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Fall  2013 Seminar Schedule

 
Department of Chemistry & Biomolecular Science
Clarkson University
PhD Defense
 
Thursday, December 5, 2013
9:00 a.m.
CAMP 372

Xing X. Liu
PhD Candidate, Clarkson University

will speak on

Complementary coordination bonding and its application for site selective derivatization of recombinant proteins

 

Abstract:

Metal-ligand interactions have been emerged as an efficient synthetic tool in coordination-driven self-assembly. Despite its rapid growth and broad applications, preferential binding of different types of ligands by metal ions has not been properly understood. To better understand the effect of ligand electric charge on formation of heteroleptic metal complex, we have synthesized a number of neutral and monoacidic tridentate ligands. Study of their formation of heteroleptic iron(III) complexes with a diacidic tridentate ligand was conducted with UV-vis titration and quantitative mass spectrometry. Equilibrium constants obtained from mass spectrometry were in a reasonable agreement with ones obtained from UV-vis titration. A substantial preference was found in formation of ternary complexes with neutral but not monoacidic tridentate ligand.

Selective formation of complementary metal complexes was further applied to selective derivatization of recombinant proteins. The major challenge in the field of protein modification is achieving site selectivity. To overcome this challenge, we developed a new method for site-specific modification of hexahistidine-tagged recombinant proteins through intramolecular alkylation of an imidazole residue in the hexahistidine tag site in a complementary complex with a nitrilotriacetate tethered alkylating agent. Model reactions with the glutarate tethered nitrilotriacetate Baylis-Hillman ester ligand were found to be to confirm feasibility of the approach for alkylation of N-acetylhexahistidine. The optimized model reaction conditions were further employed for covalent derivatization of recombinant hexahistidine tagged Protein A to introduce alkynyl functionality for subsequent "click" bioorthogonal cycloaddition. This two-stage approach for site-specific modification of the recombinant protein A with alkynyl group followed by cycloaddition with azide functionalized fluorescent label has demonstrated the success of this method as evidenced by SDS-PAGE analysis and In-Gel fluorescence imaging results. Quantization study of recombinant Protein A labeling efficiency was independently conducted with UV-vis spectroscopy and HPLC analysis.

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Department of Chemistry & Biomolecular Science
Clarkson University
PhD Defense
 
Monday, December 2, 2013
4:00 p.m.
169 B. H. Snell

Anton Grigoryev
PhD Candidate, Clarkson University

will speak on

Composite Functional Microfibers for Control of Wetting, Uptake and Release

 

Abstract:

Functional composite microfiber-based structures for regulating wetting properties, uptake and release are studied in this work. A novel strategy to produce arrays of metallic nanowires and micronail structures with re-entrant profile is developed. The method combines two template-assisted nanofabrication/patterning methods¬¬: electrochemical growth of metal nanowires in nanoporous sacrificial templates and partial masking of the surface with a self-assembled colloidal monolayer. A great potential of this novel approach to fabricate 1D-structures is demonstrated with an example of the fabrication of omniphobic surfaces comprised of nickel micronails whose density is varied to approach the highest possible contact angles of liquids.

Universal remote control of wetting behavior enabling the transition from superomniphobic to omniphilic wetting state in an external magnetic field via the alternation of reentrant curvature of a microstructured surface is demonstrated.  This reconfigurable microtexture made of Ni micronails repels water, water-surfactant solutions and practically all organic liquids, whereas it gets wetted by all these liquids after a pulse of magnetic field.

Wet-spun stimuli-responsive composite fibers made of covalently crosslinked alginate with a high concentration of single-walled carbon nanotubes (SWCNTs) are electroconductive and sensitive to humidity, pH and ionic strength due to pH-tunable water absorbing properties of the covalently cross-linked alginate. The conductivity depends on the material swelling in humid atmosphere and aqueous solutions: the greater the swelling, the smaller the electrical conductivity. The fibers can be used as a simple, robust, disposable and biocompatible platform for electroconductive textiles, biosensors and flexible electronics in biomedical and biotechnological applications.

A novel synthetic approach for the fabrication of wound-healing materials using covalently cross-linked alginate fibers loaded with silver nanoparticles is developed. Our study suggests that the silver nanoparticle loaded fibers may be easily applied in a wound healing paradigm and promote the healing process through the promotion of fibroblast migration to the wound area, reduction of the inflammatory phase, and the increased epidermal thickness in the repaired wound area, thereby improving the overall quality and speed of healing.

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Friday, November 22, 2013
3:30 p.m.
214 B. H. Snell

Kevin MacVittie
Department of Chemistry & Biomolecular Science
Clarkson University

will speak on

Multiple Realizations of Biochemical Associative Memory via Enzymatic Systems"
 

Abstract:

A surge of interest has occurred in the past decade in the development of chemical and biochemical systems capable of mimicking electronic / digital processes, thus revolutionizing the field of biocomputing, a burgeoning subset of unconventional computing. Rather than attempting to compete with silicon based computing, most biocomputing is based around the interfacing of traditional digital computing with biological systems, focused primarily on biosensing and biomedical applications. As this research progresses, researchers have looked to nature for inspiration for the next-stage in biochemical memory systems. Well discussed in psychology, the concept of associative memory has proven an intriguing motif for use in the biochemical regime.

Two such projects will be discussed. The first consisting of two parallel biocatalytic cascades, where a two-enzyme “correct” pathway, and an additional two-enzyme “wrong” pathway were used to illustrate the concept of “training.” This allowed for the application of an incorrect input to result in a system response indistinguishable from the “correct” input.  The system represents the first realization of associative memory based on enzymatic reactions in vitro. The second project demonstrates a similar associative memory signal/information processing system based on enzyme-catalyzed biochemical reaction. Following similar conventions of applying “correct” and “incorrect” signals to stimulate “training,” this second system varies in that it utilizes additional biomolecules, other than enzymes, for demonstrating these characteristics. Such processing steps promise applications of bio-inspired/memory-involving components in networked (bio)molecular processes for multi-signal sensing and complex information processing.

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Friday, November 15, 2013
3:30 p.m.
214 B. H. Snell

Shay Mailloux
Department of Chemistry & Biomolecular Science
Clarkson University

will speak on

A Biochemical System for Triggered Drug Release based on Enzymatic Cascades’’
 

Abstract:

Electrode interfaces, functionalized with signal-responsive materials, find application in biocomputing, biosensing, and, specifically, triggered release for biomedical applications. Iron alginate allows for an electrochemical signal, inducing release of an entrapped species using potential supplied from either an external source or a second biochemically responsive electrode.

Previously, lysozyme has been released upon application of an external potential and gold nanoparticles have been released using a signal from a second electrode, functionalized with PQQ-GDH, producing potential upon application of the biochemical stimulus glucose. Presented is a new system, allowing for a wide range of versatility in the triggering signal. PQQ itself is immobilized on an electrode surface, producing a negative potential in the presence of NADH. NADH, a common cofactor in many biochemical reactions, acts as a trigger for the production of negative potential. This trigger can be generated from many different signals, however, given that NADH can be produced easily in situ from numerous enzymatic cascades.

The system demonstrates great progress for future developments in ‘Sense and Treat’ systems offering great versatility for many applications.

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Friday, November 8, 2013
3:30 p.m.
214 B. H. Snell

Ming-Cheng Cheng
Associate Professor
Dept of Electrical & Computer Engineering
Clarkson University, Potsdam, NY 13699-5720

Thermal Modeling of Semiconductor Devices and Integrated Circuits”.
 

Abstract:

As the integrated circuit (IC) density in semiconductor chips increases aggressively in recent years, the power density in the chips is substantially enhanced. This results in temperature escalation and formation of hot spots in the chips and leads to severe performance and reliability degradation.  Heating has therefore been recognized as one of the major obstacles in developing emerging semiconductor technologies, including 3D stacked IC’s. To understand and minimize the heating effects and to take into account these effects in IC design, capability of predicting thermal profiles and hot spots in semiconductor chips is essential.  Capture of the hot spots in these structures however requires detailed numerical solution that is in general prohibitive for large IC structures.

In this talk, 2 different thermal modeling methods for different levels of IC design will be presented. These methods provide efficient approaches to capture hot spots accurately. The first model is based on the concept of characteristic thermal length to account for heat losses and thermal couplings for heat flow along wires and fins. This physics-based thermal model has been applied to different semiconductor device and circuit structures, including SOI MOSFETs and FinFETs. The second model is based on a reduced order modeling technique using proper orthogonal decomposition (POD).  The approach projects the problem onto a functional space in order to reduce the numerical degrees of freedom. The POD model has been applied to 3D metal-wire and FinFET structures subjected to power pulses initiated by digital signals.  It has been demonstrated that the POD model offers accurate thermal solution as detailed as numerical simulation and is able to reduce numerical degrees of freedom by 5 to 6 orders of magnitude in 3D structure.  Application of a block-based approach using the POD model for large IC structure will also be discussed. 

Chemistry Seminar

Professor Costel Darie of Chemistry and Biomolecular Science (left) and Professor Ming-Cheng Cheng from the Department of of Electrical & Computer Engineering, Clarkson University.

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Friday, November 1, 2013
3:30 p.m.
214 B. H. Snell

Dr. Dawei Liu
Materials Science and Engineering Kazuo Inamori School of Engineering
New York State College of Ceramics Alfred University

“ NANOSTRUCTURED OXIDES WITH MODIFIED SURFACE CHEMISTRY FOR EFFICIENT LITHIUM ION INTERCALATION”.
 

Abstract:

In the past decades, lithium ion batteries have played their important roles in powering small electronic devices. With the rising demand for clean energy, they are now carrying more expectations and being studied for possible applications in more stressful situations, such as those requiring large current densities. As a result, many novel approaches have been developed to gain high energy storage capacities and charge/discharge rates. Nanostructured electrodes are seemingly the most promising candidates for future lithium ion batteries. They possess better gravimetric energy density and better gravimetric power density as compared to bulk electrodes. However, cyclic stability and safety issues, especially at elevated temperatures, are still big concerns for them due to their high surface energy that could induce complicated interface problems. Appropriate modification of the electrode surface chemistry has proved to be highly effective in improving the intercalation capabilities and stability of nanostructured electrodes. It can be realized by a variety of methods e.g. subjecting nanostructured electrodes to carefully designed gas or liquid environment. This seminar presentation will focus on advanced nanostructured oxides with modified surface chemistry as lithium ion storage electrodes that have demonstrated noticeably improved performance.

Chemistry Semistry

Professor Silvana Andreescu (left) and Professor  Dawei Liu from the Department of Materials Science and Engineering,  Kazuo Inamori School of Engineering, New York State College of Ceramics,  Alfred University.

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Department of Chemistry & Biomolecular Science
Department of Physics
Clarkson University
JOINT COLLOQUIUM
 
Friday, October 25, 2013
3:30 p.m.
214 B. H. Snell

Dr. Victor Zhirnov
Semiconductor Research Corporation, Director
Durham, North Carolina
 

"Future Microsystems for Information Processing: Limits and Lessons from the Living Systems."

 

Abstract:

The presentation will address the impact of the physics of extremely scaled information processing devices and systems, with a focus on energy minimization. The fundamental limiting factors for electronic information processors are: 1) the tunneling limit on the minimal size due to small mass of electrons, 2) excessive energy consumption in metal wires used for rigid interconnect systems, and 3) heat generation in a small volume. There are also proposals for alternative future information processing technologies based on information carriers other than electrons, however the potential for using them in future ICT systems remains unclear.

In the second part of the presentation, entirely new information processing concepts are discussed based on learning from examples in nature, specifically, the individual living cell will be considered in the context of information processing. In the paper, a bacterial cell, such as E.coli of about one cubic micrometer volume is shown to be a very efficient and powerful information processor, far surpassing conceivable performance in the same volume by an ultimately scaled semiconductor system. Advances in the science of synthetic biology are beginning to suggest possible pathways for future information processing technologies. It might be possible that some of the physical limits faced by semiconductor technology may in fact be overcome by borrowing from synthetic biology principles.

Chemistry Seminar

Professor Evgeny Katz, Milton Kerker Chaired Professor of Colloid Science (left) and Dr. Victor Zhirnov, Director, Semiconductor Research Corporation, Durham, North Carolina.

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Friday, October 18, 2013
3:30 p.m. 214 B. H. Snell

Dr. James Hougland
Department of Chemistry
Syracuse University


“Chemistry and Biology of Protein Lipidation”

 

Abstract:

Post-translational modifications play an essential role in regulating protein structure, function, and cellular localization.  For example, many proteins undergo lipidation modifications that enhance membrane affinity and modulate protein-protein interactions.  Enzymes that catalyze these modifications must often selectively recognize and modify multiple substrate proteins from among a plethora of non-substrates with similar structures and amino acid sequences, thereby overcoming a significant challenge of molecular recognition.  In many aspects, protein lipidation presents an ideal system for investigating how a small number of chemical modifications can control complex biological pathways.

In our studies of protein lipidation, we focus our work on two forms of modification – protein prenylation by protein farnesyltransferase (FTase) and protein geranylgeranyltransferase (GGTase-I) and acylation of the peptide hormone ghrelin by ghrelin O-acyltransferase (GOAT).  We combine chemical and biological techniques to investigate enzyme selectivity, catalytic mechanisms, and the impact of lipidation on the modified target protein/peptide.  Understanding lipidation enzyme specificity provides insight into the strategies used by these enzymes to recognize wide pools of substrates and will aid in identifying lipidation-dependent pathways involved in biological signaling and regulation.

Chemistry Seminar

Professor Costel Darie of Chemistry and Biomolecular Science Department (left) and Professor James Hougland from the Department of Chemistry, Syracuse University.

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Friday, October 11, 2013
3:30 p.m.
214 B. H. Snell

Professor Thomas M. Holsen
Department of Civil & Environmental Engineering
Clarkson University

"Legacy and Emerging Contaminant Concentrations in Great Lakes Fish: Pushing the Science"
 

Abstract:

The Great Lakes Fish Monitoring and Surveillance Program is funded by the U.S. Environmental Protection Agency’s Great Lakes National Program Office. This program focuses on monitoring contaminant trends in the open waters of the Great Lakes (using fish as biomonitors). Historically this program has focused on legacy contaminants like PCBs and pesticides that are ubiquitous in the environment.  Recently the focus has moved towards new classes of contaminants like flame retardants, musks, pharmaceuticals and other chemicals that are widely used in industry. In this talk an overview of the numerous threats facing the Great Lakes will be presented including trends of contaminant concentrations in top predator fish and our current efforts to identify new chemicals that are impacting the Great Lakes.  

Chemistry Seminar

Professor Costel Darie of Chemistry and Biomolecular Science (left) and Professor Thomas M. Holsen from the Department of Civil & Environmental Engineering, Clarkson University.
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Friday, October 4, 2013
3:30 p.m.
214 B. H. Snell
 

Dr. Christof Grewer

Department of Chemistry, Binghamton University

"Functional analysis of ion-coupled solute transporters"

Abstract:

Small organic molecules, such as amino acids that are important for cellular function and metabolism, are transported across cell membranes by specific transporter proteins.  If the transport is uphill, against a transmembrane concentration gradient of the organic molecule, it is often coupled to the co- or counter-transport of a driving inorganic ion, which provides free energy by flowing down its own transmembrane concentration gradient.  In mammalian cells, active amino acid transport is often driven by the co-transport of Na^+ ion(s).  The transporters are thought to catalyze transport by simultaneously binding extracellular amino acid and Na+ ion(s) in their transmembrane domain, followed by a structural rearrangement of the transporter-amino-acid-Na+ complex to allow dissociation of the substrates into the intracellular space.  Therefore, transport is a multistep process that is composed of a number of sequential, individual reaction steps.  Here, I describe ongoing efforts in our laboratory to dissect the mechanism of this multistep transport reaction, by applying rapid chemical kinetic techniques and measuring thermodynamic parameters of amino acid interaction with the transport protein in two different model systems, the glutamate transporter EAAC1, and the neutral amino acid transporter SNAT2.  We have also identified novel sites of interaction with the cation in these transporters. 

Chemistry Seminar 

Professor Silvana Andreescu (left) and Professor Christof Grewer from Binghamton University.

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Friday, September27, 2013
3:30 p.m. 214 B. H. Snell
 

Professor Diana S. Aga

Chemistry Department, University at Buffalo, SUNY, Buffalo NY

"Emerging Contaminants and their Metabolites: Analysis, Treatment, and Implications for Public Health"

 

Abstract:

This presentation will focus on our current research activities on the degradation and metabolism of Emerging Contaminants, which include previously neglected pollutants (e.g. pharmaceuticals) and recently used industrial chemicals (e.g. brominated flame retardants) that end up in the environment. These compounds that are known to contaminate our environment can have adverse effects on public health, including disruption of the endocrine system, carcinogenic effects, and promotion of antibiotic resistance in pathogenic bacteria. Residues of pharmaceuticals are introduced into the environment via a number of pathways, primarily from discharges of wastewater treatment plants (WWTPs), or land application of animal manure. This presentation will include results from our recent work on the effectiveness of advanced oxidation process, followed by biodegradation in removing emerging contaminants in wastewater. I will also present some data on the changes in estrogen concentrations in dairy manure using anaerobic digestor. Finally, the analytical challenges involved in identifying and quantifying emerging contaminants and their metabolites in environmental and toxicological studies will be highlighted in the talk.

Chemistry Seminar

Professor Silvana Andreescu (left) and Professor Diana S. Aga from SUNY, Buffalo, NY.

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Friday, September 20, 2013
3:30 p.m.
214 B. H. Snell

Professor Guojun Liu
Chemistry Department
Queens University, Kingston, Ontario
 
"Designer Architectural Materials of Block Copolymers"

Abstract:

Block copolymers consist of two or more distinct chains of repeating molecular units.  This multi-component feature allows block copolymers to form a vast array of elaborate and ordered nanostructures in solution or the solid state.  More exotic block copolymer nanostructures can be created using novel generic methods developed by us.  While the diversity and complexity of these structures are fascinating in their own right, these materials are also extremely useful.  They can provide robust protective coatings that repel water- and oil-based pollutants alike or particles that reduce friction and engine wear. 

seminar

Professor Sergiy Minko, the Egon Matijevic' Chair of Chemistry and Biomolecular Science (left) and Professor Guojun Liu from Queens University, Kingston, Ontario.

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Friday, September 13, 2013
3:30 p.m.
214 B. H. Snell

Mingjie Zhong
Clarkson University

"Role of 1,2,4-Triazole as a Passivating Agent for Cobalt during Post-Chemical Mechanical Planarization (CMP) Cleaning"

Abstract:

Cobalt (Co) has been considered as one of the candidates for the barrier material in copper (Cu) interconnects. As a metal that is less noble than copper, Co poses two challenges for integration into the production of interconnects. For example, during the post-CMP cleaning step, corrosion of Co and galvanic corrosion between Co and Cu may occur. To minimize such corrosion, a corrosion inhibitor is often added into the post-CMP cleaning solution. The present study investigates the interaction between these metals and a representative corrosion inhibitor, 1,2,4-triazole (TAZ). More specifically, this study uses various analytical techniques to elucidate the mechanism with which TAZ reduces the corrosion current density of Co and Cu and prevent the galvanic corrosion between the two metals. Furthermore, it is found that TAZ preferentially forms a passivating film on Co surface containing cobalt hydroxide (Co(OH)2), not on oxide free metallic Co surface. The corrosion protection for cobalt at pH 10 in presence of TAZ is mainly attributed to the physisorption and chemisorption of TAZ molecules on oxide-covered Co surface. It is anticipated that the same passivation mechanism may also be applicable to other structurally similar corrosion inhibitors.

Chemistry Seminar

Professor Devon Shipp with graduate student Mingjie Zhong.

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Friday, September 6, 2013
3:30 p.m.
214 B. H. Snell

Armand Ngounou
Biochemistry and Proteomics Group

"Functional investigation of the tumor differentiation factor (TDF) protein"

Abstract:

Recently, a novel protein was discovered in the human pituitary. This protein has a specific differentiation activity on breast and prostate cancer cells and was named tumor differentiation factor (TDF).

However, the function and mode of action of TDF are still not uncovered. Here, we present preliminary findings from the analysis of the secretome as well as cell lysates from treated and untreated cells by nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) that hopefully will allow us to gain some insights into the possible function of TDF protein and of TDF signaling pathway. We also investigated the presence of tdf mRNA transcripts in rat brain and of the TDF protein in zebra fish. Altogether, these data will shed light on the mode of action of TDF as a differentiating agent and speed its potential applicability in the treatment of prostate and breast cancers.

Chemistry Seminar

Professor Costel Darie with graduate student Armand Ngounou.

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Friday, August 30, 2013
3:30 p.m.
214 B. H. Snell 

Dr. Richard Stephenson
President and CEO of Stephenson & Associates, Inc., Silicon Valley, California
 
"Aspects of Synthesis and Performance Comparisons of LSM Materials for Solid Oxide Fuel Cell Applications"

Abstract:
Many alternative energy solutions are actively being explored and employed to meet the ever growing demands of power generation.  One of the most promising is solid oxide fuel cell (SOFC) technology. Vital to the electrode arrangement of SOFC’s is the cathode material.  A variety of synthesis methodologies are used industrially to manufacture suitable particulate materials and are compared.  Performance characteristics as cathode layers are examined.

Chemistry Seminar

From left: Senior University Professor Richard Partch, Dr. Richard Stephenson, President and CEO of Stephenson & Associates, Inc., Silicon Valley, California and CAMP Distinguished Professor Dan Goia.

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Spring - Summer 2013 Seminar


Monday, July 1, 2013
M.S. Defense 2:00 p.m. CAMP 372

Yuanfang Lu
Chemistry & Biomolecular Science Department Clarkson University

"Post-Chemical Mechanical Planarization Cleaning: A NiP Substrate Study"

Abstract: With the capacity of hard disk drives (HDDs) increasing by 60% per year, it is required that the surface of HDD substrates reaches atom-scale planarization after chemical mechanical polishing (CMP). Surface roughness, particle residues, metallic contaminants and corrosion spots on the disk surface may result in HDD crashes. Therefore, the surface of HDD must be ultra-clean. During post-CMP cleaning, the cleaning solution plays a key role in cleaning efficiency. In this study, both acidic and alkaline cleaner solutions were investigated for HDD post-CMP cleaning. Surfactant TMN10 are found to be efficient in the cleaning solution and pH is also a dominant factor of cleaning efficiency. Atomic force microscopy (AFM) and optical microscope analysis indicated that both acidic and alkaline cleaners facilitate the removal of silica particles from NiP substrates and alkaline cleaner performs better than acidic cleaner. X-ray photoelectron spectroscopy (XPS) results revealed that different surface layers formed on the NiP after the acidic and alkaline cleaning treatments.

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Friday, June 7, 2013
M.S. Defense

9:00 a.m.
CAMP 372

Yan Mu
Chemistry & Biomolecular Science Department
Clarkson University

"Chemical Mechanical Planarization of Hard Disk Drive (HDD) Substrates"

Abstract:
Nickel–Phosphorous (NiP) materials have been widely used as computer hard disk drive (HDD) substrates. With the rapid increase of data storage density on computer HDDs, the operation distance between read/write head and disk surface has fallen to just a few nanometers. In order to avoid crash of the read/write head onto the disk, the NiP substrate must be perfectly flat and free of defects such as pits, scratches, and bumps. Chemical mechanical planarization (CMP) has been selected as the best process to produce high quality surface finish during the manufacturing of NiP substrates for HDD applications. The CMP process includes the use of a pad and slurry that usually contains a particle-based abrasive, oxidizers and other additives.  In this talk, the effect of particle size, particle concentration and hydrogen peroxide as an oxidizer on the CMP performance of NiP hard disk substrates were investigated. X-ray photoelectron spectroscopy revealed the chemical changes of a NiP substrate surface, which aided the understanding of the mechanism of the polishing process. Benzotriazole (BTA) as a passivating agent was introduced into the slurry for the first time to decrease the surface roughness (Ra).

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Friday, May 31, 2013
PhD Defense

9:00 a.m.
213 B.H. Snell Hall

Izabela Sokolowska
PhD Candidate,
Chemistry & Biomolecular Science Department
Clarkson University

"Investigation of Tumor Differentiation Factor (TDF) and its putative receptor (TDF-R)"

Abstract:
TDF is an under-investigated 12 kDa protein produced by the pituitary and secreted into the blood stream. TDF protein and TDF-P1 (a peptide selected from the open reading frame of TDF) have differentiation activity on breast and prostate cancer cells, suggesting a possible endocrine role. Yet, to date TDF has no definitive function and its characterization is incomplete.

Therefore to investigate the signal transduction pathways that are activated by TDF we used TDF-P1 to identify and purify TDF-R candidates from human breast and prostate cancer cell. We identified members of the Heat Shock 70 ka family of proteins as potential receptor candidates (GRP78 and HSP70). These results also suggest that TDF protein may interact with GRP78 and/or GRP78 in complex with HSP70 to promote differentiation in breast and prostate cancer cells through a steroid-independent pathway.

To gain more knowledge about TDF protein itself we over-expressed and characterized recombinant TDF (rTDF). Our experiments suggest that rTDF is expressed mostly as an insoluble monomeric form. Mass spectrometry-based analysis was used as a direct evidence of TDF existence. In addition, we assessed the potential three dimensional structure of TDF including disulfide connectivities using molecular modeling.

Lastly, we analyzed distribution of TDF expression in the body. TDF mRNA was initially detected in brain but not in other tissues such as heart, lung, liver, pancreas or skeletal muscles. However it was not known precisely which cells in the brain produce TDF. Therefore, we investigated the distribution of TDF protein in the rat tissues using fluorescent immunohistochemistry (IHC). TDF protein was expressed in select cells in breast, pituitary and select neurons in brain. Double-staining for neuronal and glial markers showed that TDF is expressed in some neuronal cells but not in astrocytes. Further experiments revealed that the GABAergic subtype of neurons seem to be TDF-positive.

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Friday, May 3, 2013
212 B.H. Snell Hall

Yuanfang Lu
Chemistry & Biomolecular Science Department
Clarkson University


"Post-Chemical Mechanical Planarization Cleaning: A NiP Substrate Study"

Abstract:
With the hard disk drive (HDD) capacity increasing by 60% per year, the surface of HDD substrate has reached atom-scale planarization after chemical mechanical polishing (CMP). Surface roughness, particle residues, metallic contaminants and corrosion spots on the disk surface may lead to head crashes, so the surface of HDD must be ultra clean. During post-CMP cleaning, cleaning solution plays a key role in cleaning efficiency. In this study, both acidic and alkaline cleaners were investigated for HDD post-CMP cleaning. Atomic force microscopy (AFM) and optical microscope analysis indicated that both acidic and alkaline cleaners facilitate the removal off silica from NiP substrates. And XPS is also used to explore the cleaning mechanism.

Chemistry SeminarProfessor Devon Shipp with graduate student Yuanfang Lu.

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Friday, April 26, 2013
212 B.H. Snell Hall

Professor James F. Rusling

Chemistry Department, University of Connecticut
Department of Cell Biology, University of Connecticut
School of Chemistry, National University of Ireland at Galway

"Nanoscience-based microfluidic arrays for cancer diagnostics by detection of biomarker panels"

Abstract:
Sensitive measurement of biomarker proteins overexpressed in individuals with cancer holds great promise for early detection and personalized therapies. Broad implementation of diagnostic strategies requires reliable, inexpensive devices to measure multiple proteins in patient samples. Emerging aspects of nanotechnology and microfluidics provide exciting new opportunities to design and fabricate such devices. In this talk, we discuss advances for the ultrasensitive multiplexed detection of proteins in patient serum. Approaches are based first on nanostructured sensor surfaces coupled with novel labeling strategies that achieve very large signal amplification. Microfluidic immunoarrays utilizing amperometry, electrochemiluminescence, or surface plasmon resonance are interfaced with microfluidics to achieve unprecedented sensitivities for detection of biomarker proteins into the low fg/mL range in serum. High sensitivity can also be traded for speed to achieve immunoassays in less than 10 min.

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Friday, April 19, 2013
212 B.H. Snell Hall

Dr. Daniel S. Spellman

Principal Scientist, Group Leader, Proteomics and Metabolomics, West Point Molecular Biomarkers (MBMx), PPDM, Merck Research Laboratories

"Mass Spectrometry-based Biomarkers as Tools for Decision Making in the Drug Development Process"

Abstract:
Identification of biomarkers from accessible tissues and biofluids is important to drug discovery and development, with the goal of enabling decision making at critical stage gates during the development process. A general proteomic approach for the discovery and identification of protein biomarkers, differential mass spectrometry (dMS), based on the analysis of full scan mass spectrometry data, has been previously described. Examples of how such a quantitative label-free proteomics approach can be applied to characterize changes resulting from pharmacological intervention, disease state, and observed clinical characteristics will be described.  A workflow for translating protein markers from discovery to robust, quantitative triple-quadrupole mass spectrometry assays that are more amenable to measuring large numbers of clinical samples will also be presented.

Chemistry SeminarDr. Daniel Spellman from Merck Research Laboratories (left) and Professor Costel Darie.

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Friday, April 12, 2013
212 B.H. Snell Hall

Erica Sharpe

Chemistry Department
Clarkson University

"Portable nanoparticle-based sensors for characterization of antioxidant-containing samples"

Abstract:
With increased awareness of nutrition and the advocacy for healthier food choices, there is need for a simple, easy-to-use test that can reliably measure the quality and content of food antioxidants.  We report development of the first portable nanoparticle-based sensor for the detection of antioxidants.  It offers three tiers of analysis, which sets it apart from other antioxidant assays: it is capable of analyzing samples for 1) antioxidant activity 2) constituent concentration 3) constituent identity. The platform is based on immobilized nanoparticles that show a distinct color change in the presence of antioxidants by means of redox and surface chemistry reactions.  The sensor operates in a variety of environments and food products; it does not require specialized equipment or external reagents and can be used by unskilled personnel as well as the general population. Multiple sensing-components have been found to produce unique colorimetric responses, creating opportunities for cross-validation of assay results using more than one sensor type. This presentation will discuss fabrication and performance evaluation of this assay for the detection of common food-antioxidants, and describe functionality of the assay in real samples including tea infusions, botanical extracts, and human serum. This sensing method will be compared to a commonly used USDA assay; and future work including the development of a high-throughput analysis method and the creation of a portable electronic color-reference database will be discussed.

seminar
Professor Silvana Andreescu with graduate student Erica Sharpe.

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Friday, April 5, 2013
212 B.H. Snell Hall

Yan Mu

Chemistry Department
Clarkson University

"Chemical Mechanical Polishing of Hard Disk Drive (HDD) Substrates: preliminary experimental investigation"

Abstract:
Nickel–Phosphorous (NiP) substrates have been widely used as computer hard disk drive (HDD) substrate. With rapid increase of data storage density on computer HDD, the operation distance between read/write head and disk surface has fallen into few nanometers. In order to avoid crash of read/ write head on to the disk, the NiP substrates must be perfectly flat and free of defects such as pits, scratches, and bumps. Chemical mechanical polishing (CMP) can produce high quality surface of substrates with NiP plating for HDD application. In this talk, I will discuss the effect of particle size, hydrogen peroxide as an oxidizer and BTA as a passivating agent in chemical mechanical planarization (CMP) of hard disk substrates with nickel–phosphorous plating. NiP-CMP was studied using material removal rate measurement and etching rate measurements in solutions containing the oxidizer and passivating agent. X-ray photoelectron spectroscopy was also done to understand the mechanism of NiP-oxidant interaction during polishing.

Yan Mu Talk
Professor Devon Shipp with graduate student Yan Mu.

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Friday, April 5, 2013
9:00 a.m.
169 B.H. Snell Hall

Lu Lu 
Chemistry Department
Clarkson University

"Preparation and Formation Mechanisms of Metallic Particles with Controlled Size, Shape, Structure and Surface Functionality"

Abstract:
Due to their excellent conductivity and chemical stability, particles of silver (Ag), gold (Au), copper (Cu) and their alloys are widely used in the electronic industry. Other unique properties extend their uses to the biomedical, optical and catalysis fields. All these applications rely on particles with well controlled size, morphology, structure, and surface properties. Chemical precipitation from homogeneous solutions was selected as the synthetic route for the investigations described in this work. Based on the evaluation of key process parameters (temperature, reactant concentrations, reactant addition rate, mixing, etc.) the general formation mechanisms of metallic particles in various selected precipitation systems were investigated and elucidated.

Five different systems for preparing particles with controlled size, morphology, structure and surface functionality are discussed. The first system involves the precipitation of Ag nanoparticles with spherical and anisotropic (platy or fiber-like) morphology. It will be shown that the formation of a stable Ag/Daxad complex has a significant impact on the reaction kinetics, and the chromonic properties of Daxad molecules are responsible for the particle anisotropy. In the second system, Au-Ag core-shell nanoparticles were prepared in aqueous solution by a two-step precipitation process. The optical properties of these particles can be tailored by varying the thickness of the Ag shell. It was also determined that the stability of the bimetallic metallic sols depends on the Cl- ions concentration in solution. The third system discussed deals with the preparation by the polyol process of well dispersed Cu nanospheres with high crystallinity and excellent oxidation resistance. We show that the heterogeneous nucleation (seeding) approach has significant merit in controlling particle size and uniformity. The functionalization of the Au nanoparticles surface with glutathione molecules is discussed in the next section. The developed method is used to quantify the maximum adsorption load of glutathione on the gold particles and assess their potential in biomedical applications. Finally, a process capable of generating uniform Ag particles with diameters ranging from 80 nm to 60 µm and with controlled crystallinity/internal structure is described.

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Friday, March 29, 2013
212 B.H. Snell Hall

Dr. Gabriel Caruntu

Chemistry Department
University of New Orleans

"Polar Ordering in Nanoscale Ferroic Oxides and its Control via Colloidal Processing"

Abstract:
Research on nanoscale ferroic oxides has developed at a truly relentless pace due to their wide variety of outstanding properties and limited availability of similar materials to meet the increasing technological demands of present and future applications. Although of prime technological interest is the existence of a switchable polarization with direct applicability in memory devices for computer bit storage, these materials are the leading candidates for the design of novel probes in cellular imaging, due to their biocompatibility and outstanding optical properties. Although much progress has been made in understanding the proprieties of nanoscale magnetic materials, the current knowledge is far less advanced in the case of low-dimensional ferroelectrics despite their enormous technological potential.  Based upon empirical observation, it is believed that when the size of a ferroelectric is reduced, the polar ordering decreases exponentially and vanishes below a critical size. Despite years of intense research in this field, a clear understanding whether a polar ordering still exist in low-dimensional perovskite structures is still lacking and several fundamental questions should be addressed before nanoscopic perovskites become feasible for applications.

In this talk I will try to address this long-standing fundamental question by using, aggregate-free, monodisperse colloidal nanocrystals of BaTiO3, an archetypal ferroelectric material as a model system. Selective solvent evaporation techniques enable the manipulation and isolation of individual nanoparticles allowing the examination of the local structural and electrical behavior at nanometer length scales. Although the average structure of the nanocrystals seems to be metrically cubic, at microscopic scales they retain an acentric structure down to a size of 5 nm, the smallest accessible length scale. Moreover, in-situ electron microscopy investigations revealed that nanocrystals retain a primarily linear, monodomain dielectric polarization, despite the theoretical predictions of vortice-like structures in nanoscale ferroelectrics. These findings they provide for the first time a glimpse of the structural and electrical manifestation of the polar ordering down to its ultimate size limits. Such fundamental knowledge of the nanoscale polar ordering can potentially result in the improvement of the actual design technologies in smart perovskite materials with programmable ferroelectric, dielectric and piezoelectric properties.

Seminar
Professor Gabriel Caruntu from University of New Orleans (left) and Professor Egon Matijević, Victor K. LaMer Chair of Colloid and Surface Science at Clarkson University.

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Friday, March 19, 2013,
11:00 a.m
212 B.H. Snell Hall

Dr.Manfred Stamm
Leibniz Institute of Polymer Research in Dresden

"THE CHALLENGE OF POLYMER NANOSTRUCTURES AND FUNCTIONALITIES AT SURFACES: FROM SINGLE MOLECULES TO BRUSHES AND NANOTEMPLATES"

Manfred Stamm graduated in physics at the University of Frankfurt am Main/Germany in 1974, followed by his PhD on determination of polymer chain conformations at Mainz University in the group of Prof. E.W. Fischer.

He then spent three years at the CNRS and Max‐Planck Institute of Solid State Physics in Grenoble/France. After some neutron work at Forschungszentrum Jülich and interface analysis at Brookhaven National Lab/USA, he got his habilitation at University of Mainz in physical chemistry on the investigation of polymer surfaces and interfaces with nanometer resolution. He became staff scientist at the Max Planck Institute on Polymer Research in Mainz before he took a professorship on physical chemistry of polymeric materials at the Technische Universität Dresden in 1999. At the same time, he became Head of the institute of Physical Chemistry and Physics of Polymers at the Leibniz Institute of Polymer Research in Dresden. His main areas of work are connected with nanostructured polymers, polymer interfaces, advanced polymer materials and characterization techniques.

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Friday, March 15, 2013
212 B.H. Snell Hall

Katie L. Poetz
Chemistry Department
Clarkson University

"Erosion and Release Studies from Polyanhydrides"

Abstract:
Polyanhydrides are degradable polymers known to often undergo surface erosion, which is where the erosion is limited to the surface of the polymer.  This is beneficial because this allows for near zero-order release kinetics of drugs in addition to the mechanical properties of the polymer being conserved throughout most of the degradation process.  Polyanhydrides have been traditionally synthesized through polycondensation reactions, which limits their applications. In this work, we have successfully synthesized polyanhydrides through thiol-ene polymerizations.  Thiol-ene polymerizations occur via radical intermediates but molecular weight development is akin to what is seen in step-growth polymerizations.  These unique features decrease the susceptibility to undergo shrinkage, oxygen inhibition and are also able to form a more uniform crosslink density. We have shown that these polymers undergo surface erosion, in addition to exhibiting near zero-order release kinetics for the release of a drug mimic. 

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Friday, March 8, 2013
212 B.H. Snell Hall

Xing X. Liu
Chemistry Department
Clarkson University

"Templated Functionalization of Recombinant Proteins"

Abstract:
Application of synthetic organic chemistry for modification of proteins has found a common use in academic research and industry. The conventional method for production of protein conjugates has changed little in the last twenty years mostly relying on reactions of side chains of cysteine and lysine residues. Due to the presence of large numbers of similar reactive amino acid residues in proteins common synthetic methods generally produce complex mixtures of products which are difficult to separate. The lack of selectivity in these reactions constitutes the major challenge for preparation of pure protein derivatives. We explore a new approach toward functionalization of recombinant proteins that involves formation of a covalent bond with a hexahistidine tag (his-tag) present in recombinant proteins. This reaction will be specific to hexahistidine sequence and will not interfere with other amino acid residues in the molecule of protein. The approach is based on formation of a complementary complex of the hexahistidine sequence with a metal cation chelated by ligand bearing a group capable of subsequent formation of a covalent bond with one of the histidine residues of the His-tag. We will discuss reactions of alkylation of histidine residues with Baylis-Hillman esters and pathways to increase activity of these agents, design and synthesis of ligands combining Baylis-Hillman group with nitrilotriacetate function, choice of appropriate metal cations to template this reaction, and our model alkylation of N-acetylhexahistidine polypeptide by this approach. Finally, we will discuss application of this approach for chemoselective derivatization of recombinant Protein A with a fluorescent group through two step methodology using a "click" cycloaddition reaction.

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Friday, March 1, 2013
212 B.H. Snell Hall

Olivia Z Durham
Chemistry Department
Clarkson University

"Water-Borne Crosslinked Polymer Microspheres Prepared by Thiol-Ene Suspension Photopolymerization"

Abstract:
We present here the first instance of spherical, crosslinked polymer microspheres that are prepared by a water-borne thiol-ene suspension photopolymerization process.  The reaction mechanism behind thiol-ene chemistry is well understood and offers many practical advantages to polymer synthesis for water-based systems as well as for the development of multifunctional materials.  The step-growth mechanism of a thiol-ene polymerization means that the production of highly crosslinked water-borne microspheres is fundamentally different from the chain-growth polymerizations normally associated with emulsion, dispersion, and suspension polymerizations of acrylic and styrenic monomers.  We demonstrate here that thiol-ene polymerizations can be conducted in a water-borne system to yield crosslinked spherical particles that have diameters in the range of sub-micron to hundreds of microns.  Homogenization energy (mechanical shear), surfactant concentration, and surfactant species greatly influence colloidal stability, particle size, and the particle size distribution of the microspheres.  Further development of this approach offers great potential for various applications and additional research into water-borne materials.

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Friday, February 15, 2013
212 B.H. Snell Hall

Dr. Karina Ckless
Chemistry Department
SUNY Plattsburgh, Plattsburgh NY

"Redox regulation of NLRP3-inflamassome"

Abstract:
The focal point of this presentation will be on how reactive oxygen species (ROS), commonly known as “free radicals”, participate and even enhance the inflammatory response. Inflammatory diseases in general include several conditions that are associated in some extent with inappropriate production of pro-inflammatory mediators, the cytokines, such as interleukin 1β (IL-1β). The secretion of IL-1β by inflammatory cells involves activation of the muti-protein complex called NLRP3-inflammasome. In addition to inappropriate production of cytokines, an inflammatory process also can generate high amounts of ROS. These ROS can promptly attack important macromolecules in our cells, such as proteins. Attack of ROS on proteins is known as protein oxidation, or oxidative post-translational modifications (oxPTM). When proteins involved in an inflammatory complex protein network undergo oxidation they can become dysfunctional. Dysfunctional proteins can be responsible for augmentation of inflammatory processes, including those that are in the NLRP3-inflamassome/ IL-1β secretion.  In this presentation we will focus on the participation of ROS on the oxidation of NLRP3, the major protein responsible for regulating the pro-inflammatory cytokine, interleukin 1β. We will also discuss the contribution of mitochondria as the main source of ROS that are potentially causing oxidation of NLRP3 and the consequences for the augmented secretion of IL-1β by inflammatory cells.

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Friday, February 8, 2013
212 B.H. Snell Hall

Dr. Vivekananda Shetty
Progenics Pharmaceuticals, Inc
Tarrytown, NY

"Investigation of Cancer Associated Sialylation Changes in N-linked Glycopeptides by Quantitative Proteomics"

Abstract:
Over the years a great deal of attention has focused on the study of glycosylation aberration in N-linked glycopeptides due to the implication of specific glycosylation changes, in particular sialylation changes in cancer. The level of sialic acid was observed to be significantly elevated in the N-linked glycoproteome of patients with many types of cancers compared to the healthy controls. In view of this, we recently developed a novel lectin-directed tandem labeling (LTL) quantitative proteomics method to probe sialylation changes between normal and cancer serum samples. We employed the LTL method to unambiguously identify N-linked sialylation sites and accurately identified the changes in sialylation between normal and cancer serum samples based on the N-deglycosylated peptide analysis. These results were further validated by non-glycosylated peptide analysis as well as by western blot experiments to understand if these changes indeed occur at the N-linked glycosylation sites. The results of the sialylation aberration analysis of both prostate cancer and ovarian cancer N-linked glycoproteome will be discussed in this presentation.

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Friday, January 25, 2013
212 B.H. Snell Hall

Shay Mailloux

Chemistry Department
Clarkson University

"Iron-Alginate Systems for Controlled Signal-Responsive Electrochemical Release"

Abstract:
Switchable electrode interfaces, functionalized with signal-responsive materials, have become useful in a diverse range of applications, specifically for biocomputing, “smart” biosensing, and biomedical applications. Iron-alginate allows for an electrochemically responsive matrix capable of the entrapment and release of biomolecules, triggered by applied potential from en external source or from a second biochemically responsive electrode. Two systems are demonstrated.

Lysozyme is entrapped in the alginate matrix and released upon application of an electrochemical signal. The bactericidal outcome of the released lysozyme is measured using Gram-positive bacterium and shown to be comparable to the commercial product before entrapment. In the consequent project, the release system is advanced to releasing upon application of a biochemical stimulus using a second electrode with immobilized enzyme, PQQ-GDH, producing a negative potential in the presence of glucose. The alginate/PQQ-GDH system is shown to release the ‘drug’ only in the presence of glucose. Leakage is controlled using Au nanoparticle supports. Versatility of the system allows for a variety of drugs to be used, given that the Au nanoparticles can be easily functionalized.

The systems demonstrate straightforward, applicable concepts for future development in diabetes and cancer treatment, centered on ‘Sense and Act’ methodology, resulting in unparalleled rapid injury diagnosis and treatment.

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Friday, January 23, 2013
9:30 a.m.
CAMP 372

Yongqing Lan
Chemistry Department
Clarkson University

"Low Defect Chemical Mechanical Planarization of Copper"

Abstract:
Chemical mechanical planarization (CMP) has become an essential step in the fabrication of ultra-large-scale integration (ULSI) devices. Continuous miniaturization and introduction of reactive and fragile materials, such as copper and low K dielectrics, require every step of the manufacturing process including CMP process with low defects for each generation of the new devices. The key objective of this work is to explore low defect CMP process solutions at a fundamental level from a slurry formulation point of view. The use of specialty organic polymer particles to carry out the functions of abrasive, stability, and selectivity control is investigated.  In order to achieve these functions, low stiffness polymer particles are surface modified with chemical groups and tested in copper CMP. The performance of polymer particle containing slurries was found dependent on selection of functional groups. However, polymer particles carrying strong reactivity often generate heavy residues on polished copper substrate. Surface analysis indicates that the residues are mainly polymer particle films related to strong adsorption of polymers on the copper film during polishing. Solutions to eliminate the polymeric residue from copper film by adjusting reactivity of functional groups or slurry formulation were studied.  Hybrid inorganic/organic, organic/organic abrasives, and thermally sensitive polymers were also tested for low defect copper CMP. Aspects of slurry handling, a process that may cause particle agglomeration and lead to severe damage to the substrate during polishing, were also investigated

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Friday, January 18, 2013
212 B.H. Snell Hall

Izabela Sokolowska

Chemistry Department
Clarkson University

"Characterization of Tumor Differentiation Factor (TDF), novel factor expressed in select neurons"

Abstract:
Tumor Differentiation Factor (TDF) is a 17 kDa protein produced by the pituitary and secreted into the blood stream that has differentiation activity on breast and prostate cancer cells.  Yet, to date TDF has no definitive function and its characterization is incomplete. To gain more knowledge about TDF protein we over-expressed and characterized recombinant TDF (rTDF). Our experiments suggest that rTDF is expressed mostly as an insoluble monomeric and dimeric form. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified peptides that are part of the TDF protein. So far, the existence of TDF was demonstrated only through indirect methods (mRNA and Western Blotting identification), therefore our mass spectrometry identification is the first direct proof of TFD existence. In addition, we assessed the potential three dimensional structure of TDF with disulfide as its connectivity using molecular modeling, which suggests linkage between four cysteine residues within TDF (Cys17 – Cys98 and Cys70 – Cys97).

TDF was discovered indirectly in pituitary extract almost a decade ago. cDNA of tdf gene encoding a 108 amino acids was isolated from human pituitary cDNA library. TDF mRNA was detected in brain but not in other tissues such as heart, lung, placenta, liver, pancreas or skeletal muscles. However TDF has an unclear function and it is not known precisely which cells in the brain produce TDF. Therefore, we investigated the distribution of TDF protein in the rat brain using fluorescent immunohistochemistry (IHC). TDF protein was expressed in pituitary and select cells in brain. Double-staining for neuronal and glial markers showed that TDF is expressed in some neuronal cells but not in astrocytes. Further experiments revealed that the GABAergic subtype of neurons seem to be TDF-positive. These cells are inhibitory and therefore may counteract excitatory glutamate release during brain insults or disease, conferring neuroprotection. A neuroprotective role of TDF is further supported by its upregulation by oxidative stress in cultured neuroblastoma cells. In addition, we found that TDF protein is expressed in previously unreported select cells of mammary and prostate glands. It may suggest that TDF is a novel factor derived from select neurons in central nervous system (CNS) and pituitary with yet unknown functional activity on breast and prostate.

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Friday, January 11, 2013
212 B.H. Snell Hall

Dr. Steven R. Goodman
Institute of Biomedical Sciences and Technology
SUNY Upstate Medical University

"The Proteomics and Interactomics of Sickle Cell Disease"

Abstract:
My red blood cell (RBC) studies began over 30 years ago with the co-discovery of the spectrin membrane attachment protein subsequently named ankyrin. My laboratory worked out many of the protein interactions that make up the RBC membrane skeleton and then in 1981 we published an article in the Proceedings of the National Academy of Science that demonstrated for the first time that spectrin was present in diverse eukaryotic cells in addition to RBCs. This study led, over the next twenty years, to my laboratory’s complete characterization of the location, sequence, and interactions of multiple spectrin isoforms in brain and the demonstration that the axonal isoform plays an essential function as an initial docking site for small synaptic vesicles at the active zone of the presynaptic plasma membrane.

We also turned our attention to the role of the RBC membrane skeleton in hemolytic anemias including sickle cell disease. We demonstrated how oxidative stress leads to altered spectrin and actin causing the locked membrane skeleton that is the molecular basis of the irreversibly sickled cell. We also demonstrated how this altered redox status in sickled RBCs leads to a defective Gardos Channel, potassium loss, and dehydration of Sickle Cell RBCs. This work led to our determining that n-acetyl cysteine (NAC) can block dense ISC formation in vitro and in phase II clinical trials. Indeed, in the phase II clinical trial the end result was that crisis rate could be lowered by 60% in sickle cell subjects receiving 2400 mgs of NAC per day.

Over the past eight years we have performed the first complete study of the RBC proteome, demonstrated how it changes in sickle cell disease, how it is affected by drug treatments (pharmaco-proteomics) and most recently demonstrated twenty one monocyte protein biomarkers that are predictive of sickle cell crisis rate. These latter studies could transform the sickle cell field by laying the groundwork for personalized medicine for sickle cell patients that will be able to be applied within the first few months of life. A by-product of our proteomic studies on the RBC was the discovery of proteasomal subunits where the dogma had been that mature RBCs contain no proteasomal activity. Our subsequent work has demonstrated that RBCs do indeed contain functional 20S proteasomes that can degrade specific proteins.

We performed the first interactome mapping on erythrocytes. We analyzed the normal and sickle cell interactome using network centrality measures, statistical clustering methods, and most recently the Voronoi Diagram for Graphs (VDG). We were the first to use VDG to assess interactome networks and demonstrated that this technique is superior to network centrality measures and statistical clustering methods in that it tells which other proteins in a cluster are most affected by the disease altered protein; also it has a shorter computational running time.  This lecture will focus primarily, but not exclusively, on the last eight year’s research.

Professor Peploski