How Does DNA Fingerprinting Work?

Gosh Baig

People everywhere expected the new millennium to bring surprises. But the particular shock and horror that rippled through the international viticulture community in 2000 was most unexpected. It had been found that sixteen of the most highly prized varieties of wine-making grapes were the products of mating between the classic Pinot and the classically undervalued Gouais grape.
This blew the proverbial cork off the industry's bottle because the Gouais was considered such an inferior specimen that there were even attempts to ban its cultivation in France during the Middle Ages. This proves that humble origins can still produce superior quality. More practically, though, knowledge of their heritage allows improved breeding of highly desirable subspecies of grape. And viticulturists everywhere had DNA fingerprinting technology to thank.
DNA fingerprinting is a term that has been bandied about in the popular media for many years, largely due to its power to condemn and save, but what does it involve? In short, it is a technique for determining the likelihood that genetic material came from a particular individual or group. 99% of human DNA is identical between individuals, but the 1% that differs enables scientists to distinguish identity. In the case of the grapes, scientists compared the similarities between different species and were able to piece together parent subspecies that could have contributed to the present prize-winning varieties.
The DNA alphabet is made up of four building blocks – A, C, T and G, called base pairs, which are linked together in long chains to spell out the genetic words, or genes, which tell our cells what to do. The order in which these 4 DNA letters are used determines the meaning (function) of the words, or genes, that they spell.
But not all of our DNA contains useful information; in fact a large amount is said to be “non-coding” or “junk” DNA which is not translated into useful proteins. Changes often crop up within these regions of junk DNA because they make no contribution to the health or survival of the organism. But compare the situation if a change occurs within an essential gene, preventing it from working properly; the organism will be strongly disadvantaged and probably not survive, effectively removing that altered gene from the population.

Left - DNA fingerprints from 6 different people, 1 in each lane (column). DNA can be cut into shorter pieces by enzymes called "restriction endonucleases". The pieces of DNA can then be separated according to their size on a gel. Each piece of DNA forms a band (the white lines on the gel). The smallest pieces travel the furthest and are therefore closest to the bottom of the gel. The larger pieces travel shorter distances and are closer to the top.

For this reason, random variations crop up in the non-coding (junk) DNA sequences as often as once in every 200 DNA letters. DNA fingerprinting takes advantage of these changes and creates a visible pattern of the differences to assess similarity.
Stretches of DNA can be separated from each other by cutting them up at these points of differences or by amplifying the highly variable pieces. ‘Bands’ of DNA are generated; the number of bands and their sizes give a unique profile of the DNA from whence it derived. The more genetic similarity between a person – or grape – the more similar the banding patterns will be, and the higher the probability that they are identical.

In the non-coding regions of the genome, sequences of DNA are frequently repeated giving rise to so-called VNTRs - variable number tandem repeats. The number of repeats varies between different people and can be used to produce their genetic fingerprint. In the simple example shown above, person A has only 4 repeats whilst person B has 7. When their DNA is cut with the restriction enzyme Eco RI, which cuts the DNA at either end of the repeated sequence (in this example), the DNA fragment produced by B is nearly twice as big as the piece from A, as shown when the DNA is run on a gel (right). The lane marked M contains marker pieces of DNA that help us to determine the sizes. If lots of pieces of DNA are analysed in this way, a 'fingerprint' comprising DNA fragments of different sizes, unique to every individual, emerges.

But why bother? After all, I know where my wine comes from – Tesco's, right? Well, there are many relevant applications of DNA fingerprinting technology in the modern world, and these fall into three main categories: To find out where we came from, discover what we are doing at the present, and to predict where we are going.
In terms of where we came from, DNA fingerprinting is commonly used to probe our heredity. Since people inherit the arrangement of their base pairs from their parents, comparing the banding patterns of a child and the alleged parent generates a probability of relatedness; if the two patterns are similar enough (taking into account that only half the DNA is inherited from each parent), then they are probably family. However, DNA fingerprinting cannot discriminate between identical twins since their banding patterns are the same. In paternity suits involving identical twins - and yes, there have been such cases - if neither brother has an alibi to prove that he could not have impregnated the mother, the courts have been known to force them to split child care costs. Thankfully there are other, less “Jerry Springer-esque”, applications that teach us about our origins. When used alongside more traditional sociological methodologies, DNA fingerprinting can be used to analyse patterns of migration and claims of ethnicity.
DNA Fingerprinting can also tell us about present-day situations. Perhaps best known is the use of DNA fingerprinting in forensic medicine. DNA samples gathered at a crime scene can be compared with the DNA of a suspect to show whether or not he or she was present. Databases of DNA fingerprints are only available from known offenders, so it isn't yet possible to fingerprint the DNA from a crime scene and then pull out names of probable matches from the general public. But, in the future, this may happen if DNA fingerprints replace more traditional and forgeable forms of identification. In a real case, trading standards agents found that 25% of caviar is bulked up with roe from different categories, the high class equivalent of cheating the consumer by not filling the metaphorical pint glass all the way up to the top. DNA fingerprinting confirmed that the ‘suspect’ (inferior) caviar was present at the crime scene.

In the example shown on the left, DNA collected at the scene of a crime is compared with DNA samples collected from 4 possible suspects. The DNA has been cut up into smaller pieces which are separated on a gel. The fragments from suspect 3 match those left at the scene of the crime, betraying the guilty party.

Finally, genetic fingerprinting can help us to predict our future health. DNA fingerprinting is often used to track down the genetic basis of inherited diseases. If a particular pattern turns up time and time again in different patients, scientists can narrow down which gene(s), or at least which stretch(es) of DNA, might be involved. Since knowing the genes involved in disease susceptibility gives clues about the underlying physiology of the disorder, genetic fingerprinting aids in developing therapies. Pre-natally, it can also be used to screen parents and foetuses for the presence of inherited abnormalities, such as Huntington’s disease or muscular dystrophy, so appropriate advice can be given and precautions taken as needed.

Acknowledgement: This article was co-authored with Dr Chris Smith, who also compiled the images.

Turning your Brain into Blood_How Stem Cells Work

Imagine if you could turn your muscles into blood cells, or turning your bone marrow into muscle. How about changing your blood to brain cells, then back again, or making a spare liver from your bone marrow? Or, best of all, mutating your fat into muscle cells! These events are not the fanciful dreams of futuristic sci-fi film directors, but are real changes that have been brought about in laboratories over the past five years. Scientists have been investigating the properties of certain cells in many adult organs, and found that these so-called stem cells have the remarkable property of "plasticity". This means that they can change from being one sort of cell (such as a nerve cell) to being another type (such as an immunological blood cell) after being treated in special ways.
But we know that in real life our livers don't suddenly dissolve into our bones, and that our brains don't liquefy into blood, so what's the deal here? This research is so important because stem cells from adult organs could be of major therapeutic use in treating diseases such as leukaemia, Parkinson's and many others. Stem cells could be changed ("differentiated") into the cell type that is damaged in that particular disease, then transplanted into the affected area.
However, if the stem cells come from a different person or animal to the one they are to be transplanted into, immune rejection may occur. Obtaining stem cells is also a problem. You may have heard of embryonic stem cells, which can be made from embryos only a few days old. Another potent source of stem cells is the developing foetus. Yet it is difficult to derive these cells from humans, both technically and ethically. An easily obtainable source of stem cells taken from adult organs would therefore be an immense boon, as they could be taken from any unaffected organ in the patient, differentiated into the new cell type, then returned.
A recent paper published by a group of scientists at the University of Durham (UK) demonstrated an intriguing new source of stem cells- your hair! The researchers took hair follicles from rats and mice, and grew them in culture under special conditions. Almost unbelievably, the follicle cells began to change into myeloid blood cells- the type that form the white cells in the immune system. Even more exciting was the discovery that these cultured cells could then be transplanted into animals which had all their myeloid cells removed by radiotherapy. The transplanted cells were capable of replacing all the missing components of the immune system, an effect which lasted for over a year. Thinking therapeutically, this could be of immense use in treating blood disorders such as leukaemia, in which the white blood cells multiply out of control. Often it is treated by using radiotherapy to kill all the patient's rogue cells, then performing a bone marrow transplant using tissue from a relative or similar donor. But there can be serious compatibility problems between the donor and patient due to the different genetic makeup of the two people. Using the patient's own hair cells would remove these problems, providing a pool of genetically identical stem cells. Perhaps in the future hair cells could be persuaded to adopt other fates, such as becoming nerves- these could be transplanted to reverse the effects of neurodegenerative diseases like Parkinson's.
This is all very exciting, but what's the catch? Unfortunately adult stem cells are somewhat limited in the cell types they can become. This is mainly because they have already made several choices about what they are going to be, unlike embryonic stem cells, meaning that it is harder to reverse those decisions and adopt a different fate. Researchers are currently directing their attention to how cells make those choices, how they remember them, and how we can reverse them. This work will hopefully open the door to new therapies for what are currently incurable diseases.

Untangling, The Model Muddle

It isn't feasible to study every single species on the planet in depth- there are hundreds and thousands of types of insects alone! Fortunately, it has become clear that there are often many parallels between the biological systems at work in many types of creature, from yeast to humans. This had led to the establishment of a number of so-called "model organisms", which are studied consistently by investigators the world over. The consistent use of these particular critters allows us to make and test ideas about biology in a rapid and reproducible way. In the case of some very important mechanisms, the use of very simple animals has managed to tell us a great deal about humans. To do the same experiments with people would be very time-consuming (not to mention unethical).

The vast majority of model organisms used by scientists in the UK are small simple animals. The most common of these include microscopic nematode worms, fruit flies and African claw-toed frogs. Or to give them their official names, Caenorhabditis elegans, Drosophila melanogaster and Xenopus laevis. I'll stick with worms, flies and frogs to keep it simple. All these animals have the advantage of being available in large numbers, and are easy to breed. In the case of worms and flies, we have the complete sequence of their DNA. This makes it very easy to spot important genes and to use them for further study. As well as the breeding benefits, these animals have told us much about how animals develop from the egg. In particular, we have discovered how simple creatures work out which way is up, down, left and right when they are developing. Unfortunately, mammals such as mice and humans don't develop in the same way.
Plant biologists often use a specific type of cress as a model, although you probably wouldn't want to sprinkle Arabidopsis thaliana on your egg sandwiches. Many experiments are also performed on brewer's yeast, a.k.a. Saccharomyces cerevisiae. Let's hope the Campaign for Real Ale don't get too upset. This may seem unbelievable, but these yeasty beasties have huge similarities to the cells found in more complex animals, even humans. For example, the way that DNA is wrapped up to fit in the cell is the same in all these organisms, from yeast upwards. Similarly, the basic ways that genes are activated and turned off is preserved. Even the way that cells from yeast and animals multiply is the same. For me, one of the most breath-taking things about studying biology is finding that a gene that plays a particular role in the humble yeast is also of paramount importance in humans.
So why can't we just study yeast and flies to learn all about humans? The simple answer is that although many systems are the same in most cells, many are not- or have fundamental differences. As I mentioned before, mammals such as mice and humans don't make their embryos in the same way as flies, frogs or worms. The use of mammals in research is an emotive issue for some people, yet it is an inescapable fact that to study certain things only a mammalian model will do. In the UK, the use of such animals is very tightly regulated to ensure that only essential experiments are performed. There is a dazzling array of technology available to study the effects of genes in mice. This has led to the development of mice which model a wide range of human diseases, including diabetes, Down Syndrome, muscular dystrophy, obesity, deafness and many other inherited syndromes. The list goes on, as do the exploitable benefits to our understanding and treatment of human diseases. These "diseased" mice are created by the removal (or addition) of a particular gene by genetic engineering. Although the majority of disease models are mad in mice, there are a few syndromes which can be mimicked in other animals. For example, it's possible to breed fruit flies that have some of the symptoms of Alzheimer's disease.
One other technology which is developing into a model system in its own right is the growing of cells on plastic dishes in incubators, known as cell culture. Cultured cells can be taken from a wide range of sources. These may include human donors with particular diseases, such as cancers or inherited diseases. Cells can also be taken from animals such as the genetically engineered mice already mentioned. The only problem with devoting all our studies to cultured cells is the sad fact that the characteristics of these cells tends to change over time. This is because the cells pick up mutations from the culturing process. Some cell types, particularly the most popular ones, are now so mutated that they are like another organism altogether. So we must still always refer back to real animals to make sure our studies are really relevant and accurate. Scientists are therefore very lucky to have models that certainly will get out of bed for less than ten thousand pounds a day! It saves us a fortune on champagne as well… #Gosh

Cloning, The Good, The Bad and The Ugly....

Gosh

Good news! Cloning can cure genetic diseases! Bad News! You die younger. The scientific press has recently thrown up both good news and bad news for those of us interested in the field of cloning. Work from America has shown that a genetic deficiency can be cured by using cloning techniques, while Japanese scientists tell us that cloned animals tend to die young. So what exactly do these papers say? And what do they mean for the future of cloning research?

The success story comes from the lab of Rudolf Jaenisch, using mice deficient in a gene called Rag2 which is important for the immune system. Without this gene, the animals are highly susceptible to infections. Notably, a similar condition exists in humans defective for the equivalent gene. The American researchers took cells from the tail tips of the mutant mice, and injected them into eggs from which the DNA had previously been removed. These eggs were then allowed to develop to an early stage of development known as a blastocyst. Mouse blastocysts have an intriguing property in that certain cells from these embryos can be maintained indefinitely in culture (in plastic dishes), becoming embryonic stem cells.
These embryonic stem cells (or ES cells, as they are more often known) can be replaced in blastocysts and will develop into normal mice, or they can be treated with various chemicals to turn them into a wide range of other cell types. The researchers took the ES cells from the cloned blastocysts lacking the Rag2 gene, and repaired the mutation using standard genetic engineering techniques. These mended ES cells were then used in two different ways. Firstly, they generated new embryos from the ES cells and allowed them to develop into mice.
These "healed" mice were then used as bone marrow donors, replacing the defective immune cells in the mutant mice with functional repaired cells. Because the donors and the mutants are derived from mice with the same genetic background (apart from the Rag2 mutation), there are no problems with rejection of the donated cells. Analysis of the treated mutants showed a complete restoration of the immune system, making this method a great success.
A second approach involved growing the repaired ES cells in culture with certain factors which convert them into specialised immune system stem cells. These artificially generated immune stem cells could then be transplanted back into the mutant mice. Unfortunately, the mutant mice rejected these transplanted cells, perhaps due to changes which happen to the cells during the culturing process. The transplants were only successful when the Rag2 mutants were given treatment to further damage their already compromised immune systems, as it is the remaining immune components that cause the rejection. But what does this research mean practically? Can we transfer this knowledge to human therapies?
Sadly, it would appear not at the moment. In the successful first experiment, the scientists used the cloned repaired ES cells to generate a whole new donor mouse. If we translate this to humans, this would mean generating an adult clone as a "spare part" donor, an act that most people would view as morally questionable in the extreme. A less extreme but perhaps comparable situation might be the furore that surrounded the announcement that a couples undergoing IVF had genetically selected their embryos to be cell donors for their other child. Although the second approach, growing the cells in culture, had some success when the mutant host animals were treated with immunosuppressants, this is also a far from ideal situation as the whole point of the therapy is to restore immune function.
Another nail in the coffin of this idea is the fact that human ES cells do not have exactly the same properties as mouse ES cells. Indeed, the difficulty of working with these cells (both technically and legally) has meant that researchers know very little about the properties and potential of human ES cells. However, this research does at least give a glimmer of hope that one day cloning and stem cell technology could be used in this way to treat human diseases.
In the other corner of the world, both scientifically and geographically, Japanese scientists led by Atsuo Ogura have demonstrated that cloned mice die significantly sooner than normal mice, or mice generated by artificial injection of sperm into the egg. Over eighty percent of the clones had died after 2 years and 2 months, while the normal mice were still going strong. The clones were found to suffer from severe penumonia and liver failure. Other researchers have also shown clones to have excessive obesity, birth defects and a high rate of death immediately after birth. This is true not just of mice, but of other animals such as cows.
The recent claim in the media by human cloning guru Severino Antinori that at least one woman is currently pregnant with a cloned human is enough in itself to warrant a shiver of fear in the scientific community. As the evidence grows that cloning directly to make whole new individuals (not ES cells, as with the American experiments) leads to defects and problems, the likelihood of generating viable human clones recedes. The attack of the clones, at least as the science fiction writers would have it, seems to be just as far away as ever.
#Gosh

Magnetic monster NGC 1275.

Magnetic monster NGC 1275...

This stunning image of NGC 1275 was taken using the NASA/ESA Hubble Space Telescope's Advanced Camera for Surveys in July and August 2006. It provides amazing detail and resolution of the fragile filamentary structures, which show up as a reddish lacy structure surrounding the central bright galaxy NGC 1275. These filaments are cool despite being surrounded by gas that is around 55 million degrees Celsius hot. They are suspended in a magnetic field which maintains their structure and demonstrates how energy from the central black hole is transferred to the surrounding gas.

By observing the filamentary structure, astronomers were, for the first time, able to estimate the magnetic field's strength. Using this information they demonstrated how the extragalactic magnetic fields have maintained the structure of the filaments against collapse caused by either gravitational forces or the violence of the surrounding cluster during their 100-million-year lifetime.

This is the first time astronomers have been able to differentiate the individual threads making up such filaments to this degree. Astonishingly, they distinguished threads a mere 200 light-years across. By contrast, the filaments seen here can be a gaping 200 000 light-years long. The entire image is approximately 260 000 light-years across.

Also seen in the image are impressive lanes of dust from a separate spiral galaxy. It lies partly in front of the giant elliptical central cluster galaxy and has been completed disrupted by the tidal gravitational forces within the galaxy cluster. Several striking filaments of blue newborn stars are seen crossing the image.

what kind of things - science related - do you find most interesting?

The most interesting thing for me is consciousness. Can we make robots that are actually and truly conscious, just like you and me? That is, they are aware of themselves, they have feelings, etc. ? And if not, why not? What do we have that computers don’t have? We are just complex machines, and we can make complex machines,and I believe we can make them do anything that we can do. But if you make a robot that really is conscious, should have a birth certificate? Should it fill in a census form? Would it be allowed to take part in Britain’s Got Talent? I’m equally interested in fundamental physics (wave, particles, their interactions,quantum stuff, string theory, etc…) since,ultimately, that’s what consciousness, just like everything else, is made of (probably).
 

How do you think about science comment below.....

Preventing Acoustic Feedback On Stage

Whether you're a performer or an engineer, these simple feedback-reducing tips should ensure your gigs remain free from squeaks and howl-rounds!

 

Anyone who's ever played or engineered a live music performance being amplified through a PA will be familiar with the sound of feedback — that nasty squealing or howling sound that gets louder and louder until either someone turns something down or something breaks! This unpleasant phenomenon is not only annoying for members of the audience, it can also be extremely distracting for the musicians and, if left unchecked, could easily ruin a performance.

In general, it's the job of the engineer to minimise the risk of technical problems, leaving the musicians to concentrate on what they do best, which is playing music! That said, however, a little knowledge on the part of the performers about what causes feedback, and the steps that can be taken to minimise it, will help the engineer enormously — not to mention the performers themselves.

 

Theory Lesson

Wherever possible, the front-of-house speakers should be placed in front of the stage, so as not to direct any sound back into the microphones.Wherever possible, the front-of-house speakers should be placed in front of the stage, so as not to direct any sound back into the microphones.

The theory goes that if too much of the sound from the PA speakers leaks back into a microphone, it will circulate around the system, growing louder all the time and quickly building up into a continuous whine or whistle. With sufficiently high gain, where the overall loop gain is greater than unity (ie. the sound going into the mic from the PA is loud enough to loop back into the PA), an oscillation will occur, just as in the oscillator circuit of a synthesizer. This phenomenon is often called a 'howl-round'. Where the gain is high, but less than unity, the system can sometimes appear to 'ring', when, for example, someone speaks into one of the microphones. The more of the sound from the speakers that is able to find its way back into the microphone(s), either directly or via reflections from walls and ceilings, the more likely it is that feedback will become an issue.

It's very important to note that the onset of feedback is linked to system gain, not to the absolute volume level at which you're running your microphones. So a very loud singer working close to a mic may create no feedback problems, because the mic gain can be kept fairly low, while a singer with a quieter voice, or one who may not be quite as close to the mic, will be more likely to give rise to feedback. The quieter singer needs more mic-amp gain to bring up their level, and as the gain goes up, so does the risk of feedback.

 

Speaker's Corner

Feedback FormIf you're using a cardioid mic (left), the monitor should be placed directly behind the microphone, as that is where the mic is least sensitive. For hypercardioid mics (right), that point is normally 45 degrees off the back of the mic, so you're better off keeping the mic horizontal and moving the monitor around to the side.If you're using a cardioid mic (left), the monitor should be placed directly behind the microphone, as that is where the mic is least sensitive. For hypercardioid mics (right), that point is normally 45 degrees off the back of the mic, so you're better off keeping the mic horizontal and moving the monitor around to the side.

That's the theory covered, so now let's turn to the practical measures that can be taken to keep feedback problems to a minimum.

From what we've already explained, it should be pretty obvious that if your main PA speakers are behind the microphones, a lot more signal will find its way back into the mics than if the microphones are well behind the speakers. There are speakers, such as the columns made by Bose, that are designed to spread the sound over a very wide angle, and these can often be used behind the microphones if the amount of volume needed is modest, but the laws of physics still apply, so you'll be able to achieve more level if they're placed in front of the mics.

The quality of the speakers also makes a difference. Most PA speaker systems don't have a perfectly flat frequency response, and the off-axis response is invariably worse than the on-axis response. The frequencies most likely to cause feedback problems are the ones that are emphasised the most in the area where the microphones are placed, relative to the PA. So the more even a speaker's off-axis frequency response is, the better. But the quality of loudspeaker isn't the only important factor: any EQ boosts in the system, either from a graphic EQ or via channel EQ on a mixer, will essentially increase the gain at whatever frequencies are boosted — which, again, equals a greater risk of feedback.

 

Angle Delight

It's not just the main PA that can cause feedback, either. Monitor speakers are particularly problematic, as they tend to be even closer to the microphones and backline, but correct positioning can significantly improve the situation. Cardioid mics, such as the ubiquitous Shure SM58, are least sensitive to sounds arriving from the rear of the microphone, so these should be aimed directly away from the monitor. Some live vocal mics have a hypercardioid polar pattern, however, and these usually have their dead zone somewhere between 30 and 45 degrees off the rear axis, so the relative angle between them and any nearby monitors should be adjusted accordingly. Check your mic's manual or spec sheet for a polar diagram, see at what angle the best rejection occurs, and set the mic up with that area aimed at the monitor. Some people even go to the trouble of making a cardboard template cut at the correct angle, so they can align their mics with reasonable accuracy.

Mic Technique

Feedback FormVocal mics should be held along the body, as above, and not in such a way that the singer's hand cups the basket (below). Doing this blocks the mic's internal tuning ports, making the mic more omnidirectional and increasing the risk of feedback.Vocal mics should be held along the body, as above, and not in such a way that the singer's hand cups the basket (below). Doing this blocks the mic's internal tuning ports, making the mic more omnidirectional and increasing the risk of feedback.

That's all very well if the mic is placed on a stand and isn't going to be moved around, of course, but where the singer intends to hand-hold the mic and walk about on stage, they need to be aware of which part of the mic they're allowed to point at the monitors! In general, though, when the singer isn't actually singing into the mic, they should be holding the mic more or less upright, and not letting it point straight down towards the monitors, as this is almost certain to cause feedback if the monitors are playing at any kind of volume.

The chance of feedback can further be reduced if the singer holds the mic as close to their mouth as possible. This way, the amount of singing being picked up by the mic will be very high relative to the amount of extraneous sounds there are on stage (from drums, backline and monitors, for example), which means that the engineer will be able to keep the mic gain lower. They should avoid the temptation, however, to hold the mic right up by the basket. Most vocal mics have tuning ports inside the basket to make them directional, and if these are blocked by someone holding the mic too high up, this can change the directionality of the mic, essentially making it more omnidirectional and thus making feedback more likely.

On Reflection

Hard surfaces, such as walls behind the stage, will tend to reflect sound from the monitors back into the mics. Hanging some absorbent material, such as a thick curtain, behind the stage should help.Hard surfaces, such as walls behind the stage, will tend to reflect sound from the monitors back into the mics. Hanging some absorbent material, such as a thick curtain, behind the stage should help.

Direct sound from the speakers isn't the only hazard, however. There's reflected sound to worry about, too, so if the stage has a hard rear wall rather than heavy curtains, especially if it is close to the mic, your feedback worries have just got worse. A low, solid ceiling over the stage area also reflects sound. If you can bring some heavy drapes to hang behind you at venues that are known to be problematic, you may be able to improve the situation.

Going back to your choice of speakers (both mains and monitors) for the moment, having a flat frequency response and good off-axis performance gives you the best chance of using higher gains without provoking feedback, but the design of your mains can also have a profound effect. For example, most simple 'one woofer plus horn' boxes radiate roughly the same amount of sound vertically as they do horizontally and all speakers, regardless of design, tend to widen their coverage pattern at lower frequencies, becoming almost omnidirectional at bass frequencies. Column speakers and small line-arrays differ from 'single woofer and horn speakers', in that the way the sound combines from the various drivers reduces the vertical angle of coverage, while widening the horizontal coverage. There are other benefits, too, such as better coverage towards the rear of the room, but in the feedback stakes, the fact that the sound is spread over a wider area means that reflections from surfaces that steer sound back into the microphones are likely to be less problematic. There will also be less reflection from the ceiling to worry about. Where the system has a separate sub, try to keep that as far away from the mics as possible, to prevent rumbling low-frequency feedback; switching in the low-cut filters on the vocal mic inputs will help with this too.

This doesn't mean to say that you can't achieve good results with more conventional boxes, but you have to position them carefully. A useful strategy is to place the speakers on stands above the heads of those standing near the front (which prevents the people from soaking up all the sound and also avoids deafening them!) and then angle the speakers slightly inwards and downwards so that they aim at around two-thirds of the way into the audience. Some speakers have angled tilt mounts built in, and if yours don't, it may be worth investing in stands that have tiltable heads.

Ringing Out

Graphic EQs can be useful for dealing with feedback at specific frequencies. Just turn up the main speakers until the feedback starts, identify the feedback's frequency, and turn that slider down. Repeat until the most troublesome frequencies have been identified and pulled back.Graphic EQs can be useful for dealing with feedback at specific frequencies. Just turn up the main speakers until the feedback starts, identify the feedback's frequency, and turn that slider down. Repeat until the most troublesome frequencies have been identified and pulled back.

Assuming, then, that you have the best gear you can afford, and that it's set up in the best place in the room, what else can you do? The usual setup procedure for a PA system involves a process called 'ringing out' the room. This means turning up the gain on each mic until feedback just starts, and then backing it off by a few dBs. Once this has been done for all the mics individually, you do it again with them all turned up and, if you hear ringing or feedback, reduce the master level slightly.

My quick and dirty way of ringing out for small gigs is to set all the mic channel faders to 0dB, then turn up each mic trim one by one, until feedback starts, after which I back it off until the feedback just stops. I do this for each mic in turn, check again with all the mics turned up, then pull the master mix fader down by 5dB. This not only checks for feedback problems but also leaves all the faders in more or less the same position, with room to go both up and down in level.

The situation will probably get better when the audience starts filing in (bodies are very good at soaking up sound which might otherwise be reflected back!), but it's always worth leaving at least 5dB of fader headroom between your operating level and the point where feedback starts, so that you can turn things up, if needed, when the musicians start playing.

Graphic Detail

Feedback suppressors, such as this popular Behringer model, work by automatically detecting feedback and then re-tuning their filters to cut the relevant frequency. They're not a substitute for proper engineering, but they can obtain you a few extra decibels of level before feedback starts to set in.Feedback suppressors, such as this popular Behringer model, work by automatically detecting feedback and then re-tuning their filters to cut the relevant frequency. They're not a substitute for proper engineering, but they can obtain you a few extra decibels of level before feedback starts to set in.

Where feedback is particularly troublesome at one or two specific frequencies, a third-octave graphic equaliser may be used to reduce the gain by a few dB at those frequencies. The process for setting these up is much as described earlier: turn up the master level until feedback starts, then try to identify the frequency at which it is taking place and turn that frequency down on the EQ. Then turn the master fader up again until a different frequency starts howling, and notch that one down too!

Be aware, though, that the overall tonality of the system will be affected as the graphic EQ bands are far wider than the feedback spots they're trying to notch out, so use as little cutting as you can get away with. Unless you're dealing with a very specific problem, you shouldn't be cutting more than a handful of decibels from any band, and boosting is generally considered pretty unwise if you're suffering from any feedback problems!

Graphic EQs may also be used in the monitor feeds, which can be 'rung out' like the main speakers. Do these first in isolation, to check that everything is coming through OK, then check them again with the front-of-house system turned up, and fine-tune as necessary.
 

Automatic For The People

In recent years, there's been a lot of interest in automatic anti-feedback devices. These use filters, just as a graphic EQ does, but they're able to identify the precise feedback frequencies and then retune their own filters to exactly match those frequencies. The filters are very much narrower than those in a third-octave graphic equaliser — usually just a fraction of a semitone wide — so their effect on the overall tonality is significantly less.The usual way of using these devices is to turn up the system gain slowly until feedback occurs, then to wait for the filter to lock on and notch it out. Then the gain can be turned up a little more until a new feedback frequency starts up, and again it will be notched out. If you do this for the first four or five main feedback frequencies, you can then set any remaining filters to 'roam', so that they can pounce on any feedback that occurs during the performance but that isn't covered by one of the fixed bands — for example, if a singer accidentally points their mic at a monitor. Such systems can claw back a few more decibels of usable headroom and also eliminate the ringing that occurs near feedback, but they're not a complete cure. They'll make life easier and give you a few more dB to play with, but that's about it.While stereo feedback killers can be placed across the entire mix (and maybe others across the monitor mixes), there are also personal vocal pedals, such as those made by TC, that include feedback suppression, although, of course, these only provide benefits to the individual performers using them. They will, however, be effective on both the main and monitor speakers, as the filtering occurs at source.So there you have it! While there's no such thing as a single, definitive cure for acoustic feedback, you'll find your situation much improved if you take the time to understand how and why feedback occurs, and then take these simple steps to minimise it. #Mirza_Arshad_Baig

Science In Everyday Life

In its broadest meaning of 'knowledge', science enters the life of even the most primitive human being, who knows the safe fr
om the poisonous berry, who has stored up some rudimentary ideas about building a hut, sharpening a spear, and fishing in the river. this knowledge, or accumulation of experience, distinguishes man from the animal which has to rely on instinct.
Yet, for most people 'science' means a number of abstract subject such as physics, chemistry, biology and mechanics, to quote a few, which have to be learnt as part of 'education', yet which seem to have little bearing on everyday living. How wrong this is. Our way o life is completely dependent on science and its fruits surround us on all sides.
The Renaissance first taught man to realize the value of scientific progress, but it was not until the 18th century that the Industrial Revolution in the West really showed the impact science could have on living through developments in land-tillage, commercial production, transportation, and the beginning of the supply of mass-produced consumer goods. Until about 1920, progress was steady but in the last 45 years, the process of applying of science to the needs of living has accelerated enormously. This has been proportionate to the rate of scientific discovery itself.
Today, there is available an enormous range of consumer goods from the simple frying-pan to the jet plane, from the alarm-clock to the computer. All these things serve to make life easier and more pleasant, yet in themselves do not constitute civilization -- merely its comfortable adjuncts. Progress in real living is achieved less through 'things' than through education, the arts and the love of beauty. Science has nothing to say to us in these categories, merely providing aids and short-cuts. Without them, life would be no more than the struggle for survival; there would be no time or incentive to pursue higher things.
Science gives us safe food, free from harmful bacteria, in clean containers or hygienic tins. It also teaches us to eat properly, indicating a diet balanced in protein and carbohydrate and containing vitamins. The results is freedom from disease and prolonged life. In pre-scientific days, food was monotonous and sometimes dangerous; today it is safe and varied. It is varied because through improved sea, land and air transport food can now be freely imported and exported. Science has also improved clothing and made it more appropriate for climatic and working conditions. Man-made fibers and versatile spinning machines, today enable us to dress in clothes both comfortable and smart without being expensive.
Home, school and office all bear witness to the progress and application of science. Nowadays, most homes possess electric lighting and cooking, but many also have washing machines, vacuum cleaners and kitchen appliances, all designed to increase comfort and cleanliness and reduce drudgery. Science produces the fan which cools the air, the machinery which makes the furniture and fabrics, and hundred and one other features for good living. The books and papers are at school, and again everything from the piece of chalk to the closed-circuit television of instruction are the direct or indirect results of scientific progress. Learning is therefore easier. And clerical work is made far more speedy and efficient by the office typewriter, quite apart from the hundreds of different machines which relieve the manual worker of so much slow and monotonous toil in the factories.
In the old days, the idea of travel or taking a holiday was the monopoly of the privileged few. Today, science has given us the steamer, the aircraft and the motor-car. New horizons are opened to us and the increase of wealth brought about by science has given us the means to enjoy the new leisure we have been given. But to enjoy life at all, we must be healthy and it is perhaps in the sphere of medicine that some of the greatest advances have been made. Today, because of the use of antibiotic and isotopes, many diseases are speedily cured and man has become, on the whole, a healthier being, set free from pain and illness.
Science has been completely beneficial to ordinary living when properly applied. When misused, it is equally harmful. Land can be poisoned by chemicals, workers can suffer industrial disease, war can mobilize science to man's own destruction. Science is a good servant, but man must remain master.

The Center of a Black Hole: Infinitely Massive Singularity or Portal into another Universe?

Black holes are one of the most nagging peculiar objects in the universe. Beyond the event horizon of a black hole, our equations are turned upside down; they also get turned inside out when we attempt to fathom the singularity at its center when using the equations given to us by Einstein. To make life simpler, what if we removed the singularity all together? There is some math for that.

 Quantum gravity is an attempt in theoretical physics to explain gravity and the behavior of gravitational fields at the quantum scale. In other words, quantum gravity is one possible ‘Theory of Everything’ scientists are considering. When you apply the framework of quantum gravity to a black hole, some very interesting things happen, among the most interesting is the vanishing singularity. Instead of a singularity, quantum gravity replaces the center of a black hole with science-fiction’s best friend – a portal to another universe. How many times have we seen our hero (or the villain) fall into a black hole and avoid a crushing death by being transported to another universe? That might not be so far from the truth. Disregarding the fact that our favorite sci-fi movies get a boost of scientific accuracy, such a model immediately helps physicists resolve the black hole information paradox. The paradox basically addresses two parts of scientific theory that are butting heads with each other. On one hand, general relativity combined with quantum mechanics seems to suggest that information can permanently vanish when it’s devoured by a black hole. In contrast, a common tenet of science states that information cannot be permanently destroyed. OK, back to the singularity, or lack thereof. As most of you are aware, flying into a black hole is a very poor life choice. According to relativity, tidal forces from the black hole will elongate you in a process affectionately called ‘spaghettification’ – and all of this happens before you cross the event horizon. After you pass the point of no return, you’ll continue to fall to the singularity (the point at the center of the black hole where gravity is infinitely strong and all matter is crushed into an infinitely dense point–fun times). What happens next? We have no idea. General relativity simply stops working and breaks down when trying to describe the singularity. Singularities aren’t the only thing relativity has problems with. Einstein’s crowning achievement also breaks down when describing the big bang. In 2006, a team of physicists used loop quantum gravity in an attempt to explain the big bang; their results were very interesting. Again, the singularity commonly thought to exist at the start of the universe disappeared and was replaced with something the team described as a “quantum bridge” that brought the team into an older universe that existed before ours. Relativity is a fascinating theory that is nothing short of remarkable, but maybe it’s playing with an incomplete deck when it comes to black holes and their inner singularities. Perhaps a comprehensive theory of everything will reveal hidden portals within one of nature’s most fearsome creations.

Researchers announced they had derived stem cells from cloned human embryos, a long-awaited research coup that Science‘s editors chose as a runner-up for Breakthrough of the Year.

After more than a decade of failed attempts, it finally worked. This year, researchers announced that they had cloned human embryos and used them as a source of embryonic stem (ES) cells—a long-cherished goal. Able to develop into any tissue while providing a perfect genetic match to the cell that was cloned, the ES cells could prove a powerful tool for research and medicine. However, concerns about destroying embryos and the emergence of a cheaper, easier rival technique might keep human cloning for stem cells from becoming standard practice.The cloning technique, called somatic cell nuclear transfer (SCNT), is the same one used to clone Dolly the sheep 17 years ago. Scientists remove the nucleus from an egg cell and then fuse the remaining cell material with a cell from the individual to be cloned. They then give the fused cell a signal to start dividing, and when things go right an embryo develops. Scientists have used SCNT to clone mice, pigs, dogs, and other animals, but human cells proved trickier to work with. Years of trying—and a high-profile fraud—yielded nothing more than a few poor-quality embryos, unable to produce ES cells.

At the Oregon National Primate Research Center in Beaverton, however, researchers finally cloned monkey embryos and derived ES cells from them in 2007. In the process, they discovered a number of tweaks that made SCNT more effective for primate cells, including human ones. The final recipe worked surprisingly well, yielding ES cells in about one in 10 tries. One key ingredient seems to be caffeine, which appears to help stabilize key molecules in the delicate human egg cells.

How important the technique will be in the long run is an open question. In the years since human cloning was first attempted, researchers found that they can make patient-specific stem cells by “reprogramming” adult cells into induced pluripotent stem (iPS) cells. That method, which scientists adapted to human cells in 2007, eliminated the need for human eggs and does not involve embryos, two aspects that make SCNT controversial and expensive. But some experiments have suggested that, at least in mice, ES cells from cloned embryos might be of better quality than iPS cells. Now, investigators will be able to compare the two types of human stem cells side by side.

The feat also raises concerns about cloned babies. But that seems unlikely for now. Despite hundreds of tries, the Oregon researchers say, none of their cloned monkey embryos have established a pregnancy in surrogate females.

Do brain differences really explain gender behavior?

 Gender Differences in the Brain Explain Behaviour, Truth or Delusion?

An over-hyped study claims brain differences underlie gender-specific behaviors.

You have most likely already heard of this study if you keep up to date with the science news. Published in PNAS, the authors report “hardwired” differences between the connections in male and female brains and claim these correlate with certain behaviours. Society is gender-obsessed and the science of gender differences is riddled with controversy. Is this just another example of the mass media and scientists over-interpreting these differences to fit in with the popular notion of gender stereotypes?

Nature versus nurture

Is gender predominantly defined by nature or nurture? There are subtle gender differences in the brain, and hormones that regulate reproduction are also important for gender-specific brain development and function. Although biology is an important influence, when it comes down to gender roles it may be upbringing that plays the most powerful role. It is, nonetheless, still unclear what the consequences of gender differences in the brain are.

The study in question

The study, published in PNAS last week, comprised 949 youths ranging from 8 to 22 years old. The authors used a technique called diffusion tensor imaging (DTI) to map the structural connections within and between the left and right hemispheres. Male brains reportedly showed more connections within hemispheres and female brains displayed more between the two hemispheres. The authors went on to conclude “male brains are structured to facilitate connectivity between perception and co-ordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes”. Professor Verma, who led the study, later added in an interview that such intuitive behaviours in females are linked with good mothering skills. Such conclusions are, nonetheless, just assumptions as the authors did not measure behaviours in the present study.

What other experts in the field think..

Since the publication of the study, experts in the field have shared their thoughts on the study’s claims.

1. Correlating wiring with behaviour

The authors correlate these apparent differences in connectivity with cognition, but no effort was made to measure cognition. Professor Dorothy Bishop, based at University of Oxford, stated, “it is going well beyond the data to draw conclusions about the functional significance of these effects.”

Dr Adam Hampshire, a Senior Lecturer in Restorative Neurosciences at Imperial College London, said that such a conclusion “would require that correlations were examined between cognitive measures (e.g. working memory capacity) and connection strengths within [each] group”.

2. Brain size as a confounding factor

The technique used in the present study, DTI, is sensitive to the physical distance between connections and yet brain size was not considered here. Dr Adam Hampshire rightly points out “males tend to have slightly larger brains, which would certainly drive illusory differences in connectivity”.

3) Experience-dependent brain plasticity

The authors claim “hardwired” differences in connections exist between the genders, but this is completely misleading. Professor Heidi Johansen-Berg from the University of Oxford stated, “we know that there is no such thing as ‘hard wiring’ when it comes to brain connections. Connections can change throughout life, in response to experience and learning”. Indeed, brain connections are constantly forming, strengthening, weakening and degrading.

So perhaps these subtle gender differences in brain structure are due to differences in upbringing; an individual’s gender has a large impact on their experiences such as education, hobbies, and sport activities.

Evidently, it is easy to draw the wrong conclusions. The majority of the news articles covering the study content further exaggerated the far-fetched conclusions to help explain the popular notion that men are from Mars and women are from Venus. Whether that notion holds any truth or is entirely delusional is something we are yet to find out.

#Gosh

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How Bees Avoid Difficult Choices

Today our Class was discussing on bees, Our Biology teacher tell us very useful information... I decided to post it on my blog Hope you like my posts;

Humans who are faced with difficult choices are often tempted to simply opt out of making a choice, especially when they realize that they cannot easily resolve their uncertainty as to which choice is the better choice. Some researchers consider this ability to opt out as an indicator of “meta-cognition”, a term used to describe “thinking about thinking”. Instead of plowing ahead with a random choice, humans can recognize that they lack adequate information and choose not to make a decision. Humans are not the only animals who engage in meta-cognition. Recent studies have shown that dolphins or non-human primates also have the capacity for meta-cognition and when faced with difficult decisions may also choose to opt out of the decision-making process.
The new study “Honey bees selectively avoid difficult choices” published on November 4, 2013 in the Proceedings of the National Academy of Sciences suggests that honey bees can exhibit complex decision making skills and opt out of making difficult choices. The researchers Clint Berry and Andrew Barron studied the behavior of honey bees in containers who were given two choices: flying towards targets containing either a reward (sweet sucrose solution) or a punishment (bitter quinine solution), as well as an opt-out choice in which they could exit the container. In the first stage of the experiment, the bees were trained to recognize the targets by using horizontally drawn reference lines and placing the reward and punishment targets clearly above or below the reference lines. The bees gradually learned to distinguish between reward and punishment by using the reference lines. In subsequent experiments, the researchers challenged the trained bees by making it more difficult for them to distinguish between reward targets and punishment targets. They placed the targets closer and closer to the reference line, to the point where it even became impossible for the bee to "guess" which target would contain the sweet sucrose solution and which one was the bitter quinine solution. As this distinction became more difficult, an increasing number of bees simply chose to not make a decision at all and instead opted out of the test by flying into another container via an "exit hole".This study shows that bees have some degree of adaptive or complex decision making capacity. Bees can learn and remember different stimuli, and that the difficulty of the decision influences their behavior. It also has some strengths such as the straightforward experimental design and the inclusion of control experiments, such as the fact that the researchers alternated the positions of rewards and punishments to make sure this was not a confounding factor. However, it would be premature to call this study evidence of meta-cognitive thinking, as suggested in the press release by the university. There are important limitations to this research, such as the fact that the study conclusions regarding the decision-making of bees is based on merely ten individual bees, some of whom responded very differently from each other. This is rather surprising since the experimental set-up appears fairly simple and a higher sample size could have bolstered the marginally significant results.  Furthermore, it is not possible to interrogate bees to ascertain their motivations or rationale. Merely opting out of a difficult choice by flying into a different container is not really sufficient to invoke “meta-cognition”, a complex process that should only be used when one can investigate the cognitive process itself and understand how decisions are made. The discussion section of the paper even goes into speculations about neuronal pathways that bees may use, but at no point were neuronal pathways even assessed in the study. In summary, this is an interesting study that informs us about the complex learning capacity of bees and reminds us that non-mammals may have learning, memory and decision making skills that need to be investigated. Its major limitations make it difficult to draw definitive conclusions about “meta-cognition” in bees, but hopefully, this study will inspire future research that investigates non-mammalian decision-making in more depth.@Gosh

Children living with a dog are significantly healthier than those living without it.

 Children with a dog at home were healthy for about 73% of the time, while the percentage on children without a dog was of 65%. According to the study, the former ‘had fewer respiratory tract symptoms or infections’, as well as ‘less frequent otitis and tended to need fewer courses of antibiotics’ than those without dog contacts. Moreover, when dogs spent most of their time outside the home, the babies were healthier.  The study emphasizes the benefits of exposure to animals, at least when it comes to the so-called ‘man’s best friend’. The researchers also analyzed cat contacts, but it seems that the influence of cats on the baby’s health was weaker.Children living with a dog are significantly healthier than those living without it. The researchers followed up 397 Finnish children, asking their parents to fill in weekly questionnaires about their health until they were 1 year old. Scientists believe that this is so because dog contact helps the babies build up their immune system.

English Paper

Today was my English paper.
Yesterday I wanted to prepare it but my English helping book was not in my bag Actually my friend borrow it for some days but he don't return it....
I was very helpless about my paper I try to connect my academy teacher but she was not at home. I came back home and turn on my computer with name of God and browse on Google about the notes of English I get some results That was really an awful sight when I found site of interactive publishers I download  their key book of FSc... I start reading it I consecrate on pair of the word which was very useful in getting some marks after pair of the words, I review the tenses for fill in blanks. These were very boring but I concentrate on it. At morning I was late from my collage but Security guard allow me to come in I was late in examination hall superintend didn't gave my objective paper he only held subjective paper and answer sheet in my hands when take a look on paper all of the pair of words was those which i prepare in night, story was Honesty is the best policy OR greed is a curse. I attempt honesty is best policy and wrote the story of wood cutter and angel. Punctuation was very easy, application was for full fee concession etc,
But I'm very sad about objective paper it was of 20% marks which I don't saw, Even that he didn't give it to me for take a look on it the what was the objective....

My First Day At College

1 March 2013 was my last day at my school. I'm Biology student, now I'm student of Lahore Garrison University. When I passed my Matric examination with A grade from Lahore Board I was very excited to join any college. The first college in my mind it was Diyal Singh College but my parents not agreed for that college. they asked for another college then I choose Garrison University. When first day I went there, there was great hustle and bustle for prospectus after a long time I got a prospectus I was very happy to get it. I was unaware that it's not the enough to get admission I fill this form and submitted there. But it was rejected because My form was not attested by headmaster of my school. then I came back and ask ed the headmaster for attest he Attest my prospectus then it was accepted after 15 day days they hang out the list of pupils who get admission. I was on merit but my name was not in the list that was very shocking news for me that my form was misplaced. And they denied to give me another I was very helpless. All of sudden a plan come into my mind I report this to the Original Office(Educational board) the take action on it that why they was so careless after 8 day I receive a call from Original Office of my admission it was really a very amazing day for me.

On first day at college I went there without uniform I was wearing black genes, blue shirt, wrist watch and cell phone was in my hand they don't allow me to enter in college. my first experience was really very bad :) 

My first Post regarding my FSc Education

Dear All ts my first post regarding my daily activities ,from now onwards i will make sure to post my daily activities in my collage class and other.