ko S, Jang M, Kim J, Kim G, Lee J, et al. New Cyclic Lipopeptides of the Iturin Class Produced by Saltern-Derived Bacillus sp. KCB14S006. Mar Drugs. 2016;14: pubmed publisher
    ..Moreover, in an in vitro enzymatic assay, compound 4 showed a significant inhibitory activity against indoleamine 2,3-dioxygenase. ..
  29. Doroudgar M, Lafleur M. Ceramide-C16 Is a Versatile Modulator of Phosphatidylethanolamine Polymorphism. Biophys J. 2017;112:2357-2366 pubmed publisher
    ..scanning calorimetry, and sequential 2H and 31P solid-state nuclear magnetic resonance spectroscopy. A partial phase diagram is proposed...
  30. Lokeshwari D, Rekha N, Srinivasan B, Vivek H, Kariyappa A. Design, synthesis of novel furan appended benzothiazepine derivatives and in vitro biological evaluation as potent VRV-PL-8a and H+/K+ ATPase inhibitors. Bioorg Med Chem Lett. 2017;27:3048-3054 pubmed publisher
    ..This finding presents a promising series of lead molecules that can serve as prototypes for the treatment of inflammatory related disorder that can mitigate the ulcer inducing side effect shown by other NSAIDs. ..
  31. Kuwabara T, Abe K. Synthesis and unusual response to potassium of bipyridinium-benzocrown ether conjugate. Bioorg Med Chem Lett. 2017;27:2083-2086 pubmed publisher
    ..An unusual CT response to K+ for 1 was observed and could be applicable for K+ sensing. ..
  32. Hu K, Sun C, Yu M, Li W, Lin H, Guo J, et al. Dual In-Tether Chiral Centers Modulate Peptide Helicity. Bioconjug Chem. 2017;28:1537-1543 pubmed publisher
    ..This strategy provides an on-tether modification site that does not interrupt the secondary structure of the peptide...
  33. Sperlazza M, Bilinovich S, Sinanan L, Javier F, Williams D. Structural Basis of MeCP2 Distribution on Non-CpG Methylated and Hydroxymethylated DNA. J Mol Biol. 2017;429:1581-1594 pubmed publisher
    ..Based on these findings, we suggest that MeCP2 recognition of methylated/hydroxymethylated CpA dinucleotides functions as an epigenetic switch redistributing MeCP2 among mCG and mCA loci. ..
  34. Ma L, Wang P, Wang J, Tong X, Shan W, Zhang H, et al. New Eudesmane Sesquiterpenoids from Salvia plebeia R. Br. Chem Biodivers. 2017;14: pubmed publisher
    ..Salplebeone A was an eudesmane lactone, while salplebeones B and C were rare eudesmane sesquiterpenoids, containing 12,8-lactam groups. Antiproliferative activities of salplebeones A - C to myeloid leukemia cell lines were evaluated. ..
  35. Ma Q, Han L, Mu Y, Guan P, Lei H, Wang Z, et al. New Iridoids from Scrophularia ningpoensis. Chem Pharm Bull (Tokyo). 2017;65:869-873 pubmed publisher
    ..Compound 11 exhibited significant inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. ..
  36. Martínez Cifuentes M, Cardona W, Saitz C, Weiss López B, Araya Maturana R. A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding. Molecules. 2017;22: pubmed publisher
    ..Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules. ..
  37. Neira J, Florencio F, Muro Pastor M. The isolated, twenty-three-residue-long, N-terminal region of the glutamine synthetase inactivating factor binds to its target. Biophys Chem. 2017;228:1-9 pubmed publisher
    ..IF7pep did not inactivate GS, suggesting that there were other IF7 regions important to carry out the inactivating function. Binding of IF7pep to GS was electrostatically-driven and it did not follow a kinetic two-state model. ..
  38. Antcliffe D, Jimenez B, Veselkov K, Holmes E, Gordon A. Metabolic Profiling in Patients with Pneumonia on Intensive Care. EBioMedicine. 2017;18:244-253 pubmed publisher
    ..Metabolic profiling shows promise to aid in the diagnosis of pneumonia in ventilated patients and may allow a more timely diagnosis and better use of antibiotics. ..
  39. Pankow J, Kim K, McWhirter K, Luo W, Escobedo J, Strongin R, et al. Benzene formation in electronic cigarettes. PLoS ONE. 2017;12:e0173055 pubmed publisher
    ..S. For non-smokers, chronically repeated exposure to benzene from e-cigarettes at levels such as 100 or higher ?g/m3 will not be of negligible risk. ..
  40. Spengler N, While P, Meissner M, Wallrabe U, Korvink J. Magnetic Lenz lenses improve the limit-of-detection in nuclear magnetic resonance. PLoS ONE. 2017;12:e0182779 pubmed publisher
    ..For the first time we experimentally demonstrate the use of Lenz lenses in magnetic resonance and provide a compact mathematical description of the working principle. Through simulations we show that optimal arrangements can be found. ..
  41. Vazquez L, E Lima L, Almeida M. Comprehensive structural analysis of designed incomplete polypeptide chains of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus. PLoS ONE. 2017;12:e0182132 pubmed publisher
  42. Xu W, Hou X, Yang K, Cao F, Yang R, Wang C, et al. Nigrodiquinone A, a Hydroanthraquinone Dimer Containing a Rare C-9-C-7' Linkage from a Zoanthid-Derived Nigrospora sp. Fungus. Mar Drugs. 2016;14: pubmed publisher
    ..Compound 4 displayed mild antiviral activity against coxsackie virus (Cox-B3) with the IC50 value of 93.7 ?M, and 5 showed an IC50 value of 74.0 ?M against respiratory syncytial virus (RSV). ..
  43. Hemdane S, Jacobs P, Bosmans G, Verspreet J, Delcour J, Courtin C. Study on the effects of wheat bran incorporation on water mobility and biopolymer behavior during bread making and storage using time-domain 1H NMR relaxometry. Food Chem. 2017;236:76-86 pubmed publisher
    ..Textural quality during storage was less affected for coarse or ground bran-rich bread compared to wheat flour bread, which could be principally attributed to retardation of amylopectin retrogradation in the presence of bran. ..
  44. Wu H, Dachet F, Ghoddoussi F, Bagla S, Fuerst D, Stanley J, et al. Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy. Epilepsia. 2017;58:1626-1636 pubmed publisher
    ..of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis...
  45. Tolbert M, Morgan C, Pollum M, Crespo Hernandez C, Li M, Brewer G, et al. HnRNP A1 Alters the Structure of a Conserved Enterovirus IRES Domain to Stimulate Viral Translation. J Mol Biol. 2017;429:2841-2858 pubmed publisher
    ..Thus, this work provides key details into how an EV71 IRES structure adapts to hijack a cellular protein, and it suggests that the SLII domain is a potential target for antiviral therapy. ..
  46. Do N, Chung W, Truong T, Heddi B, Phan A. G-quadruplex structure of an anti-proliferative DNA sequence. Nucleic Acids Res. 2017;45:7487-7493 pubmed publisher
    ..The structure of the anti-proliferative DNA sequence AT11 will allow greater understanding on the G-quadruplex folding principles and aid in structural optimization of anti-proliferative oligonucleotides. ..
  47. Aksamija A, Polidori A, Plasson R, Dangles O, Tomao V. The inclusion complex of rosmarinic acid into beta-cyclodextrin: A thermodynamic and structural analysis by NMR and capillary electrophoresis. Food Chem. 2016;208:258-63 pubmed publisher
    ..In conclusion, RA, an efficient phenolic antioxidant from rosemary with a marketing authorization, spontaneously forms a relatively stable inclusion complex with CD in water. ..
  48. Hajirezaee S, Mirvaghefi A, Farahmand H, Agh N. NMR-based metabolomic study on the toxicological effects of pesticide, diazinon on adaptation to sea water by endangered Persian sturgeon, Acipenser persicus fingerlings. Chemosphere. 2017;185:213-226 pubmed publisher
    ..9 mg L-1 diazinon treatment) elevated significantly after 24 h acclimation in BW (P < 0.05). Our results may help to understand the effects of pesticides on fish osmoregulation from a metabolic approach. ..
  49. Kamio M, Nagakura Y, Yano H. The Molting Biomarker Molecule Exists as 2-Acetamido-2-deoxy-gluconic Acid in Urine of Blue Crabs and Helmet Crabs. Chem Biodivers. 2017;14: pubmed publisher
    ..6 within 24 h, which is identical to the state in urine with or without phosphate buffer. Thus, we conclude that the molting biomarker sensed by male crabs is 3. ..
  50. Nasta V, Giachetti A, Ciofi Baffoni S, Banci L. Structural insights into the molecular function of human [2Fe-2S] BOLA1-GRX5 and [2Fe-2S] BOLA3-GRX5 complexes. Biochim Biophys Acta Gen Subj. 2017;1861:2119-2131 pubmed publisher
    ..All these observed differences provide the first indications discriminating the molecular function of the two [2Fe-2S] heterocomplexes. ..
  51. Popolin C, Reis J, Becceneri A, Graminha A, Almeida M, Corrêa R, et al. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells. PLoS ONE. 2017;12:e0183275 pubmed publisher
    ..Complex (4) should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment. ..
  52. Greene J, Louis J, Korostynska O, Mason A. State-of-the-Art Methods for Skeletal Muscle Glycogen Analysis in Athletes-The Need for Novel Non-Invasive Techniques. Biosensors (Basel). 2017;7: pubmed publisher
    ..These include the gold standard muscle biopsy, histochemical analysis, magnetic resonance spectroscopy, and musculoskeletal high frequency ultrasound, as well as pursuing future application of ..
  53. Zhang X, Wiklund P, Wu N, Yang Y, Zhuang H, Cheng S. Association of leisure time physical activity and NMR-detected circulating amino acids in peripubertal girls: A 7.5-year longitudinal study. Sci Rep. 2017;7:14026 pubmed publisher
    ..2 years) to early adulthood (mean age 18.2 years). Circulating amino acids were assessed by nuclear magnetic resonance spectroscopy. LTPA was assessed by self-administered questionnaire...