Papers by Mohammed Shameem
European Journal of Environmental and Civil Engineering
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Reinforcement corrosion is considered to be the major contributor to the deterioration of concret... more Reinforcement corrosion is considered to be the major contributor to the deterioration of concrete. It is caused either due to carbonation or the diffusion of chloride ions to the steel surface. However, chloride-induced reinforcement corrosion significantly outweighs that due to carbonation of concrete. Though the role played by the chloride ions in initiating reinforcement corrosion is not very clear, limitations are placed on their quantity from the perspective of inhibiting reinforcement corrosion. However, these limitations do not consider the effect of sulfate ions on the chloride threshold. Also, the quality of concrete has improved significantly since the threshold values were established by international standards and codes of practices. Consequently, there is a need to establish chloride threshold values for avoiding concrete deterioration due to reinforcement corrosion. This paper presents results of a study conducted to evaluate the chloride threshold values for high qua...
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Cement and Concrete Composites, 2011
The use of supplementary cementing materials, such as silica fume, fly ash, blast furnace slag, a... more The use of supplementary cementing materials, such as silica fume, fly ash, blast furnace slag, and natural pozzolans, has been promoted by their technical and economic advantages. However, in certain parts of the world, where these materials are not ...
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The efficiency of generic and proprietary corrosion inhibitors (based on nitrite, amine carboxyla... more The efficiency of generic and proprietary corrosion inhibitors (based on nitrite, amine carboxylate or amino alcohol) in corrosion mitigation of carbon steel, which is exposed to concrete solutions with different amounts of chloride as well as sulfate, was studied. The corrosion protection provided by the selected corrosion inhibitors was investigated by performing a potentiodynamic polarization study. In addition, the surface morphological properties of carbon steel samples exposed to the electrolyte mixed with or without inhibitors was also evaluated by scanning electron microscopy. The potentiodynamic polarization measurements showed that the evaluated inhibitors decreased the corrosion current density by 1.6 to 6.7 times depending on the type of inhibitor and the level of sulfate concentration in the electrolyte. The performance of inhibitors based on nitrite was better than that of inhibitors based on amine carboxylate or amino alcohol. The possible mechanisms of the inhibition...
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mAbs, Jan 21, 2016
With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein ... more With the rapid growth of biopharmaceutical product development, knowledge of therapeutic protein stability has become increasingly important. We evaluated assays that measure solution-mediated interactions and key molecular characteristics of nine formulated monoclonal antibody (mAb) therapeutics, to predict their stability behavior. Colloidal interactions, self-association propensity and conformational stability were measured using effective surface charge via zeta potential, diffusion interaction parameter (kD) and differential scanning calorimetry (DSC), respectively. The molecular features of all nine mAbs were compared to their stability at accelerated (25°C and 40°C) and long-term storage conditions (2-8°C) as measured by size exclusion chromatography. At accelerated storage conditions, the majority of the mAbs in this study degraded via fragmentation rather than aggregation. Our results show that colloidal stability, self-association propensity and conformational characterist...
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Journal of chromatography. A, Jan 29, 2016
Analysis of oxidation of monoclonal antibodies (mAbs) in most cases relies on peptide mapping and... more Analysis of oxidation of monoclonal antibodies (mAbs) in most cases relies on peptide mapping and LC-MS, which is time consuming and labor-intensive. A robust chromatography based method that is able to resolve and quantitate mAb oxidation variants due to oxidized methionine or tryptophan is highly desired. Here we developed a novel mixed mode chromatography method using the unique property of Sepax Zenix SEC-300MK column to analyze mAb oxidation levels. The separation of oxidized species relied upon the mixed mode of size exclusion and hydrophobic interaction between the resin and antibodies. The chromatography was performed in a regular SEC mobile phase, PBS, containing NaCl at a concentration (0-2.4M) specific for individual antibodies. This method was able to resolve and quantitate the oxidized antibodies as prepeaks, of either methionine-oxidized species induced by the common oxidants TBHP, tryptophan-oxidized species triggered by AAPH, or oxidized species by UV photo-irradiati...
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Molecular Pharmaceutics, Feb 17, 2012
Monoclonal antibodies display highly variable solution properties such as solubility and viscosit... more Monoclonal antibodies display highly variable solution properties such as solubility and viscosity at elevated concentrations (>50 mg/mL), which complicates antibody formulation and delivery. To understand this complex behavior, it is critical to measure the underlying protein self-interactions that govern the solution properties of antibody suspensions. We have evaluated the pH-dependent self-association behavior of three monoclonal antibodies using self-interaction chromatography for a range of pH values commonly used in antibody formulations (pH 4.4-6). At low ionic strength (<25 mM), we find that each antibody is more associative at near-neutral pH (pH 6) than at low pH (pH 4.4). At high ionic strength (>100 mM), we observe the opposite pH-dependent pattern of antibody self-association. Importantly, this inversion in self-association behavior is not unique to multidomain antibodies, as similar pH-dependent behavior is observed for some small globular proteins (e.g., ribonuclease A and α-chymotrypsinogen). We also find that the opalescence of concentrated antibody solutions (90 mg/mL) is minimized at low ionic strength at pH 4.4 and high ionic strength at pH 6, in agreement with the self-interaction measurements conducted at low antibody concentrations (5 mg/mL). Our results highlight the complexity of antibody self-association and emphasize the need for systematic approaches to optimize the solution properties of concentrated antibody formulations.
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Reinforcement corrosion is considered to be the major contributor to the deterioration of concret... more Reinforcement corrosion is considered to be the major contributor to the deterioration of concrete. It is caused either due to carbonation or the diffusion of chloride ions to the steel surface. However, chloride-induced reinforcement corrosion significantly outweighs that due to carbonation of concrete. Though the role played by the chloride ions in initiating reinforcement corrosion is not very clear, limitations are placed on their quantity from the perspective of inhibiting reinforcement corrosion. However, these limitations do not consider the effect of sulfate ions on the chloride threshold. Also, the quality of concrete has improved significantly since the threshold values were established by international standards and codes of practices. Consequently, there is a need to establish chloride threshold values for avoiding concrete deterioration due to reinforcement corrosion. This paper presents results of a study conducted to evaluate the chloride threshold values for high qua...
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Journal of Raman Spectroscopy, 2015
ABSTRACT Structural complexity of biological drug products presents an analytical challenge in te... more ABSTRACT Structural complexity of biological drug products presents an analytical challenge in terms of early detection of aggregation and/or degradation. In the present study, Raman and Raman optical activity (ROA) were evaluated for their sensitivity to detect heat-induced molecular instability in an Immunoglobulin G4 subclass therapeutic monoclonal antibody present in its formulation matrix. The therapeutic antibody was subjected to heat stress at 50 °C and was analyzed at various time points up to 1 month. The current results suggest that Raman and ROA are sensitive to early-stage detection of heat-induced instability of the antibody, in which significant changes could be observed at 1 week of stress. ROA could provide early detection of the subtle differences at the tertiary structure level in a heat-stressed monoclonal antibody and Raman/ROA spectra could provide early detection in secondary structural changes as well. Copyright © 2015 John Wiley & Sons, Ltd.
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Journal of pharmaceutical sciences, 2014
A limitation of using mAbs as therapeutic molecules is their propensity to associate with themsel... more A limitation of using mAbs as therapeutic molecules is their propensity to associate with themselves and/or with other molecules via nonaffinity (colloidal) interactions. This can lead to a variety of problems ranging from low solubility and high viscosity to off-target binding and fast antibody clearance. Measuring such colloidal interactions is challenging given that they are weak and potentially involve diverse target molecules. Nevertheless, assessing these weak interactions-especially during early antibody discovery and lead candidate optimization-is critical to preventing problems that can arise later in the development process. Here we review advances in developing and implementing sensitive methods for measuring antibody colloidal interactions as well as using these measurements for guiding antibody selection and engineering. These systematic efforts to minimize nonaffinity interactions are expected to yield more effective and stable mAbs for diverse therapeutic applications...
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Proceedings of the ICE - Construction Materials, 2010
... Minerals, Dhahran, ARABIE SAOUDITE (4) Institute, King Fahd University of Petroleum and Miner... more ... Minerals, Dhahran, ARABIE SAOUDITE (4) Institute, King Fahd University of Petroleum and Minerals, Dhahran, ARABIE SAOUDITE (5) Institute, King Fahd University of Petroleum and Minerals, Dhahran, ARABIE SAOUDITE ... Faire une nouvelle recherche Make a new search.
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Molecular Pharmaceutics, 2012
Monoclonal antibodies display highly variable solution properties such as solubility and viscosit... more Monoclonal antibodies display highly variable solution properties such as solubility and viscosity at elevated concentrations (>50 mg/mL), which complicates antibody formulation and delivery. To understand this complex behavior, it is critical to measure the underlying protein self-interactions that govern the solution properties of antibody suspensions. We have evaluated the pH-dependent self-association behavior of three monoclonal antibodies using self-interaction chromatography for a range of pH values commonly used in antibody formulations (pH 4.4-6). At low ionic strength (<25 mM), we find that each antibody is more associative at near-neutral pH (pH 6) than at low pH (pH 4.4). At high ionic strength (>100 mM), we observe the opposite pH-dependent pattern of antibody self-association. Importantly, this inversion in self-association behavior is not unique to multidomain antibodies, as similar pH-dependent behavior is observed for some small globular proteins (e.g., ribonuclease A and α-chymotrypsinogen). We also find that the opalescence of concentrated antibody solutions (90 mg/mL) is minimized at low ionic strength at pH 4.4 and high ionic strength at pH 6, in agreement with the self-interaction measurements conducted at low antibody concentrations (5 mg/mL). Our results highlight the complexity of antibody self-association and emphasize the need for systematic approaches to optimize the solution properties of concentrated antibody formulations.
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Journal of Pharmaceutical Sciences, 2013
Differential scanning fluorimetry (DSF) has gained wide acceptance in the therapeutic protein dev... more Differential scanning fluorimetry (DSF) has gained wide acceptance in the therapeutic protein development. However, the effects of dyes and surfactants that may affect structural transitions have not been studied thoroughly to date. We therefore first optimized the DSF method by studying surfactant-containing formulations and found that the presence of surfactants generally required medium-to-high protein concentrations and that high SYPRO® Orange concentration in a DSF experiment may lower protein thermal transitions. We also benchmarked DSF against differential scanning calorimetry (DSC) and evaluated the capability of thermal parameters (from DSF/DSC) to predict real-time thermal aggregation kinetics monitored by size exclusion chromatography (SEC) and analytical ultracentrifugation (AUC) in different scenarios. For monoclonal antibody (MAb) fragment, both DSF and DSC were predictive of thermal aggregation rate. For MAb3, a good correlation was observed between DSF and DSC, none of which was, however, indicative of protein aggregation kinetics. In a surfactant ranging study, DSF did not agree with DSC and was not predictive of the aggregation kinetics of the MAb fragment. The concentration-dependent thermal behavior was also studied by DSF. Although higher concentration, in general, tends to lower protein transition temperature, case where it was independent of protein concentration was also presented.
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International Journal of Biological Macromolecules, 2013
This research focused on evaluation and application of two methods in studying weak protein-prote... more This research focused on evaluation and application of two methods in studying weak protein-protein interactions, i.e. diffusion interaction parameter (KD) and second virial coefficient (B22), both of which are first-order coefficients of protein interactions. Although the plate-based KD method successfully distinguished KD values with relatively large difference in a pH ranging study, it failed to make a consistent statistical decision to determine close interactions as shown by the comprehensive ANOVA analysis. We also validated the DLS-based B22 method by using a model protein lysozyme. The dramatic change of solution appearance for lysozyme as a function of NaCl concentration highlighted the importance of B22 in understanding protein interactions. Moreover, B22 measurement for a MAb fragment suggested a more repulsive protein interaction in histidine buffer than in citrate buffer. The coefficient of variation was <10% when B22 was on an order of magnitude of 10(-4) L mmol/g(2) in contrast to >30% when it approached 10(-5) L mmol/g(2). In this research, we also made an attempt to study protein-protein interactions in concentrated MAb fragment solutions (e.g. >50 mg/mL). Our data suggested that such interactions could be empirically modeled by high-order virial expansions.
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Infrared Physics & Technology, 2012
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Construction and Building Materials, 2009
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Construction and Building Materials, 2011
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Construction and Building Materials, 2008
Large quantity of dust, commonly known as cement kiln dust (CKD), is produced during the producti... more Large quantity of dust, commonly known as cement kiln dust (CKD), is produced during the production of Portland cement. In order to meet environmental requirements, CKD is disposed off in land fills. Recently, there has been a trend of utilizing it for soil stabilization, treatment of sewage, etc. Also, attempts were made at using it in cement products. This paper reviews the work conducted on the latter aspect and reports results of tests conducted by the authors to investigate the properties of cement-CKD combination. Results indicate that CKD does not adversely affect the properties of cement mortar. However, the implication of high chloride concentration and alkalinity of CKD on concrete durability needs to be studied.
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Construction and Building Materials, 1996
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Papers by Mohammed Shameem