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دکتر محسن شهلایی

 


 
 

Mohsen Shahlaei

Date of Birth: 20/10/1980

Nationality: Iranian

Marital Status: Married

Address: Department of Medicinal Chemistry,

Faculty of Pharmacy, Kermanshah University of Medical Sciences http://www.kmui.ac.ir

E-mail: mohsenshahlaei@yahoo.com

 

Education:

BSc.: Department of chemistry, Faculty of Science, Razi University, Kermanshah, IRAN (2004).

MSc.: Department of chemistry, Faculty of Science, Razi University, Kermanshah, IRAN (2007).

Ph.D. Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IRAN (2012).

Academic Appointment:

2012- present  Assistant Professor, Department of Medicinal Chemistry, Kermanshah University of Medical Sciences

Executive Positions and Appointments

  1. Executive manager of the Journal of Reports in Pharmaceutical Sciences, since 2012.
  2. Information Technology (IT) Manager, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Iran, since 2012.

 

 

Honors:

  1. Distinguished researcher in pharmaceutical sciences, faculty of pharmacy, Isfahan University of Medical Sciences (2009).
  2. Distinguished researcher in Shamsipur convention in medicinal sciences category (2010).
  3. Membership in Talented Assembly of Kermanshah.
  4. Membership in Talented Assembly of Isfahan.
  5. Distinguished researcher in pharmaceutical sciences, faculty of pharmacy, Isfahan University of Medical Sciences (2010).
  6. Distinguished Ph. D candidate researcher of Isfahan University of Medical Sciences (2010).
  7. Distinguished student researcher of Kermanshah University of medical sciences (2010).
  8. Distinguished student researcher of Kermanshah University of Medical Sciences (2011).
  9. Distinguished Ph. D candidate researcher of Isfahan University of Medical Sciences (2011).
  10. Distinguished researcher student in the pharmaceutical sciences part of the 17th Razi festival- Tehran (2011).
  11. Distinguished researcher of Kermanshah University of Medical Sciences (2012).
  12. Distinguished researcher of Kermanshah University of Medical Sciences (2013).
  13. Distinguished teacher of Kermanshah University of Medical Sciences (2013).
  14. Distinguished researcher of Kermanshah University of Medical Sciences (2014).

 Published Manuscripts:

  1. Pourhossein, A*, Madani, M,. Shahlaei, M. Evaluation of an ultrasound–assisted digestion method for determination of arsenic and lead in edible citric acid samples by ETAAS. Canad. J. Anal. Scie.  Spec. 54 (2009) 39-44.
  2. Gholivand, MB., Shahlaei, M., Pourhossein, A. New Zn(II)-Selective Potentiometric Sensor Based on 3-Hydroxy-2-Naphthoic Hydrazide. SENSOR LETTERS 7 (2009) 119-125.
  3. Gholivand, MB.*, Pourhossein, A., Shahlaei, M., Determination of Trace amounts of Lead by Adsorptive Cathodic Stripping Voltammetry With L-3-(3,4 Dihydroxyphenyl) Alanine, Collect. Czech. Chem. Commun. 74 (2009) 599–610.
  4. Gholivand, MB.*,  Pourhossein, A.,  Shahlaei, M., Application of Adsorptive Cathodic Stripping Voltammetry for Determination of Trace Amounts of Zinc Using Nalidixic Acid as a Chelating Agent, Chem. Anal. (Warsaw), 54, (2009) 655-666. 
  5. Shahlaei, M., Gholivand, MB.*, Pourhossein, A. Simultaneous Determination of Tyrosine and Histidine by Differential Pulse Cathodic Stripping Voltammetry Using H-point Standard Addition Method in Tap and Seawater, Electroanalysis 21(2009) 2499 – 2502.
  6. Pourhosseina, A., Madani, M., Shahlaei, M., Fakhri, K., Alimohamadi, P., Amiri, M. Ultrasound assisted pseudo-digestion for determination of iron and manganese in citric acid fermentation mediums by electrothermal atomic absorption spectroscopy, Cent. Eur. J. Chem. 7(2009) 382-387.
  7. Shahlaei, M., Gholivand,MB.*, Pourhossein, A. Application of Adsorptive Stripping Voltammetry for Determination of Uranium in the Presence of 3-Hydroxy-2-Naphthoic Hydrazide, Anal. Lett. 42 (2009) 3085-3095.
  8. Sabet, R,  Shahlaei, M., Fassihi, A.  QSAR study of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2 using different chemometrics tools, Recent Advances in Biology, Biophysics, Bioengineering and Computational Chemistry (2009) 119-125.
  9. Shahlaei, M., Fassihi, A.*, Nezami, A. QSAR Study of some 5-methyl/trifluoromethoxy- H-indole-2,3-dione-3-thiosemicarbazone derivatives as antitubercular agents, Research in Pharmaceutical Sciences 4(2009)123-131.
  10. Arkan, E., Shahlaei, M., Pourhossein, A., Fakhri, K., Fassihi, A.*, Validated QSAR Analysis of Some Diaryl Substituted Pyrazoles as CCR2 Inhibitors by Various Linear and Nonlinear Multivariate Chemometrics Methods. Euro. J. Med. Chem. 45 (2010) 3394-3406.
  11. Shahlaei, M.,  Fassihi, A.*, Saghaie, L. Application of PC-ANN and PC-LS-SVM in QSAR of CCR1 antagonist compounds:A comparative study. Euro. J. Med. Chem. 45 (2010) 1572–1582.
  12. Shahlaei, M., Sabet,R., Bahman Ziari, M., Moeinifard, B., Fassihi, A.*, Karbakhsh, R. QSAR study of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2 using LS-SVM and GRNN based on principal components, Euro. J. Med. Chem. 45 (2010) 4499-4508.
  13. Saghaie, L., Shahlaei, M., Madadkar-Sobhani, A., Fassihi, A.* Application of Partial Least Squares and Radial Basis Function Neural Networks in Multivariate Imaging Analysis-Quantitative Structure Activity Relationship: Study of Cyclin Dependent Kinase 4 Inhibitors, J. Mol. Graph. Model, 29 (2010) 518–528.
  14. Shahlaei, M., Fassihi, A,*, Saghaie, L., Shamshirian, D., Sakhi, HR. Comparative Quantitative Structure–Activity Relationship Study of Some 1-Aminocyclopentyl-3- Carboxyamides as CCR2 Inhibitors using Stepwise MLR, FA-MLR, GA-PLS, Med. Chem. Res. 21(2012)100-115.
  15. Saghaie, L., Shahlaei, M.*,  Fassihi, A., Madadkar-Sobhani, A., Gholivand, MB., Pourhossein, A. QSAR analysis for some Diaryl Substituted Pyrazoles as CCR2 Inhibitors by GA-Stepwise MLR, Chem. Biol. Drug Des.  77(2011)75-85.
  16. Ayatollahi, AM., Ghanadian, M*, Afsharypuor, S., Choudhary, MI., Abdella, OM., Mohsen Shahlaei, M., Farzandi, G., Mostafavi, H., Cycloartanes from Euphorbia aellenii Rech. f. with their antiproliferative activity, Iran. J. Pharm. Res. 10 (2011) 105-112
  17. Shahlaei, M., , Madadkar-Sobhani, A.*, Mahnama, K., Fassihi, A.*, Saghaie, L., Mansourian, M. Homology modeling of human CCR5 and analysis of its binding properties through molecular docking and molecular dynamics simulation. Biochim. Biophy. Acta-Biomembrane 1808 (2011) 802–817.
  18. Shahlaei, M., Fassihi, A*. Saghaie, L., Arkan, E., Pourhossein, A. A modeling study of aldehyde inhibitors of human cathepsin K using partial least squares method. Research in Pharmaceutical Sciences 6 (2011) 71-80.
  19. Fassihi, A.*, Shahlaei, M., Moeinifard, B., Sabet, R. QSAR study of anthranilic acid sulfonamides as methionine aminopeptidase-2 inhibitors. In Press, Monatshefte fur Chemie 143 (2011) 189-198.
  20. Shahlaei, M., Madadkar-Sobhani, A., Fassihi, A*. Saghaie, L. Exploring a Model of a Chemokine Receptor/Ligand Complex in an Explicit Membrane Environment by Molecular Dynamics Simulation: The Human CCR1 Receptor. J. Chim. Inform. Model. 51 (2011) 2717-2730.
  21. Gholivand, MB.*, Pourhossein, A., Shahlaei, M., Simultaneous determination of copper and cadmium in environmental water and tea samples by adsorptive stripping voltammetry. Turk. J. Chem. 35 (2011) 839-846.
  22. Shahlaei, M., Fassihi, A*., Saghaie, L., Arkan, E., Madadkar-Sobhani, A., Pourhossein, A. Computational evaluation of some indenopyrazole derivatives as anticancer compounds; application of QSAR and docking methodologies. J. Enz. Inhib. Med. Chem. 28(2013) 16-32.
  23. Moradkhani, S., Ayatollahi, AM., Ghanadian, M., Moin, MR., Razavizadehe, M., Shahlaei, M. Phytochemical analysis and metal-chelation activity of Achillea tenuifolia Lam. Iran. J. Pharm. Res. 11 (2012) 177-183
  24. Shahlaei M., Madadkar-Sobhani, A., Fassihi A., Saghaie, L., Arkan, E. QSAR study of some CCR5 Antagonists as Anti HIV agents using radial basis function neural network and general regression neural network on the basis of Principal Components. In Press, Med. Chem. Res. (2011)
  25. Shahlaei M., Fassihi A.*, Saghaie L., Arkan E., Pourhossein A. A QSAR study of some cyclobutenediones as CCR1 antagonists by artificial neural networks based on principal component analysis, Accepted, DARU 19 (2011) 376-384.
  26. Shahlaei M., Madadkar-Sobhani, A., Saghaie, L., Fassihi A*. Application of an expert system based on genetic algorithm- adaptive neuro-fuzzy interference System (GA-ANFIS) in QSAR of cathepsin K inhibitors. Expert systems with applications 39 (2012) 6182-6191.
  27. Saghaie, L., Sakhi, H., Hassan Sabzyan,H.*, Shahlaei,M., Shamshirian D., Stepwise MLR and PCR QSAR study of the pharmaceutical activities of antimalarial 3-hydroxypyridinone agents using B3LYP/6-311++G** descriptors. In Press, Med. Chem. Res. 22 (2013) 1679-1688
  28. Shahlaie, M.*, Fassihi, A., Pourhossein, A., Arkan, E., Statistically validated QSAR study of some antagonists of the human CCR5 receptor using least square support vector machine based on the genetic algorithm and factor analysis. In Press, Med. Chem. Res. 22 (2013) 1399-1414.
  29. Shahlaei, M., Ghanadian, SM.*, Ayatollahi, AM, Mesaik, MA., Abdalla, OM., Afsharypour, S., Rabbani, M., Molecular modeling, structure activity relationship and immunomodulatary properties of lupeol derivatives,  Med. Chem. Res. 22 (2013) 1795-1803
  30. Shahlaei, M.*, Pourhossein, A., Direct determination of arsenic in potassium citrate tablet using graphite furnace atomic absorption spectrometry, J. Rep. Pharm. Sci, 1(2012) 15-18.
  31. Saghaie, L., Shahlaie, M.*, Fassihi, A. Quantitative structure activities relationships of some 2-mercaptoimidazoles as CCR2 inhibitors using genetic algorithm-artificial neural networks, Research in Pharmaceutical Sciences 8 (2013) 97-112.
  32. Pourhossein, A.*, Shahlaei, M. Direct determination of arsenic in beet sugar molasses using nickel as chemical modifier by electrothermal atomic absorption spectrommetry 60 (2013) J. Chinese Chem. Soc. 241-244.
  33. Shahlaei, M.*, Pourhossein, A. A 2D image based method for modeling some c-Src tyrosine kinase inhibitors Med. Chem. Res 22 (2013) 3012–3025.
  34. Shahlaie, M.*, Fassihi, A. QSAR Analysis of Some 1-(3, 3-diphenylpropyl)-piperidinyl Amides and Ureas as CCR5 Inhibitors Using Genetic Algorithm- Least Square Support Vector Machine, Accepted (2012) Med. Chem. Res.
  35. Shahlaei, M.* Pourhossein, A. Modeling of CCR5 antagonists as anti HIV agents using combined genetic algorithm and adaptive neuro-fuzzy inference system (GA–ANFIS), 22 (2013) Med. Chem. Res. 4423-4436
  36. Maghsoudi, S. Ashrafi, MR.* Shahlaei, M. Ghadami, SA. Ghobadi, S. Mostafaie, A. Khodarahmi, R*.  Comparative Evaluation of Amphotericin B Binding to the Native and  Modified Forms of Rice Lipid-Transfer Protein (LTP1): A Possible Perspective on Improving the Drug Binding Affinity and Specificity, 10 (2013) J. Iran. Chem. Soc. 937-950
  37. Shahlaei, M.* Zare, A., Saghaie, L., Fassihi, A. Prediction of partition coefficient for some 3-hydroxy pyridine-4-one derivatives using combined partial least square regression and genetic algorithm, 9 (2013) Res. Pharm. Sci. 143-153
  38. Shahlaei, M. Pourhossein, A.* Biomass of Aspergillus Niger: Uses and Applications, J. Rep. Pharm. Sci, 2(2013) 67-73.
  39. Shahlaei, M.*, Fassihi, A., Papaleo, E., Pourfarzam, M. Molecular Dynamics Simulation of Chemokine Receptors in the Lipid Bilayer: A Case Study on CCR2.   82 (2013) Chem. Biol. Drug Des. 534-545
  40. Shahlaei, M.* Descriptor selection methods in QSAR studies: a review study. Chemical Reviews 113 (2013) 8093–8103.
  41. Shahlaei, M.*, Nazari, Z. Computational neural network analysis of the affinity of 2-pyridyl-3,5-diaryl pyrroles analogs for the human glucagon receptor using density functional theory 23 (2014) Med. Chem.  Res. 2046-2061
  42. Shahlaei, M., Pourhossein, A.*, Determination of Arsenic in Drinking Water Samples by Electrothermal Atomic Absorption Spectrometry after Preconcentration Using the Biomass of Aspergillus Niger Loaded on Activated Charcoal, 2014 (2014) Journal of Chemistry
  43. Shahlaei, M.*, Nazari, Z. Prediction of Glucagon Receptor Antagonist Activities of Some Substituted Imidazoles Using Combined Radial Basis Function Neural Network and Density Functional Theory, Accepted, (2013) Medicinal Chemistry  Research
  44. Shahlaei, M*, Nowroozi, A, Khodarahmi, R. A combined DFT and QSAR calculations to study substituted biphenyl imidazoles as bombesin receptor subtype-3 agonists, 11, (2014) Letters in Drug Design & Discovery, 665-676
  45. Mohsen Shahlaei, Ehsan Sohrabi, Jaber Emami, Farshid Hassanzadeh, Lotfollah Saghaie* Simultaneous spectrophotometric determination of Amlodipine and Metoprolol by principal component regression multivariate calibration and comparison with HPLC, 2 (2013) J. Rep. Pharm. Sci. 179-189
  46. Shahlaei, M*. Nowroozi, A. Khodarahmi, R. Application of radial basis function neural network and DFT quantum mechanical calculations for the prediction of the activity of 2-biarylethylimidazole derivatives as bombesin receptor subtype-3 (BRS-3) agonists. 23 (2014) Med. Chem.  Res. 3681-3693
  47. Shahlaei, M . Saghaie, L* Prediction of p38 Inhibitory activity of 3,4-Dihydropyrido[3,2-d] pyrimidone derivatives using an expert system based on principal component analysis and least square support vector machine Accepted, (2014) Research in Pharmaceutical Sciences
  48. Shahlaei, M *. Mousavi, A. A 3D Model for Human Melanocortin 4 Receptor Refined with Molecular Dynamics Simulation. 3 (2014) J. Rep. Pharm. Sci. 42-53
  49. Shahlaei, M *. Andisheh, H. Derakhshandeh, K. Sadrjavadi, K. A novel method for simultaneous determination of codeine and acetaminophen in plasma by combination of UV-Vis spectroscopy and artificial neural network, 3 (2014) J. Rep. Pharm. Sci. 141-162
  50. Sadrjavadi, K. Shahlaei , M*. Bahrami, G, Majnooni,  MB. Mohebbi . M Comparison of Correlation Ranking and Eigenvalue Ranking Unfolded Principal Component Regression for Direct Determination of Naproxen in Human Serum using Excitation–Emission Matrix Fluorescence Spectroscopy. 12  (2015) Journal of Iranian Chemical Society, 967-977
  51. Shahlaei, M *. Mousavi, A. A Conformational Analysis Study on the Melanocortin 4 Receptor Using Multiple Molecular Dynamics Simulations 86 (2015) Chem. Biol. Drug. Des. 309-321
  52. Shahlaei, M *. Rahimi, B. AshrafiKoshk, R.  Sadrjavadi, K. Khodarahmi, R Probing of possible olanzapine binding site on Human Serum Albumin: Combination of spectroscopic methods and molecular dynamics simulation, 158 (2015) J. Luminescence 91-98
  53. Shahlaei , M*. Bahrami, G, Abdolmaleki, S. Sadrjavadi, K. Majnooni Application of Unfolded Principal Component Analysis-Radial Basis Function Neural Network for Determination of Celecoxib in Human Serum by Three-Dimensional Excitation–Emission Matrix Fluorescence Spectroscopy. 138 (2015) Spectrochimica acta Part A 675-683
  54. Elham Esmaili, Mohsen Shahlaei*. Analysis of flexibility and stability of Magainin Structure in a Bilayer, Aqueous and Nonaqueous Solutions using Molecular Dynamics Simulations 21 (2015) J. Mol.  Model. 1-15
  55. Moradi, N. AshrafiKoshk, R, Ghobadi, S. Shahlaei, M. Khodarahmi, R* Spectroscopic Study of drug-binding characteristics of unmodified and pNPA-based acetylated human serum albumin: Does esterase activity affect microenvironment of drug binding sites on the protein? 160 (2015) J. Luminescence 351-361
  56. Bahrami, G. Nabiyar, H. Sadrjavadi, K. Shahlaei,*M. A Linear Principal Component Regression and Nonlinear Neural Network Model for Determination of Indomethacin in Plasma Samples Using UV-Vis Spectroscopy and Comparison with HPLC 4(2015)  J. Rep. Pharm. Sci, 82-100
  57. Ahmadi, M. Shahlaei,* M. Quantitative structure–activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods.  10 (2015) Res.  Pharm. Sci. 307-325
  58. Doosti, E. Shahlaei,* M. Armin Madadkar- Sobhani. QSAR Analysis of Some Antagonists for p38 map kinase Using Combination of Principal Component Analysis and Artificial Intelligence. 18 (2015) Combinatorial chemistry & high throughput screening 767-783
  59. Ahmadi, M. Nowroozi, A. Shahlaei, M*. Constructing an atomic-resolution model of human P2X 7 receptor followed by pharmacophore modeling to identify potential inhibitors 61 (2015) J. Molec. Graph. Modell. 243-261
  60. Shahabadi*, N. Moradi Fili, S. Shahlaei, M. Synthesis, characterization and comparative DNA interaction studies of new copper (II) and nickel (II) complexes containing mesalamine drug using molecular modeling and multispectroscopic methods 68 (2015) J. Coord. Chem. 68 3667-3684
  61. Kiani, A.  Almasi, K.  Shokoohinia, Y. Sadrjavadi, K. Nowroozi, A.  Shahlaei,* M. Combined Spectroscopy and Molecular Modeling Studies on the Binding of Galbanic Acid and MMP9 81 (2015) International Journal of Biological Macromolecules 308-315
  62. Shahlaei,* M. Rahimi, B. Nowroozi, A. Ashrafi-Kooshk, MR. Sadrjavadi, K. Khodarahmi, R. Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies 242 (2015) Chemico-biological interactions 235-246
  63. Yalda Shokoohinia, Shayesteh Gheibi, Amir Kiani, Komail Sadrjavadi, Amin Nowroozi, Mohsen Shahlaei*Multi-spectroscopic and molecular modeling investigation of the interactions between prantschimgin and matrix metalloproteinase 9 (MMP9) 31 (2016) Luminescence 587–593
  64. Mehrabi, M. Khodarahmi, R. Shahlaei,* M. Critical Effects on Binding of Epidermal Growth Factor Produced by Amino Acid Substitutions. Accepted, Journal of Biomolecular Structure and Dynamics
  65. Mansouri,* K. Mostafie,* A. Rezazadeh, D. Shahlaei, M.  Modarressi, MH. New function of TSGA10 gene in angiogenesis and tumor metastasis: a response to a challengeable paradox 25 (2016) Human molecular genetics 233-244
  66. Shahlaei,* M. Doosti, E. Virtual screening based on pharmacophore model followed by docking simulation studies in search of potential inhibitors for p38 map kinase. 80 (2016) Biomedicine & Pharmacotherapy 352-372
  67. S Gheibi, S. Shokohinia, Y. Kiani, A. Sadrjavadi, K. Nowroozi, A. Shahlaei,* M. Molecular insight into the Grandivitin-matrix metalloproteinase 9 interactions 162 (2016) Journal of Photochemistry and Photobiology B: Biology 162, 493-499

Teaching History

  1. Teaching of medicinal chemistry I, II and III, Kermanshah University of Medical Sciences, since 2011.
  2. Teaching of instrumental analysis, Kermanshah University of Medical Sciences Since 2011.
  3. Teaching of General chemistry, Kermanshah University of Medical Sciences, since 2013.
  4. Teaching of Physical chemistry, Kermanshah University of Medical Sciences, since 2013.
  5. Several Molecular Modeling workshops

Theses (Supervised or consulted) 

  1. Alireza Zare, Prediction of partition coefficient for some 3-hydroxy pyridine-4-one derivatives using combined partial least square regression and genetic algorithm. Role: Supervisor
  2. Ehsan Sohrabi, Simultaneous spectrophotometric determination of Amlodipine andMetoprolol by principal component regression multivariate calibration and comparison with HPLC. Role: Supervisor
  3. Sajjad Abdolmaleki, Determination of celecoxib by fluorescence spectroscopy and  chemometrics methods and comparison with HPLC method. Role: Supervisor
  4. Mehdi Ahmadi, Homology modeling, pharmacophore modeling and molecular docking study of some P2X7 receptor antagonists. Role: Supervisor
  5. Hadi Andisheh, Simultaneous Spectroscopic Determination of Acetaminophen and Codeine in serum using chemometric methods and comparison with HPLC. Role: Supervisor
  6. Behnoosh Rahimi, Study of interactions of olanzapine and sertraline with human serum albumin using combination of spectroscopic and molecular modeling methods . Role: Supervisor
  7. Elham Esmaili, The study of the interaction of magainin with phospholipid membrane and different solvents (water and methanol) using molecular dynamics simulation. Role: Supervisor
  8. Shayesteh Gheibi, Effects of dihydropyranocoumarins from Ferulago macrocarpaon VEGF, MMP9, MMP2 and study of binding modes using computational methods. Role: Consultant
  9. Hamid Nabiyar, Determination of indomethacin and ibuprofen by fluorescence spectroscopy and chemometrics methods  and comparison with HPLC method. Role: Supervisor
  10. Zohreh Nazari, Homology modeling, Molecular Dynamics Simulation, Docking and QSAR study of some pyrroles and imidazoles based antagonists of human glucagon receptor. Role: Supervisor
  11. Amin Nowroozi, Homology modeling, Molecular Dynamics Simulation, Docking and QSAR study of some biaryl ethyl imidazole based agonists of human bombesin receptor subtype-3. Role: Supervisor
  12. Atefeh Mosavai, Homology modeling, Molecular Dynamics Simulation and Docking of some carboxamide agonists of melanocortin subtype 4 receptor. Role: Supervisor

 

Reviewer of International Journals:

Medicinal Chemistry Research

European Journal of medicinal Chemistry

Research in Pharmaceutical sciences

Current Medicinal Chemistry

Computational and Mathematical Methods in Medicine

Molecular Simulation

Operating System Skills

Windows, Linux

Instrumental Skills:

UV/Visible, Polarogeraph, Spectrofluorimeter, Some Skills in Synthesis of organic compounds

Programming Skills

C++, MATLAB, Shell programming

Software Skills:

HyperChem, Dragon, Gaussian, Gaussview, AutoDock, SPSS, Minitab, Chemoffice, web lab viewer, VMD and Gromacs.