Madumali Kalubowilage - Academia.edu (original) (raw)

Papers by Madumali Kalubowilage

Kansas. Dept. of Transportation, 2020

2020PDFTech ReportBossmann, Stefan H.Kalubowilage, MadumaliKansas State University, ManhattanKans... more 2020PDFTech ReportBossmann, Stefan H.Kalubowilage, MadumaliKansas State University, ManhattanKansas. Dept. of TransportationKansas. Dept. of TransportationUnited StatesAdhesionChemical agentsComposite materialsConcreteCorrosion protectionEpoxy coatingsMicroscopyNuclear magnetic resonancePolymersProtective coatingResinsSpectroscopic analysisThermal analysisKS-20-01C2119Final Report, January 2018\u2013March 2019Polyepoxy and polyisocyanate resins are currently in use for protecting concrete and especially steel structural elements in concrete from water-induced corrosive processes. The newest class of materials consists of polyepoxy/polyisocyanate composite resins. The underlying paradigm of using these composite materials is that they show structural synergy, leading to improved material properties, such as improved adhesion to concrete surfaces and higher durability, resilience, and weather resistance. The first phase of this research project consisted of the synthesis and chemical characterization of the required polyisocyanate resins and polyepoxy/amine resins. These resins are required, because their interaction with each other when adsorbed on concrete will be studied in Phase 2. The research team then investigated the chemical interaction between the model resins that were optimized in the first phase of this project in Phase 2. The thermal stabilities of the resulting composite materials were studied to estimate their resistance against weathering. Researchers could observe enhanced stability of polyisocyanate/polyepoxy/amine co-resins at very broad mixing ratios (5:95 to 95:5 weight ratios), with a maximum of thermal stability at 75:25 polyisocyanate to polyepoxy resin precursors. The observed increase in thermal stability was attributed to the formation of urea-type bonds between isocyanates and amines. This reaction can only occur if the resin precursors for polyisocyanates and polyepoxy/amines are mixed. This formation of novel bonds has been corroborated by nuclear magnetic resonance (\ub9H-NMR) spectroscopy. The third phase of this research project consisted of the atomic force microscopy (AFM) and magnetic resonance imaging (MRI) of two types of wafers that were provided by Kansas Department of Transportation (KDOT), as well as coated wafers. The final phase of this research project consisted of MRI of optimized polyepoxyamine resin (B) on the surfaces of Type 2 concrete model wafers provided by KDOT. Fast low angle shot MRI (FLASH), rapid imaging with refocused echoes (RARE), and Turbo-RARE imaging clearly demonstrated that polyepoxyamine resin (B) is a very suitable polymer coating for Type 2 concrete wafers. This proves that ultra-high-field MRI imaging is an excellent method for imaging polymerconcrete interfaces. The results clearly demonstrate that polyepoxyamine resins are, principally, superior as protective concrete coatings to polyurethane coatings, which were found not to be strongly adhesive. Mixtures of polyepoxyamine and polyurethane resins were dominated by their polyurethane content and, therefore, not as suitable as pure polyepoxyamine resins.104

Cell Tracking, 2020

This chapter discusses a methodology for simultaneously imaging stem cells and endothelial cells ... more This chapter discusses a methodology for simultaneously imaging stem cells and endothelial cells within polysaccharide-based scaffolds for tissue engineering. These scaffolds were then implanted into nude mice. Human mesenchymal stem cells (HMSCs) were labeled with the T 1-marker Gd(III)-DOTAGA-functionalized polysiloxane nanoparticles (GdNPs), whereas endothelial umbilical vein cells (HUVECs) were labeled with citrate-stabilized maghemite nanoparticles (IONPs), which predominantly shorten the T 2-relaxation times of the water molecules in scaffolds and tissue. Dual cell detection was achieved by performing T 1-and T 2-weighted MRI in both tissue scaffolds and in vivo.

Cancer is a group of diseases that are characterized by uncontrolled growth and spread of cells. ... more Cancer is a group of diseases that are characterized by uncontrolled growth and spread of cells. In order to treat cancer successfully, it is important to diagnose cancers in their early stages, because survival often depends on the stage of cancer detection. For that purpose, highly sensitive and selective methods must be developed, taking advantage of suitable biomarkers. The expression levels of proteases differ from one cancer type to the other, because different cancers arise from different cell types. According to the literature, there are significant differences between the protease expression levels of cancer patients and healthy people, because solid tumors rely on proteases for survival, angiogenesis and metastasis. Development of fluorescence-based nanobiosensors for the early detection of pancreatic cancer and non-small-cell lung cancer is discussed in this thesis. The nanobiosensors are capable of detecting protease/arginase activities in serum samples over a broad rang...

Nanomedicine: Nanotechnology, Biology and Medicine, 2021

We report the design and adaptation of iron/iron oxide nanoparticle-based optical nanobiosensors ... more We report the design and adaptation of iron/iron oxide nanoparticle-based optical nanobiosensors for enzymes or cytokine/chemokines that are established biomarkers of lung diseases. These biomarkers comprise ADAM33, granzyme B, MMP-8, neutrophil elastase, arginase, chemokine (C-C motif) ligand 20 and interleukin-6. The synthesis of nanobiosensors for these seven biomarkers, their calibration with commercially available enzymes and cytokines/chemokines, as well as their validation using bronchoalveolar lavage (BAL) obtained from a mouse model of TLR3-mediated inflammation are discussed here. Exhaled Breath Condensate (EBC) is a

ACS Omega, 2021

A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphyl... more A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillinresistant S. aureus (MRSA) were synthesized, characterized, and tested against the MSSA strain Newman and the MRSA Lac strain (a USA300 strain), respectively. These drugs feature an NNSN structural motif, which enables the binding of copper. In the absence of copper, no activity against MSSA and MRSA at realistic drug concentrations was observed. Although none of the novel drug candidates exhibits a stereocenter, sub-micromolar activities against SA Newman and micromolar activities against SA Lac were observed in the presence, but not in the absence, of bioavailable copper. Copper influx is a component of cellular response to bacterial infections, which is often described as nutritional immunity.

Journal of Clinical Oncology, 2019

296 Background: Early detection of pancreatic cancer would allow for improved survival outcomes. ... more 296 Background: Early detection of pancreatic cancer would allow for improved survival outcomes. Methods: We retrospectively evaluated serum protease levels and the survival of 15 pancreatic cancer patient samples (6 localized and 9 metastatic) at the KU Cancer Center. Available serum protease assays measured matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), arginase, neutrophil elastase (NE), cathepsin B (CTSB) and cathepsin E (CTSE). The assays utilize fluorescent nanoparticle-based nanobiosensors which increase fluorescence upon posttranslational modification or enzymatic cleavage of targeted compounds and were read by a Spectral scan plate reader. Survival analysis was performed using Kaplan-Meier methods. Results: Baseline characteristics for all 15 patients are in (Table). Median OS was 18.8m in patients with high CTSB expression (mean >51968.9) vs 9.7m in low CTSB expression (p=0.04). Similarly, median OS was 20.4m in high CTSE expression (>123264...

RSC Advances, 2019

Advances in the synthesis and processing of graphene-based materials have presented the opportuni... more Advances in the synthesis and processing of graphene-based materials have presented the opportunity to design novel lithium-ion battery (LIB) anode materials that can meet the power requirements of next-generation power devices.

Applied Sciences, 2019

Magnetic nanoparticles have continuously gained importance for the purpose of magnetically-aided ... more Magnetic nanoparticles have continuously gained importance for the purpose of magnetically-aided drug-delivery, magnetofection, and hyperthermia. We have summarized significant experimental approaches, as well as their advantages and disadvantages with respect to future clinical translation. This field is alive and well and promises meaningful contributions to the development of novel cancer therapies.

Metallomics, 2019

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections poses a therapeuti... more The treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections poses a therapeutic challenge as even last resort drugs become increasingly ineffective. As the demand for antibiotics with novel modes of action is growing, new approaches are needed to probe a greater spectrum of antimicrobial activities for their potential efficacy against drug-resistant pathogens. The use of copper (Cu) by the innate immune system to mount an antimicrobial response against bacterial invaders has created an opportunity to explore a role for Cu in antimicrobial therapy. Here we describe pyrazolopyrimidinones (PZP) as novel copper-dependent inhibitors (CDI) of S. aureus. 5-Benzyl-3-(4-chlorophenyl)-2-methyl-4H,7H-pyrazolo[1,5-a]pyrimidin-7-one (PZP-915) showed potent bactericidal properties at sub-micromolar concentrations and activity against clinical MRSA isolates and biofilms cultures. This cupricidal activity is founded on the molecule’s ability to coordinate Cu and induce accumulati...

RSC Advances, 2018

The structure of novel binary nanosponges consisting of (cholesterol-(K/D) n DEVDGC) 3-trimaleimi... more The structure of novel binary nanosponges consisting of (cholesterol-(K/D) n DEVDGC) 3-trimaleimide units possessing a trigonal maleimide linker, to which either lysine (K) 20 or aspartic acid (D) 20 are tethered, has been elucidated by means of TEM. A high degree of agreement between these findings and structure predictions through explicit solvent and then coarse-grained molecular dynamics (MD) simulations has been found. Based on the nanosponges' structure and dynamics, caspase-6 mediated release of the model drug 5(6)-carboxyfluorescein has been demonstrated. Furthermore, the binary (DK20) nanosponges have been found to be virtually non-toxic in cultures of neural progenitor cells. It is of a special importance for the future development of cell-based therapies that DK20 nanosponges were taken up efficiently by leucocytes (WBC) in peripheral blood within 3 h of exposure. The percentage of live cells among the WBC was not significantly decreased by the DK20 nanosponges. In contrast to stem cell or leucocyte cell cultures, which have to be matched to the patient, autologous cells are optimal for cell-mediated therapy. Therefore, the nanosponges hold great promise for effective cell-based tumor targeting.

ACS Applied Bio Materials, 2018

Peptide nanosponges of low polydispersity are spontaneously formed from trigonal supramolecular b... more Peptide nanosponges of low polydispersity are spontaneously formed from trigonal supramolecular building blocks in aqueous buffers, which feature cationic and/or anionic oligopeptides (n=5-20) and a hydrophobic unit. In contrast to classical liposomes/vesicles, nanosponges feature interwoven hydrophilic and hydrophobic nanodomains, and are readily taken up by mammalian cells. Perillyl alcohol is known to be a simple, but effective small molecule drug against glioma multiforme. However, its efficacy is limited by poor bioavailability. In order to make perillyl alcohol bioavailable, two nanosponges consisting of 10 aspartates, to which perillyl alcohol is attached by means of an ester bond, and 20 lysines or arginines (type (D-POH)10K20 and (D-POH)10R20) were synthesized, purified, and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). These nanosponges were then tested in cell cultures of murine glioma cells (GL26) and murine neural progenitor cells (NPC), because the latter was previously utilized in cell-based cancer therapy. The two nanosponges exhibited significantly different biophysical properties (size distribution and zeta potentials). Consequently, different efficacies in killing GL26 and NPC were observed in serum containing culture media. The results from these experiments confirmed that the type (D-POH)10K20 nanosponge is a promising candidate for the (cell-mediated) cytotherapy of glioblastoma.

Theriogenology, 2017

Metritis, a uterine disease caused by bacterial infection, is highly prevalent in dairy cattle af... more Metritis, a uterine disease caused by bacterial infection, is highly prevalent in dairy cattle after parturition. Uterine disease has negative effects on milk production and reproductive efficiency. Finding markers or indicators that can predict cows at greater risk for uterine disease could be beneficial to mitigating these deleterious effects. This study investigates the immune-derived enzymes arginase and matrix metalloproteinase-8 (MMP-8) as potential markers for development of metritis in dairy cows. In a retrospective matched case-control study, 53 lactating Holstein cows diagnosed with metritis were matched and paired to 53 lactating Holstein control cows. In addition to examining cows for diagnosis of metritis on d 4, 7, 10, and 14 after parturition, occurrence of retained fetal membranes, gender of the calf, and the event of a stillbirth were recorded. Blood samples were collected 7 ± 3 d before calving, on the day of calving, and 7 ± 3 d after calving and were assayed for activity of arginase and MMP-8. Associations between metritis and activity of arginase or MMP-8 were determined by conditional logistic regression at each individual sampling time point. An interaction between activity of arginase, before and on the day of parturition, and retained fetal membranes tended (P 0.13) to be associated with metritis. After parturition, activity of arginase and the interaction between activity of arginase and retained fetal membranes were not (P ! 0.22) associated with metritis. Activity of MMP-8 was not (P ! 0.20) associated with metritis in the periparturient period. Retained fetal membranes were associated with the odds of developing metritis. Activity of arginase before and at the time of parturition might be a potential marker for occurrence of metritis, especially in cows that develop retained fetal membranes. MMP-8 does not seem to be a potential indicator for metritis.

Journal of Extracellular Vesicles, 2017

Background: Extracellular vesicles contain biological molecules specified by cell-type of origin ... more Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or −80°C. Exosomal structure was assessed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and charge density (zeta potential, ζ). Exosomal protein content, including leaking/dissociating proteins, were identified by label-free LC-MS/MS. Results: Freshly isolated BALF exosomes exhibited a mean diameter of 95 nm and characteristic morphology. Storage had significant impact on BALF exosome size and content. Compared to fresh, exosomes stored at +4°C had a 10% increase in diameter, redistribution to polydisperse aggregates and reduced ζ. Storage at −80°C produced an even greater effect, resulting in a 25% increase in diameter, significantly reducing the ζ, resulting in multilamellar structure formation. In fresh exosomes, we identified 1140 high-confidence proteins enriched in 19 genome ontology biological processes. After storage at room temperature, 848 proteins were identified. In preparations stored at +4°C, 224 proteins appeared in the supernatant fraction compared to the wash fractions from freshly prepared exosomes; these proteins represent exosome leakage or dissociation of loosely bound "peri-exosomal" proteins. In preparations stored at −80°C, 194 proteins appeared in the supernatant fraction, suggesting that distinct protein groups leak from exosomes at different storage temperatures. Conclusions: Storage destabilizes the surface characteristics, morphological features and protein content of BALF exosomes. For preservation of the exosome protein content and representative functional analysis, airway exosomes should be analysed immediately after isolation.

Nanomedicine : nanotechnology, biology, and medicine, Jan 25, 2017

A novel type of supramolecular aggregate, named a "nanosponge" was synthesized through ... more A novel type of supramolecular aggregate, named a "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)nDEVDGC)3-trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n=5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer cholesterol-(K)nDEVDGC)3-trimaleimides and a 1:1 mixture of cholesterol-(K/D)nDEVDGC)3-trimaleimides forms stable nanosponges, whereas cholesterol-(D)nDEVDGC)3-trimaleimide is unable to form supramolecular aggregates with itself. The structure of the novel nanosponges was investigated through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells.

Analytical Chemistry, 2016

A microfluidic device is reported that employs an out-of-plane optical fiber bridge to generate t... more A microfluidic device is reported that employs an out-of-plane optical fiber bridge to generate two excitation and two detection spots in a microfluidic channel using only one excitation source and one detector. This fiber optic bridge was integrated into a single cell analysis device to detect an intact cell just prior to lysis and the injected lysate 2, 5, 10, or 15 mm downstream of the injection point. Using this setup the absolute migration times for analytes from cells stochastically entering the lysis intersection could be determined for the first time in an automated fashion. This allowed the evaluation of several separation parameters, including analyte band velocity, migration time drift, diffusion coefficient, injection plug length, separation efficiency (N), and plate height (H), which previously could only be estimated. To demonstrate the utility of this system, a peptide substrate for protein kinase B (PKB) was designed, synthesized, and loaded into T-lymphocytes in order to measure PKB activity in individual cells. The optical fiber bridge is easy to implement, inexpensive, and flexible in terms of changing the distances between the two detection points.

Nanomedicine : nanotechnology, biology, and medicine, Aug 18, 2018

Numerous proteases, such as matrix metalloproteinases (MMPs), cathepsins (CTS), and urokinase pla... more Numerous proteases, such as matrix metalloproteinases (MMPs), cathepsins (CTS), and urokinase plasminogen activator (UpA), are dysfunctional (that is, over- or under-expressed) in solid tumors, when compared to healthy human subjects. This offers the opportunity to detect early tumors by liquid biopsies. This approach is of particular advantage for the early detection of pancreatic cancer, which is a "silent killer". We have developed fluorescence nanobiosensors for ultrasensitive (sub-femtomolar) arginase and protease detection, consisting of water-dispersible Fe/FeO core/shell nanoparticles and two tethered fluorescent dyes: TCPP (Tetrakis(4-carboxyphenyl)porphyrin) and cyanine 5.5. Upon posttranslational modification or enzymatic cleavage, the fluorescence of TCPP increases, which enables the detection of proteases at sub-femtomolar activities utilizing conventional plate readers. We have identified an enzymatic signature for the detection of pancreatic adenocarcinomas ...