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    Thursday, 12 September 2013 11:26

    The Secret Lives (and Deaths) of Neurons

    As the human body fine-tunes its neurological wiring, nerve cells often must fix a faulty connection by amputating an axon -- the "business end" of the neuron that sends electrical impulses to tissues or other neurons. It is a dance with death, however, because the molecular poison the neuron deploys to sever an axon could, if uncontained, kill the entire cell.

    Researchers from the University of North Carolina School of Medicine have uncovered some surprising insights about the process of axon amputation, or "pruning," in a study published May 21 in the journal Nature Communications. Axon pruning has mystified scientists curious to know how a neuron can unleash a self -destruct mechanism within its axon, but keep it from spreading to the rest of the cell. The researchers' findings could offer clues about the processes underlying some neurological disorders.

    "Aberrant axon pruning is thought to underlie some of the causes for neurodevelopmental disorders, such as schizophrenia and autism," said Mohanish Deshmukh, PhD, professor of cell biology and physiology at UNC and the study's senior author. "This study sheds light on some of the mechanisms by which neurons are able to regulate axon pruning."

    Axon pruning is part of normal development and plays a key role in learning and memory. Another important process, apoptosis -- the purposeful death of an entire cell -- is also crucial because it allows the body to cull broken or incorrectly placed neurons. But both processes have been linked with disease when improperly regulated.

    The research team placed mouse neurons in special devices called microfluidic chambers that allowed the researchers to independently manipulate the environments surrounding the axon and cell body to induce axon pruning or apoptosis.

    They found that although the nerve cell uses the same poison -- a group of molecules known as Caspases -- whether it intends to kill the whole cell or just the axon, it deploys the Caspases in a different way depending on the context.

    "People had assumed that the mechanism was the same regardless of whether the context was axon pruning or apoptosis, but we found that it's actually quite distinct," said Deshmukh. "The neuron essentially uses the same components for both cases, but tweaks them in a very elegant way so the neuron knows whether it needs to undergo apoptosis or axon pruning."

    In apoptosis, the neuron deploys the deadly Caspases using an activator known as Apaf-1. In the case of axon pruning, Apaf-1 was simply not involved, despite the presence of Caspases. "This is really going to take the field by surprise," said Deshmukh. "There's very little precedent of Caspases being activated without Apaf-1. We just didn't know they could be activated through a different mechanism."

    In addition, the team discovered that neurons employ other molecules as safety brakes to keep the "kill" signal contained to the axon alone. "Having this brake keeps that signal from spreading to the rest of the body," said Deshmukh. "Remarkably, just removing one brake makes the neurons more vulnerable."

    Deshmukh said the findings offer a glimpse into how nerve cells reconfigure themselves during development and beyond. Enhancing our understanding of these basic processes could help illuminate what has gone wrong in the case of some neurological disorders.

    Published in News

    13338 influenzaMicroneedles is a medium for supply of influenza vaccine, which avoids the pain associated with conventional needles. They are only seven tenths of a millimeter, and the volume of vaccine - an essential factor in pain - is small.
    Instead of liquid, whole killed or attenuated viruses, using dry vaccines virus-like particles (VLPs) that simply coating the needles in the presence of the basic stabilizer, eliminating the need for cooling - the possible handover for use in developing countries.The lower dose required when using microneedles also reduces the potential for side effects, such as lung inflammation.
    "This method can induce higher levels of IgG2a antibody and quick recall to elicit an immune response to infection lethal. Our previous studies showed that the microneedle vaccination enhances antibody-producing cells in the spleen and bone marrow induced compared to intramuscular vaccination" says Sang Moo Kang Georgia State University, researcher of the study.
    Previous studies by this group has shown that an influenza VLP-coated microneedles indeed produce higher short-term protection than traditional intramuscular immunization. In this study, researchers tested how effective long-term protection of the vaccine. Mice that received the vaccine were 100 percent protected against a lethal challenge with influenza virus 14 months after vaccination.
    Kang says that his goal was to develop a simple and painless method of administration of vaccines. He also says that the patient would probably use this system to be vaccinated.

    Published in News

    Experts in the field of engineering, chemical compounds from MIT (Massachusetts Institute of Technology, MIT, USA) showed that the matrix consisting of billions of nanoscale sensors have unique properties that can enhance the safety and efficiency of various drugs, particularly drugs, based on antibodies.

    With these sensors, the scientists were able to characterize the different types of interactions of drugs based on antibodies, which in the long run will help in the development of effective treatments for cancer and other diseases. The sensors can be used to assess the structure of antibody molecules and determining their content of sugar chains that prevent their functioning.

    "Pharmacological method can help companies identify the reason for a certain technology of preparation of medicines work better than others, which will increase the efficiency of production", - says Michael Strano (Michael Strano), a professor of chemical engineering at MIT, one of the authors of the Nanoscale sensors, recently published in the journal ACS Nano.

    According to Strano, the research team also demonstrated how nanosensor matrix can be used to determine the most productive and preferred cells in a population of genetically modified cells that synthesize drugs.

    Evaluating the effectiveness of drugs

    nano-teratoma-teratoma-service-ipscThe results of previous studies conducted by countries and other scientists have shown that the use of the finest nanoscale sensors, such as carbon nanotubes, is an effective method to determine the chemical compounds present in the solution in small amounts. Carbon nanotubes are 50 thousand times thinner than a human hair. They are able to join the proteins recognize specific Targeted molecule. If the solution contains Targeted molecule fluorescent signal produced by the carbon nanotube varies and it can be detected.

    For the simultaneous determination of a large number of different targets in solution, some scientists are trying to use a large array of nanosensors, in particular, carbon nanotubes or semiconductor nanowires, each of which focuses on a specific targeted molecule. In the new study, Strano and his colleagues studied the unique properties of large sensors that detect the same chemical.

    The first property, scientists detected nanosensors - is that the matrix consisting of equally spaced sensors can measure the force distribution compounds arising in complex proteins such as antibodies.

    Antibodies - the body naturally synthesized molecules that play a key role in the immune response. In recent years, scientists have developed antibodies to treat various diseases, including cancer. The addition of these antibodies to surface proteins of cancer cells stimulates an immune response to the tumor.

    To drugs based on antibodies to be effective, they must be specifically attached to its target. However, the process of antibody production , which is dependent on engineering cells does not always lead to the production of consistently and uniformly acceding parties antibodies.

    Currently, for testing batches of drugs in order to confirm their compliance with the performance standards used by pharmaceutical companies for long time and expensive analytical processes. The new sensor, developed by scientists from MIT, can greatly speed up the process, allowing scientists not only to more effectively monitor and control the process of production of drugs, but also to fine-tune their production. This will result in a more uniform product synthesized.

    Measurements of weak interactions

    Another nice feature of sensors is their ability to measure the weak binding interactions that can also help in the production of drugs based on antibodies.

    Normally, this process of protein glycosylation antibodies surface is covered with long chains of carbohydrates which provide drug efficacy. But sugar chain is extremely difficult to detect, since they interact with weak bonds with other molecules. Organisms that produce antibodies are programmed in such a way as to connect the chain of sugars. However, this process is difficult to control, and it largely depends on the environment surrounding the cells, including the temperature and acidity.

    If an antibody is introduced into the patient will not be glycosylated proteins, they can cause the development of an unwanted immune response or be destroyed by the patient's own cells, making them useless.

    According to Strano, drug companies and scientists who have tried to identify glycosylated proteins by recognizing the hydrocarbon chains, experienced difficulties. "Nanosensor matrix can greatly increase the possibility of determining the rare events of joining molecules. You will be able to measure something that is not able to estimate with a large sensor with the same sensitivity, "- says the country.

    The new method could help scientists determine the optimal conditions for adjusting the degree of glycosylation of proteins that facilitate the production of equally effective drugs.

    The definition of the product obtained

    The third property of nanoscale sensors, studied by scientists - is the ability to detect the synthesis of a molecule of interest. According to Strano, professionals want to be able to identify specific strains of microorganisms that synthesize the necessary medicines. "There are many ways to do this, but none of them is not easy," - says the country.

    The research team from MIT found that culturing the cells on the surface coated with a matrix of nanoscale sensors that can help identify the location of the majority of synthesizing cells. In the new study, the researchers studied the antibodies are synthesized artificially synthesized human embryonic kidney cells. However, established engine also can be individually configured to proteins and other organisms.

    According to Strano, immediately after the detection of the most productive cells, scientists are studying the genes that distinguish these cells from other cells that have a lower efficiency in the production of medicines. As a result, they create a new strain having increased ability to synthesize the desired chemical compounds.

    Scientists have created a prototype of a portable sensor, which they plan to test in the pharmaceutical company Novartis. The study will be funded by Novartis and the National Science Foundation (National Science Foundation, USA).

    Published in News
    Thursday, 29 August 2013 12:17

    DNA Damage: The Dark Side of Respiration

    Adventitious changes in cellular DNA can endanger the whole organism, as they may lead to life-threatening illnesses like cancer. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich now report how byproducts of respiration cause mispairing of subunits in the double helix.

    The DNA in our cells controls the form and function of every cell type in our bodies. The instructions for this are encoded in the linear sequence of the four subunits found in DNA, the bases adenine (A), cytosine (C), guanine (G) and thymine (T). Random changes in the sequence can lead to cell dysfunction, and may result in unrestricted cell proliferation and malignancies. Mutations can be induced by a variety of agents. For example, cellular respiration, i.e. the reduction of inspired oxygen to water, which powers cell function, also generates highly reactive oxygen species that can damage DNA, with the purine bases G and A being particularly susceptible to this kind of attack.

    "Reactive oxygen species are responsible for two different sorts of DNA damage, as they induce formation of both 8-oxo-G and FaPy-G," says Professor Thomas Carell of the Department of Chemistry at LMU. In 2004, work done by Carell and his team defined how 8-oxo-G generates mutations. However, the basis for the mutagenic effect of FaPy-G has remained obscure -- until now. In their latest publication, Carell and his colleagues describe how FaPY-G leads to mispairing of bases in the double helix.

    Pernicious partner swapping One G in one strand of the double helix normally matches up with a C on the other, forming a G:C pair. But as a consequence of damage by reactive oxygen species, the guanine base may be transformed into FaPy-G, so that we get a FaPy-G:C base pair. "We have now shown that, in the course of DNA replication prior to cell division, FaPy-G interacts with adenine, leading to the formation of FaPy-G:A base pairs. This partner swap is unusual, since unmodified guanine normally does not team up with adenine," Carell notes.

    FaPy-G is subsequently recognized as abnormal and is removed by DNA repair enzymes. The missing base is replaced by a T -- which is the usual partner for A. The net result is that the original G:C base pair has been converted into an A:T pair, and the base sequence has undergone a potentially dangerous mutation.

    This outcome is made possible by the fact that the cell's damage-control systems find it surprisingly difficult to distinguish the normal guanine base from its aberrant derivative FaPy-G during DNA replication. "That this defect then leads to mispairing with adenine is one of the main reasons for the spontaneous development of tumors," says Carell. "So with every breath we take, our risk of getting cancer goes up by a teeny-weeny bit." Further insights into the reasons why FaPy-G often eludes the cell's detection and correction systems could help to improve the treatment of cancer, as the inhibition of DNA repair processes in tumor cells increases their sensitivity to chemotherapeutic drugs.

    The study was supported by DFG grants awarded to Collaborative Research Centers 646 and 749 and the Center for Integrated Protein Science Munich (CIPSM), an Excellence Cluster.

    Published in News

    The level of antibodies targeted at the "head" of the virus, with time growing up.A natural reaction to the pandemic influenza virus - an ideal model, suitable for a universal flu vaccine. According to Live Science, researchers specifically examined the changes in the immune system caused by constant exposure to the virus of influenza. Analysis was applied to blood samples from 40 people 35-70 years of age.

    People are faced with two strains of the pandemic virus (H2N2 - in 1957 and H1N1 - in 1977), had elevated levels of immune proteins - a broad spectrum neutralizing antibodies. These antibodies attack the part of the virus, called a "trunk". It differs only slightly depending on the strain. But the "head" of the virus changes frequently. If you find a way to increase the concentration of these antibodies, you get a new vaccine against influenza.

    However, such antibodies do not normally produced in large quantities when in contact with the seasonal influenza. The body realizes that it is now important to produce antibodies that attack the "head" of the virus.

    And only if the virus is very different from the previous ones by the structure of the "head" (it comes with a pandemic strain), the body begins to increase the concentration of neutralizing a broad spectrum of antibodies that work against the "trunk". The aim - to create a vaccine conditions similar to those that are added when pandemic influenza.

    The highest concentration of neutralizing antibodies in humans was facing more than one pandemic. If a person is in contact with H2N2, and H1N1, the figures are higher by 3.8 times compared to a person, only bolevshim H1N1.

    The level of antibodies targeted at the "head" of the virus, eventually grew - despite the fact that the contact with the pandemic virus was only once. From this, scientists have concluded that immunity to this strain of flu remains active for a long time. And in fact, the body is constantly enhances protection against strains with which the person met.

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    Published in News
    Thursday, 29 August 2013 11:23

    Flu antibodies can make disease worse

    antibodySome antibodies to flu viruses may actually make patients sicker, a new study of pigs suggests.

    The finding, published August 28 in Science Translational Medicine, may point to problems with catchall influenza vaccines.

    Pigs vaccinated against a seasonal strain of influenza made antibodies to that strain. Some of the antibodies could also latch on to a different flu virus that caused a pandemic among humans in 2009, report scientists led by Hana Golding of the Food and Drug Administration’s Center for Biologics Evaluation and Research in Bethesda, Md., and Amy Vincent of the Department of Agriculture’s National Animal Disease Center in Ames, Iowa.

    Instead of protecting the pigs against the 2009 pandemic flu, the broad-range antibodies actually helped the virus invade lung cells, causing pneumonia and lung damage.

    Scientists hoping to create a universal flu vaccine need to learn how the pigs’ antibodies and viruses interacted to make the disease worse, James Crowe Jr. of Vanderbilt University writes in a commentary in the same issue of the journal.

    And vaccines aren't the only problem, Crowe says. Natural infections may provoke similar disease-worsening problems.

    Published in News

    mouseResearchers at Columbia University, in collaboration with biologists in Baylor College of Medicine, have made a significant step in understanding and imaging protein synthesis, pinpointing exactly where and when cells produce new proteins. Assistant Professor Wei Min's team developed a new technique to produce high-resolution imaging of newly synthesized proteins inside living cells. The findings were published in the July 9th issue of The Proceedings of the National Academy of Sciences (Volume 110; Issue 28).

    Proteins carry out almost every crucial biological function. Synthesis of new proteins is a key step in gene expression and is a major process by which cells respond rapidly to environmental cues in physiological and pathological conditions, such as cancer, autism and oxidative stress. A cell's proteome (i.e., the sum of all the cell's proteins) is highly dynamic and tightly regulated by both protein synthesis and disposal to maintain homeostasis and ensure normal functioning of the body. Many intricate biological processes, such as cell growth, differentiation and diseases, involve new protein synthesis at a specific location and time. In particular, long-lasting neuronal plasticity (changes in neural pathways and synapses that come from alterations in behavior, environment and bodily injury), such as those underlying learning and long-term memory, require new protein synthesis in a site- and time- dependent manner inside neurons.

    Min and colleagues' new technique harnesses deuterium (a heavier cousin of the normal hydrogen atom), which was first discovered by Harold Urey in 1932, also at Columbia University. When hydrogen is replaced by deuterium, the biochemical activities of amino acids change very little. When added to growth media for culturing cells, these deuterium-labeled amino acids are incorporated by the natural cell machineries as the necessary building blocks for new protein production. Hence, only newly synthesized proteins by living cells will carry the special deuterium atoms connected to carbon atoms. The carbon-deuterium bonds vibrate at a distinct frequency, different from almost all natural chemical bonds existing inside cells.

    The Columbia team utilized an emerging technique called stimulated Raman scattering (SRS) microscopy to target the unique vibrational motion of carbon-deuterium bonds carried by the newly synthesized proteins. They found that by quickly scanning a focused laser spot across the sample, point-by-point, SRS microscopy is capable of delivering location-dependent concentration maps of carbon-deuterium bonds inside living cells.

    "Incorporation of deuterium-labeled amino acids to new proteins is minimally disruptive, and their biochemical properties are almost identical to their natural counterparts," says Lu Wei, the lead author of the paper. "Our technique is highly sensitive, specific, and compatible with living systems under physiological conditions that don't require killing cells or staining."

    Prior to this discovery, the ability to observe protein synthesis in living cells had eluded scientists, who devoted extensive efforts to achieving this goal. A classic strategy that involves labeling amino acids with radioisotopes to trace and quantify proteome dynamics requires the samples be killed and exposed to films. Fluorescence microscopy, another popular method, takes advantage of the inherent glowing of green fluorescent protein (GFP) to follow a protein. While this process does work on individual proteins, scientists can't observe the cell's entire proteome. A third technique, bioorthogonal noncanonical amino acid tagging (BONCAT) metabolically incorporates unnatural (biosynthetic) amino acids containing reactive chemical groups. However, the method generally requires killing cells and subsequent dye staining, a process that presents an issue for live tissues and animals. Therefore, it is extremely challenging and desirable to quantitatively image proteome synthesis in living cells, tissues and animals with high resolution. Min's research opens the door for a new method to study living cells, presenting opportunities to understand previously unanswered questions about the behavior of cells as they perform their functions.

    The next step for Min's team is to capture where and when a new protein is produced inside brain tissues when an animal is subject to various lab exercises to form long-term memory. "Our new technique will greatly facilitate understanding the molecular mechanisms of many complex behaviors such as learning and diseases," he says.

    Published in News
    Wednesday, 28 August 2013 10:57

    Bat brought deadly new infection MERS

    grey-long-eared-bat-plecotus-astriacus-in-front-of-white-background-studio-shotBats in Saudi Arabia are the source of a mysterious virus that sick nearly 100 people and half of them died, said, "New York Times". For the Middle respiratory syndrome coronavirus (MERS) to speak a little more than 15 months after the infection started to kill people in the Middle East and traveled far Europeans. The virus causes severe pneumonia with respiratory failure. With the increase in not only the region but also in Europe, the World Health Organization warned that could lead to an epidemic. The first fear is for the upcoming Hajj, when millions of pilgrims gather in Mecca. Forbid a blast, but the disease has not abated with time.

    Initially the virus was associated with the cause of TORS, which has spread to 30 countries and killed 800 people in 2003, but later it turned out that the two strains are genetically different.

    In a study published on Wednesday, an international team of doctors attributed the spread of new species of small mammals. But cautioned that many questions remain.

    The virus was detected in faecal sample of bat species Taphozous perforatus, who inhabit abandoned buildings and even tombs. But it is not clear how dangerous infection has come to humans because these animals usually do not bite people, and there is no way to contaminate food. According to veterinarian Dr. Jonathan Epstein, who helped in the study, it is possible that infection occurred through inhalation of dust from the droppings of "flying mice". Most likely when cleaning. Similarly hantaviruses is now transmitted by the mice of people.

    But it is also possible coronavirus bat first passed in pets and they do it "moved" to the people. Days ago scientists announced they had found a similar virus antibodies in camels in Oman. And even appear hypothesis that they are the source of infection.

    Bat with MERS was found in an abandoned house in the date palms in a small town in Saudi Arabia. Near this place had the first store ill man - a wealthy businessman, who died two weeks after entering the hospital. He was the owner and 4 camels. Provide separate houses for his three wives and planned to take a fourth wife, suggesting that he was in good health. But most were infected with weakened immune systems or have chronic problems such as diabetes or cardiovascular disease. The virus does not spread easily from person to person, but there are already cases of illness of a family or people were in close contact.

    According to participate in the study, Dr. Ziad Memish needed more tests on animals, and not just bats and camels, but also sheep, goats and cows.

    Published in News

    Protein IL7 PDB 1IL7-gentaur-antibodiesThe molecule interleukin-7 (IL-7) is an important immune system messengers that a sufficient number of T cells guaranteed at present in the body's defenses. ETH Zurich researchers have now shown that IL-7 has another important function: it improves the function of the lymphatic drainage collect moisture that has leaked from the blood vessels into the body tissues and back into the bloodstream. In the future, these insights for lymphedema patients, the lymphatic system is not working properly useful, what tissue to become fluid retention and swelling.

    The predisposition to the development of lymphedema can on the one hand, are hereditary. On the other hand, lymphedema often. During the period after a tumor operation Primary tumors are surgically excised tumor and lymph nodes are often removed because they can contain metastases. Tumor in the course of such a surgical procedure is the lymphatic tissue is damaged. This tissue fluid is often not properly arranged, so that the occurrence of lymphedema in 20 to 30 percent of patients.

    No drug treatment yet

    Currently wearing the only treatment options for patients with lymphedema compression stockings and undergoing a medical manual lymphatic drainage massage therapist. "In IL-7, we have a molecule and a mechanism for improving lymphatic drainage for lymphedema therapy, useful to be discovered," says study leader Cornelia Halin, Assistant Professor of Drug Discovery Technologies.

    In their study, the researchers found that IL-7, which shape is formed by the so-called endothelial cells. The lymphatic vessel wall These cells also bear receptors, IL-7 in a certain way based on the lock-and-key principle. "Although we have not formally proven that so far, we assume that the lymphatic endothelial cells produce the neurotransmitter, may directly affect their own function," says Halin. To date, IL-7 is one of only a few molecules have been identified that support lymphatic drainage. A few years ago, researchers discovered that the other endogenous growth factor VEGF-C, a molecule of interest in this context is perhaps also.

    Findings from an animal model

    Halin and her colleagues showed the drainage support function of IL-7 by drainage experiments in mice, where blue, albumin-binding dye in the skin of the mouse injected ear. It is noteworthy that albumin, a naturally occurring protein that is transported from the tissues via the lymphatics. By quantifying the dye in the tissue remained one day after the injection, the researchers were able to determine how well worked the lymphatic these animals.

    In carrying out this experiment, mice, in which a functional IL-7 receptor, it is noted that these mice to only remove half the dye out of the ear skin in order to compare with a functional mouse IL-7 receptor. However, they observed a significant increase in lymphatic drainage in mice with increased IL-7 production. Finally she IL-7 protein is in a third experiment, unchanged administered healthy mice and found that a therapeutic treatment done to improve lymphatic drainage function.

    Been tested in patients

    The researchers are now planning similar experiments in mice in which lymph vessels are surgically destroyed, similar to the situation in patients after cancer surgery. Here, the researchers want to test whether treatment with IL-7 or IL-7 could lymphedema would be prevented. Reduce the existing lymphedema administered

    The long-term goal is to explore the potential of IL-7-based drugs for lymphedema. In particular, IL-7 has been tested in clinical trials, although for different indications: due to its immune-stimulatory activity on T cells, IL-7 is currently undergoing in patients with immunodeficiency diseases such as HIV or hepatitis infection or bone marrow tested transplants.

    Published in News

    bottles-gentaur-antibodiesPRODUCT DESCRIPTION:
    Influenza viruses are enveloped viruses with a diameter of 80-120 nm, and contain a singlestranded, segmented, negative-sense RNA within a nucleocapsid. Influenza virus is propagated in the MDCK cell line. Influenza Culture Fluid is sold in 1.0 mL aliquots, and is shipped on dry ice. Viral culture fluids consist of virus, cells, and media taken directly from the tissue culture flask. Each lot of viral culture fluid is assayed for its Tissue Culture Infective Dose (TCID50), and sold with titers >105 U/ml. Custom orders are available, including specific titers and package sizes.

    INTENDED USE:
    This product is intended for research, product development testing, or quality assurance testing. Viral culture fluids are sold as consumable testing materials, and are not for propagation or commercialization. Applications include:
    - Nucleic Acid / Molecular Testing
    - Limit of Detection (LOD) Studies
    - Cross-reactivity Studies
    - Other Viral-based Assays

    TIOLOGIC STATUS/BIOHAZARD TESTING:
    Influenza virus is a Biosafety Level 2 organism.

    PRECAUTIONS:
    USE UNIVERSAL PRECAUTIONS when handling this product! Viral Culture Fluid is live and infectious!! This material should be handled as if capable of transmitting infectious agents.

    RECOMMENDED STORAGE:
    Viral culture fluid is stable for at least one year when stored at -65ºC or below. To avoid repeat freeze-thaws, which could negatively impact product performance, culture fluid should be stored in aliquots upon receipt.
    DO NOT USE IN HUMANS!
    These products are NOT intended for use in the manufacture or processing of injectable products subject to licensure under section 351 of the Public Health Service Act, or for any other product intended for administration to humans.

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