An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types: paracentric and pericentric.
Paracentric inversions do not include the centromere and both breaks occur in one arm of the chromosome. Pericentric inversions include the centromere and there is a break point in each arm.
Cytogenetic techniques may be able to detect inversions, or inversions may be inferred from genetic analysis. Nevertheless, in most species small inversions go undetected. In insects with polytene chromosomes, for example Drosophila, preparations of larval salivary gland chromosomes allow inversions to be seen when they are heterozygous. This useful characteristic of polytene chromosomes was first advertised by Theophilus Shickel Painter in 1933.
Inversions usually do not cause any abnormalities in carriers as long as the rearrangement is balanced with no extra or missing genetic information. However, in individuals which are heterozygous for an inversion, there is an increased production of abnormal chromatids (this occurs when crossing-over occurs within the span of the inversion). This leads to lowered fertility.
Families that may be carriers of inversions may be offered genetic counseling and genetic testing.
The most common inversion seen in humans is on chromosome 9, at inv(9)(p11q12). This inversion is generally considered to have no deleterious or harmful effects, but there is some evidence it leads to an increased risk for miscarriage for about 30% of affected couples.
Mutations are changes to the nucleotide sequence of the genetic material of an organism. Mutations can be caused by copying errors in the genetic material during cell division, by exposure to ultraviolet or ionizing radiation, chemical mutagens, or viruses, or can occur deliberately under cellular control during processes such as hypermutation. In multicellular organisms, mutations can be subdivided into germ line mutations, which can be passed on to descendants, and somatic mutations, which are not transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant). A new mutation that was not inherited from either parent is called a de novo mutation.
Mutations create variations in the gene pool. Less favorable (or deleterious) mutations can be reduced in frequency in the gene pool by natural selection, while more favorable (beneficial or advantageous) mutations may accumulate and result in adaptive evolutionary changes. For example, a butterfly may produce offspring with new mutations. Many times those are have no effect; but one might change the color of one of the butterfly's offspring, making it harder (or easier) for predators to see. If this color change is advantageous, the chance of this butterfly surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a larger percentage of the population.
Neutral mutations are defined as mutations whose effects do not influence the fitness of an individual. These can accumulate over time due to genetic drift. It is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. Also, DNA repair mechanisms are able to mend most changes before they become permanent mutations, and many organisms have mechanisms for eliminating otherwise permanently mutated somatic cells.
DNA sequencers have become more important due to large genomics projects and the need to increase productivity.
Modern automated DNA sequencing instruments (called DNA sequencers) are able to sequence as many as 384 fluoresecently labeled samples in a batch (run) and perform as many as 24 runs a day. These perform only the size separation and peak reading; the actual sequencing reaction(s), cleanup and resuspension in a suitable buffer must be performed separately.
The magnitude of the fluorescent signal is related to the number of strands of DNA that are in the reaction. If the initial amount of DNA is small, the signals will be weak. However, the properties of PCR allow one to increase the signal by increasing the number of cycles in the PCR program.
A simple DNA sequencer will have one or more lasers that emit at a wavelength that is absorbed by the fluorescent dye that has been attached to the DNA strand of interest. It will then have one or more optical detectors that can detect at the wavelength that the dye fluoresces at. The presence or absence of a strand of DNA is then detected by monitoring the output of the detector. Since shorter strands of DNA move through the gel matrix faster they are detected sooner and there is then a direct correlation between length of DNA strand and time at the detector. This relationship is then used to determine the actual DNA sequence.
Chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. It is detected on cytogenetics or a karyotype of affected cells. There are two main types, reciprocal (also known as non-Robertsonian) and Robertsonian. Also, translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes).
Reciprocal translocations are usually an exchange of material between nonhomologous chromosomes. They are found in about 1 in 600 human newborns. Such translocations are usually harmless and may be found through prenatal diagnosis. However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations leading to miscarriages or children with abnormalities. Genetic counseling and genetic testing is often offered to families that may carry a translocation.
Robertsonian translocations
This type of rearrangement involves two acrocentric chromosomes that fuse near the centromere region with loss of the short arms. The resulting karyotype in humans leaves only 45 chromosomes since two chromosomes have fused together. Robertsonian translocations have been seen involving all combinations of acrocentric chromosomes. The most common translocation in human involves chromosomes 13 and 14 and is seen in about 1 in 1300 persons. Like other translocations, carriers of Robertsonian translocations are phenotypically normal, but there is a risk of unbalanced gametes which lead to miscarriages or abnormal offspring. For example, carriers of Robertsonian translocations involving chromosome 21 have a higher chance to have a child with Down syndrome.
Some human diseases caused by translocations are:
* Cancer: several forms of cancer are caused by translocations; this has been described mainly in leukemia (acute myelogenous leukemia and chronic myelogenous leukemia).
* Infertility: one of the would-be parents carries a balanced translocation, where the parent is asymptomatic but conceived fetuses are not viable.
* Down syndrome is caused in a minority (5% or less) of cases by a Robertsonian translocation of about a third of chromosome 21 onto chromosome 14.
Coronary artery bypass grafting (CABG) is a type of surgery called revascularization (re-VAS-kyu-lar-i-ZA-shun), used to improve blood flow to the heart in people with severe coronary artery disease (CAD).
CAD occurs when the arteries that supply blood to the heart muscle (the coronary arteries) become blocked due to the buildup of a material called plaque (plak) on the inside of the blood vessels. If the blockage is severe, chest pain (also called angina), shortness of breath, and, in some cases, heart attack can occur.
CABG is one treatment for CAD. During CABG, a healthy artery or vein from another part of the body is connected, or grafted, to the blocked coronary artery. The grafted artery or vein bypasses (that is, it goes around) the blocked portion of the coronary artery. This new passage routes oxygen-rich blood around the blockage to the heart muscle. As many as four major blocked coronary arteries can be bypassed during one surgery.
Overview
CABG is the most common type of open-heart surgery in the United States, with more than 500,000 surgeries performed each year. Doctors called cardiothoracic (KAR-de-o-tho-RAS-ik) surgeons perform this surgery.
CABG isn’t used for everyone with CAD. Many people with CAD can be treated by other means, such as lifestyle changes, medicines, and another revascularization procedure called angioplasty.
CABG may be an option if you have severe blockages in the large coronary arteries that supply a major part of the heart muscle with blood—especially if the heart’s pumping action has already been weakened.
CABG may also be an option if you have blockages in the heart that can’t be treated with angioplasty. In these situations, CABG is considered more effective than other types of treatment.
If you’re a candidate for CABG, the goals of having the surgery are to:
Improve your quality of life and decrease angina and other symptoms of CAD
Resume a more active lifestyle
Improve the pumping action of the heart if it has been damaged by a heart attack
Lower the chances of a heart attack (in some patients, such as those with diabetes)
Improve your chance of survival
Repeat surgery may be needed if grafted arteries or veins become blocked, or if new blockages develop in arteries that weren’t blocked before. Taking medicines as prescribed and making lifestyle changes that your doctor recommends can lower the chance of a graft becoming blocked.
In people who are candidates for the surgery, the results are usually excellent, with 85 percent of people having significantly reduced symptoms, less risk for future heart attacks, and a decreased chance of dying within 10 years following the surgery.
During the last three decades careful studies have clearly shown that coronary artery bypass surgery relieves angina pectoris and other symptoms caused by coronary artery disease and, for some patients, prolongs their lives. However, coronary artery bypass surgery alone does not remove the metabolic causes of coronary artery disease and even after successful operation the occurrence of new obstructions may cause problems as the years ago by. These new obstructions may develop either in the patient’s own coronary arteries (progression of native coronary artery disease) or in bypass grafts, particularly in saphenous vein grafts.
Saphenous vein graft
Within a decade of the development of bypass surgery it became apparent that obstructions could develop in saphenous vein to coronary bypass grafts and that the likelihood of obstructions developing was related to time. Within 5 years of surgery approximately 20% of saphenous vein grafts developed partial or total obstructions, and between 5 and 10 years after operation these processes continued to progress such that by 10 years after operation almost half of saphenous vein grafts were either totally obstructed or showed some angiographic evidence of pathologic changes .
Since those early days of bypass surgery progress has been made in the treatment of patients with vein grafts that decreases the rate of vein graft failure. Taking aspirin early after operation increases the percentage of grafts that are functioning well a year after surgery and, more recently, treatment with HMG-CoA reductase inhibitors, also known as "statin" type drugs, has been shown to have long term benefit. However, the failure of vein grafts over the long term remains a significant problem effecting outcomes after bypass surgery and it is the single greatest cause of the need for repeat surgery for bypass grafting .
Internal thoracic artery (ITA, also called mammary artery) graft
(bypass graft using left and/or right internal thoracic artery from the chest wall)
Distal end of ITA attached to LAD
Fortunately there have been other bypass grafts available that are resistant to a late failure - internal thoracic (mammary) artery grafts. Internal thoracic artery (ITA) grafts were used from the beginning of bypass surgery although at relatively few centers during the early years.
Most commonly the left ITA was left attached at its origin from the left subclavian artery and the distal end was dissected away from the chest wall, swung over, and its distal end was attached with sutures to the side of the left anterior descending (LAD) coronary artery.
Multiple vein bypass graft
In the most common situation the left ITA was used as a graft to the LAD coronary artery and saphenous vein grafts were used from the aorta to the other coronary vessels. Studies of angiograms performed after bypass surgery have shown that not only did the LITA to LAD graft have a more than 90% chance of functioning well early after operation, but that these grafts continued to function well for many years and that even 20 years after operation the development of obstructions in these grafts is extremely uncommon (Ref 1).
Long-term follow-up studies done at The Cleveland Clinic Foundation during the 1980s show that not only is the LITA-LAD graft likely to stay functioning over the years but also, that graft has an important long-term effect on clinical outcomes. Over time, patients with a LITA-LAD graft are less likely to die or to need a reoperation when compared with patients who received only vein grafts (Ref. 3). Since these studies have been completed the LITA-LAD graft has become a standard part of operations for coronary bypass grafting.
There are two internal thoracic arteries, one on either side of the sternum (breast bone) and more extensive use of ITA grafts can be accomplished by using the right ITA as an in situ graft (left attached to the right subclavian artery), as a "free" graft from the aorta to the coronary artery, or attached to the left ITA as a composite graft.
ITA as in situ graft ITA as "free" graft ITA as composite graft
Despite the logic that more extensive ITA grafting would be an advantage over the use of only one ITA graft it has only recently been shown by long-term follow-up studies from The Cleveland Clinic Foundation that bilateral ITA grafts further decrease the long-term risks of death and reoperation when compared to patients receiving only one ITA graft (Ref 4). The use of both ITAs as bypass grafts is a more complicated operation and there are some patients where this strategy is not appropriate. However, two ITA grafts do produce better outcomes than just one ITA graft for many patients.
Gastroepiploic graft
Because of the success of ITA grafts, surgeons have search for other arterial bypass grafts. The gastroepiploic artery (GEA) is a branch of the blood supply to the stomach (an organ with a very rich blood supply) that has been used as a bypass graft usually to the right coronary artery. This is a technically difficult operation to perform and it has not become a popular bypass graft but it has a high likelihood of good long-term functioning when used in the proper situation and in some patients represents a significant advantage over vein grafts.
Radial artery graft
(bypass graft using artery from inner forearm)
Radial artery graft
The radial artery was used as a bypass graft in the early years of coronary surgery but its use was abandoned for a number of years because of the occurrence of graft occlusions. In the past few years, its use was revived because of the hope that new methods of preparation and drug treatment with antispasm agents might improve the long-term results. The advantage of radial artery grafts is that they are easy to prepare. The hope is that they will be resistant to the development of atherosclerosis, a problem that has plagued vein grafts. However, the long-term (more than 10 years) of outcomes of radial artery grafts are as yet unknown.
Our data indicates that the long-term results of radial artery grafts are not as good as those for ITA grafts, in particular we have seen more early graft failures. In fact, radial artery graft patency was not better than for saphenous vein grafts. We continue to recommend and use radial artery grafts, particularly for young patients with hyperlipidemia (high cholesterol or triglycerides) who have a relatively high risk of vein graft failure because of the occurrence of vein graft atherosclerosis. In patients who are 70 years or older we use radial artery grafts more cautiously, mainly when alternative grafts are not available. In addition, a radial graft needs a severe blockage or stenosis in the native artery to be grafted, to have a better chance to be promoted and to stay open.(Ref.5)
Total revascularization
It is very clear that the internal thoracic arteries are the best bypass grafts that we have. Because not all patients can be completed treated with just the internal thoracic arteries, the search continues to go on for other arterial bypass conduits and/or total arterial revascularization.
Angiogenesis is the creation of new blood vessels. The term comes from 2 Greek words: angio, meaning "blood vessel," and genesis, meaning "beginning."
Normally, this is a healthy process. As the human body grows and develops, it needs to make new blood vessels to get blood to all of its cells. As adults, we don't have quite the same need for making new blood vessels, but there are times when angiogenesis is still important. New blood vessels, for instance, help the body heal wounds and repair damaged body tissues.
But in a person with cancer, this same process creates new, very small blood vessels that provide a tumor with its own blood supply and allow it to grow.
Anti-angiogenesis is a form of targeted therapy that uses drugs or other substances to stop tumors from making new blood vessels. Without a blood supply, tumors can't grow.
The ear is the sense organ that detects sounds. The vertebrate ear shows a common biology from fish to humans, with variations in structure according to order and species. It not only acts as a receiver for sound, but plays a major role in the sense of balance and body position. The ear is part of the auditory system.
The word "ear" may be used correctly to describe the entire organ or just the visible portion. In most animals, the visible ear is a flap of tissue that is also called the pinna. The pinna may be all that shows of the ear, but it serves only the first of many steps in hearing and plays no role in the sense of balance. In people, the pinna is often called the auricle. Vertebrates have a pair of ears, placed symmetrically on opposite sides of the head. This arrangement aids in the ability to localize sound sources.
Audition is the scientific name for the perception of sound. Sound is a form of energy that moves through air, water, and other matter, in waves of pressure. Sound is the means of auditory communication, including frog calls, bird songs and spoken language. Although the ear is the vertebrate sense organ that recognizes sound, it is the brain and central nervous system that "hears". Sound waves are perceived by the brain through the firing of nerve cells in the auditory portion of the central nervous system. The ear changes sound pressure waves from the outside world into a signal of nerve impulses sent to the brain.
The outer part of the ear collects sound. That sound pressure is amplified through the middle portion of the ear and, in land animals, passed from the medium of air into a liquid medium. The change from air to liquid occurs because air surrounds the head and is contained in the ear canal and middle ear, but not in the inner ear. The inner ear is hollow, embedded in the temporal bone, the densest bone of the body. The hollow channels of the inner ear are filled with liquid, and contain a sensory epithelium that is studded with hair cells. The microscopic "hairs" of these cells are structural protein filaments that project out into the fluid. The hair cells are mechanoreceptors that release a chemical neurotransmitter when stimulated. Sound waves moving through fluid push the filaments; if the filaments bend over enough it causes the hair cells to fire. In this way sound waves are transformed into nerve impulses. In vision, the rods and cones of the retina play a similar role with light as the hair cells do with sound. The nerve impulses travel from the left and right ears through the eighth cranial nerve to both sides of the brain stem and up to the portion of the cerebral cortex dedicated to sound. This auditory part of the cerebral cortex is in the temporal lobe.
The part of the ear that is dedicated to sensing balance and position also sends impulses through the eighth cranial nerve, the VIIIth nerve's Vestibular Portion. Those impulses are sent to the vestibular portion of the central nervous system. The human ear can generally hear sounds with frequencies between 20 Hz and 20 kHz (the audio range). Although the sensation of hearing requires an intact and functioning auditory portion of the central nervous system as well as a working ear, human deafness (extreme insensitivity to sound) most commonly occurs because of abnormalities of the inner ear, rather than the nerves or tracts of the central auditory system.
The pinna collects the sound.The ear drum is a muscle thet vibrates.The small bones pass the vibrations to the cochlea.The cochlea turns vibrations into electricty.The electricity moves through the auditory nervet to the brain.
Animals can hear many different sounds these are same order of how their hearing is:Human Grandparent,Elephant,Human Parent, Yound Human,Dog,Cat,Bat and Dolphin.This order is worst to best hearing.
Pharmacogenetics offers the potential to optimize treatment for individual patients by using genetic information to improve efficacy or avoid side effects. While there are a number of examples in which the approach is already in routine clinical usage, exploitation of this approach in asthma is still under development. A number of examples of possible pharmacogenetic approaches that may prove of value in the management of asthma.
Protein structure prediction is one of the most important goals pursued by bioinformatics and theoretical chemistry. Its aim is the prediction of the three-dimensional structure of proteins from their amino acid sequences, sometimes including additional relevant information such as the structures of related proteins. In other words, it deals with the prediction of a protein's tertiary structure from its primary structure. Protein structure prediction is of high importance in medicine (for example, in drug design) and biotechnology (for example, in the design of novel enzymes). Every two years, the performance of current methods is assessed in the CASP experiment.
A good introductory lecture on protein structure Prediction
The Human Genome Project (HGP) was an international scientific research project with a primary goal to determine the sequence of chemical base pairs which make up DNA and to identify the approximately 25,000 genes of the human genome from both a physical and functional standpoint.
The project began in 1990 initially headed by James D. Watson at the U.S. National Institutes of Health. A working draft of the genome was released in 2000 and a complete one in 2003, with further analysis still being published. A parallel project was conducted by the private company Celera Genomics. Most of the sequencing was performed in universities and research centers from the United States, Canada and Great Britain. The mapping of human genes is an important step in the development of medicines and other aspects of health care.
While the objective of the Human Genome Project is to understand the genetic makeup of the human species, the project also has focused on several other nonhuman organisms such as E. coli, the fruit fly, and the laboratory mouse. It remains one of the largest single investigational projects in modern science.
The HGP originally aimed to map the nucleotides contained in a haploid reference human genome (more than three billion). Several groups have announced efforts to extend this to diploid human genomes including the International HapMap Project, Applied Biosystems, Perlegen, Illumina, JCVI, Personal Genome Project, and Roche-454.
The "genome" of any given individual (except for identical twins and cloned animals) is unique; mapping "the human genome" involves sequencing multiple variations of each gene. The project did not study the entire DNA found in human cells; some heterochromatic areas (about 8% of the total) remain un-sequenced.
Background
Initiation of the Project was the culmination of several years of work supported by the United States Department of Energy, in particular workshops in 1984 and 1986 and a subsequent initiative the US Department of Energy.This 1987 report stated boldly, "The ultimate goal of this initiative is to understand the human genome" and "knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine." Candidate technologies were already being considered for the proposed undertaking at least as early as 1985.
James D. Watson was head of the National Center for Human Genome Research at the National Institutes of Health (NIH) in the United States starting from 1988. Largely due to his disagreement with his boss, Bernadine Healy, over the issue of patenting genes, he was forced to resign in 1992. He was replaced by Francis Collins in April 1993, and the name of the Center was changed to the National Human Genome Research Institute (NHGRI) in 1997.
The $3-billion project was formally founded in 1990 by the United States Department of Energy and the U.S. National Institutes of Health, and was expected to take 15 years. In addition to the United States, the international consortium comprised geneticists in China, France, Germany, Japan, and the United Kingdom.
Due to widespread international cooperation and advances in the field of genomics (especially in sequence analysis), as well as major advances in computing technology, a 'rough draft' of the genome was finished in 2000 (announced jointly by then US president Bill Clinton and British Prime Minister Tony Blair on June 26, 2000).Ongoing sequencing led to the announcement of the essentially complete genome in April 2003, 2 years earlier than planned.In May 2006, another milestone was passed on the way to completion of the project, when the sequence of the last chromosome was published in the journal Nature.
State of completion
There are multiple definitions of the "complete sequence of the human genome". According to some of these definitions, the genome has already been completely sequenced, and according to other definitions, the genome has yet to be completely sequenced. There have been multiple popular press articles reporting that the genome was "complete." The genome has been completely sequenced using the definition employed by the International Human Genome Project. A graphical history of the human genome project shows that most of the human genome was complete by the end of 2003. However, there are a number of regions of the human genome that can be considered unfinished:
First, the central regions of each chromosome, known as centromeres, are highly repetitive DNA sequences that are difficult to sequence using current technology. The centromeres are millions (possibly tens of millions) of base pairs long, and for the most part these are entirely un-sequenced.
Second, the ends of the chromosomes, called telomeres, are also highly repetitive, and for most of the 46 chromosome ends these too are incomplete. It is not known precisely how much sequence remains before the telomeres of each chromosome are reached, but as with the centromeres, current technological restraints are prohibitive.
Third, there are several loci in each individual's genome that contain members of multigene families that are difficult to disentangle with shotgun sequencing methods - these multigene families often encode proteins important for immune functions.
Other than these regions, there remain a few dozen gaps scattered around the genome, some of them rather large, but there is hope that all these will be closed in the next couple of years.
In summary: the best estimates of total genome size indicate that about 92% of the genome has been completed and it is likely that the centromeres and telomeres will remain un-sequenced until new technology is developed that facilitates their sequencing. Most of the remaining DNA is highly repetitive and unlikely to contain genes, but it cannot be truly known until it is entirely sequenced. Understanding the functions of all the genes and their regulation is far from complete. The roles of junk DNA, the evolution of the genome, the differences between individuals, and many other questions are still the subject of intense interest by laboratories all over the world.
Goals
The sequence of the human DNA is stored in databases available to anyone on the Internet. The U.S. National Center for Biotechnology Information (and sister organizations in Europe and Japan) house the gene sequence in a database known as Genbank, along with sequences of known and hypothetical genes and proteins. Other organizations such as the University of California, Santa Cruz, and Ensembl present additional data and annotation and powerful tools for visualizing and searching it. Computer programs have been developed to analyze the data, because the data themselves are difficult to interpret without such programs.
The process of identifying the boundaries between genes and other features in raw DNA sequence is called genome annotation and is the domain of bioinformatics. While expert biologists make the best annotators, their work proceeds slowly, and computer programs are increasingly used to meet the high-throughput demands of genome sequencing projects. The best current technologies for annotation make use of statistical models that take advantage of parallels between DNA sequences and human language, using concepts from computer science such as formal grammars.
Another, often overlooked, goal of the HGP is the study of its ethical, legal, and social implications. It is important to research these issues and find the most appropriate solutions before they become large dilemmas whose effect will manifest in the form of major political concerns.
All humans have unique gene sequences. Therefore the data published by the HGP does not represent the exact sequence of each and every individual's genome. It is the combined genome of a small number of anonymous donors. The HGP genome is a scaffold for future work in identifying differences among individuals. Most of the current effort in identifying differences among individuals involves single nucleotide polymorphisms and the HapMap.
Almost all the goals that the Human Genome Project has set for itself have been completed earlier than predicted. The Human Genome Project actually exceeded the projected finishing time by two years. The Human Genome Project set a reasonable, attainable goal of 95% of DNA to be sequenced. Not only did the researchers surpass that goal, they shattered their prediction, and were able to sequence 99.99% of a human's DNA. Not only did The Human Genome Project exceed all goals and standards, it still continues making progress on those goals already achieved.
How it was accomplished
Funding came from the US government through the National Institutes of Health in the United States, and the UK charity, the Wellcome Trust, who funded the Sanger Institute (then the Sanger Centre) in Great Britain, as well as numerous other groups from around the world. The genome was broken into smaller pieces; approximately 150,000 base pairs in length. These pieces were then spliced into a type of vector known as "bacterial artificial chromosomes", or BACs, which are derived from bacterial chromosomes which have been genetically engineered. The vectors containing the genes can be inserted into bacteria where they are copied by the bacterial DNA replication machinery. Each of these pieces was then sequenced separately as a small "shotgun" project and then assembled. The larger, 150,000 base pairs go together to create chromosomes. This is known as the "hierarchical shotgun" approach, because the genome is first broken into relatively large chunks, which are then mapped to chromosomes before being selected for sequencing.
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