T h e U n i v e r s i t y o f A l a b a m a at B i r m i n g h a m
Volume 3 • 2009
Inquiro © 2009
The rights to the papers published in
this work are retained by the authors.
Authors may publish their work in any
other media, with the exception of
another undergraduate publication.
This is an internal document of
Front cover art:
Anna Stein, psychology major
Inside cover art:
Jackson Echols, art studio major
specializing in photography
the university of alabama at birmingham | inquiro • 1
Volume 3 • 2009
Founded and staffed by undergraduate
students at the University of Alabama
at Birmingham, Inquiro is an annual
research journal produced as an outlet
for the publication of undergraduate
scientific research. UAB is an excellent
undergraduate research university,
and with the addition of a journal such
as Inquiro in which to publish their
findings, the package is complete. Any
undergraduate student at UAB, as well
as any student participating in a summer
program at the university, is eligible to
submit research. The rights to every paper
published in Inquiro are retained by the
author, leaving each individual free to
submit to and publish in a larger national
journal or magazine. Students are
invited to submit research papers, short
reports derived from posters or research
narratives throughout the year.
2 • inquiro | no. 3 | 2009
inquiro staff from the editors
Inquiro: to search; to know. Curiosity about the natural world has been
a defining trait of our species since the beginning of time. Ancient civilizations all
over the world developed methods to harness the power of nature and to explain
the mysteries of the universe. The human spirit of discovery has survived millennia
and flourishes now more than ever before. As we uncover the secrets of the human
genome, the laws of modern physics, and the delicate balance of our environment,
we embark on unprecedented journeys into the unknown. Furthermore, it is a
journey which allows us to escape national borders, age differences, and even
language barriers. This journey is for all humanity.
This journey of inquiry is like gravity: its potency pulls us in to discover the
answers of the unknown. Because of the atmosphere at the University of
Alabama at Birmingham (UAB) and its dedication to scientific research, many
students have been enticed by the world of research, like Andrew and I.
However, we don’t just stop there; we don’t just stop at finding solutions. We
want to share our findings, our passion, with our peers. Why do research if you
don’t share it with others to allow for further discoveries and improvements?
Inquiro is our solution.
The first issue of Inquiro was published in 2007 when Andrew and I were
in our first year in college. We realized quickly what an impressive journal it
was because it solely involved undergraduates as contributors and editors.
Our first step was to join the 2008 Inquiro editorial board. As staff writers
our sophomore year, we were deeply involved in the process of editing and
reviewing submissions, writing articles, or conducting interviews. This was not
our first time being part of a publication committee: in high school, Andrew
was involved his school’s yearbook and I was involved in my school’s literary
magazine. Despite our prior experience that rooted our joy for producing
publications, working on Inquiro was perhaps more satisfying and exhilarating
because of its relatedness to scientific curiosity, being a part of a process that
displayed our peers’ hard work to the community.
After a successful second issue of Inquiro, we wanted to remain a part of the
editorial board. Our growing passion for the journal and constant need to seek
the next tier of challenges motivated us to apply for the Chief Editor positions.
Receiving this position, we were overwhelmed with excitement to play an
integral part in the publication of the journal. We had ambitions of making the
journal bigger and more diverse, a feat we like to think we have accomplished.
Inquiro, now in its third issue, has exceeded all of the expectations set by
the inaugural issue. This journal is admired and supported by all students,
faculty, and administration. UAB, more than any other institution in the
state, encourages students to participate in research, and students are
certainly responding. This year, not only did we have more involvement and
submissions than previous years, but we had more diversity in submissions as
well. For instance, in this issue, we have published papers on neuroscience,
we have more research narratives outside of the editorial board, and we have
Chief Editors
Andrew Buie
Shweta Patel
Editorial Board
Atbin Doroodchi
Danuel Laan
Natalie Mitchell
Matt Morton
Aaron Neal
Ashruta Patel
Toral Patel
Courtney Sparkman
Celeste Stuart
Pratik Talati
Timmy Wang
the university of alabama at birmingham | inquiro • 3
table of contents
Letter from the Editors 2
Science News 4
Research Narratives
Finding a Lab: My Niche 10
The Incision into the Realm of Science 12
Scientific Research? Child’s Play... 14
Transitional Research for Undergraduate Students 17
You’re Not in High School Anymore 19
Adventures in Deutschland: Laboratory Learning 21
Faculty Interview: Dr. James Ward, Mathematics 23
Short Reports
Accelerating Lossless Data Compression with Graphics 24
Processing Units
A Preliminary Characterization of Btbd9 Knockout Mice 28
The Effect of Mimetic Peptide 4F on Paraoxonase-1 30
Faculty Interview: Dr. Thane Wibbels, Biology 34
Papers: Biology
A Caenorhabiditis elegans Mutagenesis Screen to Identify 37
Candidate Human Cystic Kidney Disease Genes
Environmental Tobacco Smoke: Role in Progression of 46
Diabetic Nephropathy
Evaluating Sex Ratios of Hawksbill Hatchlings on 50
St. Croix, U.S. Virgin Islands
Spatial Analysis of Environmental Factors Related to 57
Lyme Disease in Alabama Using NASA Earth
Obeservation Systems
Paper: Biomedical Engineering
Single Walled Carbon Nanotubes as a Regenerative 70
Substrate in Spinal Cord Injury
Faculty Interview: Dr. Jacqueline Nikles, Chemistry 76
Paper: Chemistry
Microcrystal Analysis of Cocaine Hydrochloride and 78
Added Adulterants
Faculty Interview: Dr. J. David Sweatt, Neuroscience 80
Papers: Neuroscience
Cognitive Abilities and Cortical Activity: a functional MRI 82
Investigation of Figurative Language Comprehension
Obese Women with Greater Impulsivity Show Reduced 85
Executive Function Brain Activation During Delay
Discounting
Faculty Interview: Dr. Bradley Newcomer, Physics 96
Student Feature: UAB’s 2009 Goldwater Representatives 97
Inquiro staff 98
Submission Guidelines for 2010 99
Acknowledgments 100
accepted our first computer science paper. With more
high-quality submissions also came more competition
for acceptance. The success of Inquiro is a testament
to the unique atmosphere at UAB that encourages
undergraduate students to participate in research.
Because UAB is research-oriented, Inquiro was
established from the need of an outlet through which
UAB undergraduates can display their ground-breaking
research. Every year, students have the opportunity to
work in research labs, whether it is through summer
programs, departmental honors, or independent
studies. Although many university departments hold
research symposiums throughout the year, such
as the annual UAB Expo held in April, it is rare for
students to have the opportunity to display their work
before peers and faculty from other disciplines, as
well as to the university community as a whole. These
symposiums provide undergraduates ample opportunity
to perfect their presenting skills; however, Inquiro
allows undergraduates to polish their scientific-writing
skills. While undergraduates may work in labs for a
few semesters or a summer, it is unusual for students
to publish their work in internationally peer-reviewed
journals, simply due to time constraints.
This third issue of Inquiro helps to embody the
unyielding legacy of the University of Alabama at
Birmingham. This journal gives students the opportunity
to partake in the scientific process and prepare their
research for publication. Each paper is reviewed by at
least one or two faculty members, so that students get
a feel for submission and revision processes, preparing
students for the graduate and professional world. The
concept of the undergraduate journal has previously
been embraced by other universities such as Harvard,
Columbia, and Yale. With the continued success of
Inquiro, UAB students now have the opportunity of
ascending to the undergraduate publishing ranks with
the best and brightest students in the nation. Please join
us as we blaze the trail for the future of undergraduate
research at the University of Alabama at Birmingham!
—Andrew Buie and Shweta Patel
Chief Editors
Volume 3 • 2009
4 • inquiro | no. 3 | 2009
science news
Snow on the peaks of one of the
world’s tallest mountains is melting
at an extremely rapid rate and may
disappear by the 2020s. According to
scientists, dark rocks surrounding the
ice on Mount Kilimanjaro in Tanzania
absorb sunlight, causing an increased
melting rate of ice on the mountain.
Findings published in Proceedings
of the National Academy of Sciences
(November 2009) report that the melt-ing
is occurring at an alarming rate.
From 1912 to 1953, ice coverage
declined by only 1.1 percent per year;
however, from 1989 to 2007, that rate
increased to 2.4 percent per year. An
astounding eighty-five percent of the
ice cover has vanished since 1912.
Studies have also indicated that one
quarter of the ice cover present in
2000 had disappeared by 2007.
Current debate centers on whether
Mount Kilimanjaro’s ice loss stems
from melting caused by global warm-ing
or from increased sublimation.
However, no definite conclusion can
be made regarding the role of either
human activity or climatological influ-ences
on the melting. Researchers
do stress that that the melting seen
on the mountain is paralleled by melt-ing
occurring in ice fields elsewhere
throughout the world, including South
America and Indonesia. Thus, more
conclusive research must be con-ducted
in order to generate a clearer
picture of this startling situation.
New Gene Therapy to Repair Damaged
Lungs for Transplantation
Timmy Wang
Melting on
Mount Kilimanjaro
Natalie Mitchell
World’s Most Powerful X-ray Laser Created
Natalie Mitchell
It is a widely known fact that
a shortage of organs, such
as kidneys, lungs, and livers, ex-ists
in the United States. As a
result of this shortage, waiting
lists of patients hoping for a
second chance at life from or-gan
transplantation continue to
grow. However, cutting edge
research from Toronto’s University Health
Network may provide a way through gene
therapy to actually repair lungs that would
have once been discarded due to dam-age
and/or inflammation of the airways.
This especially bodes well for the supply
of lungs for transplants as only 15% of
lungs from organ donors are qualified for
transplant. The therapy was devised in a
two step process experiment by Dr. Shaf
Keshavjee, the chief of lung transplant at
University Health Network. The first step
began by taking damaged lungs from pigs
as well as 10 donated human lungs. These
lungs were each placed into a dome which
mimicked the internal temperature, nutri-ents,
and oxygen concentration of the hu-man
body. Essentially, the dome was able
to keep the lung cells alive outside of the
body. The second step was the introduc-tion
of a gene known as interleukin-10
(IL-10), which, when expressed, is able to
prevent the inflammation of the lungs cells
and any further damage of the lungs as a
transplant is taking place. This second step
began by first inserting the interleukin-10
gene into an adenovirus. The adenovirus
was placed in the airways of the lung to al-low
the cells to take in the virus along with
the interleukin-10 gene. From the study,
the research team found that the when the
gene-treated lungs were transplanted into
pigs, there was a significant improvement
in the lungs’ ability to exchange carbon
dioxide and oxygen within four hours of
the transplantation compared to that of an
untreated lung transplantation. Dr. Kes-havjee
also noted that it may be possible
“to transduce the cells in the lungs to be-come
little IL-10 factories. It’s personal-ized
medicine for the organ, if you will.”
This would mean that the lungs will also
not have any post-surgery inflammation.
As of yet, there have been no human lung
transplants using this IL-10 gene therapy
treatment as most specialists believe that
more studies need to be conducted on
animals before starting human trials. Ad-ditionally,
others, such as Indiana Univer-sity’s
Dr. David Wilkes, have noted that
previous studies using the adenovirus as
a vector for gene therapy has caused some
side effects. However, Dr. Keshavjee made
note that the adenovirus disappeared after
it delivered the gene into the lung cells,
meaning there was less chance of side ef-fects.
Overall, if proven effective, both
sides agree that this new treatment would
improve the lives of many more patients
who are still waiting on the list.
Initial experimentation has begun using the world’s most power-ful
X-ray laser, the Linac Coherent Light Source (LCLS). Lo-cated
at the Department of Energy’s SLAC National Accelerator
Laboratory, the LCLS will provide researchers with the ability
to illuminate objects at extraordinary speed. The machine can
resolve the size of atoms at ten billion times the brightness of any
other X ray source.
top of page 5
the university of alabama at birmingham | inquiro • 5
Nearly 40 years ago, a two mile linear accelerator (SLAC) was
built to study the building blocks of the universe. With distinct
modifications to this accelerator, the LCLS was formed and
allows scientists to investigate energy science, structural biology,
physics and assorted other fields.
After the SLAC Linac accelerates short pulses of electrons to
99.9999999 percent the speed of light, the LCLS takes them
through a 100 meter stretch of alternating magnets that force the
electrons to move back and forth emitting X-rays. The X-rays
become synchronous with the electron pulses, resulting in the
world’s brightest X-ray laser pulse. The laser pulses combine as
many as 10 trillion X-ray photons into a pulse that is 100 femto-seconds
in duration (the time it takes light to travel the width of
a human hair). Experiments using this instrument have revealed
aspects regarding the basics of atomic physics. Specifically,
researchers have been able to completely strip neon atoms of all
their electrons due to the extreme brightness of the laser beam.
Five other instruments are being planned for the LCLS to gain
understanding of how ultra-bright beams interact with matter.
Future experiments will create stop-action movies of molecules
in motion. This will ultimately allow scientists to watch chemical
bonds forming and breaking in real time.
Father of Green Revolution Dies at 95
Aaron Neal
encountered harsh criticism for his approach. Many opponents
of the Green Revolution considered Borlaug’s genetic cross-breeding
of plants to be unnatural or to have negative effects.
Others criticized his emphasis of large-scale, input-intensive
farming techniques over the subsistence farming countries typi-cally
relied on. Borlaug took these concerns seriously, though he
dismissed many critical Westerners by saying, “If they lived just
one month amid the misery of the developing world, as I have
for fifty years, they’d be crying out for tractors and fertilizer and
irrigation canals and be outraged that fashionable elitists back
home were trying to deny them these things.”
Despite his enormous success, Borlaug remained humble and
dedicated to solving the world’s hunger problem. He took a
distinguished faculty position at Texas A&M University in 1984,
where he continued developing disease-resistant crops in ad-dition
to teaching students and advocating the elimination of
global hunger. “I want to see science serve a useful purpose
to improve the standard of living for all people,” Borlaug said.
“You can’t build a peaceful world on empty stomachs and hu-man
misery.”
The legacy of Norman Borlaug is undoubtedly felt on every
continent by millions and millions of people every day. It is esti-mated
that every day, half of the world’s population, over three
billion people, consume grain descended from Borlaug’s wheat
varieties. As the father of the Green Revolution, Borlaug did
more to advance agricultural self-sufficiency and sustainability
than anyone before him, especially in under-developed nations.
“Dr. Norman Borlaug’s life and achievements are testimony to
the far reaching contribution that one man’s towering intellect,
persistence, and scientific vision can make to human peace and
progress,” said Indian Prime Minister Manmohan Singh. “One
of Dr. Borlaug’s favourite quotations was to ‘reach for the stars’.
In doing so, Dr. Borlaug helped millions of people escape from a
life of hunger and deprivation.”
On September 12, 2009, the world mourned the loss of plant
scientist and Nobel Peace Prize laureate Norman Borlaug.
Though his name never reached household use like scientists
Einstein, Fleming, or Curie, Borlaug is considered by many to be
the greatest person to have ever lived. “Norman E. Borlaug saved
more lives than any man in human history,” said U.N. World Food
Program Executive Director Josette Sheeran. “His heart was as
big as his brilliant mind, but it was his passion and compassion
that moved the world.”
Born in 1914 to the descendants of Norwegian immigrants,
Borlaug spent most of his youth working on his family’s farm
near Protivin, Iowa. In 1933, he enrolled at the University of
Minnesota where he subsequently received his Bachelor of
Science degree, Master of Science degree, and Ph.D. in plant
pathology and genetics. In 1944, Borlaug accepted an appoint-ment
organizing and directing the Cooperative Wheat Research
and Production Program in Mexico, a joint undertaking by the
Mexican government and the Rockefeller Foundation.
To combat the rapid spread of newly emerging wheat rusts, par-asitic
plant fungi capable of destroying entire wheat harvests,
Borlaug developed hardy, disease-resistant varieties of wheat
through crossbreeding and genetic engineering. A mere twenty
years after arriving in Mexico, his wheat varieties increased the
country’s wheat harvest six-fold, allowing Mexico to become
self-sufficient and a net exporter of the crop. Borlaug’s immense
success quickly gained the attention of other nations, leading
to the spread of his wheat varieties and the transformation in
global agriculture known as the “Green Revolution.”
In 1970, the Nobel Peace Prize committee recognized Norman
Borlaug’s efforts by selecting him for the award. “More than any
other single person of this age, he has helped provide bread
for a hungry world. We have made this choice in the hope that
providing bread will also give the world peace.”
While Borlaug’s efforts have saved over one billion lives, he
6 • inquiro | no. 3 | 2009
Laser-scanning Microscope Images
Brain Cells In Freely Moving Animals
Courtney Sparkman
Scientists at the Max Planck Institute for Biological Cybernet-ics
in Tubingen, Germany have designed a Laser-Scanning
microscope small enough to be worn by freely moving rats. This
new technology will provide critical information for studies of
attention and perception processes because of the way that
neurons can now be observed:
“We need to let the animal behave as naturally as possible if
we want to understand how its brain operates during interac-tion
with complex environments. The new technology is a major
milestone on the way to helping us understand how perception
and attention work,” says Jason Kerr, lead author of the study.
“We need to let the animal behave
as naturally as possible if we
want to understand how
its brain operates during
interaction with complex
environments.”
Source: www.sciencedaily.com
Cancer Vaccinations
Ashruta Patel
“Cancer is projected to become the leading cause of death
worldwide in the year 2010,” with increases in the num-ber
of cancer incidences and death rates. There are many types
of cancer that result from an uncontrollable growth of abnormal
cells. A significant amount of research is conducted on cancer to
help discover possible treatments for its prevention, one of which
includes implementing the use of cancer vaccines. Cancer vac-cinations
could increase the immune system’s ability to protect
the body from infections related to cancer-causing viruses. On the
other hand, cancer vaccines have the potential to depress immune
functions, risking the contraction of many more diseases.
Cancer vaccines can significantly decrease the occurrence of virus
strains in the body by enhancing the function of the immune sys-tem.
Vaccines are being considered for cancer treatments because
This new, non-invasive microscope uses a high-powered pulsing
laser and fiber optics to scan cells beneath the surface of the
brain. Insertion of electrons, therefore, is not necessary. The
lightweight, miniaturized laser scanning microscope images
fluorescent neurons while animals are awake and active.
Attention and perception are complex processes that involve
the utilization of senses simultaneously to construct our view
of the world. In the past, it has been difficult for researchers to
study such processes because information about attention and
perception are dependent on the observance of meaningful
signals from groups of neurons while the organism is in motion.
Past study methods include presenting a restrained animal with
movies, images, and scenes while observing brain activity.
of their medicinal properties capable of boosting the immune
system’s natural ability for protection against various foreign mi-crobes,
such as bacteria, fungi, parasites, or viruses. Once a cancer
vaccine is injected, the immune system eliminates the substances
from the body and develops a memory to protect the system
from future threats posed by cancerous cells. White blood cells
help the vaccine stimulate the immune system by protecting the
body against any abnormal or damaged cells. Successful advances
of such vaccines have been made, and implementing their use
has led to a decreased number of patients suffering from certain
cancer-causing virus strains.
There currently are two cancer preventative vaccines approved by
the U.S. Food and Drug Administration (FDA) which have been
responsible for cancer not developing in healthy people. There are
the university of alabama at birmingham | inquiro • 7
vaccines against the hepatitis B virus and types 16 and 18 human
papillomavirus (HPV), which can cause liver and cervical cancer,
respectively. Both of these vaccines consist of harmless viruses
that “take a substance from a cancer cell’s surface and attach it
to something the immune system already recognizes as foreign,”
indirectly training the immune system to kill something. The in-creased
use of these vaccines has led to positive outcomes because
of their ability to stimulate the immune system. A study con-ducted
with vaccinated women that were not infected with HPV-
16/18 showed a high efficacy and proven ability to reduce the in-cidence
of intraepithelial lesions. Not only does the HPV vaccine
have the ability to significantly reduce cervical cancer rates, but it
is also associated with other health benefits. Chronic infections
can arise from one or both of the virus types, which are associated
with cancers of the anus, penis, and oropharynx. If one vaccine
can assist in a better immunity towards other cancers, continued
tests and studies could provide further health advantages.
Additional research using experimental vaccinations for prostate
cancer, melanoma (skin disease), lymphoma, and neuroblastoma
(childhood tumor) all gave positive results over past treatments
such as surgery, chemotherapy, or radiation. The side effects vary
from patient to patient and the type of vaccine; however, most
side effects reported include mild and limited inflammation.
Thus, with accurate experimental designs, cancer vaccines can be
promising for many other virus strains because science reports are
readily available to back up improvements.
Cancer vaccines increase immune response against cancer cells
already present within the body. Vaccines target viruses that cause
the cancer rather than cancer cells themselves. Although cancer
vaccines have made progress and improvements, additional re-search
still needs to be devoted to the field to eliminate any un-certainties
with recent or future discoveries.
Although, cancer vaccinations have been studied for several years,
not many advances have been made in the past. Cancer comes
from our own cells, making it difficult for the immune system to
distinguish normal cells from cancer cells. Despite the discovery
of two cancer vaccines, it is difficult to develop effective ones
with numerous types of cancer existing. Some cancers “can es-cape
detection by the immune system or weaken natural immune
responses against cancer cells.” The immune system is the body’s
only defense against disease, and a temporary immunity from the
vaccine can make it vulnerable to developing other infections. The
chemicals contained within vaccines can depress the immune sys-tem,
the virus can depress immune function, and foreign DNA/
RNA from tissues can depress immunity.
Vaccinations can reduce immunity in many ways. They contain
immuno-suppressing chemicals and heavy metals which can alter
the function of white blood cells and deplete the body of vital
nutrients. Even though many studies have been conducted, it is
difficult to consider vaccines as the best preventative medications
for cancer. The lengths of the benefits are unknown, and many
vaccines for certain cancers need to be looked at individually for
each patient. The vaccines become impractical in this case, and
the costs of executing such practices are high.
There are numerous ways cancer can be prevented in a practical
fashion. Instead of individually treating each cancer patient and
putting money into drug companies for questionable vaccines,
increasing education and outreach efforts could be more advanta-geous.
For example, employing regular screening for cervical cancer
and eradicating barriers for individuals to access all health services
could lower cancer incidences knowing that third-world countries
have a greater number of cancer rates. By simply improving life-style,
cancer deaths can significantly decrease. Changes to lifestyle
include not smoking, eating a diet rich in fruits and vegetables,
protection from the sun’s rays, or practicing safe sex. For instance,
the HPV infection can be reduced by practicing safe sex; however, a
vaccine against it provides optimal protection. In contrast, the HPV
vaccine has many implications related to its use.
The human papillomavirus is common in many women world-wide,
yet the vaccine is not effective in women who already have
the virus. The vaccine is predominantly used in North America,
where cases are low, and an alternative method of prevention can
be done by regular pap smears. Countries that require greater at-tention
do not have the vaccine marketed because of the high cost
for the series of vaccinations per person. Although there was a
significant amount of time and effort designated to discover the
vaccine, there is no proof that the Gardasil will prevent cervical
cancer. Many of the experimental tests were performed on women
whose ages did not realistically match with the average diagnosis
age of cervical cancer. For this reason, Gardasil’s manufacturer
includes “no claims to proof of cervical cancer prevention should
be made” and “vaccine has not been tested for its own ability to
cause cancer.” These statements signify that the vaccine does not
have enough evidence to consider it efficient in the long run.
Cancer vaccinations have many positive and negative outcomes
associated with their use. Cancer is a growing cause of concern,
and efforts to prevent or treat the illness should be continued. The
discovery of vaccines has helped many individuals from contract-ing
the virus, and further experiments may lead to a more efficient
approach. Despite all the drawbacks involved with vaccinations,
it appears more probable to continue testing scientific studies to
maintain the progression of cancer research. Perhaps, persistent
studies could lead to a universal vaccine capable of sufficing the
most prevalent cancers.
References
American Cancer Society. "Cancer Projected To
Become Leading Cause Of Death Worldwide
In 2010." ScienceDaily 9 December 2008. 12
September 2009 <http://www.sciencedaily.com/
releases/2008/12/081209111516.htm>
8 • inquiro | no. 3 | 2009
Figure 1 – the processes that occur when a vaccine is injected into the body
Figure 2 - mutation steps in cancer cells
Encarta Encyclopedia. "Cancer (medicine)".Encarta Online Encyclopedia
2009. 2009. 15 September 2009.
<http://encarta.msn.com>
Hakim and Dinh. “Worldwide Impact of the Human Papillomavirus Vaccine.”
Springer Science and Business Media. Houston: The Methodist Hos-pital,
2009.
Mercola. “Vaccines and Immune Suppression.” 2009. 10 September 2009.
<http://www.mercola.com/article/vaccine/immune_suppression.htm>
MSNBC. “Cancer vaccines offer new way to fight disease.” 31 May 2009. 10
September 2009. <http://www.msnbc.msn.com/id/31019270/ns/
health-cancer>
National Cancer Institute. “Cancer Vaccines.” 17 March 2009. 12 September
2009. <http://nci.nih.gov/cancertopics/factsheet/Therapy/cancer-vaccines>
Richardson and Rex. “Proposed Childhood Cervical Cancer Vaccine Mandate:
Bad Policy, Questionable Science.” January 2007. 12 September 2009.
<http://www.whale.to/vaccines/rex.html>
iPS Cells Yield a Live Mouse
Atbin Doroodchi
Consider making a live animal from their skin cells. It sounds
cool and scary at the same time. Induced pluripotent stem
cells (iPS) are stem cells that are derived from non-pluripotent
cells, i.e. skin cells. Since 2006, the year when iPS cells were
discovered, scientists have tried to generate a live animal
from iPS. In the summer 2009, scientists made a live mouse
from a group of iPS cells in a petri dish. Fanyi Zeng, one of
the investigators from Shanghai University, told The Scientist
magazine that he had created 27 live mice from 37 iPS cell
lines. The researchers told The Scientist that the mice had
some abnormalities that weren’t described in the paper. In the
second study, which was published in the journal of Cell: Stem
Cell, Dr. Shaorong Gao of the National Institute of Biological
Sciences created four live iPS mice from five iPS cell lines, one
of which survived to adulthood; according to the paper, it was
completely healthy. Yet the production of a live animal from
iPS is not as effective as it should be. Only half of the iPS cell
lines in Zeng’s study yielded live mice. Also, one out of five iPS
cell lines in Gao’s study resulted in a live animal. In my opin-ion,
this technique still needs to be improved. These studies
showed that iPS cells have the potential of being as powerful
and pluripotent as embryonic stem cells.
the university of alabama at birmingham | inquiro • 9
Nobel Prizes are Awarded
Atbin Doroodchi
The 2009 Nobel prizes were announced in October. The
Nobel Prize in Chemistry was awarded to Venkatraman
Ramakrishnan, Thomas Steitz, and Ada Yonath for their stud-ies
of the structure and function of ribosomes. Ribosomes are
essential cellular components responsible for translating mes-senger
RNA into complex proteins. In Physics, the prize was
shared between Charles Kao, for his groundbreaking achieve-ments
regarding light transmission through optic fibers, and
the scientists Willard Boyle and George Smith for their inven-tion
of the charged coupled devices (CCD) sensor, an imaging
semiconduc-tor
circuit.
Fiber optic
cables consist
of glass or
plastic fibers
that carry light
along their
pathway, and
they are used
extensively
in medicine,
the military,
and telecom-munications.
CCD is a de-
Carol Greider Thomas Steitz George Smith
Artificial Germ Cells May Hold the Key to Studies of Early Human Development
Timmy Wang
Recently at Stanford University, researchers have been able to
control and differentiate embryionic stem cells into germ cells. In
certain cases, the germ cells were able to mature even further into
spermatids. Previously, the research had only produced immature
versions of germ cells, but researchers at Stanford were able to
push the differentiation process into the creation of viable germ
cells through a complete meiosis. The research team hopes that
these germ cells will be a great help in the study of meiosis in hu-man
cells as well as in the early development of the human em-bryo
since the only research conducted in this area has been mice
embryos. This sets a limitation regarding the knowledge of what
humans know about their own reproduction as the reproductive
genes in humans are unique, according to Dr. Reijo Pera, profes-sor
of obstetrics and gynecology at Stanford University of Medi-cine.
The team plans on continuing research in order to produce a
human oocyte. If this becomes possible, the team hopes that the
research will be able to further help infertile couples, who make
up 10 to 15 percent of all infertile couples, that are unable to
produce their own sperm or eggs. This will allow couples to have
their own children as well as help prevent the possibility of birth
defects, such as Down’s Syndrome, that may arise due to incor-rect
meiosis of the germ cells. However, this does not mean that
the purpose of this research is to make artificial children as the
current germ cells do not contain human DNA but rather foreign
DNA, known as transgenes. It would be considered unethical to
make children who have foreign DNA. Due to this concern, Dr.
Pera says that the research team is still “waiting for guidelines and
regulations regarding how to go about using artificial germ cells.”
Yet she remains hopeful that these germ cells will be able to ac-celerate
research in future projects.
vice used to displace electrical charges, usually from within
the device to an area where the charge can be manipulated.
CCD is used in digital cameras, allowing the captured image
to be converted to a digital signal. The Nobel Prize in Medicine
was awarded to Elizabeth Blackburn, Carol Greider, and Jack
Szostak for their discovery of how chromosomes are protected
by telomeres and the enzyme telomerase. Telomerase rebuilds
the tips of chromosomes and ultimately determines the life
span of cells. Their finding is extremely important in many
fields, particularly the study of genetic diseases and cancers.
science news research narrative
10 • inquiro | no. 3 | 2009
Each year, countless birds migrate to more acceptable liv-ing
conditions with the changing of the seasons. They do
so by using a previously misunderstood ‘sixth sense’ that allows
them to detect the Earth’s inherent magnetic field and orient
themselves accordingly. Until recently, many researchers at-tributed
this ability to iron-based receptors in cells of the upper
beaks of migratory birds. However, a recent study published in
Nature suggests that much of this magnetic sense is the result
of specialized light-sensing cells of the eye that send signals to
a light-processing part of the brain known as cluster N. Henrik
Mouritsen of the University of Oldenburg in Germany claims
that special proteins, cryptochromes, in birds’ eyes play a large
role in light-dependent magnetic sensing. When struck by light,
the proteins produce a pair of molecules known as free radicals.
Unpaired electrons on the free radicals have a spin property
that may be susceptible to magnetic fields. Signals generated
by these electron spins may then travel to cluster N where the
brain interprets the signal and informs the bird which direction
is North. To test this hypothesis, Mouritsen and his team caught
36 migratory European robins, all of which were able to correct-ly
orient themselves under both natural and induced magnetic
fields. In one group of robins, the trigeminal nerve, which con-nects
the beak cells to the brain, was severed. In the other group,
researchers damaged brain cells in cluster N known to receive
light signals from cells of the eye. Those robins with the severed
trigeminal nerve were still able to orient correctly, but those with
damage to cluster N were not. Since information was unable to
travel from the beak to the brain in the group of birds with the
severed trigeminal nerve, this study suggests that the beak cells
and trigeminal nerve play little, if any, role in orientation, though
Mouritsen thinks the beak cells may still be responsible for
detecting minute changes in magnetic field strength along the
north-south axis. The study has important implications for con-servation
efforts focused on the relocation of migratory species.
These birds often return to their migratory grounds after reloca-tion,
but if scientists are able to understand exactly how birds
navigate then conservationists may be able to fool birds into per-manently
relocating to safer, more habitable environments.
Which Way is North?
Matt Morton
Finding a Lab: My Niche
Toral Patel
Before coming to the University of Alabama at Birming-ham
(UAB), my career goal had always been to be a doc-tor.
Not sure about the specialty, I held onto the options of
being a cardiologist, endocrinologist, or oncologist. Swayed
by family and my interest in helping people through the use
of medicine, I decided to pursue Molecular Biology and a
pre-medical degree…only to realize that at UAB I would be
inspired by research.
Spurred by a genuine curiosity in developing and answer-ing
questions that could increase our understanding of the
world and enable us to save lives, I began a search for labo-ratories
I could become a part of. I looked for opportunities
in which I could fulfill my desire to travel the bridge between
practical science and a clinical setting. With no knowledge
of the office of undergraduate research or faculty at UAB,
I narrowed my interests to the pathogenesis of cancer
and cardiovascular disease. From there I began an online
search and came to the page of Dr. Dale Benos, Ph.D., Chair
and Professor in the Department of Physiology and Biophys-ics.
I was intrigued by his molecular-based research in eval-uating
potential mechanisms involved in the pathogenesis
of cancer, human immunodeficiency virus (HIV), and cystic
fibrosis. I learned of and established techniques such as tis-sue
passaging, cell counting, basic light and fluorescent mi-croscopy,
wound-healing or scratch assays, quantification by
spectrophotometry, Real Time-PCR, restriction digests, gel
extraction, subcloning, and minipreps of bacteria. I began to
understand what a true hands-on experience in science was
as I applied what I had just been taught.
With the thrill of being able to perform experiments and de-velop
new findings in a particular field, I volunteered in the
Department of Physiology at The University of South Alabama
with Dr. Mary Townsley, Ph.D. After being shown a few of the
basics, I was given responsibilty for my own research project
in determining the presence of certain TRP isomers in whole
lung samples and pulmonary microvascular endothelial cells
(PMVEC). Specifically, I examined TRPV1 and TRPV4 through
PCR and gel electrophoresis. My findings informed Dr.
Townsley's own research project, but more important the
work allowed me to think independently and to apply what
I knew without someone’s assistance. Being able to work
alongside researchers who were eager to share their passion
with students and heighten our experiences in research was
invaluable. The support and guidance I received ultimately
persuaded me to consider a Ph.D. in the future.
While working in both Dr. Benos and Dr. Townley’s labs, I re-image
from Henrik Mouritsen
the university of alabama at birmingham | inquiro • 11
alized that there was
an interdisciplinary if
not multidisciplinary
nature of science and
research. In order to
further understand re-search,
I ventured into
the world of research
seminars and confer-ences,
where posters,
powerpoint presenta-tions,
lectures, and
national meetings
embodied the work of
many individuals and
greatly displayed the
collaboration of many
disciplines. These seminars and meetings fea-tured
research in everything from physics and
biomedical sciences to biology and biochem-istry.
There were many scientific implications
of the experiments done by other people, but
none of them seemed to satisfy my own de-sire
to experience the entire adventure from
writing a proposal to running experiments and
evaluating data.
While participating in seminars during the
fall semester of my sophomore year, I came
across a laboratory in the Department of Med-icine
that used molecular-based techniques
to work on projects for understanding the role
of novel synthetic drugs (specifically peptides)
in atherosclerosis. Branching medicine and
coronary artery disease together, I was in-trigued
by the approach and began to familiar-ize
myself with the laboratory and the research projects. After
a year in the lab, I began my own research project under the
supervision of Dr. David Garber, Ph.D. I have been able to work
with Dr. Garber in determining the effect of the mimetic pep-tide
4F on the enzyme paraoxonase-1 (PON-1). I was given the
opportunity to work with human cell lines, primary mouse he-patocytes,
and animal models. Working in the Atherosclerosis
Research Unit is great as I use an interdisciplinary approach to
determining the effects of the peptide and the requirement of
the enzyme for the anti-oxidative effects of peptide 4F. I have
been able to take what I learn from my classes in molecular
genetics, biochemistry, and organic chemistry and incorporate
it into my understanding of this topic. Today, I can look back on
my journey from not quite understanding research to finding
my niche in a lab that bridges both basic science and medi-cine
and excels in developing novel therapeutic interventions
that I could one day use as a physician.
I advise, if not encourage, students with curiosity and eager-ness
to explore new areas to try research. Go into a lab and
learn its techniques and experience thinking independently
and incorporating everything you have learned from your
classes. Even if you are not interested in lab-bench science,
other opportunities for research in other fields can be found
on campus and can allow you to gain an appreciation for how
scientific or medical research is conducted.
The best part of research for me has been getting involved in
behind the scene research that might be applied to medical
practice in the future. Even though my journey in research has
led me through many labs and through much searching into my
own personal motivation and determination, there are many
programs at UAB through which students can explore fields of
science, enhance their creativity and intelligence, and work with
nationally and internationally claimed researchers.
12 • inquiro | no. 3 | 2009
research narrative
Suddenly, in the midst of mid-afternoon, my cell phone rings with the tune of a familiar number. I answer the
phone with a friendly, “Hello, Leslie,” not knowing what to expect. I was soon asked to enroll in a newly
restructured advanced dissection class with Dr. Dana Peterson and Leslie Hendon as the instructors. “Oh my,
I have a full schedule this semester, there is no way I can do this,” I replied with great apprehension.
“I think that you can handle it, it will be an awesome experience.
Besides it will take your mind off the rest of your classes and at
the same time, you will be earning credit. And, you will have so
much fun!” Leslie exclaimed.
As the conversation continued, I began to think to myself, “Why
not? I already have so many positive academic activities; why not
dive into another course that I can be passionate about.” As a
result, I answered, “Okay, okay, I will do it!” It was that particular
telephone call that would add hours to my fall semester class
schedule and a new excitement in life.
When my partner Jason Neeley and I unzipped the cadaver
bag for the first time, I was overwhelmed with emotion. I was
there. I was about to dissect a human cadaver and I am not
even in medical school, let alone a doctor of any sort – just an
undergraduate student that has a passion for medicine and all the
surprises it offers. I soon grasped the scalpel with a nervousness
that I had never felt before. It was as if I had fallen asleep and
had begun to dream just as a child would if they had discovered
the pot of gold at the end of
the rainbow and didn’t know
what to do. As time passed and
the integument was removed,
there were several incisions that
I made that were deeper than I
had wanted, but as I glanced at
the hour hand on my wrist watch
during our initial lab session, I
discovered that Jason and I had
already been in the lab for four
hours. It was now time to go
home and get some rest before my
eight o’clock class the following
day.
Lying there in bed that
Wednesday night reflecting back
on my first time with a scalpel
in my hand, I was both a happy
The Incision
into the Realm of Science
Chase Taylor
& Jason Neeley
and frustrated young man. I had made an incision in the skin of the
posterior torso with the intention of removing the integument from
around the area of the trapezius and latissimus dorsi while leaving
behind the superficial nerves and veins. No more did I advance the
length of my incision in the medial to lateral direction than I realized
I had severed the latissimus dorsi. Not only was this a terrible feeling
to have on the first night in the lab, but it also made me realize that
there is a little more to dissecting a cadaver than simply slicing away
until revealing musculature as perfect as the anatomy diagrams from
my dissection book. Although I was not careless with my dissection,
I learned that there are certain precautions and techniques that must
be practiced in the laboratory. Also, I concluded that there would be
challenges that I would have to overcome in order to gain the most
from this course. For instance, I had never held the tools that one
uses to dissect or manipulate the human body. The only information
that I came into lab knowing was what I had read from the required
textbook, Grant’s Dissector, and the knowledge I had gained from
the human anatomy course that I had taken previously. I initially
followed the instructions of which instruments to use during my
dissection, but I quickly realized that this was a unique experience
Right Brachial Plexus
a) Medial cord
b) Ulnar nerve
c) Median nerve
d) Musculocutaneous nerve
e) Lateral cord
f) Posterior cord (Radial nerve)
the university of alabama at birmingham | inquiro • 13
and that in order for my dissections to be perfected, I would need
to develop my own unique methods. In doing so, I have learned
that the careful execution and time that I put into each dissection
is precious.
So, Jason and I continued on with countless hours of dissection
on numerous occasions inside the cadaver lab, studying and
examining every aspect of the cadaveric anatomy that we revealed.
As a result, we were able to turn what were initially amateurish,
casual explorations, into impressively detailed dissections.
However, our expertise did not come without cost. We spent
approximately fifteen to twenty hours per week in the lab in order
to meet the goals that we had set for ourselves, in addition to the
many study hours the rest of our courses demanded for success.
Trust me, there were times we would much rather have chosen
to be at home on the weekends watching college football and
visiting with friends and family, but we were committed to our
dissection efforts.
As we acquired a new respect for the value of the hands-on
experience gained during our time in lab, another aspect of
our lab experience began to hit us in a very profound way. The
reality that total strangers donate their bodies to science so that
we might gain intellectual insight struck both Jason and I as an
invaluable gift. I never imagined that taking a biology class in
college would change my view on science so drastically. It is only
science – how sentimental could it be? Well, in fact, it has the
ability to be very sentimental. It is one thing to know that my
family supports my future academic goals, but knowing there are
people in the community that I have never met or even knew
existed, that care just as much, if not more, that are invested in
our futures as health care professionals, is truly inspiring. There
were times in the lab when I was exhausted and wanted to lay
down my scalpel and go home, but I always remembered how
much this research meant to the individual who donated his/
her body to science and realizing this inspired me to maintain
concentration and carry on with the tasks for that day. Overall,
the immense appreciation that Jason and I gained from this
course was moving and life-changing.
Nevertheless, aside from the newly acquired dissection skills and
the new appreciation for science, our work continued to be mostly
tedious. It was paramount never to rush any dissection procedure,
whether it was removing the superficial fascia from the skeletal
muscles or separating the individual nerves of the brachial plexus.
In addition, it became particularly important to be aware of what
was in the immediate proximity of the area being dissected. If
these structures are not clearly understood it is easy to reveal
the unforgiving nature of the scalpel. However, our time spent
dissecting progressed with great speed. For example, I went to the
lab one morning at six o’clock with the intent of spending a couple
of hours dissecting and leaving in time to take a shower and make
it to class by ten. However, I suddenly realized that four hours had
already passed and there was now no time to shower before class
started. Needless to say, I went to class smelling of formaldehyde,
but with the glow of satisfaction from the opportunity to gain
greater understanding and appreciation of human anatomy.
...I was overwhelmed with emotion. I was there. I was about to
dissect a human cadaver and I am not even in medical school,
let alone a doctor of any sort – just an undergraduate student
that has a passion for medicine and all the surprises it offers.
Structures of Right Femoral Triangle
a) Femoral nerve
b) Femoral artery
c) Femoral vein
d) Great saphenous vein
top of page 14
14 • inquiro | no. 3 | 2009
research narrative
The decision to enroll in an
advanced cadaveric dissection
course, BY 398, with instructors
Dr. Dana Peterson and Leslie
Hendon, has been one of the
most valuable and rewarding
choices of my academic
career. UAB is one of the few
institutions in the nation that
offers a cadaveric anatomy
course to undergraduates. I
would encourage all those
who have decided on a future
career in science or medicine
to consider enrolling in the
advanced dissection class, so
that they too, might uncover
their own passion for science
and research.
Posterior Right Forearm and Wrist
a) Abductor pollicis longus muscle
b) Extensor pollicis brevis muscle
c) Extensor retinaculum
d) Extensor pollicis longus tendon
e) Extensor digitorum tendons
f) Extensor digiti minimi tendon
Scientific
Research?
hild’s Play… Harrison To
Lunchtime is long past due. The cafeteria’s indistinguishable chat-ter
has grown weary. The early morning ritual PB & J sandwich
mommy fixed for me has been devoured, my Capri-Sun drained,
and applesauce inhaled. My yellow Pokémon lunchbox is a pigsty
of breadcrumbs, Ziploc bags, empty cartons, and a half-eaten cook-ie.
Time drags by. Anticipation mounts as the teacher approaches.
One by one, my classmates rise and line up behind one another.
RECESS TIME!!
Recess was always my favorite part of the day. It was my chance to escape the uniformity
of the classroom where every student read the same books, spelled the same words, and
worked the same math problems. During recess time, I was at total liberty to immerse myself
in the sand pit where I manipulated my surroundings to dig the deepest trenches or build the
biggest forts, castles, caves–whatever my creativity could harness. The jungle gym was a rainforest
of equipment–decked with slides, swings, stairs, ropes, and poles–waiting to be explored from every
aspect. Grasshoppers, ant colonies, and ladybugs in the field were specimens to be collected and ob-served.
Every fallen branch, mud clot, and pinecone was a resource to personify my imagination.
Recess was when I flourished. I dreaded getting older, because I would eventually be forced to relinquish
the freedom recess provided me and enter the monotonous realm of sipping coffee all day, talking about
the weather, and working in the “grown-up world.”
Having been raised in a small college town where my dad was a biological engineering research
mentor, I always felt that performing scientific research was somehow a passage of manhood for
me–I hated it. I used to sit in my dad’s office each evening after school and overhear his students
the university of alabama at birmingham | inquiro • 15
conversing with one another about their research as I mined
through the puzzles in the latest issue of Highlights or played
on my Gameboy.
“Hey, Tim, how do you plan to handle sustained injuries with
the limited healing capacity of the cartilage?”
“Well, I figured since the tissue is avascular, the invasion of
undifferentiated MSC’s might…”
….Blah, blah, blah, blah. As I meandered the hallways warding off
the Green-Goblin and ridding the world of evil with my spidey
senses and indestructible spider webs woven together in my mind,
I often stumbled upon the students’ presentation posters displayed
on the wall. Production of Hyaline-Like Cartilage by Bone Marrow
Mesenchymal Stem Cells in a Self-Assembly Model (Elder, 2008).
The diction was a foreign language to me, composed strictly of
convoluted words and abbreviations that only left me totally
discombobulated and tongue-tied whenever I tried to follow. If
becoming of age meant that I had to face that abominable nem-esis
called Research, I would kindly welcome the Green-Goblin
into my life any day.
I’m a freshman in college now, and my passage into manhood has
already dawned upon me in the form of neurology. I entered the
photo by Aaron Lamplugh
lab for the first time bracing myself with the few general science
courses I had under my belt, ready to get tossed and turned by the
storms of adulthood. The lab was a wreck–maybe the storms had
already passed and I could leave. My mentor approached–maybe
not. Either way, resignation seemed welcoming. With a wide grin
stretched across his face, my mentor greeted me, his pleasant tone
immediately throwing my expectation for turbulence off course.
“Hi, Harrison! I’m Dr. Li. Welcome to the lab.”
He apologized for the cluttered workbenches, mentioning that
they were currently performing their annual inventory check. Dr.
Li then blatantly told me that I would not be performing any ac-tual
lab work for my first semester. I would simply be reading up
on lab-related material and observing the researchers’ techniques
and habits so I could begin actual work later on. Good, he was
cutting me a break. Maybe I had hope after all. After meeting his
research assistants, Dr. Li handed me a stack of research articles
to read as an introduction to the lab. For the first time since I
came to college, I gazed into the eyes of evil on top of the stack:
Generation and characterization of Dyt1 ΔGAG knock-in mouse as
a model for early-onset dystonia (Dang, 2005). The little optimism
I had accumulated from my first minute with Dr. Li was im-mediately
crushed as my childhood horrors resurfaced, plunging
me into a sea of despair with nothing but a useless stack of paper
16 • inquiro | no. 3 | 2009
suns. My conversations with people might have become a little
duller, having been polluted with grueling homework assign-ments,
the weather, and yes, research. However, all those group
“study” sessions, spontaneous 3:00 a.m. Waffle House runs, parties
not beyond recollection, and endless waves of resulting college
drama make my life far from droning. I have yet to learn what it’s
like to work for a living, but my experience in the research lab has
broadened my horizons tremendously. Do I plan to do research
for a living? I don’t know. Do I understand all that complicated
diction that baffled me as a kid? Nope–don’t think I will for a
while either. Albert Einstein once stated, “The whole of science
is nothing more than a refinement of everyday thinking” (Abra-jano,
2007). After having been exposed to the world of research, I
think I kind of know what he meant and how it can be applied to
research in general. The most difficult feat to overcome in per-forming
scientific research is simply obtaining a firm grasp of the
concepts and terms in a particular field of science through a pro-cession
of education. Once you reach that level of understanding
where you are able to freely manipulate your scientific knowledge,
the research laboratory that was once an enemy lair becomes a
playground. The abyss of mesenchymal stem cells is sand at your
fingertips and transgenic mouse breeding a jungle gym. Anticipa-tion
mounts. It’s recess time.
Works Cited
Dang, Mai., Fumiaki, Yokoi., McNaught, Kevin., Jengelly,
Toni-Ann., Jackson, Tehone., Li, Jianyong., Li,
Yuqing (2005). Generation and characterization of
Dyt1 ΔGAG knock-in mouse as a model for early-onset
dystonia. Illinois: Science Direct.
Elder, Steven., Cooley, Avery., Borazjani, Ali., Sowell,
Brittany., To, Harrison., Tran, Scott (2008).
Production of Hyaline-Like Cartilage by Bone Marrow
Mesenchymal Stem Cells in a Self-Assembly Model.
Mississippi: Tissue Engineering.
Abrajano, Joseph (2007). Cover to Cover. New York: Einstein
Journal of Biology and Medicine.
and a few staples to save me. Those gigantic words seemed just as
horrifying as when I was in the third grade, except this time I was
actually expected to know, or at least learn, what they all meant. I
then looked back up at Dr. Li, forced a smile, and replied, “Thank
you.”
Two weeks passed, and I grew more familiar with life in the lab;
however, I still loathed my days in the research facility. I attended
the weekly lab meetings where the workers presented updates to
one another. Each meeting was an epic battle to stay awake as
my attention span was burned to ash during the first two min-utes
of each presentation by seemingly indiscernible diagrams
and terminology. I always forced myself to pretend that I learned
something in the end so as not to look stupid. I soon gave into
my shame as I admitted to myself that I could not maintain this
facade for a whole semester. I raised my white flag as I openly
confessed to Chad, one of the research assistants, that I had no
earthly idea about what was going on in the lab. To my surprise,
he simply chuckled and replied, “Neither did I the first two
semesters I was here.” I showed Chad the research papers Dr.
Li gave me the first day, and he patiently sat with me and broke
down each of the papers into their individual units, filling me in
with general concepts and common terminology in neuroscience.
Gradually, the crashing waves of research and scientific articles
that had attacked me my whole life began to recede. Within a few
hours the whole research process seemed elementary. All those
articles simply said was, “Hey, if I put this disease in a mouse and
find changes in its brain activity, maybe I can revert this activ-ity,
apply this finding to humans, and find a cure for the disease.”
As my time in the lab passed, my understanding of research
deepened. I learned that the actual execution of a lab blueprint is
an extensive succession of experiments that can take decades to
complete. Before a disease can be studied, it must first be placed
into countless specimens. Upon having been properly transmitted,
the condition must be diagnosed through a myriad of recordings
and tests for symptoms both anatomically and physiologically at
the molecular level. Next comes the treatment, followed by hu-man
studies where the cycle then starts over. Of course, this is all
assuming no errors were made in the process. By the end of the
day, I was exhausted from having absorbed so much information.
But I reigned victorious over a looming enemy finally conquered.
So now that I’m in college, I guess I’m about to become a part
of that grown-up world I always feared entering. Ironically, I
feel just as much a kid as I did during my playground days. I still
despise the bitter taste of coffee with the passion of a thousand
So now that I’m in college, I guess I’m about to become a part of
that grown-up world I always feared entering. Ironically, I feel just
as much a kid as I did during my playground days. I still despise
the bitter taste of coffee with the passion of a thousand suns.
research narrative
the university of alabama at birmingham | inquiro • 17
Translational Research for Undergraduate Students
Nicole Guyette and Karin Tran
Undergraduate research provides students with opportunities to
gain a broader perspective on the scope of the field of science.
Students introduced to research at an earlier stage are able to ex-plore
areas they may have never previously considered. Presently,
professional schools are encouraging undergraduate students to
participate in research, anticipating that more students will return
and accept faculty positions as clinical researchers. Therefore, un-dergraduate
students interested in scientific research should con-sider
the possibility of researching with their professional school
of interest.
As founding officers of the Pre-Optometry Club at UAB, Karin
Tran and I learned about the possibility of research at the school
of optometry through Keely Stewart, our advisor for the organi-zation
and student affairs representative for the UAB School of
Optometry. I had never done research before and wanted to ex-plore
the research aspect of optometry. Karin, on the other hand,
spent her previous semester conducting research with Dr. Thane
Wibbels but wanted a more optometry-related research experi-ence.
After visiting different laboratories, we both decided to
work with Dr. Rod Fullard, whose translational research (moving
basic science into clinical practice) focuses on dry eye studies, tear
collection, and cytokine analysis. We spent the spring semester of
our junior year assisting Dr. Fullard’s Ph.D student Lucy Kehinde
with her research on varying cytokine levels in extended versus
daily contact lens wear. The tear col-lection
training and monitoring
required for this study enabled
us to gain patient interac-tion
experience. In addition,
we were able to utilize the
pipetting techniques we
had learned from multiple
chemistry labs.
Currently, Karin and I are conducting our own independent
research study as part of the honors biology research program,
validating the tear levels for chemokines Interleukin 8 and IP-
10 measured by Cytometric Bead-Based Assay (CBA) with the
corresponding levels for identical duplicate samples by enzyme-linked
immunosorbent assay (ELISA). Some researchers believe
that both chemokines have misleading tear concentrations as a
result of assay interference by tear components. By comparing
the two assay types for each chemokine, our studies will provide
validation of the CBA measured tear levels. The basis of our proj-ects
entails collecting nonstimulated and stimulated tear samples
from twenty participants in order to run the CBA and ELISA.
Getting Involved in Undergraduate Research
To gain a broader perspective on how research can help under-graduate
students learn about the range of possibilities of their
professional school choice, we interviewed two UAB School of
Optometry faculty members, Dean John Amos and Dr. Keshia
Elder. The UAB School of Optometry houses world-class inves-tigators.
As such, it provides ample research opportunities for un-dergraduate
students. When asked about his view on undergradu-ate
research at the school, Dean John Amos of the UAB School
of Optometry said that he strongly supports the idea of getting
interested students in-volved
in the many
research opportu-nities
the school
has to offer. Pre-viously,
students
were responsible
for seeking out
research op-
18 • inquiro | no. 3 | 2009
portunities by individually contacting research profes-sors
at the school. However, with the newly established
Pre-Optometry Club at UAB, Dean Amos believes the
organization will serve a critical role in recruiting more
students to research at the school as an alternative to the
undergraduate campus. The club creates relationships
between pre-optometry students and the faculty at the
school of optometry, allowing students to gain a broader
view of the different areas of research in order to find one
that best fits their interests. For pre-optometry students,
especially, researching at the optometry school would be
more relevant to their career interests. Dean Amos fur-ther
believes that participation in undergraduate research
at the school of optometry will provide a more in depth
understanding of basic and clinical research that may
lead to a future concentration in a research career.
According to ocular surface disease investigator Dr. Kes-hia
Elder, “Undergraduate research allows students to get
a good taste of what research is like, so they can decide
if they are interested without becoming fully commit-ted.”
Her statement describes exactly how undergraduate
research has provided us with the opportunity to attain
a fast-track Master of Science degree. Being able to use
our undergraduate honors research project as the basis of
our Master of Science project has relieved the pressure
of balancing the Master of Science program with the
optometry program. Undergraduate research experience
at the UAB School of Optometry has also made us more
competitive as prospective optometry students because
of the relationships we have formed with researchers
and professors. Although Karin and I are both pursuing
the O.D/M.S. degree, students do not have to be pre-optometry
to participate in research at the school. The
Department of Vision Science offers Master of Science
and Ph.D. programs for those who are interested solely
in vision research.
Overall, research is a learning experience, and we advise
students to explore undergraduate research. If students
already have a professional program of interest, they
should experience the clinical side of that program
through research. Researching through the professional
school builds a network of connections among the fac-ulty,
thereby creating a more competitive application.
Research could be an unknown interest waiting to be
discovered by the right student.
Undergraduate research allows students to get a good
taste of what research is like, so they can decide if they are
interested without becoming fully committed.
research narrative
the university of alabama at birmingham | inquiro • 19
You’re Not in High School Anymore
Russell K. Fung
As a senior in high school, chemistry was always my fa-vorite
science subject to study. Whether learning about
Gauss’s law or how to work a stoichiometry problem, I took
pleasure in learning the wide range of chemistry topics
taught at Hoover High School. When it came to working in
chemistry lab, however, things couldn’t be less enjoyable.
Each week, I performed a chemistry lab by following a set
of instructions and then wrote up a lab report. This experi-ence
led me to believe that labs were all about following
instructions, replicating a set of procedures that had been
performed previously. If all I was doing in a lab was replicat-ing
a set of procedures, though, then what must professional
researchers do in their laboratories? As luck would have it,
my question was answered when I received the opportunity
to work in a research facility at UAB.
Lab experience at UAB
I first considered joining a research lab after talking to a friend
who had worked in a research facility at UAB as a junior in high
school. Given my experience with labs at the time, replicating
similar procedures for a whole summer didn’t seem all that
appealing. But I was encouraged to apply and work at the
research lab anyway, with the idea that I would be exposed to
a “real” research facility at UAB. The summer before entering
college, I entered my first research facility at the Atherosclero-sis
Research Unit (ARU) at UAB, placed to work as a laboratory
assistant under Dr. Vinod Mishra.
I soon realized that Dr. Mishra is an excellent laboratory men-tor
who has made astounding achievements in the biochemi-cal
sciences. He is a researcher who was previously involved
in the development of different biophysical methods in India
that allow for the study of peptides and lipids. At UAB, Dr.
Mishra is part of the Atherosclerosis Research Unit, headed
by Dr. G.M. Anantharama. The unit is divided into different
areas of expertise but specializes in studying a cardiovascu-lar
disease known as atherosclerosis. Dr. Mishra’s areas of
study include the functions of lipoproteins, specifically the ef-fect
of High Density Lipids (HDL) on atherosclerosis. Working
under Dr. Mishra, I was able to learn about his line of work
and perform many sub-projects that relate to his project as a
whole. Although many of these tasks do require me to follow
a set of instructions, to the best of my knowledge, most of
these instructions were probably not completed previously,
since most of the protocols were instructions that I had cre-ated
myself.
My first day working at the lab was quite an experience. I
was asked to prepare a diluted chemical sample of peptides
that was to be analyzed in a spectrometer. I realized that
I needed the knowledge of past high school chemistry lec-tures
for me to be able to perform this task. Without know-ing
about molarity or stoichiometry, I would not have known
how to perform this simple task. In addition, a spectrometer
was needed to find the absorption spectrum of a peptide
sample. Since I had learned how to operate one in my high
school chemistry class, I could perform the task with ease.
To make an agarose gel, for example, I needed to know the
concept of molarity for measuring the exact amount and
concentration of agarose. Dr. Mishra routinely made sure I
understood the necessary background information before
a test was performed. This in turn has helped me to under-stand
the reasons why the test was performed at all for a
given sample and what was happening as I followed the
protocol.
Of course, if all tests were conducted the way they are in
high school, research would take forever. At the lab, many
tedious steps of calculation are simplified with new tech-niques
and methods, oftentimes performed by computers
rather than by hand. For instance, it is reasonable to find
an absorption spectrum of one sample with a spectrometer
manually. However, by using a computer, multiple absorp-tion
spectrums can be found for different samples in less
time. In high school labs, there’s no rush to produce results
from simple replicated experiments with a known outcome.
Each technique is performed and explained thoroughly
such that the concept is comprehendible. Many errors will
be made, though they are acceptable as long as they are
understood by the student. But in a research facility, experi-ments
are performed to answer specific research questions
that are possibly unknown to the scientific community.
Unlike high school labs, errors in procedures will not only
affect the reliability of the results, but will also waste valu-able
resources. Each procedure must also be performed
swiftly so that the results can be evaluated to produce the
next set of research questions that needs to be answered.
Therefore, many basic methods are maximized by machines
in order to reduce experiment time and produce relatively
quick and errorless results.
During my time at the research facility, I’ve learned several
different techniques that have helped me to obtain the data
necessary for different types of analysis for lipids and pep-tides.
Many of these techniques include the makeup of dif-ferent
assays that test the concentration of factors added
to the lipoprotein samples. Some of these assays include
PON, PAF-AH, and DCFA assays that test for different factors
such as cholesterol and phospholipids for each sample.
Many of these new techniques are not taught in high school
laboratories, and the samples don’t come readily available.
20 • inquiro | no. 3 | 2009
In a professional lab, each sample is made separately each
time to avoid contamination and chemical changes over
time. Precision takes a great deal of time and is needed to
obtain satisfactory results. Even with the technology today,
some samples take hours to prepare and usually come in
small volumes. In addition, some tests take hours to com-plete
at a time. Making one mistake could require a repeti-tion
of an experiment, which may take up a lot more time
than needed to finish the experiment!
Science as a Team
Working in a research laboratory at UAB gave me a new per-spective
on laboratory work and research in general. Many
other student lab assistants and researchers also worked in
other labs within the ARU. It’s interesting how the concept of
teamwork is seen in real life settings within the lab. I used
to think research was something performed by a single per-son.
But if that was the case, then science would hardly be
advancing at the rate it is now. The Atherosclerosis Research
Unit best portrays the elements of teamwork within a re-search
environment. Different areas of expertise are separat-ed
into their respective groups to study the different factors
that may influence cardiovascular diseases. However, even
with different perspectives of study, it is the interactions be-tween
the different groups that essentially show the depen-dency
between labs. . For instance, Dr. Mishra might prepare
peptide samples that may potentially have an effect on the
disease, while Dr. Handattu, a researcher in a separate lab
within the Atherosclerosis Research Unit, would verify the
sample by testing them on mice. The level of collaborative
effort within the lab has shown me what it means to work as
a team and how much more efficient the process of research
can be than when working individually.
From a career perspective, I’ve always thought of scientific
research as a long and tedious process, repeating the same
tests over and over again. But while some of that is true, re-search
also allows researchers to think independently about
which steps to take. Unlike high school laboratories where
old experiments are repeated, I learned to think critically
about a completely new procedure in order to obtain the nec-essary
results to progress. In short, I think research is almost
like a never-ending challenge, always looking for ways to
advance to the next step in an experiment. As Dr. Handattu
from the ARU would say, “For every one step you take in re-search,
you’ll have to take three steps back.”
According to Dr. Mishra, it is important and highly recom-mended
for undergraduates to be actively engaged in re-search,
regardless of their major. Research experience is a
benefit for students working in the sciences because they are
exposed to multiple areas of sciences. Dr. Mishra proposes
to anyone who is interested in the sciences to find a few cat-egories
of interest before finding a mentor. This way, the best
match for a research mentor can be found. Entering UAB as
a Science and Technology Honors Program student, I realized
the vast amount of research opportunities and resources
there were available to me as a freshman. Although I am cur-rently
not working in a laboratory with a mentor, I will be look-ing
forward to my next lab experience at UAB!
From a career perspective, I’ve always thought of
scientific research as a long and tedious process, repeating
the same tests over and over again. But while some of that
is true, research also allows researchers to think independently
about which steps to take. Unlike high school laboratories
where old experiments are repeated, I learned to think
critically about a completely new procedure in order to obtain
the necessary results to progress.
research narrative
the university of alabama at birmingham | inquiro • 21
Adventures in
Deutschland:
Laboratory Learning Elise Ottenfeld
One December day after working at a Chemistry Open
House, my research mentor, Dr. David Graves of the
chemistry department, caught me in the stairwell and
tossed “Want to go to Germany?” my way. Five months
later, I was working overseas with a doctoral student on his re-search
project. Better yet, I was being paid.
From May until August 2009, I participated in the DAAD-RISE
program. Funded by the German Academic Exchange Service,
the Research Internships in Science and Engineering program
allows North American and United Kingdom undergraduates to
apply to work on specific projects based upon their areas of study.
Students apply to a total of three projects offered by different
German Ph.D. students, and then the RISE committee pairs stu-dents
with projects based upon their preferences. As a chemistry
major, I applied to work on a biochemistry project that aimed
to characterize the structure of the DNA fragmentation factor
or DFF protein. DFF, as I learned from the description written
by my PhD student Daniel Kutscher, was the major nuclease
responsible for degrading the genome during apoptosis or cell
22 • inquiro | no. 3 | 2009
death. For some time I had been learning about apoptosis and its
relationship to DNA from the work I performed in Dr. Graves’s
lab in conjunction with Dr. Katri Selander at the Comprehensive
Cancer Center; so I was more than interested in the opportunity
to learn the full process of cell death.
My journey began in Berlin where I spent two weeks with a
group of fellow RISE students traipsing through the basics of the
German language as well as the historical city. Seemingly no time
passed before I was onto Giessen, my home for the next three
months and the site of my research group. After one day of rest,
Daniel began immersing me into workings of the Justus-Liebig
University-Giessen’s Biochemistry department. The first day he
explained the basics of my project: I was to use polymerase chain
reaction (PCR) techniques to systematically change the amino
acid sequence of the DFF45 subunit of the DFF protein (DNA
fragmentation factor), also called ICAD (Inhibitor of caspase
activated DNase), for the mouse protein and then use them in
enzymatic assays in order to determine the sites important in its
chaperon function, leading to proper folding of the nuclease sub-unit,
DFF40, of DFF. It sounded so simple!
What I learned in the following weeks was that making protein
variants was anything but simple. Even though making protein
variants was problematic from the beginning, during my three
month stay I successfully learned techniques such as DNA mu-tagenesis,
protein expression and purification, and DNA cleav-age
experiments. Additionally, I learned how to make and run
several types of electrophoresis gels and to whip up a new batch
of buffers in a heartbeat. Even though our experiments would
not always work, I carried them out independently - trying, fail-ing,
and learning on my own - with Daniel nearby to consult on
my results and to offer helpful wisdom for next time. However,
laboratory techniques were not the only thing I learned during
my stay; twice a week the entire lab group of around 30 people
met to either discuss and review a paper or learn how the projects
were going from various lab members. Though I did not accom-plish
any lab work during the seminars, I found them helpful for
learning how to critique a journal article properly, something that
I with my love of English literature had always abhorred. Group
seminars also helped me get to know the people I was working
with, and to learn that shuffling into morning seminar clutching a
cup of coffee is a universal bonding experience.
Overall, my summer experience helped me develop my analyti-cal
skills with regard to both practice and theory, which I have
brought home to my lab work at UAB. While working in a lab at
home was always the most intriguing part of my studies, work-ing
in a lab at Justus-Liebig allowed me the opportunity to truly
absorb what it means to be a researcher. Everyone I encountered
was more than helpful in pointing me the right way and, with no
language barrier for everyone spoke English, in laughing with me
while I fumbled with my German. I strongly encourage all science
students, no matter what your goals may be at this point, to seek
out the opportunity to work in a research lab, not necessarily for
the elaborate techniques you’ll learn but for the value of patience
and teamwork you’ll experience.
...my summer experience helped me develop my analytical skills with
regard to both practice and theory, which I have brought home to
my lab work at UAB. ...working in a lab at Justus-Liebig allowed me
the opportunity to truly absorb what it means to be a researcher.
the university of alabama at birmingham | inquiro • 23
An Interview with James Ward, Department of Mathematics
Ashruta Patel
This interview was conducted with Dr. James Ward, who is currently my Calculus Professor. Dr.
Ward has been associated with UAB and research for the past 20 years; his efforts have provided
many insights in mathematical concepts. I had the opportunity to discuss his career interests as a
faculty member and what suggestions he has to offer potential undergraduates passionate to pursue
a future occupation in any form of research.
faculty interview: mathematics
Q) How did you
become interested in
research?
A) Research is a
way of learning about
the world, a way of
finding what is true.
It is also a way of living. I had been interested in mathematics
and science even as a child. Of course, family influences played a
role. My family often engaged in philosophical discussions and
debates, and this encouraged analytic thinking and openness
to new ideas. By the time I went to college, I was interested in
mathematics, science, literature, and philosophy. But mathematics
had a special appeal to me. After taking calculus, I was advised
to take a topology course in my sophomore year. Topology is a
subject concerned with very general, abstract, notions related to
geometry and calculus. In the course we, the students, were given
mimeographed notes containing only definitions and statements
of theorems. Our job was to prove the theorems. If someone
found, or thought they found, a proof, they would present it to
the class. That was the whole course; there were no lectures, no
books, so it was like doing mathematics research. I loved it and
would spend hours, even days, working on a single question. Here
at UAB our Advanced Calculus course is run in much the same
way. After that topology course, I was pretty sure I wanted to be a
mathematician. My advisor, Dr. Jack Roth, who taught me topol-ogy,
abstract algebra, logic and foundations of mathematics, also
influenced me. He was a remarkable man, both a mathematician
and an award winning artist. I think mathematics, science and
the arts are complementary, and Jack Roth exemplified that. He
encouraged my further studies in mathematics. Later, in gradu-ate
school and after, there were other influences and a particular
direction for my research.
Q) Where did you do your undergraduate and graduate studies?
A) University of South Florida
Q) How long have you been at UAB, and what persuaded you
to come here?
A) I have been here since 1989, and before that I was at the Uni-versity
of Alabama. While at Tuscaloosa, I had a lot of contact with
the mathematics department at UAB. UAB seemed to offer an
excellent atmosphere for my research, which is in nonlinear analysis
and differential equations, by having faculty with similar research
interests. In addition, the people in the mathematics department
were very intent on building a strong research department to attract
good students. I think we have succeeded in that goal.
Q) Please give a basic description of your current research
interests/projects?
A) Much of my work has been in non-linear analysis and dif-ferential
equations and how solutions relate to the structure of
the equations. Another interest of mine is in bifurcation theory.
A system exhibits a bifurcation if the type or number solutions
change as a parameter changes. For example, a stable equilibrium
state might suddenly lose stability, with the stability transferred to
another, new, equilibrium, or even to a periodic solution. Bifurca-tion
phenomena are observed in physics, chemistry, and biology,
especially physiology, and elsewhere. For example, the bending of
a beam under a force and the firing of a neuron are bifurcation
phenomena. Topological notions are fundamental in the study
of bifurcation and nonlinear equations. Thus my early training
in topology probably helped! For the past several years, I have
been working with some excellent Chilean mathematicians, Raul
Manasevich and Marta Garcia-Huidobro, on some problems in-volving
nonlinear differential equations and bifurcation. Recently
we decided to look at some mathematical modeling questions in
biology and sociology, so that is a new direction.
Q) Have you ever worked with undergraduates?
A) Yes, I have often worked with mathematics fast-track stu-dents
at UAB.
Q) What advice would you give to undergraduates consider-ing
research activities both now and later as a career?
A) Take the initiative. Do lots of outside reading in your subject
and related areas. Find other students with similar interests. Make
your interests known to your professors and adviser. The UAB sci-ence
and mathematics faculty are generally very open to working
with undergraduates. It may also help to get involved with semi-nars.
Ideally, the student should be seriously interested in the sub-ject
and shouldn't be doing something just for credentials.
24 • inquiro | no. 3 | 2009
short report
Accelerating Lossless Data Compression with Graphics Processing Units
R.L Cloud, M.L. Curry, H.L. Ward, A. Skjellum, P. Bangalore
Abstract
Huffman compression is a statistical, lossless, data compression
algorithm that compresses data by assigning variable length
codes to symbols, with the more frequently appearing symbols
given shorter codes than the less. The work to be presented is a
modification of the Huffman algorithm which permits data to be
decomposed into independently compressible and decompressible
blocks, permitting concurrent compression or decompression on
multiple processors. We implemented this modified algorithm on
a NVIDIA GPU using the CUDA API as well as on a current
Intel chip and the performance results are compared, showing
higher performance compression and decompression on the GPU.
Introduction
Lossless data compression is important in application domains
and usage environments where bandwidth or storage limitations
may negatively impact application or system performance.
Generally classifiable into statistical or dictionary methods,
lossless data compression algorithms can range widely in
compression speed and efficiency (compression factor).
Certain algorithms, especially the more efficient, can be quite
computationally expensive, and as the data processing needs of
current scientific endeavor continue to scale with more rapidity
than storage or bandwidth, compression becomes increasingly
necessary, but questions remain as to how to accelerate it and how
to do so without consuming a large amount of computational
resources.
The use of graphics processing units (GPUs) for general purpose
computation, i.e. problems outside the graphical domain, is a
relatively recent development. First this was achieved though
third party toolkits, e.g. Stanford's BrookGPU, but even more
recently have GPU manufacturers themselves begun to offer
general purpose tools which give the programmer a lower level
communion with the chip than earlier GPGPU programming
interfaces which are built upon OpenGL and DirectX. One of
these, and currently the most prominent, is the Compute Unified
Device Architecture(CUDA) from the NVIDIA corporation.
The potential benefits of GPUs in general purpose computation
are great, but potential must be emphasized, more so even than
for parallel programming on the x86. To achieve anywhere near
the theoretical maximums in performance on the GPU, the
computation patterns underlying a solution's algorithm must
be very near to the traditional usage of the GPU; a prospective
algorithm's implementation on the GPU should be, in order of
importance to performance, highly data parallelizable, logically
simple, and have relatively many computations to memory
accesses. In essence, to use the GPU to maximum effect, the
abstractable computation patterns underlying a solution should
be co-linear to the GPUs original task, graphics rendering. Our
problem domain, I/O, while it does not perfectly fit these criteria,
has already benefited from GPUs to enhance storage redundancy
[5]; we attempt now their utilization in lossless data compression
One major difficulty here in achieving good speedup with slim
negative side effects is that lossless data compression algorithms
can generally not be, in their unaltered form, thought of as highly
parallelizable. Indeed, if one wishes to express these algorithms in
parallel, one often needs to consider tradeoffs between compression
efficiency and performance. Nevertheless, we hope to effectively
demonstrate that it is possible to come to a reasonable middle
ground with respect to coding acceleration and efficiency loss.
Huffman Encoding
Statistical methods of data compression perform analysis on
the nature of the data to make intelligent decisions about how
it can be represented more efficiently in compressed form. The
Huffman encoding algorithm falls within this genus and operates
by counting the appearance of every distinct symbol in the
uncompressed data, then representing the more frequent with
shorter codes than the less frequent. Every symbol in the data is
replaced with its code, and if the data is non-random, i.e. a few
symbols appear with greater frequency than others, compression
can be achieved. The Huffman compression algorithm is old by
the standards of our science [6], but is still used, and has the
attractive quality of being a primitive of several more modern
and common algorithms, e.g. Deflate [1] and potentially the
algorithm described by Burrows and Wheeler [4].
Parallel Huffman Coding
There is literature on parallel Huffman coding and of varying
goals, ranging from the actual construction of Huffman codes in
parallel [3], [2], to [7] which addresses details of decomposition
for parallel Huffman decoding and demonstrates some moderate
decoding speedups while maintaining optimally encoded data by
making use of the observation that Huffman codes can frequently
synchronize. Because of limitations in our architecture, we must
try to create the simplest encoding routine possible. In doing
this we make a minor modification to the output of the Huffman
algorithm.
A modification is necessary because of the nature of Huffman
codes, i.e. they are of a variable length; an encoded data string is
composed of these codes packed together in a nature where bit
codes can cross byte boundaries. Simple decomposition of the
encoded data stream into blocks of static size would result in the
practical certainty that decoding would take an erroneous path,
which is discussed in some detail in [7]. One counter to
the university of alabama at birmingham | inquiro • 25
A: B:
C: D:
Figure 1: A: The original ASCII encoded string. B: The binary
tree and encoded representation of the original string. C:
Decomposing the string into three symbol blocks and adding
packing bits to the nearest byte. D: The addition of a length
delimiter at the start of the block. Single bytes are used for the
overhead in the diagrams for simplicity. In our implementation,
we pack the block to four bytes and use a four byte integer to
represent the block length.
this is to pack the blocks to byte boundaries, introducing some
size overhead. One more change is necessary. Because the codes
are of variable lengths, even if we encode a constant number of
symbols in each block, the resulting length of the encoded block
will vary, sometimes dramatically. For this reason, we must encode
an indication of where the block starts and ends. Our approach
is again simple; at the start of the encoded block we give the
length of the block which is known by making an additional
pass over the unencoded block and summing the lengths of the
code representation of the symbols. Our implementation stores
this length as an unencoded four byte integer for simplicity, and
because of this and the requirements of our architecture, we pack
the blocks to four byte boundaries.
The overhead of our modifications range therefore, from between
32 bits and 63 bits per block, with the variation being because if
the size of the encoded block is evenly divisible by four bytes, it is
unnecessary to add packing bits to its tail. This overhead naturally
becomes less significant as the length of the block is increased,
which is indicated in the figure measuring block size against
overhead. The time required for summing the block lengths is
measurable but undramatic and most noticeable when comparing
the runtimes of a sequential block encoder to a sequential
traditional(non-block) encoder.
To parallelize decoding, it is sufficient to build a table of offsets
into the encoded data from these block length delimiters. The
computation threads on the GPU can then index into the
encoded data and decode in parallel, storing decoded data in a
sequential array indexable by thread and block numbers.
Performance Comparisons
Encoding
Acceleration over our sequential
implementation was achieved for
both encoding and decoding. This
comparison is most meaningful in terms
of throughputs, the amount of data which
can be encoded or decoded per second.
Following is the comparison of our
sequential encoder to our parallel GPU
encoder and a parallel CPU encoder
programmed with OpenMP. The GPU
used in these experiments is the NVIDIA
GeForce GTX 285 with 240 cores at
1.5 GHz, and the CPU used is the Intel
Core i7 Extreme Edition 965 with four
cores at 3.2 GHz. Despite the GPU
having 60 times the number of cores as
our CPU, the differences in throughput
between the GPU encoder and the
OpenMP encoder are not dramatic.
This paradox can be largely resolved by
recalling that the architecture of the
Figure 2: The size overhead of using the parallel Huffman algorithm graphed against the block size.
The number of bytes overhead per block remains a constant, so as the block size increases the overhead
becomes less significant. At large block sizes, the overhead per block can be less than one percent.
26 • inquiro | no. 3 | 2009
GPU was developed for the SIMD, single instruction multiple
data, programming model while our CPU was developed with
MIMD, multiple instruction multiple data, in mind.
The processors in the GPU are organized into 30 groups of 8
cores. Each group of cores is known as a multiprocessor and
contains a single control unit and a small amount of high speed
memory shared between the cores in the multiprocessor. The
control unit broadcasts an instruction to all the cores, and optimal
performance can only be achieved when every core can execute
it. If, for example, the instruction is a branching statement, then
there is a likelihood that some cores will not follow the jump, and
in this case, some cores must remain inactive until they either
themselves satisfy the branching instruction or control passes
beyond the branching sections of the code. Therefore, in the
worst case, when only one core can satisfy the jump and the other
seven are left idle, our GPU behaves more like a crippled 30 core
shared memory MIMD machine with a slow clock speed and no
automatic memory caching. Our encoder consists of complicated
branching statements for the bit manipulation which makes
worst case behavior relatively likely. This also illustrates that in
heterogeneous programming environments, one must be very
aware of the strengths and weaknesses of the various architectures
so that programming effort can be directed where benefits are
most likely to be found.
Decoding
Our decoding routine consists of reading bits and traversing
a binary tree repeatedly for each code string. This contains
branching instructions, but markedly fewer than the encoding
routine, and the factor of acceleration on the GPU is greater than
that of the encoding routine. Also interestingly, the measured
increases in throughput from using OpenMP on the CPU,
compared to the sequential implementation, are even better than
linear by number of cores on the CPU. By launching increasing
numbers of threads, we can hide latency by issuing more
memory requests. In this way, we saw continued performance
improvements through increasing thread counts up to 8. Intel's
Hyper-Threading technology assists significantly in this.
Figure 3: We saw superior performance with the GPU based encoder compared to our multi-core CPU encoder and our single threaded
CPU implementation
the university of alabama at birmingham | inquiro • 27
Conclusions
The data presented here
suggests that the strengths
of the GPU architecture
are robust enough to give
performance benefits to
applications which, while
data parallel, still have
a not insignificant level
of logical complexity.
Optimal use of the GPU's
SIMD cores requires the
complete elimination of
divergence within warps,
which, in practicality,
requires the complete
absence of if statements
from the GPU sub-routine;
however, sub-optimal
performance,
through the emulation
of MIMD, can still be
acceptable. Despite the
large number of divergent
threads in a warp, our
encoder kernel is capable
of throughputs, sans
memory transfer times to and from the GPU, in excess of 4 GB/
sec. Total encoding throughputs using the GPU are weighed
down by the need to transfer data to and from the card; however,
in an online system, or when encoding very large amounts of
data, this could be somewhat ameliorated by using asynchronous
data transfers with the GPU to fully exploit bus resources while
encoding.
Realistically, current performance levels for our GPU encoder and
decoder do not warrant the use of the program as a standalone
encoding system. The Huffman algorithm itself is not the best
choice for such purposes and even the strengths of the GPU
do not make up for the algorithm's deficiencies. However, our
encoding system could be used as an auxiliary process to a GPU
application. Much greater coding performance than that shown
in the above figures could be seen were the data to be encoded
already on the GPU.
References
[1] M. Adler, Deflate algorithm. http://www.gzip.org/algorithm.txt.
[2] M. J. Atallah, S. R. Kosaraju, L. L. Larmore, G. L. Miller, and
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Figure 4: Again, our GPU based decoder gave better performance than both CPU decoders.
28 • inquiro | no. 3 | 2009
short report
A Preliminary Characterization of Btbd9 Knockout Mice
Mark P. DeAndrade, Chad C. Cheetham, Fumiaki Yokoi, Yuqing Li
Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics (CNET)
Abstract
Family and twin studies strongly support a genetic contribution
to the pathogenesis of Restless Legs Syndrome (RLS). Two in-dependent
studies published recently suggest that the BTBD9
gene plays a role in RLS. We have created a line of Btbd9
mutant mice that mimic the mutation reported in RLS patients
by an insertion of a gene trap vector into the Btbd9 gene. The
Btbd9 knockout mice were born in a Mendelian ratio suggest-ing
the knockout is not lethal. However, the knockout mice
showed a retarded growth pattern and were approximately
20% smaller. Our preliminary experiments show that the
knockout mice had periodic wakefulness in sleep and had in-creased
pain sensitivity.
Introduction
Restless Leg Syndrome (RLS) is a disorder that is manifested
at rest by periodic movements in sleep and unpleasant sen-sations
deep inside the legs that are relieved partially with
movement. RLS has been associated with the central dop-aminergic
system and iron metabolism. Genome-wide asso-ciation
studies have implicated several genes in RLS including
BTBD9. In the mouse, Btbd9 is expressed almost ubiquitously
in the brain and the rest of the body and expressed both dur-ing
development as well as in adults. The function of Btbd9
protein is not known, however the family of proteins it belongs
to has function in transcriptional regulation, ion channels, and
protein ubiquitination. Additionally, the protein family has im-portant
dopaminergic and glutamatergic functions in the brain.
The human BTBD9 protein is 544 amino acids long while the
mouse Btbd9 protein is 612 amino acids long. The extra 68
amino acids in the mouse protein are located at the N-terminal
of the protein, produced by an additional exon with a methion-ine
start codon. Excluding the 68 amino acids of the N-termi-nal
addition, the remaining 544 amino acid sequences share
95.4% amino acid residue identity and 96.5% similarity. The
high homology between mouse and human BTBD9 proteins
makes it feasible to model human RLS in mice by manipulat-ing
Btbd9 gene in embryonic stem (ES) cells.
The goal of the present study is to understand the function of
Btbd9 protein by using Btbd9 knockout mice. Here we ana-lyzed
the sensory and circadian function of the mutant mice.
Our research should provide insight into the pathogenesis of
RLS and eventually new therapeutic treatments for RLS.
Methods and Materials
Generation of Btbd9 knockout mice. Considering the large
proportion of mutations in humans is contained within the
6th intron of the BTBD9 gene, we looked for mutations in
the mouse homolog gene, Btbd9. We found a gene trap
clone, BayGenomics RRE078, which contained a promoter-less
bβ-geo gene inserted inside the 6th intron. The βb-geo
protein is a fusion protein of bβ-galactosidase and neomycin
selection gene. The fusion protein has the activity of both βb-galactosidase
and neomycin. The βb-geo gene contains a stop
codon at the 3’ end thus causing an alternative splicing when
inserted into a gene (Figure 1).
Figure 1. Diagram to show insertional
mutations in mouse ES cells and the
production of truncated fusion proteins
(from www.mmrrc.org). Red lines:
predicted splicing patterns in WT and
trapped allele.
We obtained the ES cell clone contain-ing
this insertion and confirmed the
insertion of site by 5’-RACE RT-PCR
sequencing (data not shown) and the
results showed that the insertion is
in intron 6. The ES cells were then
injected into C57BL6 blastocytes, from
which we obtained 4 chimeras. One
of the chimeras transmitted the muta-tion
to germline which was confirmed
by PCR genotyping of the tails (data
not shown). These heterozygous mice
born from that chimera were then
bred to start building up a colony.
In order to determine the approximate
location of the insertion site within
intron 6, 19 pairs of primers spaced
shown). These heterozygous mice born from that chimera were then bred to start building up a
colony.
In order to determine the approximate location of the insertion site
within intron 6, 19 pairs of primers spaced about 10 kb apart within the
intron covering the entire 179.223 kb intron 6 and exons 6 and 7 were
designed. Each pair of primers then underwent long-arm (LA) PCR using
an LA PCR kit (TaKaRa). The LA PCR was conducted using templates
from control wild type DNA and DNA from a knockout mouse. After a
series of LA PCR reactions we narrowed down the insertion site to
approximately 500 bp.
Wheel running. Animals were housed in a plastic cage equipped with a
steel running wheel (Lafayette Instruments). The cages contained little
bedding with one nestlet as to avoid blockage of the wheel. Food and
water were accessible ad libitum. Wheel revolutions were measured by a
small sensor. Signals were registered on a computer using a data
acquisition system. The mice were monitored continuously for 7 days
with a 12 hr light/12 hr dark cycle. The data were imported to ClockLab
for analysis of circadian activity.
Tail flick. The distal half of the animal’s tail was placed on a platform
under a heat lamp. The lamp was rapidly heated up to a temperature of
approximately 49-53oC and the time taken to vigorous reflex withdrawal
of the tail was measured. The cut-off time for this test in the absence of a
withdrawal was 15s to prevent tissue damage.
Statistical analysis. Statistical analyses were performed using SAS Analyst (version 9) for wheel
running distance and tail flick latency. Data was analyzed using ANOVA taking into
consideration genotype, sex, age, and weight in the models. Significance was assigned at P <
0.05.
Figure 2. LA PCR
genotyping of Btbd9 KO
mice. Template DNA
used: a KO
mouse, 2 and 4 from
wild type ES cells.
Primers used for lanes 1
and 2 generate a
predicted band of 1 kb
(lane 2) and primers
used for lanes 3 and 4
should produce a band
of 500 bp. Top three
bands in lanes 3 and 4
are non-specific PCR
reaction products. Both
reactions failed in lanes
1 and 3.
Figure 2. LA PCR
genotyping of Btbd9 KO
mice. Template DNA
used: 1 and 3 from a KO
mouse, 2 and 4 from wild
type ES cells. Primers
used for lanes 1 and 2
generate a predicted band
of 1 kb (lane 2) and
primers used for lanes
3 and 4 should produce
a band of 500 bp. Top
three bands in lanes 3
and 4 are non-specific
PCR reaction products.
Both reactions failed in
lanes 1 and 3.
the university of alabama at birmingham | inquiro • 29
about 10 kb apart within the intron covering the entire 179.223
kb intron 6 and exons 6 and 7 were designed. Each pair of
primers then underwent long-arm (LA) PCR using an LA PCR kit
(TaKaRa). The LA PCR was conducted using templates from
control wild type DNA and DNA from a knockout mouse. After
a series of LA PCR reactions we narrowed down the insertion
site to approximately 500 bp (Figure 2).
Wheel running. Animals were housed in a plastic cage
equipped with a steel running wheel (Lafayette Instruments).
The cages contained little bedding with one nestlet as to avoid
blockage of the wheel. Food and water were accessible ad
libitum. Wheel revolutions were measured by a small sensor.
Signals were registered on a computer using a data acquisi-tion
system. The mice were monitored continuously for 7 days
with a 12 hr light/12 hr dark cycle. The data were imported to
ClockLab for analysis of circadian activity.
Tail flick. The distal half of the animal’s tail was placed on a
platform under a heat lamp. The lamp was rapidly heated up
to a temperature of approximately 49-53oC and the time taken
to vigorous reflex withdrawal of the tail was measured. The
cut-off time for this test in the absence of a withdrawal was
15s to prevent tissue damage.
Statistical analysis. Statistical analyses were performed using
SAS Analyst (version 9) for wheel running distance and tail flick
latency. Data was analyzed using ANOVA taking into consid-eration
genotype, sex, age, and weight in the models. Signifi-cance
was assigned at P < 0.05.
Results
The Btbd9 knockout mice were
born in a Mendelian fashion and
appeared to be healthy, sug-gesting
that the Btbd9 knockout
mice are not lethal. It was found
that the body weight of the male
homozygous knockout mice
was approximately 78% of their
control heterozygous male litter-mates
(Figure 3; p = 0.078). The
body weight difference was main-tained
at least up to 5 months
of age. There was no significant
body weight difference between wild type and Btbd9 heterozy-gous
knockout mice.
To determine if there was a sensory alteration in the heterozy-gous
Btbd9 mice we used the tail flick experiment. The
heterozygous mutant mice exhibited a significantly reduced
latency to exhibit a withdrawal reflex compared to their wild type
litter mates, by approximately 53 percent (Figure 4; p = 0.0183).
For wheel running we wanted
to analyze the data for hyper-activity
and periodic wakeful-ness
during the day as mice
are nocturnal. Data from the
wheel running experiment
showed that the heterozygous
Btbd9 mutants had a significant
increase in wheel running activ-ity
during the day compared
to that of the wild type mice
(p=0.0295). The heterozygous
mice showed an activity score
of 130 while the wild type mice
had a score close to 0. Ad-ditionally,
the typical heterozy-gous
mice appeared to have disrupted day activity (Figure 5).
The typical heterozygous mutant mouse had brief, regular ac-tive
periods during the day from 6:00 AM to 6:00 PM.
Discussion
We created a line of Btbd9 knockout mice by inserting a gene
trap vector inside intron 6 of the Btbd9 gene. Using long range
PCR we have identified an approximate location of the insert
and confirmed the insert of the vector in the Btbd9 knockout
mice. The knockout was not lethal and the mice have sur-vived
more than 6 months, albeit with a slower growth.
Preliminary behavioral and physiological experiments in the
heterozygous mice have shown hyperactivity and periodic wake-fulness
during the day. Additionally, the heterozygous mice
showed increased pain sensitivity suggesting a sensory abnor-mality
in the mice. This coincides with the sensory and circa-dian
abnormalities that are found in human patients with RLS.
Further experiments will be conducted to test for periodic leg
movements in sleep (PLMS), decreases in dopamine and its
metabolites, and decreases in iron and its transporter proteins
in the Btbd9 knockout mice.
Figure 5. (A-figure above) A typical activity plot across three
born from that chimera were then bred to start building up a
approximate location of the insertion site
primers spaced about 10 kb apart within the
kb intron 6 and exons 6 and 7 were
then underwent long-arm (LA) PCR using
LA PCR was conducted using templates
DNA from a knockout mouse. After a
narrowed down the insertion site to
housed in a plastic cage equipped with a
Instruments). The cages contained little
avoid blockage of the wheel. Food and
Wheel revolutions were measured by a
registered on a computer using a data
were monitored continuously for 7 days
The data were imported to ClockLab
animal’s tail was placed on a platform
rapidly heated up to a temperature of
time taken to vigorous reflex withdrawal
off time for this test in the absence of a
tissue damage.
analyses were performed using SAS Analyst (version 9) for wheel
latency. Data was analyzed using ANOVA taking into
and weight in the models. Significance was assigned at P <
were born in a Mendelian fashion and
suggesting that the Btbd9 knockout mice are
body weight of the male homozygous
78% of their control heterozygous
0.078). The body weight difference was
months of age. There was no significant
wild type and Btbd9 heterozygous
was a sensory alteration in the
used the tail flick experiment. The
exhibited a significantly reduced latency to
compared to their wild type litter mates, by
4; p = 0.0183).
wanted to analyze the data for
wakefulness during the day as mice are nocturnal. Data from the
showed that the heterozygous Btbd9 mutants had a significant
activity during the day compared to that of the wild type mice
Figure 2. LA PCR
genotyping of Btbd9 KO
mice. Template DNA
used: 1 and 3 from a KO
mouse, 2 and 4 from
wild type ES cells.
Primers used for lanes 1
and 2 generate a
predicted band of 1 kb
(lane 2) and primers
used for lanes 3 and 4
should produce a band
of 500 bp. Top three
bands in lanes 3 and 4
are non-specific PCR
reaction products. Both
reactions failed in lanes
1 and 3.
Figure 3. Body weight of
Btbd9 mutant mice. HET:
Btbd9 heterozygous mice;
KO: Btbd9 knockout mice.
0.0295). The heterozygous mice showed an activity score of 130 while the wild type mice
score close to 0. Additionally, the typical heterozygous mice
appeared to have disrupted day activity (Figure 5). The typical
heterozygous mutant mouse had brief, regular active periods during
from 6:00 AM to 6:00 PM.
Discussion
We created a line of Btbd9 knockout mice by inserting a gene
vector inside intron 6 of the Btbd9 gene. Using long range PCR
have identified an approximate location of the insert and confirmed
insert of the vector in the Btbd9 knockout mice. The knockout
not lethal and the mice have survived more than 6 months, albeit
slower growth.
Preliminary behavioral and physiological experiments in the
heterozygous mice have shown hyperactivity and have periodic
wakefulness during the day. Additionally, the heterozygous mice
increased pain sensitivity suggesting a sensory abnormality in
mice. This coincides with the sensory and circadian abnormalities that are found in human
patients with RLS.
Further experiments will be conducted to test for periodic leg movements in sleep
PLMS), decreases in dopamine and its metabolites, and decreases in iron and its transporter
proteins in the Btbd9 knockout mice.
Acknowledgments
Special thanks to Dr. Thomas van Groen, Miki Jinno, Jennifer Neighbors, and Veena
for technical assistance throughout the project. Additionally, thank you to Dr. Yuqing Li
support and guidance.
Figure 4. Tail flick
experiment for pain
sensation. WT: Wild type
mice; HET: Heterozygous
mutant mice.
(A) A typical activity plot across three days for a wild type mouse. (B) A typical activity plot
three days for a heterozygous mutant mouse, which includes periodic periods of wakefulness. Red
signify the approximate time the mouse goes to sleep and the black dots predict the approximate time the
wakes up predicted by ClockLab. Heights of the bars are amount of activity.
Figure 3. Body weight of
Btbd9 mutant HET:
Btbd9 heterozygous mice; KO:
Btbd9 knockout mice.
Figure 4. Tail flick ex-periment
for pain sensation.
WT: Wild type mice; HET:
Heterozygous mutant mice.
short report
30 • inquiro | no. 3 | 2009
days for a wild type mouse. (B-figure below) A typical activity
plot across three days for a heterozygous mutant mouse, which
includes periodic periods of wakefulness. Red dots signify the
approximate time the mouse goes to sleep and the black dots
predict the approximate time the mouse wakes up predicted by
ClockLab. Heights of the bars are amount of activity.
Acknowledgments
Special thanks to Dr. Thomas van Groen, Miki Jinno, Jen-nifer
Neighbors, and Veena Ganesh for technical assistance
throughout the project. Additionally, thank you to Dr. Yuqing
Li for his support and guidance.
References
1. Allen, R. P., Barker, P. B., Wehrl, F., Song, H. K., and Earley,
C. J. (2001). MRI measurement of brain iron in pa-tients
with restless legs syndrome. Neurology 56,
263-265.
2. Allen, R. P., Walters, A. S., Montplaisir, J., Hening, W.,
Myers, A., Bell, T. J., and Ferini-Strambi, L. (2005).
Restless legs syndrome prevalence and impact:
REST general population study. Arch Intern Med
165, 1286-1292.
3. Clemens, S., Rye, D., and Hochman, S. (2006). Restless
legs syndrome: revisiting the dopamine hypothesis
from the spinal cord perspective. Neurology 67,
125-130.
4. Connor, J. R. (2008). Pathophysiology of restless legs syn-drome:
evidence for iron involvement. Curr Neurol
Neurosci Rep 8, 162-166.
5. Stogios, P. J., Downs, G. S., Jauhal, J. J., Nandra, S. K.,
and Prive, G. G. (2005). Sequence and structural
analysis of BTB domain proteins. Genome Biol 6,
R82.
6. Winkelmann, J., Schormair, B., Lichtner, P., Ripke, S.,
Xiong, L., Jalilzadeh, S., Fulda, S., Putz, B., Eck-stein,
G., Hauk, S., et al. (2007). Genome-wide as-sociation
study of restless legs syndrome identifies
common variants in three genomic regions. Nat
Genet 39, 1000-1006.
The Effect of Mimetic Peptide 4F
on Paraoxonase-1
Toral Patel, Dr. David Garber Ph.D.
Department of Medicine, Atherosclerosis Research Unit
Abstract
Even though there have been many advances in the diagnosis
and treatment of coronary artery disease (CAD), CAD re-mains
to be the major cause of deaths in the U.S. In humans,
CAD is inversely related to levels of high density lipoprotein
(HDL) cholesterol. The “quality” of HDL is just as impor-tant
as the HDL levels. The major component of HDL,
apolipoprotein (apo) A-I, appears to be largely responsible
for the atheroprotective qualities of HDL. Apo A-I has been
postulated to possess eight α-helical sequences. The major-ity
of these sequences form class A structures that can be
mimicked by several 18-residue peptide analogues. One such
peptide, peptide 4F, has been found to inhibit atherosclerosis
in atherosclerosis-susceptible mouse models. Also, peptide 4F
increases paraxonase-1 (PON-1) activity in HDL in mouse
models. PON-1 is an enzyme to which many of the anti-oxidative
properties of HDL have been credited. The purpose
of this study is to determine the effect of mimetic peptide 4F
on PON-1 and provide insight into the mechanism by which
peptide 4F effects PON-1. To examine the effects of 4F on
PON-1, apo E null mice were treated with peptide L-4F and
plasma and livers were harvested. The expected result was an
increase in PON-1 activity in the plasma; however, preliminary
results were not as expected and further experiments must be
done to establish a conclusion.
Introduction
In spite of the advancement of treatments for coronary artery
disease, the mechanisms in which the drugs prevent athero-sclerosis
are still unknown. It has been established that high
levels of low density lipoproteins (LDL) and low levels of
high density lipoproteins (HDL) contribute significantly to
the development and progression of cardiovascular diseases
(Parthasarathy, 2008). High density lipoprotein (HDL) is
seen as one of the most important protective factors against
atherosclerosis. Apolipoprotein (apo) A-I, the major com-ponent
of HDL, is also inversely associated with coronary
artery disease (Wilson, 1988). The protein apo A-I consists of
234 amino acids forming eight α-helical sequences that form
class A structures. The manufacture of apo A-I is difficult and
expensive, and therefore, research has been directed towards
finding smaller peptide mimetics that produce similar results
to apo A-I but are easier to manufacture and administer.
Peptide 4F was not homologous to the amino acid sequence
in apo A-I but provided similar secondary structure, and also
the university of alabama at birmingham | inquiro • 31
contained 4 phenylalanine (F) residues on the hydrophobic face
(Datta, 2001; Navab, 2005). Compared to apo A-I, it only con-sisted
of 18 amino acids instead of 234 amino acids and 4 pheny-lalanine
groups that provided high biological activity (Figure 1).
amino acids forming eight -helical sequences that form class A structures. The manufacture of
apo A-I is difficult and expensive, and therefore, research has been directed towards finding
smaller peptide mimetics that produce similar results to apo A-I but are easier to manufacture
and administer.
Peptide 4F was not homologous to the amino acid sequence in apo A-I but provided
similar secondary structure, and also contained 4 phenylalanine (F) residues on the hydrophobic
face (Datta, 2001; Navab, 2005). Compared to apo A-I, it only consisted of 18 amino acids
instead of 234 amino acids and 4 phenylalanine groups that provided high biological activity
(Figure 1).
AspTrpPheLysAlaPheTyrAspLysValAlaGluLysPheLysGluAlaPhe
D----W----F----K----A----F----Y----D----K----V----A----E----K----F----K----E----A----F
Figure 1: The Class A structure of peptide 4F Figure 1: The Class A structure of peptide 4F
Paraoxonase-1 (PON-1) is an enzyme synthesized in the liver as
an integral membrane protein (Bradshaw, 2005) and is secreted
into the blood stream as a lipid vesicle precursor of nascent HDL
(Oda, 2001; Deakin, 2002). Once in the plasma, PON-1 binds
to apo A-I and is then found on the HDL complex (Figure 2).
Studies have also shown that PON-1 is reduced in atheroscle-rosis
and cardiovascular disease models and patients. Many anti-oxidative
qualities of HDL have also been ascribed to PON-1.
Previous research has shown that PON-1 destroys lipid hydroper-oxides
(LOOH), degrades oxidized LDL phospholipids, reduces
accumulation of oxidized lipids in LDL, hydrolyzes oxidized
LDL associated compounds, and inhibits both LDL and HDL
oxidation (Florentin, 2008).
Patel 4
1) is an enzyme synthesized in the liver as an integral membrane
is secreted into the blood stream as a lipid vesicle precursor of
Deakin, 2002). Once in the plasma, PON-1 binds to apo A-I and is
complex (Figure 2). Studies have also shown that PON-1 is reduced in
cardiovascular disease models and patients. Many anti-oxidative qualities of
to PON-1. Previous research has shown that PON-1 destroys lipid
degrades oxidized LDL phospholipids, reduces accumulation of
hydrolyzes oxidized LDL associated compounds, and inhibits both LDL
Florentin, 2008).
Figure 2: HDL complex with paraoxonase-1
increase of PON-1 activity as a result of administration of peptide
on the mechanism by which peptide 4F affected PON-1. Increased
plasma can result either from increased synthesis of the enzyme in the
sites in the plasma. In order to increase the synthesis of PON-1, the
PON-1
Apo
A-I
HD L
HDL
Figure 2: HDL complex with paraoxonase-1
After discovering the increase of PON-1 activity as a result of
administration of peptide 4F, questions began to arise on the
mechanism by which peptide 4F affected PON-1. Increased lev-els
of PON-1 in the plasma can result either from increased syn-thesis
of the enzyme in the liver or increased acceptor sites in the
plasma. In order to increase the synthesis of PON-1, the peptide
must affect mRNA levels by interacting with elements associated
to the PON-1 promoter. These interactions would affect PON-1
expression and could therefore be hypothesized as a mechanism
for 4F modulation. We hypothesize that 4F affects PON-1 by
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