Threatening Proportions of Myopia

“World has become myopic,” is a colloquial trite. But believe it or not, the situation is really alarming. A recently published article in Nature reported that East Asian countries are afflicted by threatening proportions of myopia or short-sightedness, the inability to see objects at longer distances. In China up to 90% of the teenagers are myopic and figures even disturbing for Seoul where it is 96.5%. While immediate course corrections like glasses, contact lenses and surgery can offer relief but a worst case of short sight can increase risk of cataract, retinal detachment, glaucoma and even blindness.

Myopic condition is the fall of out of the slightly elongated eyeball which causes the lens to focus light away from the object leading to formation of image in front of retina instead of direct image formation on the retina. This condition occurs most commonly in school going kids and adolescents. It is reported that nearly one-fifth of the college going kids in East Asia have an extreme form of myopia and half of them are at the risk of developing irreversible vision loss.  The burgeoning threat of myopia has propelled scientists across the world to address this issue.

Myopia was believed to be the domain of book-worms who were considered to be more prone to this defect. Famous German astronomer Johannes Kepler attributed his short-sightedness to book work. For long even ophthalmologists too believed in the same dogma. By 1960 scientists believed that it is genetically transferred as it is common in genetically identical twins than non-identical twins. Genome analysis showed that 100 regions are responsible for myopia. Increasing cases of myopia among school children in East Asian countries has been linked to enhanced educational performance where in students spend long hours before books. Researchers too have drawn an association between academic performance and the number of hours of study. On average while a Chinese teenager spends 15 hours a week on homework against 5 hrs in UK and 6 hrs in USA. Moreover with teenagers becoming addicted to televisions and hooked onto smart phones eternally, the incidence has peaked.

Documented research reports began to throw light on the deleterious effects of sustained close work capable of affecting the growth of eye ball. Scientists at the Ohio State University, College of Optometry Columbus showed that bright light is protective to eye. The research hypothesis showed that bright light stimulates release of dopamine neurotransmitter in the retina blocking the elongation of eye. Diurnal cycle of eye is strongly controlled by bright light wherein retinal dopamine turns on the cone-based vision during the day and rod-based vision at night in response to the dim light. For people working in the dim light or indoors this cycle is messed up resulting in elongation of the retina.

Research conducted by the Australian National University estimated that children need to spend a minimum of three hours of day under the light intensity of 10,000 lux to be guarded against myopia (an over-cast day provides 10,000 lux against 500 lux of class room). Consequently three hours of outdoor activity has become a norm in Australia. Now schools in China and Taiwan are making way for 3 hrs of outdoor time in the school schedule.  Preliminary findings in those schools are promising. Schools which have relatively inflexible routine are contemplating to conduct classes in rooms fitted with glass to compensate for the outdoor time. An unpublished research also indicated that as the amount of time spent increased the incidence began to lessen. Thus, three hours of outdoor time not only improves the physical well being of the children but protects them against myopia.

In the meanwhile researchers are working on special glasses and contact lenses that can alter the eye growth by focusing light from distant objects at different angles rather than just at the centre as the regular glasses do. To curtail myopic progression regular use of eye drops with a neurotransmitter-blocking drug atropine at night is also recommended. A hand book of Ophthalmic Science and practice authored by Henry Edward Juler in 1904 mentioned that myopic is stationary; change of air- or possibly a sea voyage was prescribed. It ‘as been more than hundred years it took a swarm of brilliant brains with years of dedicated research and sophisticated inventory to confirm the intuitive thinking of yesteryears. 

 

 

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Horizontal Gene Transfer in Humans

For the past few decades genetically modified (GM) crops across the World were meted with lot of resistance from green activists. Wide spread campaigns strongly denounced GM crops as monster crops. They enunciated that their cultivation would destroy the traditional agriculture and decimate human race. The pseudo-science and superstition has resulted in curbing of field trials in India. The uproar and activism against these crops pressurised the government to act against the GM crops. While several acres of land is under the cultivation of GM crops in the US but the Europe shied away from its cultivation and enforced a strict ban on all the GM crops products. Research carried out by scientists in Cambridge University shed new light on the gene transfers annihilating fears about the cultivation of GM crops.

Fundamentally genes or the hereditary material DNA is transmitted from parents to the offspring directly through vertical gene transfer. There are reported instances of alternative mechanisms of gene transfer, know as horizontal gene transfer or lateral gene transfer reported in bacteria and unicellular eukaryotes. Existence of such mechanism is not established in higher organisms like vertebrates and least known in humans. Against this back ground, the research article published in Genome Biology by Alistair Crisp and Chiara Boschetti made startling observations indicating that humans have obtained 145 genes from their ancestors. Though it is much less than 1% of 20,000 human genes it is surprising to learn that human have obtained genes from lower organisms like flies, nematodes, fungus, plants and bacteria. The classical example of Drosophila obtaining more than 1Mb of genome from Wolbachia, a bacterium indicates that HGT is very common in lower organisms.

HGT involves transfer of the genetic material between different organisms and this process has played a crucial role in acquiring antibiotic resistance in bacteria. Genes obtained by HGT are mostly associated with metabolism and code for enzymatic activity suggesting that the process contributes to biochemical diversification. Computational analysis of transcriptomes of 40 different species carried out in this paper concluded that HGT occurs at low but in appreciable levels across all animal species. It has occurred over a period of time and still continues to occur and that it originated from bacteria and Prostists. In spite of structural complexities, research shows that overall levels of HGT are not conspicuously different between vertebrates and invertebrates.

While analysing the transcriptomes (data base of the mRNAs) comparison with immediate relatives is avoided. Flies are not compared to arthropods similarly no vertebrates with primates and no nematodes with worms. The results yielded that worms had 173 HGT genes, flies 40 and primates 109. It is interesting to learn that the genes responsible for the ABO antigen system which is the basis for blood groups is bacterial in origin and the genes involved in the synthesis of the hyaluronic acid, is from fungi and the gene associated with obesity has migrated from marine algae suggesting that gene insertions played a vital role during the process of evolution.

The human genome deciphered in 2000 also suggested the presence of plant genes. But it raised severe flak from critics who enunciated alternate theories to account for those genes to gene loss, convergent or divergent evolution. Researchers now comprehend that 1% of human genome might have immigrant from different species. Scientists who are attempting to create GM crops are just invoking the process that happened in nature over a period of time. During the course of evolution, foreign genes integrated into humans which slowly began to cohabit with its genome. Activists are now rallying behind the point that natural gene transfers took place over centuries. But it has to be borne in mind that even during the natural transfers, these genes were as align as the Bt gene insertion into cotton or brinjal. In fact scientists are simply replicating the process of natural gene transfer in a controlled environment in the laboratories to obtain GM crops. To ensure complete integration of foreign gene, scientists grow these crops under strict supervision and protected environment before releasing it for commercial use. Strict regulations and checks are in place to ensure minimal gene contamination and release into the environment.

This robust research now strongly questions the stand point of the green activists who demand complete annulment of GM crops. Besides allaying the fears of common man, the paper mocks at the frivolous scientific guidelines patronised by the antagonists of GM crops.

Dark Matter may have caused the extinction of Dinosaurs

It is estimated that more than 99% of the species that lived on the Earth are extinct today owing to the competition or inability to survive and others might have perished due to periodic cataclysmic events. New York University Biology Professor Micheal Rampino in his recent research article published in the Monthly Notices of the Royal Astronomical Society suggested that astrophysical findings could help us in understanding the biological phenomena occurring on the Earth. Fossil records show that Earth experienced periodic mass extinction cycles of 26-30 Million years over the past 250 Million year cycle. All these cataclysmic events are fall outs of collisions of either asteroids or comets and extended periods of volcanic emissions. The extinction of dinosaurs, 66 million years ago is one such most extensively researched events. Palaeontologists recognise five such humongous events wherein 90% of species were lost. Though there is an ambiguity over the periodicity of the events, the new postulates suggest that Cometary collisions might  have been triggered by the gravitational disruption of the Oort Cloud, where a repository of Comets reside in the outer edge of our solar system.

Every 250 million years the Sun with its entourage of planets makes a peregrination of our Milky Way. While orbiting, Solar System oscillates up and down through the galactic disc where the Galaxy’s dark matter is concentrated. During this process the Earth too passes through the galactic disc once in every 30 million years. Galactic disc is crowded with stars, clouds, dust and elusive sub-atomic particles whose existence can be detected by their gravitational effects. In this paper Prof. Rampino tries to shed light on the impact of the dark matter in the galactic disc on the periodicity of the terrestrial events. Interestingly the periods of gravitational effects of the dark matter on the Earth were found to be in congruent with the galactic dynamics.

Earlier he postulated Shiva Hypothesis named after Lord Shiva the God of destruction to explain how mass extinctions are caused by impact events. The hypothesis suggests that the gravitational disturbances are caused as the solar system crosses the plane of the Milky Way galaxy disturbing the comets in the Oort cloud surrounding the solar system. This results in raining of comets towards the inner solar system causing the impact. These impact events that occurred every 30 million years might have led to the cretaceous- paleogene extinction event.

While the composition of the dark matter is unknown, it is known to interact with visible matter and radiation under the influence of gravity. Modern theories suggest that dark matter is accounts for 23% of all mass in the universe, 73% of Universe is dark energy and the rest 4% includes regular matter such as planets, stars and people. The dark matter tends to interact with the regular matter as Earth passes through the galactic disc and eventually results in the disruption of Oort Cloud. The gravitational attraction between the dark matter and Earth will result in the accumulation of the dark matter at Earth’s core.

Rampino believes that as the dark matter particles build up, the particles will annihilate each other and release large amounts of energy. Approximately as earth passes through the galactic plane every 30 million years, internal heating of the Earth brings about massive changes in the Earth’s magnetic field, leads to cataclysmic events like tectonic shifting, eruption of volcanoes, rise of sea levels and climate.

Another study carried out by Harvard University team of theoretical physicists Rendall and Reece in their paper published in Physical Review Letters opined that dark matter is the source of the periodic Oort Cloud perturbation. Rampino believes that Earth’s cyclical movement through the thin, invisible, disc of dark matter would also lead to perturbations in the orbits of distant comets and results in heating up of Earth’s core. Thus the Cometary collisions and eruption of volcanoes might have led to the periodic mass extinction. The  astrophysical events caused by the oscillation of Earth around the galactic disc , results in consequent accumulation of the dark matter within the Earth’s core causing dramatic changes in the geological and biological phenomena on the Earth.

This model in fact opens up new vistas for understanding the impact of the astrophysical events on other planets in our solar system. It throws up new challenges for astrophysicists to extensively work on the excruciating details of the dark matter, whose composition is not yet clearly known. While the exact details of the sequence of events elucidated in the model are not scientifically worked out, it has eclectically linked the cycles of geological and biological evolution on the Earth to the rhythms of the Galactic dynamics.

 

 

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Scientific Breakthroughs in Anti Ageing

Advances in science have entailed upon the human race the windfall of increased life expectancy. While the average life span in developed countries have registered an increase of 20 years and pegged at 82 yrs, in India it is 66.4yrs. Long life is a remarkable achievement and society yearns for the same. But long life also puts a burgeoning pressure on the resources and opportunities in developing countries. The real challenge that embodies long life is living better. Hence the real task accompanying the bantam feat is to ensure that an individual should age gracefully, physically fit, mentally sharp and economically secure.

 Extraordinary medical and scientific advances have contributed enormously towards improving the quality of living and subsequently the life expectancy surged. The phenomenon described as technophysio-evolution described by eminent economist Robert Fogel has brought about immense biological changes in the physiology of the human body which was made possible through numerous advances in technology. A steady supply of food grains, discovery of electricity, invention of techniques like refrigeration, pasteurisation, water purification, vaccination has dramatically reduced deaths due to contagious diseases and premature deaths. These changes have brought an increase in body size by over 50 % and improved robustness and capacity of vital organs too. Even our brains have begun to process information much faster. With the availability of technologically advanced devices ageing has been reduced to minor inconvenience.

Scientists have been relentlessly toiling for several decades to crack the code of ageing. Research carried out at the University of Texas Health Science Centre San Antonio, indicated that a mouse fed with rapamycin seemed to age slowly by reducing damage to certain cells. Even the vital organs like heart and liver fed with rapamycin aged very slowly and its nervous system was quite agile and extremely receptive when compared to its peers of the same age. It was devoid of tumours even. Rafamycin diet laced mouse lived 20% longer than unfed ones. Rapamycin is administered to human subjects to prevent organ rejection after transplantation. Rapamycin was obtained from soil samples in 1964 in an expedition to Easter Island. It works on a wide variety of species like yeast, flies, mice and worms and hence convenient for extensive studies.

Rapamycin works by interrupting with the functioning of a gene mTOR, found in mouse and man. mTOR controls the intake of cells and use of energy. It signals cells to absorb more nutrients when food is abundant and taps into other energy related pathways when nutrients are no longer available. It restricts intake of calories and prolongs life. Rapamycin suffers from pit falls too. In mouse it resulted in 30% smaller body size than average. Its regular use is likely to develop cataracts and increases propensity to diabetes. Male mouse tend to experience gradual loss of testicular functioning. Even human patients who took rapamycin after transplantation had higher changes of developing diabetes and risked cataracts. But it still seems to be a promising anti-ageing drug and calibrating the right doses of medication might tip the balance in favour of longevity with minimum risks.

Another well studied scientific pathway was related to dyskeratosis congentia, a condition of telomere dysfunction, wherein rapid shortening of the telomeres or the ends of chromosomes greatly enhanced ageing. Research indicated that if  cells with the disorder are rectified then premature ageing can be averted. Thus, offering a great promise of turning back the clock. Extensive research was done to understand the role played by telomeres. Carol Gredier, who discovered the enzyme telomerase and cracked the puzzle of the telomere replenishment, was awarded a Nobel Prize too.

Scientists of Harvard Stem Cell Institute hit upon an innovative technique in which a young and an old mice are conjoined in a Siamese-twin style to share the same blood system but kept everything else separate rejuvenated the older mice. They exhibited new cell growth in their brains, muscles were stronger and the enlargement of heart which comes with age was reversed. It was found that a protein GD11 abundant in the younger mice and scarce in old mice could have turned the tables in favour of anti-ageing. Further detailed investigations are to be carried out before endorsing the effects of GD11 scientifically.

In the meanwhile Dena Dubal from the University of California suggested that increase levels of the hormone klotho causes mice to live 30% longer. She suggested that nearly 20% of human beings   carry this gene and live on for an extra 3-4 years. These new discoveries added momentum to the research on longevity. Scientists are hopeful that  they can unravel several such strategies that can interrupt ageing.

Longevity research encompasses the idea of delaying ageing or facilitating slower ageing. The central focus of the research is staving off aging. It is not about extending the life indefinitely but prolonging the healthy life for little longer. No one with a fragile health would want to live long. After all, the real joy of living lies in enjoying life to its fullest in the best of physical and mental health.

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Self-Organising Tiny Robots: Kilobots

I was simply awed by the sheer intelligence and simplicity when I read about Kilobots. The marvellous, small few centimetres in diameter robots, standing on three pin legs, powered by coin batteries were developed in the laboratory of Professor Radhika Nagpal and Fred Kavali of Harvard School of Engineering and Applied Sciences. A kilo or a swarm of 1024 autonomous robots assemble into two-dimensional pattern formation upon instructions without human intervention. An initial set of instructions are beamed to the robots via infrared following which the robots would work autonomously. Four robots mark out origin of a coordinate system and the remaining will receive a 2-D image they have to mimic. Using primitive behaviour, robots follow the edge of the group, track the distance and maintain a sense of relative position. They take turns in moving towards an acceptable position and assemble into the pre-directed shape. Kilobots communicate with its neighbour through and in built infrared transmitter. They have no sense about their broader outer environment. They can locate the position of their neighbours and their point of origin and are capable of assembling into a shape by gauging the position of its neighbour.

Kilobots are very simple in design and their abilities are variable and less reliable. They are basically designed to carry out collective tasks. Just as trillions of cells that constitute a complex organism communicate with each other and carry out complex tasks. These robots demonstrate how complexity can arise from simple behaviours performed enmasse.

The team basically drew inspiration from biological systems where individuals assemble to carry out tasks. An army of ants by relaying information among themselves construct bridges and rafts to cross difficult terrains. Similarly social amoebae cooperate with each other especially when food is scarce to form a huge fruiting body and escape the harsh external environment. Even the individual cells of cuttlefish change colours to blend into its surroundings. Nagpal has earlier developed a swarm of robots TERMEs inspired by termites but its algorthim for self-assembly wasn’t demonstrated. Kilobots were inspired by the collective functioning of a colony of ants. Till date robot swarms of around 100 were constructed. Kilobots are thus a unique creation wherein coordinated action of tiny 1024 robots is demonstrated.

To cut down the cost of constructing kilobots, certain tradeoffs are made. It has a simple design and moves with two vibrating motors which allows it to slide across a surface on its rigid legs. They have built in infrared receiver and transmitter to communicate with neighbouring robots. It is myopic and has no access to birds-eye view. It can’t move in a straight line as a result its abilities are more variable and less reliable. But the strength of the swarm overcomes individual weaknesses. With the smart algorithms it can overcome its limitations and can complete human-specified tasks of assembling into a particular shape with precision. These robots are capable of correcting mistakes. If they sense traffic jam, robots moves off the course, nearby robots sense the problem and cooperate to fix it.

Kilobots functioning can be represented as a milestone for the computer scientists in the development of collective Artificial Intelligence (AI). The development of kilobots is exemplary due to inherent difficulties of algorithmic limitations on coordinating large numbers and the cost of the labour involved in fabricating such tiny devices. Kilobots are test bed for Artificial intelligence and are manipulated to carry out collective tasks. Increasingly, robots are now required in coordinated tasks like environmental clean-up or disaster relief and for self-driving on highways. The potential for such swarms is huge in construction, agriculture, mining and medicine.

 

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Cracking Protein Folding : Unboiling of an egg

At the first instance, the scientific accomplishment of getting egg protein back intact after boiling or unboiling the egg in short might sound silly and foolish accomplishment. But the seemingly frivolous task of retrieving protein in its original form is the most daunting task. Protein biologists struggle with mind boggling and finicky protein extraction protocols to obtain a functional protein in purest form but the protein becomes unusable as its gets entangled with itself or gets stuck with the containers and instruments during experimentation. Thus significant amount of precious protein is lost. This technique besides revitalising the protein holds the key for cracking the protein folding problem too. It offers a magical solution for refolding the proteins into its original shape.

Proteins are quintessential and the most indispensable tools for working in biological and chemical laboratories. In vivo protein synthesis is carried out ribosomes dictated by the genetic code. Basically proteins are made of amino acids that contain carbon, hydrogen, nitrogen, and sulphur oxygen. Functionality or the efficiency of proteins is determined by the unique nature of folding of proteins. More often the nature of bonding (hydrophilic –water loving or hydrophobic- water hating) between the molecules in the protein determines the shape and activity of the proteins. Proteins in their native state have lowest energy and are most stable.  

Scientists during the course of biological or chemical research lose significant portion of precious proteins as they get stuck to containers, instruments or get entangled with each other becoming unusable. Most often these proteins couldn’t be salvaged easily. Existing techniques are tedious, time consuming and even the amounts of protein retrieved is too low. Scientists at the University of Irvine have claimed to have discovered a technique which can help in untangling the protein and allow them to return to their original conformation.

Gregory Weiss’s lab using a vortex fluid device untangled proteins from the boiled egg. The vortex fluid device was used by an Australian lab to peel sheets of carbon of few atoms thickness from graphene. The device spins molecules in liquid state and spins them through an open- ended test tube. The liquid spreads out as a thin layer of few microns (one millionth of meter) thickness. The forces in the rapidly spinning tube transfer energy to the molecules, separating them in a controlled way. Weiss contemplated on using the machine for revitalising proteins. Egg white is watery containing several proteins besides lysozyme. Upon heating structural bonds between proteins are broken, thus they lose their native conformation and become a thick clump of solid mass. Now, scientists tried to recover lysozyme by dissolving the egg white in a solution that breaks the clumps overnight. After a day the solution becomes clear, full of unfolded proteins.

Refolding is the biggest task to restore the functionality of protein. Solution of unfolded proteins is whirled through the vortex fluid machine wherein proteins spread out as thin layer separated from its neighbour thus allowing the proteins to refold without tangling. By fine-tuning the speed and rotation of the vortex, scientists can generate the force strong enough to separate protein molecules apart from each other and gentle enough to allow them to refold into their natural shapes.  Scientists first used this technique to restore a protein from Escherichia coli, protein kinase A (PKA) three times larger than lysozyme. They slightly modified the protocol to refold the protein. They managed to manipulate the protein into refolding by hinging one end of protein onto a large bead (Ni+2charged immobilised metal affinity chromatography). This in fact is similar to the process by which proteins are folded naturally by the ribosomes.

The force requirement for different protein would vary and subsequently the protocol should be effectively reconstructed to suit to the needs. Scientists are now aiming to build a large-scale vortex machine and exploring the possibility of using different solutions, level of forces and settings suited for different proteins. This method has the ability to transform the production of proteins. Pharmaceutical companies have started creating cancer antibodies in expensive hamster ovary cells which often don’t fold properly and a misfolded protein is not functional. This technique could be of great help to pharmaceutical and biotechnology industries that work on recombinant proteins. It can aid in untangling over expressed proteins that are jettisoned into inclusion bodies as complex aggregates.

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Diaper Absorbant Enhances Resolution Capacity of Ordinary Microscope

Some of the fantastic innovations of science which brought about a tremendous change are often outcomes of ingenuity and out of box of thinking. Here is one such classical example which opened up new vistas of microscopy. Edward Boyden a neuroengineer of Massachusetts Institute of Technology (MIT) in Cambridge with his colleagues developed a novel and subtle way of observing living tissues. The technique called as expansion microscopy uses the material used in baby diapers to observe the living tissues.

Conventional Optical microscope suffers from the major impediment of distinguishing the objects which are closer together than about 200 nanometres or roughly half the wavelength of visible light. These objects appear blurred or as a blob. This resolution limit is referred to as Abbe’s diffraction limit after the scientist Ernst Abbe who first identified it in 1873. Hence the optical microscope which is otherwise desirable for identifying the cell organelles is not suitable for observing structural details. Microscopes which use electron beams instead of light have finer resolution but they can be used in vacuum hence dead tissues alone can be used. Abbe’s limit couldn’t be overcome according to laws of physics. But scientists using fluorophores or fluorescent molecules and hitting them with lasers of specific wavelength engineered new ways to resolve proteins as close as 20 nanometres in living cells. These techniques developed by three scientists independently- Stephan Hell, William Moerner and Eric Betzig were awarded the Nobel Prize in Chemistry in 2014 for the pioneering work on super-resolution microscopy. These techniques are very useful in observing the vesicle moments across the nerve synapses, cell protein complexes and spaces between rows of skeletal microtube filaments etc but these cumbersome techniques demand expertise in handling expensive and specialised equipment.

In contrast to the super-resolution microscopy, Boyden employed the super absorbent material acrylate used in diapers for resolving the structural details of the brain tissues. Acrylate has two advantages. It is capable of forming a dense mesh capable of holding the proteins in place and it swells in presence of water. Acrylate salts form water lock and gives the diapers sponginess. They have a capacity to expand four and half times the original size. In order to locate the proteins which are closely packed, the living tissues before swelling are soaked in a chemical cocktail which makes them transparent and then infused with fluorescent molecules that anchor specific proteins to acrylate. Upon adding water, the acrylate would cause the living tissues to swell uniformly in all directions. In their experiment with brain tissues of mice, Boyden and his colleagues demonstrated that proteins which were too close and probably difficult to distinguish could be identified under visual-light microscope. With this technique proteins as close as 60nm were resolved. In future with further fine tuning of the techniques the resolution can be improved.

In this new technique of expansion microscopy the original living tissues are increased in size upon absorption of water. Crucially it also maintains the relative orientation and interconnections of the proteins and other cellular structures intact. But the position of position is shifted by 1-4%. The results of the expansion microscopy were comparable to super-resolution microscopy techniques.

This novel technique was feted by scientists all around who commended its ingenuity. These kinds of unique scientific feats would lay foundation for a genre of science which circumvents the use of highly sophisticated and complicated equipment. It also opens new frontiers in science where a judicious combination of the ingenious techniques with the hardwired innovative equipment could unravel the mysteries of life. 

 

 

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