Mohammed Fazel - Academia.edu (original) (raw)

Papers by Mohammed Fazel

One hundred and thirty composite soil samples were collected from Hamedan county, Iran to charact... more One hundred and thirty composite soil samples were collected from Hamedan county, Iran to characterize the spatial distribution and trace the sources of heavy metals including As, Cd, Co, Cr, Cu, Ni, Pb, V, Zn, and Fe. The multivariate gap statistical analysis was used; for interrelation of spatial patterns of pollution, the disjunctive kriging and geoenrichment factor (EF G ) techniques were applied.

Bioconjugate Chemistry, 2009

Solid-phase peptide synthesis has been refined to a stage where efficient preparation of long and... more Solid-phase peptide synthesis has been refined to a stage where efficient preparation of long and complex peptides is now achievable. However, the postsynthesis handling of poorly soluble peptides often remains a significant hindrance to their purification and further use. Several synthetic schemes have been developed for the preparation of such peptides containing modifications to aid their solubility. However, these require the use of complex chemistry or yield non-native sequences. We describe a simple approach based on the use of penta-lysine "tags" that are linked to the C-terminus of the peptide of interest via a base-labile linker. After ready purification of the now freely solubilized peptide, the "tag" is removed by simple, brief base treatment giving the native sequence in much higher overall yield. The applicability of the method was demonstrated by the novel preparation of insulin glargine via solid-phase synthesis of each of the two chainssincluding the notoriously poorly soluble A-chainsfollowed by their combination in solution via regioselective disulfide bond formation. At the conclusion of the chain combination, the solubilizing peptide tag was removed from the A-chain to provide synthetic human glargine in nearly 10% overall yield. This approach should facilitate the development of new insulin analogues as well as be widely applicable to the improved purification and acquisition of otherwise poorly soluble synthetic peptides.

Annals of The New York Academy of Sciences, 2009

The availability of improved peptide synthesis procedures, convenient and sensitive assays for re... more The availability of improved peptide synthesis procedures, convenient and sensitive assays for receptor binding and activation, together with advances in methods for structural characterization, has enabled the key structural features of the relaxin family of peptides responsible for biological activity to be defined. Not surprisingly, despite the similarities in primary amino acid sequences, different structural domains and residues are involved in the binding and activation at the four known relaxin family peptide receptors (RXFP1 to -4). Most of our knowledge on structure and function relates to the relaxin–RXFP1, insulin-like peptide 3 (INSL3)–RXFP2, and relaxin-3–RXFP3 systems, with information accumulating not only on the critical ligand structures but also the domains and residues on the receptor itself that are required for specificity and activation. These studies provide the framework for the design of small-molecule mimetics. While the B-chain cassette R-X-X-X-R-X-X-I, defined by Büllesbach and Schwabe, is essential for binding and activation of RXFP1, it is now recognized that the A chain, particularly the N-terminal domain, is also critical for receptor specificity. Studies of the various endogenous ligand–receptor pairs have led to the design of potent and specific agonists and antagonists. The relaxin-3 A chain–INSL5 B chain chimeric peptide and analogs with C-terminal truncations of the B chain, developed by Liu and colleagues at Johnson & Johnson, have provided selective agonist and antagonist peptides that are proving invaluable for in vivo studies of the relaxin-3–RXFP3 system.

Abstract A leading edge 90 nm technology with 1.2 nm physical gate oxide, 50 nm gate length, stra... more Abstract A leading edge 90 nm technology with 1.2 nm physical gate oxide, 50 nm gate length, strained silicon, NiSi, 7 layers of Cu interconnects, and low k carbon-doped oxide (CDO) for high performance dense logic is presented. ...

A leading edge 130 nm technology with 6 layers of Cu interconnects and 1.3 V operation has previo... more A leading edge 130 nm technology with 6 layers of Cu interconnects and 1.3 V operation has previously been presented (Tyagi et al., 2000). In this work, we enhance the previous technology with the following: transistor improvements which support a 60 nm gate dimension and increased drive current, improved 6-T SRAM device matching to allow low power and high performance operation from 0.7 to 1.4 V, and a 5% linear shrink to reduce the 6-T SRAM cell to 2.00 /spl mu/m/sup 2/ while still using 248 nm lithography. Saturation drive currents of 1.30 mA//spl mu/m for N-channel and 0.66 mA//spl mu/m for P-channel low VT devices are the highest reported to date. Excellent device short channel effects are obtained for the 60 nm gate length devices as measured by the 270 mV threshold voltage and

Cheminform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

International Journal of Peptide Research and Therapeutics, 2008

The S-acetamidomethyl (Acm) protecting group is widely used in the chemical synthesis of peptides... more The S-acetamidomethyl (Acm) protecting group is widely used in the chemical synthesis of peptides that contain one or more disulfide bonds. Treatment of peptides containing S-Acm protecting group with iodine results in simultaneous removal of the sulfhydryl protecting group and disulfide formation. However, the excess iodine needs to be quenched or adsorbed as quickly as possible after completion of the disulfide bond formation in order to minimize side reactions that are often associated with the iodination step. We report a simple method for simultaneous post-cysteine (Acm) group removal quenching of iodination and isolation. Use of large volumes of diethyl ether for direct precipitation action of the oxidized peptide from the 90 or 95% aqueous acetic acid solution affords nearly quantitative recovery of largely iodine-free peptide ready for direct purification. It was successfully applied to the synthesis of various peptides including human insulin-like peptide 3 analogues. Although recovery yields were comparable to the traditionally used ascorbic acid quenching method, this new approach offers significant advantages such as more simple utility, minimal side reactions, and greater cost effectiveness.

International Journal of Advanced Manufacturing Technology, 2009

The production–distribution planning problem (PDPP) is one of the most important approaches to su... more The production–distribution planning problem (PDPP) is one of the most important approaches to support global optimization in supply chain management and should be solved within the integrated structure. This approach involves the determination of the best configuration regarding location, size, technology content, and product range to achieve the firm’s long-term goals. On the other hand, teams of autonomous agents, co-operating by sharing solutions through a common memory, have been proposed as a means of solving combinatorial optimization problems. In this paper, two scenarios are presented for solving PDPP. In the first scenario, a centralized method is employed, and a genetic algorithm (GA) is presented for solving PDPP problem. Here, the crossover is a single point in plant–plant–plant. In the second scenario, an agent-based system is developed for solving PDPP problem. In this case, three GAs are assumed to be the agents of the model. This distributed structure can help the system to select the most appropriate solution for interaction between agents, which are genetic algorithms (GA1, GA2, GA3). In each case, we compare the results of each scenario by those obtained from using LINGO software and a heuristic method (Lagrangian relaxation)

Journal of Gastroenterology and Hepatology, 2001

Biopolymers, 2010

Insulin-like peptide 3 (INSL3) is one of 10 members of the human relaxin–insulin superfamily of p... more Insulin-like peptide 3 (INSL3) is one of 10 members of the human relaxin–insulin superfamily of peptides. It is a peptide hormone that is expressed by fetal and postnatal testicular Leydig cells and postnatal ovarian thecal cells. It mediates testicular descent during fetal life and suppresses sperm apoptosis in adult males, whereas, in females, it causes oocyte maturation. INSL3 has also been shown to promote thyroid tumor growth and angiogenesis in human. These actions of INSL3 are mediated through its G protein-coupled receptor, RXFP2. INSL3, a two-chained peptide, binds to its receptor primarily via its B-chain, whereas elements of the A-chain are essential for receptor activation. In an attempt to design a high-affinity antagonist with potential clinical application as an anticancer agent as well as a contraceptive, we have previously prepared a synthetic parallel dimer of INSL3 B-chain and demonstrated that it binds to RXFP2 with high affinity. In this work, we undertook full pharmacological characterization of this peptide and show that it can antaogonize INSL3-mediated cAMP signaling through RXFP2. Further refinement by truncation of 18 residues yielded a minimized analogue that retained full binding affinity and INSL3 antagonism. It is an attractive lead peptide for in vivo evaluation as an inhibitor of male and female fertility and of INSL3-mediated carcinogenesis. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 81–87, 2011.

Amino Acids, 1999

Rumen contents from three fistulated Japanese native goats fed Lucerne hay cubes (Medicago sativa... more Rumen contents from three fistulated Japanese native goats fed Lucerne hay cubes (Medicago sativa) and concentrate mixture were collected to prepare the suspensions of mixed rumen bacteria (B), mixed protozoa (P) and a combination of the two (BP). Microbial suspensions were anaerobically incubated at 39°C for 12h with or without 1 MM ofl-phenylalanine (Phe). Phe, tyrosine (Tyr) and other related compounds in both supernatant and microbial hydrolysates of the incubations were analyzed by HPLC. Tyr can be produced from Phe not only by rumen bacteria but also by rumen protozoa. The production of Tyr during 12h incubation in B (183.6 μmol/g MN) was 4.3 times higher than that in P. One of the intermediate products between Phe and Tyr seems to bep-hydroxyphenylacetic acid. The rate of the net degradation of Phe incubation in B (76.O μmol/g MN/h) was 2.4 times higher than in P. In the case of all rumen microorganisms, degraded Phe was mainly (>53%) converted into phenylacetic acid. The production of benzoic acid was higher in P than in B suspensions. Small amount of phenylpyruvic acid was produced from Phe by both rumen bacteria and protozoa, but phenylpropionic acid and phenyllactic acid were produced only by rumen bacteria.

Iranian Studies, 1988

... cameras. Some of them even had chauffeur-driven cars. All of them were rich. We didn&... more ... cameras. Some of them even had chauffeur-driven cars. All of them were rich. We didn&amp;amp;#x27;t like them. ... contemporary. One such virtuoso was Sheikh Abdullah. As an adolescent sitting in the shadow of his mambar, I can still recall his Stentorian voice. ...

Carbon

Polytetrafluoroethylene (PTFE) is one of the most widely used solid lubricants but suffers from a... more Polytetrafluoroethylene (PTFE) is one of the most widely used solid lubricants but suffers from a high wear rate which limits its applications. Here we report four orders of magnitude reduction in the steady state wear rate of PTFE due to graphene additives. The wear rate of unfilled PTFE was measured to be 0.4⋅10Aˋ3mm3/Nmwhichisreducedto0.4 · 10 À3 mm 3 /N m which is reduced to 0.4⋅10Aˋ3mm3/Nmwhichisreducedto10 À7 mm 3 /N m by the incorporation of 10 wt% of graphene platelets. We also performed a head-to-head comparison of wear rate with graphene and micro-graphite fillers at the same weight fractions. In general, we find that graphene fillers gave 10-30 times lower wear rates than micrographite at the same loading fraction. Scanning electron microscopy analysis indicated noticeably smaller wear debris size in the case of graphene/PTFE composites indicating that graphene additives are highly effective in regulating debris formation in PTFE leading to reduced wear.

Abstract The first stage in the development of a fuzzy controller for active control of vibration... more Abstract The first stage in the development of a fuzzy controller for active control of vibration in a wind excited tall structure is reported. The initial rule base of the fuzzy controller is developed based on the input/output data obtained from the performance of the system under a state feedback controller. The performance of the developed controller is validated through computer simulation. The controller is applied to both the building model from which the rule base is extracted and another building with similar dynamics but different ...

Journal of Engineering Mechanics-asce, 2004

This paper focuses on the benchmark control problems for seismically excited nonlinear buildings.... more This paper focuses on the benchmark control problems for seismically excited nonlinear buildings. The benchmark study focuses on three typical steel structures, 3-, 9-, and 20-story buildings designed for the SAC project for the Los Angeles region. This paper reports the application of the active control scheme on the 3-and 20-story benchmark buildings, where the control action is achieved by a fuzzy logic controller. The main advantage of the fuzzy controller is its inherent robustness and ability to handle any nonlinear behavior of the ...

Bioconjugate Chemistry, 2008

An efficient solid-phase synthesis protocol has been developed which, together with regioselectiv... more An efficient solid-phase synthesis protocol has been developed which, together with regioselective sequential formation of the three disulfide bonds, enabled the preparation of specifically monolanthanide (europium)-labeled human insulin-like peptide 3 (INSL3) for the study of its interaction with its G-protein-coupled receptor, RXFP2, via time-resolved fluorometry. A commercially available chelator, diethylene triamine pentaacetic acid (DTPA), was coupled to the N-terminus of the INSL3 A-chain on the solid phase, and then a coordination complex between europium ion and DTPA was formed using EuCl 3 to protect the chelator from production of an unidentified adduct during subsequent combination of the A-and B-chains. The labeled peptide was purified in high yield using high-performance liquid chromatography with nearly neutral pH buffers to prevent the liberation of Eu 3+ from the chelator. Using time-resolved fluorometry, saturation binding assays were undertaken to determine the binding affinity (pK d ) of labeled INSL3 for RXFP2 in HEK-293T cells stably expressing RXFP2. The dissociation constant of DTPA-labeled INSL3 (9.05 ( 0.03, n ) 3) that was obtained from saturation binding experiments was comparable to that of 125 I-labeled INSL3 (9.59 ( 0.09, n ) 3). The receptor binding affinity (pK i ) of human INSL3 was determined to be 9.27 ( 0.06, n ) 3, using Eu-DTPA-INSL3 as a labeled ligand, which again is similar to that obtained when 125 I-INSL3 was used as labeled ligand (9.34 ( 0.02, n ) 4). This novel lanthanidecoordinated, DTPA-labeled INSL3 has excellent sensitivity, stability, and high specific activity, properties that will be particularly beneficial in high-throughput screening of INSL3 analogues in structure-activity studies.

Extensive livestock grazing even in unsuitable land has increasingly grown in most parts of semi-... more Extensive livestock grazing even in unsuitable land has increasingly grown in most parts of semi-arid rangeland. Therefore, it is of paramount importance to identify suitable land for livestock grazing for optimum utilization while causing minimum impact to the environment. This paper adapted the schematic model based on the concepts presented by the Food and Agriculture Organization of suitability analysis for optimal grazing management in semiarid rangeland in Iran. Factors affecting extensive grazing were determined and incorporated into the model. Semi-arid rangeland with variable such as climate and other agents were examined for common types of animal grazing and the advantages and limitations were elicited. Many ecosystem components affect land suitability for livestock grazing but due to time and funding restrictions, the most important and feasible elements were investigated. Within the model parameters, three submodels including water accessibility source, forage production, and erosion sensitivity were considered. Suitable areas at four levels of suitability were determined using geographic information systems. This suitability modeling approach was adopted due to its simplicity and the minimal time required for transforming and analyzing datasets. The most important reducing factors in model suitability were found to be: (a) land use and vegetation cover (in relation to soil erosion sensitivity), (b) the amount of the available forage in comparison with the total production, and (c) the existence of less palatability plants among the pasture plant species (forage production suitability). The results of the study would be beneficial to rangeland managers in devising measures more wisely to cope with the limitations and enhance the health and productivity of the rangelands.

Chemical Biology & Drug Design, 2009

Relaxin-3, a member of the insulin superfamily, is involved in regulating stress and feeding beha... more Relaxin-3, a member of the insulin superfamily, is involved in regulating stress and feeding behavior. It is highly expressed in the brain and is the endogenous ligand for the receptor RXFP3. As relaxin-3 also interacts with the relaxin receptor RXFP1, selective agonists and antagonists are crucial for studying the physiological function(s) of the relaxin-3/RXFP3 pair. The analog R3(BΔ23-27)R/I5, in which a C-terminally truncated human relaxin-3 (H3) B-chain is combined with the INSL5 A-chain, is a potent selective RXFP3 antagonist and has an Arg residue remaining on the B-chain C-terminus as a consequence of the recombinant protein production process. To investigate the role of this residue in the RXFP3 receptor binding and activation, the analogs R3(BΔ23-27)R/I5 and R3(BΔ23-27)R containing the B-chain C-terminal Arg as well as R3(BΔ23-27)/I5 and R3(BΔ23-27), both lacking the Arg, were chemically assembled and their secondary structure and receptor activity assessed. The peptides generally had a similar conformation but those with the extra Arg residue displayed a significantly increased affinity for the RXFP3. Interestingly, in contrast to R3(BΔ23-27)R and R3(BΔ23-27)R/I5, the peptide R3(BΔ23-27) is a weak agonist. This suggests that the C-terminal Arg, although increasing the affinity, alters the manner in which the peptide binds to the receptor and thereby prevents activation, giving R3(BΔ23-27)R/I5 its potent antagonistic activity.

Peptides, 2010

INSL3 is a member of the insulin-IGF-relaxin superfamily and plays a key role in male fetal devel... more INSL3 is a member of the insulin-IGF-relaxin superfamily and plays a key role in male fetal development and in adult germ cell maturation. It is the cognate ligand for RXFP2, a leucine-rich repeat containing Gprotein coupled receptor. To date, and in contrast to our current knowledge of the key structural features that are required for the binding of INSL3 to RXFP2, comparatively little is known about the key residues that are required to elicit receptor activation and downstream cell signaling. Early evidence suggests that these are contained principally within the A-chain. To further explore this hypothesis, we have undertaken an examination of the functional role of the intra-A-chain disulfide bond. Using solid-phase peptide synthesis together with regioselective disulfide bond formation, two analogs of human INSL3 were prepared in which the intra-chain disulfide bond was replaced, one in which the corresponding Cys residues were substituted with the isosteric Ser and the other in which the Cys were removed altogether. Both of these peptides retained nearly full RXFP2 receptor binding but were devoid of cAMP activity (receptor activation), indicating that the intra-A-chain disulfide bond makes a significant contribution to the ability of INSL3 to act as an RXFP2 agonist. Replacement of the disulfide bond with a metabolically stable dicarba bond yielded two isomers of INSL3 that each exhibited bioactivity similar to native INSL3. This study highlights the critical structural role played by the intra-A-chain disulfide bond of INSL3 in mediating agonist actions through the RXFP2 receptor.