Dynamic Aggregation of Three New Photodynamic Therapeutics
Photodynamic therapy is treatment directed towards cancer cells with the goal of
destroying them using molecular sensitizers. After cellular uptake of these molecules, subsequent
light radiation brings the sensitizers to an excited triplet state. The sensitizer then transfers this
energy to molecular oxygen, inducing the formation of singlet oxygen, which causes oxidative
stress and cell death. A drawback to photodynamic therapy is the possible aggregation of the
sensitizer, which reduces the amount of light absorbed, thus decreasing the amount of singlet
oxygen produced. This study investigated the aggregation behavior of three novel derivatives PGlu4, I-Glu4 and C-Glu4 in phosphate buffered saline (PBS). PBS was used to mimic conditions
in vitro. A cellular uptake test, using MDA-231 cancer cells, was also conducted to determine if
varying concentrations of the sensitizers would affect their uptake. It was ultimately shown that
due to their hydrophilicity, the compounds exhibited little aggregation in phosphate buffered
saline. Fluorescence microscopy results of the cellular uptake indicated that the varying
fluorescence intensities of P-Glu4, I-Glu4 and C-Glu4 were linked to differences in quantum
yields. This was the first in a series of test to qualify the P-Glu4, I-Glu4 and C-Glu4 in this
fashion. These results will help shed more light on the derivatives’ interactions with cancer cells
and their eventual use as PDT agents.
Potential Inhibitor of Protein Kinase G in the Chronic Pain Pathway
Pain is a response to an injury or abuse to the body that is both protective and
informative. When pain persists beyond the point of healing it is considered to be chronic.
Medications most frequently taken by chronic pain sufferers are opiates and N-SAIDS. These
medications cause many side effects such as nausea and drowsiness. Recently, the PKG pain
pathway was shown to be a reachable and plausible target for a pain medication. Active PKG
was chosen as a target because when inhibited, it would not affect necessary physiological
functions. Two derivatives of balanol were made and tested for their ability to inhibit PKG. An
IC50 was then performed on the better of the two, Derivative B. When at high concentrations it
blocked PKG but not Protein Kinase A. Derivative B was then found to be soluble in various
concentrations of DMSO and found to inhibit PKG in cells. This study determined Derivative B
as a lead compound that could become a drug candidate.
CpG-ODN Used as a Possible Treatment For the Effects of Alzheimer’s Disease
Alzheimer’s disease (AD) is a neurodegenerative disease that affects the brain. Amyloidbeta plaques accumulate and lead to the apoptosis of neurons. This burden is colocalized with an
inflammatory response. AD diminishes cognitive function due to a loss of memory.
Neuroinflammation is mediated by repetitive TTAGGG motifs. Bacterial DNA yields
immunostimulatory responses, which are caused by unmethylated CpGs. Synthetic, singlestranded phosphorothioate oligodeoxynucleotides (ODNs) block inflammatory responses. CpG
ODN is injected into the mice as a possible treatment. This resulted in a relief of the amyloidbeta plaque burden. It also halted the decrease of cognitive function. This procedure served as
an introductory study of a potential new treatment for the victims of AD.
Three Potent Non-Toxic Compounds with the Ability to Inhibit Cyclosporin A-Induced Cell
Death in ALS
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease, marked by the
progressive degeneration of motor neurons within the Central Nervous System (CNS). While
recent studies have investigated and found that mutations in SOD1 and excitotoxicity caused by
a reduced expression and activity of glial glutamate transporter (EAAT2 and GLT1) are causes
of ALS, investigators have aimed to look at the final events leading up to cell death. Using a
High-Throughput Screening (HTS) Assay developed from mouse neuroblastoma Neuro 2A
(N2A) cells, stably transfected with the human G85R mutated SOD1 (mSOD1) plated in 96 well
plates, this study hoped to further investigate the leading mechanisms of apoptosis in ALS.
Recognizing that the N2A cells do not die only by expressing the mutation, but also through
increased sensitivity when subjected to cyclosporin A (CyA) induced cell death, an exogenous
toxic stimulus, researchers in this study were able to test the effectiveness of a variety of
compounds in blocking or ameliorating CyA-induced death in cells expressing the SOD1
mutation. After many drug screening assays, three potent hits from 27 primary hits were
identified using the criteria EC50 ≤ 2 µM and an LD50 ≥ 20 µM. Further knowledge about the
links of these compounds to the underlying disease onset in relation to mSOD1 could lead to
treatments that delay or halt disease progression.
The Knockdown of Ikaros in Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is a common childhood cancer that has a high cure
rate. In ALL, many genetic lesions result in the development of multiple biologic subtypes. This
type of cancer is usually treated with chemotherapy and bone marrow transplants. About 15 to
20% of ALL patients suffer a relapse. Lesions that are seen in relapse are important because they
generate drug resistant cells, which are most prominent at the time of relapse. Ikaros was shown
to be one of the genes deleted during relapse. This project attempted to knockdown Ikaros using
siRNA, and to test if the chemo resistant cells were then susceptible to Etopside treatment.
Ikaros knockdown was successful, but there was no significant increase in cell death of
chemo resistant cells post-Etopside treatment. In the future, other types of drug treatments should
be used to test if siRNA Ikaros knockdown is in fact a viable method to combat drug-resistant
ALL cells.
The Effects of Interactions between African-Americans and Caucasians on Cross-Race
Identification
Cross-race effect refers to the findings that recognition memory tends to be better for
faces of members of subject's own-race than for faces of members of other races. The cross-race
effect is often present because of prejudicial social attitudes and physiognomic differences
between races. However, it is not clear the extent to which racial attitudes are related to
recognition memory performance. Researchers have argued that increased contact with otherrace individuals would increase memory performance. Another possibility is that cross-race
effect is not due to prejudice, but rather to familiarity. This project investigates the effects of
interactions between African-Americans and Caucasians on cross-race effect. Using Signal
Detection Analysis, it was confirmed that a cross-race effect does occur, but that it is lessened
when a subject uses a stricter criterion for decision making. It was also determined that there is a
slightly lessened cross-race effect when a subject has increased interaction and therefore
familiarity with the opposite race. Future research, however, must be conducted in order to
further investigate this phenomenon.
Mutant Phenotypes of the Spo11 Yeast Mutant
Meiosis is the essential process required for diploid eukaryotic cells to generate gametes,
the sex cells needed for sexual reproduction. Double-stranded breaks (DSBs), a type of DNA
damage that fractures DNA strands, actually have been found to initiate meiosis in yeast cells
and to propagate one of the hallmark features of this process, homologous recombination. Spo11
is one of the chief proteins that produce DSBs. Past studies have shown that it is specifically the
alpha helical region of this protein that is responsible for creating DSBs. However, no past
research has attempted to delete this region to test for potential mutant phenotypes. Therefore, to
do so, this project attempted to delete the alpha helical regions of pJY4, a plasmid that contains
the alpha helices, but results indicated that the deletion was unsuccessful and that much future
research is needed.
Role of Neuronal Calcium Sensors in the Trafficking of Voltage-Dependent Calcium Channels
Calcium influx through voltage-dependent calcium channels triggers the release of
neurotransmitters. Mutations in these calcium channels have been shown to lead to chronic
migraines and epilepsy. G-protein-coupled receptors (GPCRs) are membrane proteins that
transmit signals into the cell and help to regulate calcium influx into neurons by modulating
calcium channel activity. It has been reported that GPCRs can modify the number of calcium
channels in the membrane by controlling channel trafficking. In the brain, there is an abundance
of calcium sensor proteins, which include calmodulin and NCS-1, that regulate ion channels.
This research investigated the hypothesis that NCS-1 modulates channel activity through the
regulation of its trafficking. Upon activation of the GPCR, NCS-1 associates with the
internalized channel. This is the first study to find a connection between NCS-1activity and Gprotein-mediated calcium channel trafficking.
Autism-Related Symptoms in Attention Deficit/Hyperactivity Disorder
The DSM-IV does not allow a double diagnosis of autism and ADHD. However, recent
research suggests there may be an overlap between autism and ADHD. This study utilized parent
questionnaires with questions sub-grouped according to diagnostic criteria of autism. The results
showed that all individuals with ADHD scored higher on the "pure autism" questions, but a small
subgroup scored in the clinically significant range. This group differed from the others in terms
of social interaction. This is consistent with previous studies and provides more evidence to alter
the upcoming DSM-V.
Convergence of State Industrial Composition Using Gross State Products in a Similarity Index
1965-2005
Economic development within the United States is not comparable in all states.
Economic growth in the U.S. is shown to generally progress from an economy dependent on raw
goods to an economy that is dependent on manufactured goods. The final stage in the United
States economic development rests on services. The Similarity Index showed that all three stages
of development currently exist in the United States where economies move progressively
through these stages. In their studies, both Sukkoo Kim and Bernat and Repice utilized the
Similarity Index based on indicative – employment and state earnings. Given that income source
is a volatile factor, this study utilized the Gross State Product (GSP) to replace income source.
GSP is a more reliable indicator. An analysis of the top five and the bottom five states was
performed through the years 1965- 2005. This analysis confirmed that the economic
development in the U.S., over long periods of time, shifts its dependency consistently through
the stages of natural resources, manufacturing, and services.
The Effects of Literacy and Language on the Boston Naming Test
The Boston Naming Test (BNT) is the most widely used of the neuropsychological
procedures that assess naming, a key indicator of neurological diseases such as Mild Cognitive
Impairment (MCI) and Alzheimer’s disease (AD). While it has been proven to be successful in
determining ability or inability to name objects among a wide variety of people, many biases
have also been observed. In some cases, BNT performance has been shown to increase by
schooling (years of education) and literacy. When the BNT was administered in different
languages, these same conclusions were observed. However, a wider variation in responses was
seen in translated versions. Additionally, no distinction has been made between years of
schooling and literacy. Because of these results, the present study hoped to find a correlation
between literacy and performance on the 15-item BNT by using an accurate literacy measure. We
also made a comparison between Spanish and English speakers. By having participants take the
BNT and then knowing their correspondent literacy measures for their native language, it was
concluded that literacy is a significant indicator of BNT performance in both English and
Spanish speaking populations. This relationship was independent from years of schooling. The
study also discovered large variations in answers among English and Spanish speakers, thus
showing the need to improve the format of the BNT.
Measuring the Effect of CO2 Plasma Exposure on the Adhesion of Scotch Packaging Tape
Considered to be the fourth state of matter, plasma is an ionized gas that exhibits unique
properties. Through the interactions between free radicals, dissociated electrons, the gas
molecules, and the substrate’s surface molecules, plasma-enhanced chemical vapor deposition
occurs where functional groups are deposited onto the substrate’s surface. Studies have shown a
direct correlation between the number of deposited carbonyl groups and the degree of adhesion
in pressure-sensitive adhesives (PSAs). This procedure aimed at depositing carbonyl groups on
Scotch Packaging Tape by utilizing CO2 plasma. The chemical hydroxylamine hydrochloride
reacted with carbonyl groups to produce hydrochloric acid and was added to solutions containing
plasma-treated pieces of tape. A lower pH corresponded to more carbonyl deposition, which
correlated to an increase in adhesion. Lower pH values were recorded for almost every plasmatreated piece of tape, showing that increased adhesion had indeed occurred. It was also observed
that increasing the treatment time and/or the gas pressure resulted in lower pH levels until a
maximum threshold was reached, where surface degradation of the substrate began to occur.