News 16 juni 2009
UNC study suggests new approach to
common cause of blindness
Researchers at the University of North Carolina at Chapel Hill School of Medicine in
collaboration with lead investigators at the University of Kentucky have identified a new
target for the diagnosis and treatment of age-related macular degeneration, the most
common cause of blindness in older Americans. In a study published online June 14, 2009 by
the journal Nature, the researchers demonstrate that blocking the activity of a specific
protein – called CCR3 -- can reduce the abnormal blood vessel growth that leads to
macular degeneration. Furthermore, targeting this new protein may prove to be safer and
more effective than the current treatment for the disease, which is directed at a protein
called vascular endothelial growth factor or “VEGF.” The discovery -- made in
mouse models and cultured human cells -- may also enable physicians to catch the disease
in its earliest stages, before blood vessels have fully infiltrated and destroyed the
central portion of the eye’s retina -- an area known as the macula -- to cause vision
loss. “It would be much better to prevent the disease in the first place,” said
study co-author and principal investigator of the UNC study site, Mary Elizabeth Hartnett,
M.D., a professor of ophthalmology in the UNC School of Medicine. “An exciting
implication of this study was that the CCR3 protein could be detected in early abnormal
blood vessel growth, giving us the opportunity to prevent structural damage to the retina
and preserve vision.”
The Earth’s magnetic field
remains a charged mystery
400 years of discussion and we’re still not sure what creates the Earth’s
magnetic field, and thus the magnetosphere, despite the importance of the latter as the
only buffer between us and deadly solar wind of charged particles (made up of electrons
and protons). New research raises question marks about the forces behind the magnetic
field and the structure of Earth itself. The controversial new paper published in New
Journal of Physics (co-owned by the Institute of Physics and the German Physical Society),
‘Secular variation of the Earth’s magnetic field: induced by the ocean flow?’,
will deflect geophysicists’ attention from postulated motion of conducting fluids in
the Earth’s core, the twentieth century’s answer to the mysteries of
geomagnetism and magnetosphere.
Is the sky the limit for wind
power?
In the future, will wind power tapped by high-flying kites light up New York? A new study
by scientists at the Carnegie Institution and California State University identifies New
York as a prime location for exploiting high-altitude winds, which globally contain enough
energy to meet world demand 100 times over. The researchers found that the regions best
suited for harvesting this energy match with population centers in the eastern U.S. and
East Asia, but fluctuating wind strength still presents a challenge for exploiting this
energy source on a large scale.Using 28 years of data from the National Center for
Environmental Prediction and the Department of Energy, Ken Caldeira of the Carnegie
Institution's Department of Global Ecology and Cristina Archer of California State
University, Chico, compiled the first-ever global survey of wind energy available at high
altitudes in the atmosphere. The researchers assessed potential for wind power in terms of
"wind power density," which takes into account both wind speed and air density
at different altitudes.There is a huge amount of energy available in high altitude
winds," said coauthor Ken Caldeira. "These winds blow much more strongly and
steadily than near-surface winds, but you need to go get up miles to get a big advantage.
Ideally, you would like to be up near the jet streams, around 30,000 feet." Jet
streams are meandering belts of fast winds at altitudes between 20 and 50,000 feet that
shift seasonally, but otherwise are persistent features in the atmosphere. Jet stream
winds are generally steadier and 10 times faster than winds near the ground, making them a
potentially vast and dependable source of energy. Several technological schemes have been
proposed to harvest this energy, including tethered, kite-like wind turbines that would be
lofted to the altitude of the jet streams. Up to 40 megawatts of electricity could be
generated by current designs and transmitted to the ground via the tether."We found
the highest wind power densities over Japan and eastern China, the eastern coast of the
United States, southern Australia, and north-eastern Africa," said lead author
Archer. "The median values in these areas are greater than 10 kilowatts per square
meter. This is unthinkable near the ground, where even the best locations have usually
less than one kilowatt per square meter."
‘Colossal’ Magnetic
Effect Under Pressure
Millions of people today carry around pocket-sized music players capable of holding
thousands of songs, thanks to the discovery 20 years ago of a phenomenon known as the
“giant magnetoresistance effect,” which made it possible to pack more data onto
smaller and smaller hard drives. Now scientists are on the trail of another phenomenon,
called the “colossal magnetoresistance effect” (CMR) which is up to a thousand
times more powerful and could trigger another revolution in computing technology.
Understanding, and ultimately controlling, this effect and the intricate coupling between
electrical conductivity and magnetism in these materials remains a challenge, however,
because of competing interactions in manganites, the materials in which CMR was
discovered. In the June 12, 2009, issue of the journal Physical Review Letters, a team of
researchers report new progress in using high pressure techniques to unravel the
subtleties of this coupling.
Gene evolution process discovered
One of the mechanisms governing how our physical features and behavioural traits have
evolved over centuries has been discovered by researchers at the University of Leeds.
Darwin proposed that such traits are passed from a parent to their offspring, with natural
selection favouring those that give the greatest advantage for survival, but did not have
a scientific explanation for this process. In research published this week, the Leeds team
reports that a protein known as REST plays a central role in switching specific genes on
and off, thereby determining how specific traits develop in offspring.The study shows that
REST controls the process by which proteins are made, following the instructions encoded
in genes. It also reveals that while REST regulates a core set of genes in all
vertebrates, it has also evolved to work with a greater number of genes specific to
mammals, in particular in the brain – potentially playing a leading role in the
evolution of our intelligence. Says lead researcher Dr Ian Wood of the University's
Faculty of Biological Sciences: "This is the first study of the human genome to look
at REST in such detail and compare the specific genes it regulates in different species.
We've found that it works by binding to specific genetic sequences and repressing or
enhancing the expression of genes associated with these sequences. "Scientists have
believed for many years that differences in the way genes are expressed into functional
proteins is what differentiates one species from another and drives evolutionary change
– but no-one has been able to prove it until now."
Hebrew University research leads to
advanced trials of new cancer treatment
Research by a Hebrew University of Jerusalem professor has led to the development of a
product that has been shown in clinical trials to be successful in halting the growth of
various types of cancer cells. The research, conducted by Prof. Avraham Hochberg of the
Silberman Institute of Life Sciences at the university, has won for him first prize among
faculty members for this year's Kaye Innovations Awards, which was presented on June 9
during the annual Hebrew University Board of Governors meeting. Prof. Hochberg was
successful in isolating the H19 gene in humans and determining that it is significantly
expressed in over 33 different forms of cancer, including superficial bladder carcinoma
and pancreatic, ovarian and metastatic liver cancer, while laying dormant and
non-expressed in non-cancerous cells. Research has also demonstrated that the H19 gene
plays a significant role in the tumor development process by enabling tumor cells to
survive under stress conditions, such as low serum and low oxygen levels, that are typical
conditions of the environment in which cancerous cells develop. This survival supports the
growth of the tumor and the development of metastases.
GARP makes the difference
Scientists from the Helmholtz Center for Infection Research in Braunschweig, Germany and
the Medical School Hannover, Germany have succeeded in treating immune cells in a way that
enables them to inhibit unwanted immune reactions such as organ rejection. Their results
have now been published in the current issue of the scientific journal Journal of Cellular
and Molecular Medicine. The immune system keeps us healthy - day and night it protects us
against invading and harmful pathogens. But this fulltime surveillance can also turn into
a problem, for example after an organ transplant. The immune system recognizes the new
organ as "foreign" and starts fighting it. In the end, the life-saving
transplant will be rejected. Until now, only special drugs have managed to keep the immune
system silent and thus inhibit organ rejection. Theoretically, these drugs are not
necessary because the immune system has its own unique "peace makers":
regulatory T cells (Tregs), a special group of helper T cells, an important cell type of
the immune system. Tregs inhibit immune reactions and are thus of special medical
interest. Until now, distinguishing between Tregs and helper T cells has represented a
problem for scientists. Now, in co-operation with the Medical School Hannover, researchers
from the Helmholtz Centre for Infection Research in Braunschweig have identified a
molecular factor that plays an essential role in Treg function. This protein constitutes
the key difference between Tregs and helper T cells. Furthermore, the scientists have also
generated Tregs from helper T cells that permanently maintained their characteristics.
Novel discovery in dendritic cell
signalling pathways pave the way for new therapeutic targets
Scientists from A*STAR's Singapore Immunology Network (SIgN) and the University of
Milano-Bicocca, Italy, have discovered another signaling pathway for the activation and
apoptosis, or programmed cell death, of dendritic cells[1] . This discovery was published
in the advanced online publication of Nature on 15 Jun 2009. Led by Prof Paola Castagnoli,
Scientific Director of SIgN and Associate Prof Francesca Granucci of the University of
Milano-Bicocca, the team discovered that the well-studied immune receptor called CD14 in
dendritic cells could be independently activated by bacterial fragments called
liposaccharides or LPS. Once activated, the CD14 would initiate the NFAT[2] or nuclear
factor of activated T-cells pathway, which would then activate the dendritic cells to
trigger off the body's immune response. The scientists also discovered that the entire
activation by CD14 was necessary to cause apoptosis. Dendritic cells are the frontline
sentinels in the body's defence mechanisms and they are potent inducers of an immune
response against invading pathogens. Activated dendritic cells have a short life span, and
scientists have observed that they undergo apoptosis in order to protect the body from the
over-stimulation of the immune system, which could result in autoimmunity. This behaviour
is supported by Prof Castagnoli and Associate Prof Granucci's findings. "What is
exciting is the link between CD14 activation and the NFAT pathway," explained Prof
Castagnoli. "These findings have identified novel potential targets for the
development of therapeutics against diseases that are involved with the CD14-NFAT pathway.
For example, overexpression of CD14 has been associated with sepsis and chronic heart
failure. New drugs that can modulate the CD14-NFAT pathway could provide treatments for
such serious medical conditions."
Protein regulates movement of
mitochondria in brain cells
Scientists have identified a protein in the brain that plays a key role in the function of
mitochondria – the part of the cell that supplies energy, supports cellular activity,
and potentially wards off threats from disease. The discovery, which was reported today in
the Journal of Cell Biology, may shed new light on how the brain recovers from stroke.
"Understanding the molecular machinery that helps distribute mitochondria to
different parts of the cell has only recently begun to be understood," said
University of Rochester Medical Center neurologist David Rempe, M.D., Ph.D., the lead
author of the study. "We know that in some disease states that mitochondria function
is modified, so understanding how their activity is modulated is important to
understanding how the brain responds to a pathological state." Mitochondria are
cellular power plants that generate most of the cell's supply of adenosine triphosphate
(ATP), which is used as a source of chemical energy. While mitochondria are present in all
of the body's cells, some cells – because of their size and purpose – need to
transport mitochondria to distant sites within the cell to maintain proper function. A
prominent example is neurons which have a complex cellular structure that consist of a
main cell body and dendrites and axons that project out from the cell core and transmit
signals to adjoining cells via synapses at their terminus. "Neurons are at a
disadvantage in terms of their anatomy," said Rempe. "They put out enormous arms
of axons and dendrites and they have to keep supplying nutrients and everything down these
arms. The supply line is very long." The supply line includes mitochondria which the
cell must also push down the axons and dendrites to provide these parts of the cell with
energy, help with the transmission of signals, and generally maintain cellular health.
Mitochondria are constantly cycling throughout the neuron. Some are stationary while
others are moving down the arms of the cell to assume their proper position. Additionally,
for reasons not completely understood, at any given time about half of the mobile
mitochondria in the neuron are in the process of returning to the cell body – perhaps
to be recycled or replenished in some form.
Aussie and Kiwi researchers make
double MS genetic discovery
Australian and New Zealand researchers have accelerated research into Multiple Sclerosis
by discovering two new locations of genes which will help to unravel the causes of MS and
other autoimmune disease. Their findings will be published today in the prestigious
journal Nature Genetics. "For decades the cause of MS has remained a mystery. This
discovery reveals important new insights into the genetic susceptibility to the disease,
"says Professor Trevor Kilpatrick, Director for Neurosciences at the University of
Melbourne, who with Dr Justin Rubio of Florey Neurosciences Institutes coordinated the
international study. "The newly discovered gene locations in chromosomes 12 and 20,
offer very promising targets which indicate susceptibility to MS," says Professor
Kilpatrick. "They also reveal a link between genetic susceptibility to MS and other
autoimmune diseases including Type 1 diabetes, Rheumatoid Arthritis and Graves' Disease
and the also the potential involvement of Vitamin D metabolism in the risk of developing
these diseases." "These results are like the key in the door – leading us
to where to look for MS susceptibility," explains Professor Trevor Kilpatrick. The
research was conducted by members of the ANZgene consortium, more than 40 investigators
from 11 institutions in Australia and New Zealand. The three year study utilized the MS
Research Australia (MSRA) Gene Bank and involved scanning the DNA of 1,618 people with MS
and 3,413 people without MS (controls). Using a genome-wide association scan (GWAS),
researchers scanned the entire human genome in broad brushstrokes; looking at genetic
landmarks in the genome and then progressively narrowing down their search to individual
genes. Dr Justin Rubio who coordinated the GWAS says these genetic discoveries are a major
advance for the field.
NYU Langone Medical Center
researchers identify key gene in deadly inflammatory breast cancer
Aggressive, deadly and often misdiagnosed, inflammatory breast cancer (IBC) is the most
lethal form of primary breast cancer, often striking women in their prime and causing
death within 18 to 24 months. Now, scientists from The Cancer Institute at NYU Langone
Medical Center have identified a key gene—eIF4G1—that is overexpressed in the
majority of cases of IBC, allowing cells to form highly mobile clusters that are
responsible for the rapid metastasis that makes IBC such an effective killer. The new
findings, Essential Role for eIF4G1 Overexpression in Inflammatory Breast Cancer
Pathogenesis, scheduled for advance online publication on Nature Cell Biology's website
(Embargoed for June 14th, 2009 at 1:00PM EST) could lead to the identification of new
approaches, therapies and a new class of drugs to target and treat IBC. This would be a
critical development in the fight against IBC, which respond poorly to chemotherapy,
radiation or any other current treatments for breast cancer, according to the study's lead
authors Dr. Robert Schneider, associate director for translational research at The Cancer
Institute, co-director of breast cancer research, and the Albert B. Sabin Professor of
Molecular Pathogenesis at NYU School of Medicine, and Dr. Deborah Silvera, a postdoctoral
research fellow. "The tragedy of IBC is that it is often misdiagnosed and
misclassified. Rather than presenting as a 'typical' lump, IBC looks like an inflammation
of the breast and is frequently mistaken for an infection. Physicians often prescribe
antibiotics, losing valuable time for treating this fast-moving killer," says Dr.
Schneider, noting that IBC accounts for several percent of all breast cancer cases but
takes a high toll on mortality, with an incidence that is 50 percent higher in African
American women. He adds that there has been little progress in treating IBC over the past
two decades, and there are no drugs specifically for this form of cancer. "In fact,
IBC has only recently been recognized as a unique, genetically distinct form of breast
cancer."
Huntington's disease deciphered
Researchers at the University of Illinois at Chicago College of Medicine have discovered
how the mutated huntingtin gene acts on the nervous system to create the devastation of
Huntington's disease. The report of their findings is available in Nature Neuroscience
online. The researchers were able to show that the mutated huntingtin gene activates a
particular enzyme, called JNK3, which is expressed only in neurons and, further, to show
what effect activation of that enzyme has on neuron function. Huntington's disease is an
adult onset neurodegenerative disease marked by progressive mental and physical
deterioration. It has been known for more than a decade that everyone who develops the
disease has mutations in a particular gene, called huntingtin, according to Scott Brady,
professor and head of anatomy and cell biology at the UIC College of Medicine. "There
are several puzzling aspects of this disease," said Brady, who is co-principal
investigator on the study. "First, the mutation is there from day one. How is it that
people are born with a perfectly functioning nervous system, despite the mutation, but as
they grow up into their 30s and 40s they start to develop these debilitating symptoms? We
need to understand why the protein is bad at 40 but it wasn't bad at 4." The second
problem, according to Brady, is that the gene is expressed not just in the nervous system
but in other parts of the body. However, the only part of the body that is affected is the
nervous system. Why are neurons being affected? Brady, Gerardo Morfini, assistant
professor of anatomy and cell biology at UIC and co-principal investigator of the study,
and their colleagues began looking for a mechanism that could explain all the pieces of
the puzzle. They found that at extremely low concentrations, huntingtin was a potent
inhibitor of axonal transport, the system within the neuron that shuttles proteins from
the cell body where they are synthesized to the synaptic terminals where they are needed.
A neuron's critical role in making connections may require it to make the cellular trunk,
called an axon, between the cell body and the synaptic terminal to be very long. Some
cells have axons that reach half the body's length -- for a tall person, a meter or more.
But even in the brain, axonal projections are very long compared to other cells. In
addition to the challenge of distance, neurons are very complex cells with many
specialized areas necessary to carry out synaptic connections, requiring a robust
transport system. "Inhibition of neuronal transport is enough to explain what is
happening in Huntington's," said Brady. Loss of delivery of materials to the
terminals results in loss of transmission of signals from the neuron. Loss of signal
transmission causes the neurons to begin to die back, leading to reduced transmissions,
more dying back and eventual neuronal cell death. This mechanism also explains the late
onset of the disease, Brady said. Activation of JNK3 reduces transport but does not
eliminate it. Young neurons have a robust transport system, but transport gradually
declines with age.
Tracking levels of key biomarkers
reflects disease activity and progression of rheumatoid arthritis
New research has identified biomarkers associated with inflammation and progression in
joint erosion in individuals with early rheumatoid arthritis (RA), according to the
results of a new study presented today at EULAR 2009, the Annual Congress of the European
League Against Rheumatism in Copenhagen, Denmark. The researchers suggest a potential role
for these biomarkers in the monitoring of ongoing disease activity through assessing
inflammation and joint destruction, two important targets for the treatment of early
RA.Over the 12-month study period, levels of the serological biomarkers sYKL-40 and sMMP3
were consistently associated with three measures of disease activity: MRI (RAMRIS (RA MRI
score) synovitis score and RAMRIS bone marrow oedema score) and clinical scores (DAS28*)
of inflammation (p<0.05), when the analyses were corrected for age, gender, c-reactive
protein (CRP, a marker for inflammation) levels and treatment type. The bone marker sCTX1
and the cartilage marker uCTXII were also shown to be predictors of erosive progression
(RAMRIS erosion score; beta 2.42 (95%CI 0.48-4.36)). Dr Silje Syversen of Diakonhjemmet
Hospital, Norway, who led the study, said: "Disease monitoring in RA can be
problematic and patients 'at-risk' of future irreversible joint destruction can go
undetected. Current predictors of joint destruction such as radiographic abnormalities are
signs of later-stage disease development. Biomarkers could offer a novel, more sensitive,
rapid and reliable approach to disease monitoring and prediction, and importantly could be
useful predictors of bone and cartilage damage before such abnormalities have
occurred." In the study, 84 patients with early RA (disease duration <1 year, mean
age 58.4 years, 73.9% females, 55% anti-cyclic citrullinated peptide antibodies (ACPA)
positive) were assessed at baseline, 3, 6 and 12 months including clinical examination,
conventional radiographs (CR) of the hands and MRI scans of the dominant wrist. RAMRIS
score (erosions range 0-150, synovitis range 0-9 and bone marrow oedema range 0-45) was
used to evaluate MRI images and the van der Heijde modified Sharp score (vdHSS) was used
for for the CRs.
Increased levels of certain
cytokines and chemokines predict onset of rheumatoid arthritis
Up-regulation of certain cytokines and chemokines (signaling molecules involved in the
functioning of the immune system) can predict the development of rheumatoid arthritis (RA)
three years before the onset of symptoms, according to the results of a new study
presented today at EULAR 2009, the Annual Congress of the European League Against
Rheumatism in Copenhagen, Denmark. The results of the study showed that up-regulation of
certain cytokines (specifically Th1, Th2 and Treg) involved in the growth and
proliferation of various cells integral to the immune system, predicted which individuals
go on to develop RA. Interestingly, post-disease onset, chemokines, stromal cell and
angiogenic-related markers were important in differentiating up-regulation in those who
had developed RA compared to findings in the same individual before symptoms of RA.
Cytokines and chemokines are small signalling molecules which are integral to the immune
system, as they mediate and regulate immunity, inflammation, and the development of blood
cells (haematopoiesis). In this study, several of these molecules, as well as some
cytokine receptors, showed significantly increased levels before disease onset compared
with controls (median 3.3 years before symptoms), indicating general immune activation
(p<0.05-0.001)* and therefore a progression of disease activity. The levels were seen
to be particularly elevated in individuals identified as being ACPA- (anti-citrullinated
peptide antibody) and RF- (rheumatoid factor) positive (both known risk factors for RA),
and most of the concentrations increased further after disease onset. Notably, the
concentration of interleukin 17 (IL-17, a cytokine which acts as a regulator of multiple
immune functions) was found to be significantly higher before onset compared with
post-diagnosis (p>0.01). Prof Solbritt Rantapää Dahlqvist, of the University Hospital
Umeå, Sweden, who led the study said: "Our findings add another important piece to
the complex puzzle of pathophysiological processes responsible for the occurrence of RA.
Understanding more about what happens in the body, to precipitate the onset of RA, could
potentially contribute to the development of new strategies for the treatment and even
prevention of this debilitating disease."
Females are usually at higher risk
than males in a maternal history of non-GCs
Gastric cancer (GC) is a major clinical challenge because of its frequency, and poor
prognosis. The etiology of GC is still uncertain, but its familial aggregation in a
variable but significant proportion of cases suggests the importance of genetic
predisposition. Previous studies on family history of GC, the association of familial risk
of GC with the age of onset GC, with family member genders, or with family history of
non-GCs, usually yielded contrasting results. Although GC is prevalence in China, scanty
information about its family history is available. A research article to be published on
June 7,2009 in the World Journal of Gastroenterology addresses this question. The research
team led by Professor Yu-Long He from The First Affiliated Hospital, Sun Yat-Sen
University, investigated 2260 GC population in Guangdong, China and found 256 with
oncological family history. Among the 256 families, 112 were the families with history for
gastric and 144 were the families with history for non-gastric cancer. The category and
overall ranking of associated tumors in the families, gender of the affected members and
their relationship to the probands were analyzed. Through comparison of the features
between the 2 kinds of families, this study is believed that the overall ranking of
associated non-GCs in the family history of GC may depends on geographical variation;
familial predisposition to GC may be related to compound genetic and/or local
environmental factors; and a certain subtype of GC may be inherited in a female-influenced
fashion. These results represent important data about familial predisposition to GC in a
part of the world with a high prevalence, and will add to the available body of knowledge
about GC hereditary and aid in future research into this important disease. The results,
especially females are usually at higher risk than males when reporting a maternal history
of non-GCs, also help to guide genetic counseling for the relatives of GC patients.
Individuals who apply pesticides
are found to have double the risk of blood disorder
A study involving 678 individuals who apply pesticides, culled from a U.S. Agricultural
Health Study of over 50,000 farmers, recently found that exposure to certain pesticides
doubles one's risk of developing an abnormal blood condition called MGUS (monoclonal
gammopathy of undetermined significance) compared with individuals in the general
population. The disorder, characterized by an abnormal level of a plasma protein, requires
lifelong monitoring as it is a pre-cancerous condition that can lead to multiple myeloma,
a painful cancer of the plasma cells in the bone marrow. The study will appear in the June
18 issue of Blood, the official journal of the American Society of Hematology.
"Previously, inconclusive evidence has linked agricultural work to an increased
multiple myeloma risk. Our study is the first to show an association between pesticide
exposure and an excess prevalence of MGUS," said lead author Ola Landgren, MD, PhD,
of the National Cancer Institute (NCI), which is part of the National Institutes of
Health, U.S. Department of Health and Human Services. "This finding is particularly
important given that we recently found in a large prospective cancer screening study that
virtually all multiple myeloma patients experienced a MGUS state prior to developing
myeloma." "As several million Americans use pesticides, it's important that the
risks of developing MGUS from the use of pesticides is known," added senior study
author and NCI investigator Michael Alavanja, DrPH. The blood of study participants, who
were individuals licensed to apply restricted-use pesticides, was assessed for MGUS
prevalence. The median age of participants was 60 years (range 30-94 years), and all lived
in either Iowa or North Carolina. Participants also completed questionnaires providing
comprehensive occupational exposure information for a wide range of pesticides, including
information such as the average number of days of pesticide use per year, years of use,
use of protective gear while applying pesticides, and pesticide application methods.
Information on smoking and alcohol use, cancer histories of the participants' first-degree
relatives, and other basic demographic and health data were also obtained. Individuals
with prior histories of lymphoproliferative malignancies (such as multiple myeloma or
lymphoma) were excluded. Cancer incidence and mortality were monitored annually, and,
after five years, follow-up interviews were conducted to update the information about
participants' occupational exposures, medical histories, and lifestyle factors.
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