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2012

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Kleine Christliche Gemeinschaften Als Neuer Weg, Kirche Zu Warden – Gegenwart, Fortschritte Und Zunkunft, Agbonkhianmeghe E. Orobator Jan 2012

Kleine Christliche Gemeinschaften Als Neuer Weg, Kirche Zu Warden – Gegenwart, Fortschritte Und Zunkunft, Agbonkhianmeghe E. Orobator

Theology Faculty Research and Publications

No abstract provided.


The Limits Of The New Deal Analogy, Barry Cushman Jan 2012

The Limits Of The New Deal Analogy, Barry Cushman

Journal Articles

The past three years of the Obama Administration inevitably have elicited comparisons between the present day and the era of President Franklin D. Roosevelt’s New Deal. While frequently illuminating, such comparisons often overlook an important point that many may have forgotten: compared with the major reform initiatives undertaken during President Obama’s tenure, a review of the roll call votes reveals that the measures enacted by the New Deal Congresses enjoyed a remarkable degree of bipartisan support. In addition, the Democrats enjoyed large majorities in the House of Representatives from 1933 forward, and a filibuster-proof majority in the Senate after 1934. …


A Buffett Rule For Social Security And Medicare: Phasing Out Benefits For High Income Retirees, Samuel C. Thompson Jr. Jan 2012

A Buffett Rule For Social Security And Medicare: Phasing Out Benefits For High Income Retirees, Samuel C. Thompson Jr.

Faculty Scholarship

No abstract provided.


Bifunctional Bisphosphonates For Delivering Biomolecules To Bone, Jivan N. Yewle Jan 2012

Bifunctional Bisphosphonates For Delivering Biomolecules To Bone, Jivan N. Yewle

Theses and Dissertations--Chemistry

Active targeting with controlled delivery of therapeutic agents to bone is an ideal approach for treatment of several bone diseases. Since bisphosphonates (BPs) are known to have high affinity to bone mineral and are being widely used in treatment of osteoporosis, they are well-suited for drug targeting to bone. For this purpose, bifunctional hydrazine-bisphosphonates (HBPs) with spacers of various lengths and lipophilicity were synthesized and studied. Crystal growth inhibition assays demonstrated that the HBPs with shorter spacers bound more strongly to bone mineral, hydroxyapatite (HA), than did alendronate. HBPs were also demonstrated to be non-toxic to MC3T3-E1 pre-osteoblasts. The targeted …


Design, Synthesis, And Anticancer Activity Of Ruthenium Complexes, Brock S. Howerton Jan 2012

Design, Synthesis, And Anticancer Activity Of Ruthenium Complexes, Brock S. Howerton

Theses and Dissertations--Chemistry

Ruthenium complexes show promise as light activated photodynamic therapy (PDT) prodrugs. Strained octahedral complexes were synthesized that produce a cytotoxic species upon light activation. pUC19 DNA damage in vitro experiments were carried out to determine the type of damage observed. In vivo cell experiments were carried out on the non-small lung cancer A549 cell line to determine the phototherapeutic window of the synthesized complexes. One mechanism of drug resistance via elevated levels of glutathione was addressed through in vitro binding studies carried out with UV-Vis spectroscopy and in vivo glutathione titrations in the A549 cell line. Several complexes were shown …


Investigations Of Oxidative Stress Effects And Their Mechanisms In Rat Brain After Systemic Administration Of Ceria Engineered Nanomaterials, Sarita S. Hardas Jan 2012

Investigations Of Oxidative Stress Effects And Their Mechanisms In Rat Brain After Systemic Administration Of Ceria Engineered Nanomaterials, Sarita S. Hardas

Theses and Dissertations--Chemistry

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives …


Removal Of Arsenic(Iii) From Water With A New Solid-Supported Thiol, Partha Jana Jan 2012

Removal Of Arsenic(Iii) From Water With A New Solid-Supported Thiol, Partha Jana

Theses and Dissertations--Chemistry

Arsenic is a highly toxic, easily transportable and widespread contaminant in groundwater throughout the world. Arsenic causes acute toxicity by disrupting biological functions. In groundwater arsenic concentrations can reach up to a few milligrams per liter. Current regulations on arsenic content in drinking water are becoming more stringent and require the standard to be reduced to a few parts per billion. Arsenic exists as oxyanions in aqueous solution in either trivalent or pentavalent oxidation states depending on the oxidation-reduction potential and pH of the medium. Several treatment methods are available for removing arsenic from water. However, cost, operational complexity of …


Biosensing Systems For The Detection Of Bacterial Quorum Sensing Molecules: A Tool For Investigating Bacteria-Related Disorders And Food Spoilage Prevention, Nilesh G. Raut Jan 2012

Biosensing Systems For The Detection Of Bacterial Quorum Sensing Molecules: A Tool For Investigating Bacteria-Related Disorders And Food Spoilage Prevention, Nilesh G. Raut

Theses and Dissertations--Chemistry

Quorum sensing enables bacteria to communicate with bacteria of the same or different species, and to modulate their behavior in a cell-density dependent manner. Communication occurs by means of small quorum sensing signaling molecules (QSMs) whose concentration is proportional to the population size. When a QSM threshold concentration is reached, certain genes are expressed, thus allowing control of several processes, such as, virulence factor production, antibiotic production, and biofilm formation. Not only many pathogenic bacteria are known to produce QSMs, but also QSMs have been identified in some bacteria-related disorders. Therefore, quantitative detection of QSMs present in clinical samples may …


The Role Of Aspiration In Corporate Fiduciary Duties, Julian Velasco Jan 2012

The Role Of Aspiration In Corporate Fiduciary Duties, Julian Velasco

Journal Articles

Corporate law is characterized by a pervasive divergence between standards of conduct and standards of review. Courts often opine on the relatively demanding standard of conduct, but their judgements must be based on the more forgiving standard of review. Commentators defend this state of affairs by insisting that it provides guidance to directors without imposing ruinous liability. However, the dichotomy can lead many, especially those who focus on the bottom line, to call into question the meaningfulness of standards of conduct. Of particular concern is the increasing popularity, in legal and scholarly circles, of the notion that fiduciary duty standards …


Region 11 Meld Na Exception Prospective Study, Robert A. Fisher, Douglas M. Heuman, Ann M. Harper, Martha K. Behnke, Alastair D. Smith, Mark W. Russo, Steven Zacks, John W. Mcgillicuddy, James Eason, Michael K. Porayko, Patrick Northup, Michael R. Marvin, Johnathan Hundley, Satheesh Nair Jan 2012

Region 11 Meld Na Exception Prospective Study, Robert A. Fisher, Douglas M. Heuman, Ann M. Harper, Martha K. Behnke, Alastair D. Smith, Mark W. Russo, Steven Zacks, John W. Mcgillicuddy, James Eason, Michael K. Porayko, Patrick Northup, Michael R. Marvin, Johnathan Hundley, Satheesh Nair

Surgery Faculty Publications

Introduction. Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation.

Material and methods. From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception.

Results. Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to …


Primary Closure Without Diversion In Management Of Operative Blunt Duodenal Trauma In Children, Katherine Smiley, Tiffany Wright, Sean Skinner, Joseph A. Iocono, John M. Draus Jan 2012

Primary Closure Without Diversion In Management Of Operative Blunt Duodenal Trauma In Children, Katherine Smiley, Tiffany Wright, Sean Skinner, Joseph A. Iocono, John M. Draus

Surgery Faculty Publications

Background. Operative blunt duodenal trauma is rare in pediatric patients. Management is controversial with some recommending pyloric exclusion for complex cases. We hypothesized that primary closure without diversion may be safe even in complex (Grade II-III) injuries. Methods. A retrospective review of the American College of Surgeons' Trauma Center database for the years 2003-2011 was performed to identify operative blunt duodenal trauma at our Level 1 Pediatric Trauma Center. Inclusion criteria included ages < 14 years and duodenal injury requiring operative intervention. Duodenal hematomas not requiring intervention and other small bowel injuries were excluded. Results. A total of 3,283 hospital records were reviewed. Forty patients with operative hollow viscous injuries and seven with operative duodenal injuries were identified. …


Jefferson Alumni Bulletin – Volume 61, Number 1, Winter 2012 Jan 2012

Jefferson Alumni Bulletin – Volume 61, Number 1, Winter 2012

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Features:

  • The Gift of Time for Patients with Advanced Bile Duct Cancer
  • Celiac Disease: Overcoming a Stealth Public Health Menace
  • Light Therapy for a Blue Planet and Beyond


Antimicrobial Metallic Copper Surfaces Kill Staphylococcus Haemolyticus Via Membrane Damage, Christophe Espirito Santo, Davide Quaranta, Gregor Grass Jan 2012

Antimicrobial Metallic Copper Surfaces Kill Staphylococcus Haemolyticus Via Membrane Damage, Christophe Espirito Santo, Davide Quaranta, Gregor Grass

School of Biological Sciences: Faculty Publications

Recently, copper (Cu) in its metallic form has regained interest for its antimicrobial properties. Use of metallic Cu surfaces in worldwide hospital trials resulted in remarkable reductions in surface contaminations. Yet, our understanding of why microbes are killed upon contact to the metal is still limited and different modes of action have been proposed. This knowledge, however, is crucial for sustained use of such surfaces in hospitals and other hygiene-sensitive areas. Here, we report on the molecular mechanisms by which the Gram-positive Staphylococcus haemolyticus is inactivated by metallic Cu. Staphylococcus haemolyticus was killed within minutes on Cu but not on …


Multiple Exposures To Drought ‘Train’ Transcriptional Responses In Arabidopsis, Yong Ding, Michael Fromm, Zoya Avramova Jan 2012

Multiple Exposures To Drought ‘Train’ Transcriptional Responses In Arabidopsis, Yong Ding, Michael Fromm, Zoya Avramova

School of Biological Sciences: Faculty Publications

Pre-exposure to stress may alter plants’ subsequent responses by producing faster and/or stronger reactions implying that plants exercise a form of ‘stress memory’. The mechanisms of plants’ stress memory responses are poorly understood leaving this fundamental biological question unanswered. Here we show that during recurring dehydration stresses Arabidopsis plants display transcriptional stress memory demonstrated by an increase in the rate of transcription and elevated transcript levels of a subset of the stress–response genes (trainable genes). During recovery (watered) states, trainable genes produce transcripts at basal (preinduced) levels, but remain associated with atypically high H3K4me3 and Ser5P polymerase II levels, indicating …


Dfvf: Database Of Fungal Virulence Factors, Tao Lu, Bo Yao, Chi Zhang Jan 2012

Dfvf: Database Of Fungal Virulence Factors, Tao Lu, Bo Yao, Chi Zhang

School of Biological Sciences: Faculty Publications

Fungal pathogens cause various diseases for plant and animal hosts. Despite the extensive impact of fungi on human health and life, the threats posed by emerging fungal pathogens are poorly understood. Specifically, there exist few fungal virulence gene databases, which prevent effective bioinformatics studies on fungal pathogens. Therefore, we constructed a comprehensive online database of known fungal virulence factors, which collected 2058 pathogenic genes produced by 228 fungal strains from 85 genera. This database creates a pivotal platform capable of stimulating and facilitating further bench studies on fungal pathogens.


Novel Design Of Functionalized Carbon Nanotube Electrodes And Membranes For Fuel Cells And Energy Storage, Xin Su Jan 2012

Novel Design Of Functionalized Carbon Nanotube Electrodes And Membranes For Fuel Cells And Energy Storage, Xin Su

Theses and Dissertations--Chemical and Materials Engineering

A novel electrochemical method to generate nm-scale bubbles at the tips of CNTs can temporarily block the membrane. A 92% blocking efficiency is achieved when the bubbles are stabilized in 30-60 nm diameter „wells‟ at the tips of CNTs. This well is formed by the electrochemical oxidation of the conductive CNTs partially into the polymer matrix of the membrane. Meanwhile, the nanoscale bubbles can be removed with 0.004 atm pressure to recover the transport through the CNT membrane. The CNT membrane with nanoscale bubble valve system was used to demonstrate electrochemical energy storage.

Uniform ultrathin Pt films were electrodeposited onto …


Protein Based Biomimetic Approachs To Surface Hemocompatibility And Biocompatibility Enhancement, Matthew Thomas Dickerson Jan 2012

Protein Based Biomimetic Approachs To Surface Hemocompatibility And Biocompatibility Enhancement, Matthew Thomas Dickerson

Theses and Dissertations--Chemical and Materials Engineering

T. pallidum can survive a primary immune response and continue growing in the host for an extended period of time. T. pallidum is thought to bind serum fibronectin (FN) through Tp0483 on the surface to obscure antigens. A Tp0483 fragment (rTp0483) was adsorbed onto functionalized self-assembled monolayers (SAMs) with FN. FN capture by adsorbed rTp0483 depended greatly on surface chemistry with COO- groups being best for FN binding. Hemocompatibility was determined by analysis of plasma protein adsorption, intrinsic pathway activation, and platelet activation. rTp0483+FN bound an equal or lesser amount of fibrinogen (Fg), human serum albumin (HSA), and factor XII …


Effect Of Ionic Surfactants On Electrostatic Charging Of Spray Droplets, Mark T. Warren Jan 2012

Effect Of Ionic Surfactants On Electrostatic Charging Of Spray Droplets, Mark T. Warren

Theses and Dissertations--Chemical and Materials Engineering

Dust capture for small coal particles (<2.5µm) can be improved if one takes advantage of electrostatic charges that resides on the surface of coal dust particles and on the surface of water spray droplets used to capture coal dust. Traditional dust capture methods that use water sprays are ineffective in capturing small dust particles since the motion of small dust particles is governed by electrostatic forces. If additives such as ionic surfactants could be added to water that would enhance the surface charge on water spray droplets, dust capture with water sprays could be improved.

The results presented show that n-sodium octyl sulfate causes the greatest charge enhancement versus the longer chained n-sodium dodecyl sulfate and n-sodium octadecyl sulfate. This can be explained by considering the factors that lead to droplet charge enhancement. Those factors are the mass of surfactant ions at the droplet surface, and the diffusion rate of the surfactant ions from the bulk droplet to the surface of the droplet. Sodium octyl sulfate will have a faster diffusion rate to the droplet surface because of its relatively short length, and will also maximize the mass …


Nanoparticle Additives For Multiphase Systems: Synthesis, Formulation And Characterization, Vinod Kanniah Jan 2012

Nanoparticle Additives For Multiphase Systems: Synthesis, Formulation And Characterization, Vinod Kanniah

Theses and Dissertations--Chemical and Materials Engineering

Study on nanoparticle additives in multiphase systems (liquid, polymer) are of immense interest in developing new product applications. Critical challenges for nanoparticle additives include their synthesis, formulation and characterization. These challenges are addressed in three application areas: nanofluids for engine lubrication, ultrathin nanocomposites for optical devices, and nanoparticle size distribution characterization.

Nanoparticle additives in oligomer mixtures can be used to develop extended temperature range motor oils. A model system includes poly(α-olefin) based oligomers with a modest fraction of poly(dimethylsiloxane) oligomers along with graphite as nanoparticle additive. Partition coefficients of each oligomer are determined since the oligomer mixture phase separated at …


Fabrication Of An Epithelial Cell-Based Ion-Selective Electrode And Its Application For Use As Alternative Tumor Angiogenesis Assay, Christina Nicole Simmons Jan 2012

Fabrication Of An Epithelial Cell-Based Ion-Selective Electrode And Its Application For Use As Alternative Tumor Angiogenesis Assay, Christina Nicole Simmons

Theses and Dissertations--Chemical and Materials Engineering

Previous studies have provided evidence that endothelial cell-based potassium ion selective electrodes possess the ability to quantify substances that have permeability-altering effects on those endothelial cells. The capability of these so-called biosensors to detect elevated concentrations of certain chemical agents found following tumor formation make them useful in the application as an alternative tumor angiogenesis assay. In this study an epithelial cell line, human colon adenocarcinoma epithelial cells (Caco-2), was used to fabricate membranes that were used to test concentrations of these chemical agents, known as cytokines, mimicking the concentrations that have been observed in the serum of healthy individuals …


Biodegradable Hydrogels And Nanocomposite Polymers: Synthesis And Characterization For Biomedical Applications, Ashley Marie Hawkins Jan 2012

Biodegradable Hydrogels And Nanocomposite Polymers: Synthesis And Characterization For Biomedical Applications, Ashley Marie Hawkins

Theses and Dissertations--Chemical and Materials Engineering

Hydrogels are popular materials for biological applications since they exhibit properties like that of natural soft tissue and have tunable properties. Biodegradable hydrogels provide an added advantage in that they degrade in an aqueous environment thereby avoiding the need for removal after the useful lifetime. In this work, we investigated poly(β-amino ester) (PBAE) biodegradable hydrogel systems. To begin, the factors affecting the macromer synthesis procedure were studied to optimize the reproducibility of the resulting hydrogels made and create new methods of tuning the properties. Hydrogel behavior was then tuned by altering the hydrophilic/hydrophobic balance of the chemicals used in the …


Understanding Degradation And Lithium Diffusion In Lithium Ion Battery Electrodes, Juchuan Li Jan 2012

Understanding Degradation And Lithium Diffusion In Lithium Ion Battery Electrodes, Juchuan Li

Theses and Dissertations--Chemical and Materials Engineering

Lithium-ion batteries with higher capacity and longer cycle life than that available today are required as secondary energy sources for a wide range of emerging applications. In particular, the cycling performance of several candidate materials for lithium-ion battery electrodes is insufficient because of the fast capacity fading and short cycle life, which is mainly a result of mechanical degradation.

This dissertation mainly focuses on the issue of mechanical degradation in advanced lithium-ion battery electrodes. Thin films of tin electrodes were studied where we observed whisker growth as a result of electrochemical cycling. These whiskers bring safety concerns because they may …


Application Of Thin Film Analysis Techniques And Controlled Reaction Environments To Model And Enhance Biomass Utilization By Cellulolytic Bacteria, Hsin-Fen Li Jan 2012

Application Of Thin Film Analysis Techniques And Controlled Reaction Environments To Model And Enhance Biomass Utilization By Cellulolytic Bacteria, Hsin-Fen Li

Theses and Dissertations--Chemical and Materials Engineering

Cellulose from energy crops or agriculture residues can be utilized as a sustainable energy resource to produce biofuels such as ethanol. The process of converting cellulose into solvents and biofuels requires the saccharification of cellulose into soluble, fermentable sugars. However, challenges to cellulosic biofuel production include increasing the activity of cellulose-degrading enzymes (cellulases) and increasing solvent (ethanol) yield while minimizing the co-production of organic acids. This work applies novel surface analysis techniques and fermentation reactor perturbations to quantify, manipulate, and model enzymatic and metabolic processes critical to the efficient production of cellulosic biofuels.

Surface analysis techniques utilizing cellulose thin film …


Membrane Immobilized Reactive Fe/Pd Nanoparticles: Modeling And Tce Degradation Results, Ruo He Jan 2012

Membrane Immobilized Reactive Fe/Pd Nanoparticles: Modeling And Tce Degradation Results, Ruo He

Theses and Dissertations--Chemical and Materials Engineering

Detoxification of chlorinated organic compound is an important and urgent issue in water remediation nowadays. Trichloroethylene (TCE), as a model compound in this study, has been proved to be degraded effectively by bimetallic nanoparticles (NPs) in solution phase. In this study, Fe/Pd bimetallic NPs were synthesized in poly (acrylic acid) (PAA) functionalized polyvinylidene fluoride (PVDF) microfiltration membranes. TCE dechlorination with these bimetallic NPs was conducted under different pH values and different metal loadings to study the role of corrosion on reaction rates.

One-dimensional mathematical model with pseudo first-order reaction kinetic was introduced to discuss the TCE dechlorination profile in membrane …


Finite Element Analysis Of The Contact Deformation Of Piezoelectric Materials, Ming Liu Jan 2012

Finite Element Analysis Of The Contact Deformation Of Piezoelectric Materials, Ming Liu

Theses and Dissertations--Chemical and Materials Engineering

Piezoelectric materials in the forms of both bulk and thin-film have been widely used as actuators and sensors due to their electromechanical coupling. The characterization of piezoelectric materials plays an important role in determining device performance and reliability. Instrumented indentation is a promising method for probing mechanical as well as electrical properties of piezoelectric materials.

The use of instrumented indentation to characterize the properties of piezoelectric materials requires analytical relations. Finite element methods are used to analyze the indentation of piezoelectric materials under different mechanical and electrical boundary conditions.

For indentation of a piezoelectric half space, a three-dimensional finite element …


Study Of Characterization Of Submicron Coal Particles Dispersed In Air And Capture Of Coal Particles By Water Drops In A Scrubbing Column, Utshab Chakravorty Jan 2012

Study Of Characterization Of Submicron Coal Particles Dispersed In Air And Capture Of Coal Particles By Water Drops In A Scrubbing Column, Utshab Chakravorty

Theses and Dissertations--Chemical and Materials Engineering

Present day water spray based dust removal technologies do not effectively remove respirable submicron coal and silica dust particles in the underground coal mines causing Coal worker’s pneumoconiosis (CWP). The objective of this research was to study the electrostatic charges present in the airborne coal dust in order to develop efficient water spraying based dust removal technology where water drops charged using ionic compounds and surfactants would be used to capture the oppositely charged coal particles. In an experimental scrubbing column, coal particles dispersed in an air stream by a Fluidized Bed Aerosol Generator were captured by water drops sprayed …


Synthesis And Characterization Of Functionalized Naphthalenes And Anthracenes, Guang Zhang Jan 2012

Synthesis And Characterization Of Functionalized Naphthalenes And Anthracenes, Guang Zhang

Theses and Dissertations--Chemistry

Organic electronics have received significant development in the last few decades. p- Type materials are much more in availability than n-type now. There are only a few examples of air-stable n-type materials. The design and synthesis of novel air-stable ntype materials is still a focus of research. Herein is described a study to evaluate the effectiveness of a novel electron-withdrawing group, composed of three electronwithdrawing groups connected in series, to impart material properties known to be favorable for obtaining air-stable n-types. The smaller acenes, naphthalene and anthracene, carrying these electron-withdrawing groups were prepared and studied by UV-Vis absorption spectroscopy and …


Novel Aromatic Ion–Pairs: Synergy Between Electrostatics And Π-Face Aromatic Interactions, Pramod Prasad Poudel Jan 2012

Novel Aromatic Ion–Pairs: Synergy Between Electrostatics And Π-Face Aromatic Interactions, Pramod Prasad Poudel

Theses and Dissertations--Chemistry

This dissertation focuses on the design and study of charged aromatic molecules where weak π-π interactions synergize with electrostatic interactions to enhance the overall interaction between aromatic moieties. Each chapter investigates some aspect of this hypothetical synergy between electrostatics and π-face aromatic cohesion.

The first chapter unveiled the importance of electrostatics in the intramolecular stacking of flexible aromatic molecular templates 1-2Br and 2a. While our previous studies found dicationic molecular template 1-2Br to have intramolecular π-stacking between electron poor pyridinium and electron rich xylylene moieties, no such stacking interaction was observed in the neutral analog 2a.

Chapter two systematically …


Investigation Of The Critical Residues At The C-Terminus Of The E.Coli Periplasmic Chaperone, Sura, Brent Ferrell Jan 2012

Investigation Of The Critical Residues At The C-Terminus Of The E.Coli Periplasmic Chaperone, Sura, Brent Ferrell

Theses and Dissertations--Chemistry

SurA is a molecular chaperone in the periplasm of E.coli and has been implicated in the maturation of outer membrane proteins (OMPs). SurA consists of four domains, but only two of them, namely the N and C-­terminal domains, are necessary for chaperone function. Very little is known about which residues drive the interaction between the N and C-­termini that facilitates normal activity. We mutated several conserved residues on the C-terminus and generated additive truncations to observe the effects of each on the fitness of the cell. We found one mutation E(408):A was sufficient to reduce SurA activity by 3-­fold, but …


Development Of Novel Chemical Tools For Proteasome Biology & A New Approach To 1-Azaspirocyclic Ring System, Lalit Kumar Jan 2012

Development Of Novel Chemical Tools For Proteasome Biology & A New Approach To 1-Azaspirocyclic Ring System, Lalit Kumar

Theses and Dissertations--Chemistry

The proteasome, a multiprotease complex, is clinically validated as an anticancer target by the FDA approval of bortezomib and carfilzomib for the treatment of multiple myeloma. The emergence of resistance to proteasome inhibitors however remains a major clinical challenge. Recently, distinct types of proteasomes termed ‘intermediate proteasomes’, which contain unconventional mixtures of catalytic subunits, have been implicated with drug resistance of tumor cells. In elucidating the role of intermediate proteasomes in drug resistance, a crucial step is to unequivocally determine the subunit composition of intermediate proteasomes in cells. With this in mind, the goal of the studies reported in this …