Push start. Grab a weapon. Get shot. Repeat… ad infinitum. ‘Punishing’ hardly describes a session of Hotline Miami. Typically, within 10 seconds you could die three or four times. It is just as frustrating as it is challenging. Addictively, you will not give up until you pass that sneaky little passage.
Hotline Miami is an ultra-violent, psychotic game, where your only aim is to kill all the ‘bad guys’.
Yet, every little move counts, and deciding which weapons to use or which door to open first will reveal the deep strategic possibilities of the game’s intense experience. As you make your way through a pile of corpses, the suspense builds up to unbearable levels as you risk losing all in-game progress for just a little mistake. The massacre is only interrupted by brief moments that reveal details of our mysterious ‘hero’s’ back-story. Keeping true to expectation, even these interludes are awkward if not disturbing, and hardly shed light on our displaced, faceless avatar.
The excellent game tops it all with an irresistible ‘80s aesthetics and a neurotic electronic soundtrack. You’ll quickly find out why this game has stolen the show winning so many awards, and has hooked fans of Grand Theft Auto and of good old shoot’em up games. Hotline Miami is a joy in repetition, providing that being stuck in a Clockwork Orange–like scenario is your idea of joy.
Rush hours, feasts, festivals, beaches in summer, Paceville on Saturday night, all have one thing in common: traffic. Malta has one of the largest traffic problems in the world. Researchers at the University of Malta are trying to figure out what can be done to ease road rage and reduce drivers’ lost time.
We experience gravity everyday, but how it works is one of the biggest questions in physics. Einstein’s theory of relativity means that we don’t understand over 90% of the Universe. A team at the University of Malta is trying to put that in order.
I do not know what I may appear to the world, but to myself I seem to have been only like a boy playing on the seashore’, said the famous Isaac Newton. Humanity has progressed in its search for answers by always searching for the next smooth pebble, the next pretty shell. In Malta, a small group of students is trying to understand gravity through the observation of stars and galaxies that light up the night sky.
Gravity has kept our feet on the ground since we started walking upright. Early theories by the Greek philosopher Aristotle (384–322 bc) were interesting but far from the truth. His Universe was built in concentric spheres with Earth at the centre, followed by water, air, fire, and enclosed by the heavens — a rock fell to the Earth because it wanted to go to its original sphere. Clearly, he was wrong.
Aristotle’s concepts were challenged during the Renaissance when the Italian Galileo Galilei (1564–1642 ad) infamously dropped different weights from the tower of Pisa. Contrary to the Greek theory which stated that the heavier an object is, the faster it falls, Galileo saw the objects all fall at the same rate. Theories need to match observations, otherwise they fail — an invaluable technique used time and again by any decent scientist including the Malta group of astrophysicists led by Dr Kris Zarb Adami.
“Space is a dynamic entity ‘moving forward in time, the two being bound by light itself”
The first person to suggest a good theory for why rocks fall was Isaac Newton (1643–1727 ad). As the story goes, watching an apple fall triggered Sir Isaac Newton to come up with his theory of bodies. He said that anything with mass had a force that attracted everything towards it — the bigger the mass, the bigger the force. Since the apple is smaller than the Earth, it falls towards it, and since the Earth is smaller than the Sun, the Earth goes around the Sun. Newton’s law was successfully used to predict the motion of planets and helped discover Neptune.
A star burning out
By the 20th century, holes in Newton’s ideas started to appear when scientists discovered that Mercury’s orbit differed slightly from Newtonian predictions. In 1915, along came Einstein (1879–1955 ad) who again revolutionised our understanding of gravity through the introduction of his theory of general relativity. Newton had considered time and our three-dimensional space to be independent. Einstein replaced this with the notion of spacetime, which combines space and time into one continuous surface. Space is a dynamic entity ‘moving forward’ in time, the two being bound by light itself.
Large objects like the Sun bend the fabric of spacetime (it is convenient to think of spacetime as a sheet of fabric with balls lying on top of it — bigger balls curve the fabric more). Smaller objects (such as the Earth) try to follow the shortest route around the Sun. The shortest way is curved and it is easy to see how this comes about.
How the mass of the earth bends spacetime and satellites orbit the earth
Consider the shortest route from the North Pole to the South Pole, you would naturally move down a curved longitude, which forms part of a circle round the Earth. This concept also explains why the Earth traces an orbit round the Sun. The orbit is the ‘best straight line’ that Earth can trace
in the curved spacetime surrounding the Sun. As John Archibald Wheeler neatly summarises it: ‘Spacetime tells matter how to move, matter tells spacetime how to curve’.
Einstein’s biggest blunder
Einstein’s theory of general relativity describes how gravity works. Einstein wanted his equations to represent a static Universe that did not change with time. To this end, he introduced a factor called the cosmological constant that would bring the Universe to a halt. However, this idea was short-lived. Another great (though highly egotistical) physicist called Edwin Hubble discovered that the Universe was expanding; this was confirmed in the late nineties and led to a Nobel Prize in 2011. It not only means that all matter will eventually disperse throughout the Universe and future generations will see only a blank night sky, but also poses a problem in that the reason for this expansion is completely unknown and unpredicted from Einstein’s theory. And it is not a small factor at all, since this mysterious energy makes up 68% of the energy in the Universe. Nicknamed ‘dark energy’ because it is unseen, this is the biggest problem in modern astrophysics and cosmology.
“If a star’s light is being bent by a galaxy, from Earth it will appear that the star’s light has changed, when in reality it would not have changed at all”
Scientists either have to accept that dark energy is true, or that Einstein’s model has met its limits and physics needs a new way to model gravity, at least on the largest of scales. The Malta astrophysics group is trying to verify and find new models of gravity — these so-called alternative theories of gravity. The idea is to compare observations to the different gravitational theories, including Einstein’s, and see which works best.
Our focus is split two-ways: one is the effect that celestial bodies have on each other’s orbital motion and the other is the bending of light around heavenly bodies. For example, our sun bends spacetime, causing the planets to go round it in ellipses. The sun also wobbles around a very small orbit. Observations show that the orbiting objects go round a bit longer than we would expect. The extra amount is miniscule, so measurements are taken after many orbits as this magnifies the effect. We use this as a possible test to disqualify alternative theories and have already shown how an important alternative theory of gravity cannot be true.
This is how fundamental science works. If a model does not match observations it needs to be modified to arrive at something that does give all the predictions we require. The end result must be a complete theory by itself but the different components could find their birth in a wide variety of unconnected sources.
Computer simulation of dark matter
The Malta astrophysics group considered a theory called conformal Weyl gravity that is similar to general relativity in every respect except one. This theory behaves exactly like Einstein’s but imposes a further constraint — mainly that the gravitational field remains the same no matter how much it is stretched or squeezed. Simply put, as long as the mass remains the same, gravity does not change. This assumption solves many problems. It makes dark matter and dark energy unnecessary. Dark matter is needed to explain the motion of stars in galaxies. Like dark energy, it is called dark because it cannot be seen or analysed in any way. Making them irrelevant would fill a gaping hole of knowledge for astrophysics.
When the group tested the Weyl theory, it gave the same result as general relativity and a small additional term. That was not a problem, since effects of this term were so small that they could not be observed with today’s largest telescopes. The problem, as shown by the Maltese astrophysics group, is that the term grows larger with distance and contradicts observations at the largest galactic scales. This was an important nail in the coffin for the Weyl theory of gravity and Einstein’s theory still remains the best model.
Our next step is to test other alternative theories of gravity by analysing how objects orbit each other. In the same way we disproved conformal Weyl gravity, we hope that these tests will help astrophysicists to eventually come closer to a model that correctly explains the cosmos.
Bending light
Gravitational Lensing is perhaps the most sensitive test of gravity on cosmological scales. To understand how it works, consider a lit candle and a wine glass. Imagine holding the wine glass and peering at the candle through the glass’ base. The flame will be distorted and changes shape. Now picture you are with a friend who stands a couple feet by your side. The flame will appear normal to them since they are seeing it from a different perspective and the light does not pass through the glass. Two people with a different point of view see different flame shapes. The wine glass’ base distorts the flame because it acts like a lens changing the direction light travels. Obviously in the Universe there are no wine glasses between the stars and the Earth but objects with huge masses like our sun or galaxies can act like a lens and bend the direction of light by the sheer force of gravity.
The wine glass effect: gravitational lensing is explained using the base of a wine glass and a black dot
When there is no mass to affect it, light travels in straight lines, but insert a massive object and hey presto, the light deflects around it as if it were going through a curved glass lens. The area in which an object feels the gravitational pull of the Earth is called the Earth’s gravitational field. Each object in the Universe has a gravitational field and can therefore pull other objects towards it — like the Earth’s effect on the Moon, which keeps it in orbit.
Anything that enters an object’s gravitational field will feel a gravitational pull towards the center of the object. Imagine a ray of light traveling from a point to another with nothing in between. In this case the ray will travel in a straight line. Nevertheless, if the ray meets with an object along its way to the Earth, the object will pull the ray towards it as a consequence of the object’s gravity. Even though the ray of light will try to keep moving in a straight line, the gravity of the object is so strong that it bends the ray’s path. If a star’s light is being bent by a galaxy, from Earth it will appear that its light has changed, when in reality it would not have changed at all. This effect is called Gravitational Lensing and is currently one of the best tests for alternative theories of gravity, since one can measure the deflection of light and check whether it agrees with the theoretical predictions.
Gravitational lensing is clearly visible on Galaxy Cluster RCS2, as viewed using the Hubble Space Telescope
Extreme situations like the bending of light by galaxies cause problems for Einstein’s theory. When summing up the masses of the galaxies, we obtain the mass of the objects that are visible in the cluster. Comparing the predicted light deflection with the observed one, astronomers consistently find that the light is bent ‘more’ than is expected. The way to solve this issue is obvious. Introduce a completely invisible mass that increases the amount of bending until the predictions fit the observation: enter dark matter!
The idea of dark matter emerged a while ago. In 1933, Swiss astronomer Fritz Zwicky suggested it when studying how a galaxy rotation changes as one goes further away from the galaxy’s center. Zwicky observed that the speed or velocities predicted by Einstein’s theory should tear the galaxy apart. In reality, something must be keeping it whole. The idea of an invisible substance called dark matter was born.
Dark matter keeps the Universe together by opposing dark energy that pushes the Universe apart. Dark energy is related to the cosmological constant, previously discarded as Einstein’s biggest blunder, now reintroduced in astrophysicists’ equations to explain the accelerated expansion of the Universe.
The problem with dark matter is that it has never been seen. There is only indirect proof of its possible existence. Deandra Cutajar’s work focused on testing theories where no dark matter is needed. If true, this would put a small spanner into Einstein’s equations.
She tested two theories. They passed the first tests, but they have to pass many more to unseat Einstein’s general Relativity. Going back to the Swiss astronomer Zwicky, the two theories could explain why galaxies are not ripped apart by the speed with which they spin. Dark matter could be dead.
In another test, both theories failed to explain the extra gravitational effect observed in lensing. One theory failed miserably, while the other yielded less accurate results than Einstein’s general relativity. Dark matter is reborn; on the other hand, it cannot remain dark. It needs to be found and studied.
No theory of gravity has yet been found to beat Einstein’s equations. The explanation of how gravity works according to Einstein is better than Newton’s. A curved spacetime clearly explains why light is bent. Einstein’s theory of gravity still holds water and apart from the cosmological constant (his biggest blunder), he was right on most things. When his stunning prediction of how light can bend was observed, he replied, ‘I knew the theory was correct. Did you doubt it?’
What the future holds for any theory of gravity is uncertain, but what is definitely true is that the astrophysics group in Malta cannot accept the fact that we don’t understand 95% of the universe.
Video games make billions as part of the entertainment industry. Parents often view them as a waste of time. Prof. Charles L. Mifsud talks about studies showing their use in education. Cleverer, alert, interested students could be coming to a classroom near you.
Assisted conception procedures arose as a type of treatment for infertility. They opened a whole new range of possibilities for couples that were unable to have children due to a variety of problems. Initially, the difficulty addressed was of blocked or absent fallopian tubes in women. This prevented the oocyte from making contact with sperm, hence preventing the formation of an embryo. Naturally, this also prevented an embryo from moving into the uterus, implanting itself, and developing into a foetus.
In vitro fertilisation bypasses tubes by obtaining oocytes from the ovaries and fertilising these oocytes outside the body (in vitro — in glass). The procedure became a reality in humans with the pioneering work of Steptoe and Edwards and the delivery of Louise Brown in 1974. She gave birth naturally in 1999.
“In our society, infertility is becoming more common and 8 out of 10 couples can experience problems”
With the further development of ICSI (Intra cytoplasmic Sperm Injection) it was possible to fertilise an oocyte (egg) with an individual sperm. This was a breakthrough therapy for men with low or absent sperm counts. When sperm are lacking in the ejaculate, a doctor can retrieve them directly from the testicles, or the epididymis (a tightly coiled tube from the testes to the rest of the body). The procedure is known as TESA or PESA. In combination with ICSI, these techniques made it possible for these men to father children.
In our society, infertility is becoming more common and 8 out of 10 couples can experience problems. This simple statistic makes these procedures increasingly important. Nowadays, even couples with the most severe problems can become parents.
These procedures have been mixed in controversy from the beginning, with most countries allowing science to proceed within certain safeguards. This restrained approach allows for progress.
Regrettably, infertility still carries a large stigma. The thousands who have benefited from these and other simpler infertility procedures (they precede attempts for assisted conception) do not speak out. Normally they don’t because of how society would perceive them or their children.
IVF essentially means that fertilisation of the oocytes occurs out of the body. The oocytes are then fertilised with sperm and in a percentage of cases this is successful and an embryo starts to develop.
This article continues the focus on IVF from last year’s opinion piece by Prof. Pierre Mallia. Other local experts have been contacted and we are open for further opinions and comments from our readers.
Over 100 million people suffer from depression. Prof. Giuseppe Di Giovanni talks about his life’s work on the brain chemical serotonin to find a new treatment for this debilitating disease that touches so many of us
The winter rays of sunlight reflected off the snow upon Mount Maiella and the beautiful Adriatic Sea. They lit up the room where I was sitting with Dr Ennio Esposito (head of the Neurophysiology unit, Mario Negri Sud, Italy). On this cold day in February the light was blinding and it was difficult to make out my long time friend and colleague. Together we had studied the brain chemicals serotonin and dopamine vital for love, pleasure, addiction, and linked to depression — my research subject.
‘Ennio, I am tired and frustrated, I am increasingly convinced that our in vivo (whole organism) experimental approach is not the right one. There is too much variability in the results and if we really want to understand the cause of depression and find a new cure we need to get some reproducible data and change our tactic.’
“We still do not understand how many psychoactive drugs actually work, meaning that more research is needed”
At that time, I was using glass electrodes to study changes in the electrical activity of single neurons in brains. Additionally, I used a technique (microiontophoresis) that registers neuron electrical activity and also applies a very small amount of the drug. In this way, I could see which brain cell was active and how different chemicals might influence it. Surprisingly, though introduced in the 1950s, these techniques are still some of the best ways to study drug effects on a living brain.
Prof. Di Giovanni and Massimo Pierucci at the Neurophysiology Lab, Department of Physiology and Biochemistry
My research focuses on the role of two brain chemicals, dopamine and serotonin, in mental disorders. When stimulated neurons release chemicals (neurotransmitters). I am interested in dopaminergic neurons which release dopamine and serotonergic neurons that release serotonin. Once released, chemicals can pass through the spaces in between neurons and bind to another neuron stimulating or inhibiting it. They bind on proteins called receptors. When they do, they trigger the cell to fire or shut down. By triggering certain neurons in our brains, they reinforce or change our behaviour.
Dopamine is involved in the pleasure pathway. It switches on for behaviours like emotional responses, locomotion, and reinforcing good feelings. Changes in the level of dopamine effect a person’s reward and curiosity-seeking behaviour, like sex and addictive drugs. On the other hand, serotonin seems to have a more subtle role. One of serotonin’s major roles is to modulate or control the effects of other neurotransmitters, such as dopamine. In the words of Carew, a Yale researcher, ‘Serotonin is only one of the molecules in the orchestra. But rather than being the trumpet or the cello player, it’s the band leader who choreographs the output of the brain.’ The belief that serotonin is the brain’s ‘happy chemical’, that low serotonin levels cause depression and antidepressants work by boosting it is a very simplistic view. In truth, no one knows exactly how dopamine and serotonin levels induce depression.
“I have spent my life trying to figure out the role of dopamine and serotonin in the brain”
A lot of what we do know is because of animal research. The animals used to model this disease are given antidepressants to try and understand how effective they are and how they work. By studying their brains we can start to comprehend what causes depression. Right now we do not understand the whole picture behind the causes of depression and patients end up receiving inadequate treatment. We still do not understand how many psychoactive drugs actually work, meaning that more research is needed.
Most drugs were discovered by chance while being used to treat other disorders. For example, the antidepressant Iproniazid was originally developed to fight tuberculosis.
After the researchers saw less depression in patients suffering from tuberculosis they started prescribing it to depressed patients. In another example from the 1950s, clinicians discovered the first tricyclic antidepressant while searching for new drugs against other mental diseases.
Today, we fortunately have a battery of drugs that can treat depression. Unfortunately, the best drugs on the market only completely alleviate symptoms in 35 to 40 percent of patients compared to 15 to 20 percent taking a placebo (a sugar pill), a fact not publicised in pharmaceutical ads. Another problem is that when people begin taking antidepressants, mood changes can take four weeks or more to appear. This delay in action is one of the major limitations of these medications since it prolongs the impairments associated with depression, increases the risk of suicide, the probability that a patient stops treatment, and medical costs. To tackle these problems pharmaceutical companies and academic researchers want to find more effective and faster acting antidepressant drugs.
Ennio and I, together with Vincenzo Di Matteo and other researchers at the Mario Negri have tried to resolve the antidepressant lag time enigma by studying rats. We first inhibited the levels of serotonin for 3 weeks using the latest Selective Serotonin Reuptake Inhibitors (SSRIs) named fluoxetine, sertraline, and citalopram. Then we measured the electrical activity of dopamine and serotonin neurons in rat brains. We discovered that the therapeutic effect of antidepressants is not only due to their capacity to restore a normal level of serotonin activity. It also induces adaptive mechanisms in the dopaminergic system (that releases dopamine) because of repeated treatment.
How do SSRI’s treat depression? At first, these chemicals only slightly stimulate serotonin release. Long-term treatment kicks in an adaptive process. The receptor type located on serotonergic neurons which inhibit serotonin activity become insensitive. Repeated treatment frees serotonin neurons from this ‘brake’. By repeatedly using these drugs (with a lag time of 2–8 weeks), the levels of serotonin being transmitted increase and stay high for a longer time which is responsible for the SSRIs antidepressive effect.
The perfect antidepressant could lie in blocking the activity of these receptors since there would be no major delay in action. This hypothesis was confirmed by Francesc Artigas and his research group (University of Barcelona). They administered pindololo, a drug capable of blocking these serotonin receptors, and observed an increase of the antidepressive effect of the drugs paroxetine and fluvoxamine. They worked by reducing the latency period. Patients on pindololo did noticeably better and the clinical data matched that from laboratory animals. Blocking this type of serotonin receptors can be a promising therapy to reduce the latency period and possibly, increase antidepressant action.
My colleagues and I formed an alternative hypothesis as to why the clinical effects of drugs are delayed for so long focusing our attention on the dopaminergic system. We showed that acute administration of different SSRIs reduces the electrical activity of dopaminergic neurons, which release dopamine. These drugs increase the levels of serotonin, which decrease dopaminergic neuronal activity (which release dopamine) by over stimulating another inhibitory serotonin receptor this time located on dopaminergic cells. The result? The drugs taken to cure depression paradoxically initially induce a reduction of dopamine, which is meant to be the neurotransmitter of well-being and happiness! Indeed, SSRIs can worsen the depression of patients in the first few weeks of treatment.
When the drugs are used over a long period of time (3–4 weeks), the initial reduction of dopamine reverses. The change happens because the repeated treatment reduces the sensitivity of this type of serotonin receptor on dopaminergic cells freeing them from their serotonin ‘brake’.
“All of our work has made it possible to consider new treatments of depression”
We think we have found the reason why SSRI antidepressants take so long to work. Two different serotonin receptors need to become insensitive to the level of serotonin in the brain, one found on serotonergic cells, the other on dopaminergic cells. Their insensitivity allows the activity of dopaminergic neurons to return to normal even though the serotonin activity has been bumped up.
Other labs have confirmed our results, which is vital step for a theory to become fact. Cremer and his team (University of Groningen, Netherlands) have shown that blocking the same type of serotonin receptor on dopaminergic cells in rats can improve the effect of SSRIs antidepressants. Ultimately all of our work has made it possible to consider new treatments of depression, which I am very happy to see.
Many questions remain unanswered about depression. The most urgent task is to find a more effective way to treat it. This is my goal, I have spent my life trying to figure out the role of dopamine and serotonin in the brain — with some notable successes. I hope to see the next generation of antidepressants which would improve the life of 121 million depression sufferers.
Ennio listened to me as I expressed my frustration after once again obtaining conflicting results in the laboratory. ‘Giuseppe’ he said ‘You are right, billions of neurons in our brain behave differently, but as Douglas Adams said, ‘If you try and take a cat apart to see how it works, the first thing you have on your hands is a nonworking cat. Life is a level of complexity that almost lies outside our vision’ (Hitchhikers Guide to the Galaxy). If we want to break the code of the brain and hope to treat its diseases we need to take a holistic approach that takes the whole brain into account.
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Article dedicated to the prominent researcher Dr Ennio Esposito, Prof. Di Giovanni’s (Department of Physiology and Biochemistry, UoM) colleague and friend. In 2011, he died of a heart attack. During his last years, he suffered from a severe refractory bipolar depression. If interested in an M.Sc. or Ph.D. in biological psychiatry please contact Prof. Giuseppe Di Giovanni
TED talk about targeted psychiatric medications, similarly to Prof. Digiovanni borne on the realisation that current treatments are not good enough for everyone
Robotics is the future. Simple but true. Even today, they support us, make the products we need and help humans to get around. Without robots we would be worse off. Kirsty Aquilina (supervised by Dr Kenneth Scerri) developed a system where a robotic arm could be controlled just by using one’s hand.
The setup was fed images through a single camera. The camera was pointed towards a person’s hand that held a green square marker. The computer was programmed to detect the corners of the marker. These corners give enough information to figure out the hand’s posture in 3D. By using a Kalman Filter, hand movements are tracked and converted into the angles required by the robotic arm.
The robotic arm looks very different from a human one and has limited movement since it has only five degrees of freedom. Within these limitations, the robotic arm can replicate a person’s hand pose. The arm replicates a person’s movement immediately so that a person can easily make the robot move around quickly.Controlling robots from afar is essential when there is no prior knowledge of the environment. It allows humans to work safely in hazardous environments like bomb disposal, or when saving lives performing remote microsurgery. In the future, it could assist disabled people.
This research was performed as part of a Bachelor of Engineering (Honours) at the Faculty of Engineering.
Lily Agius, the artistic curator of Science in the City met up with DJ Ruby to talk about science and art. Ruby created a video for Science in the City that will be available in 2013 on scienceinthecity.org.mt
– Recently, you progressed from DJ to VJ (video jockey). Was it a hard transition?
No, not really, because it has taken quite a few years to get it in motion. For the past 5 years I have been working with videography on an amateur basis, but all of a sudden at the beginning of this year I decided to take it on professionally, and in a matter of few weeks I learned all that I needed to.
– Which was the art installation or event that you enjoyed the most?
Certainly the live music session by Andrew Alamango and Mario Sammut a.k.a Cynga. It was electronically based, which is my cup of tea.
– One of the exhibits in the exhibition at St James presented fruit flies within their own eco system in bulbs. These organisms are used to investigate muscle-wasting diseases, obesity, cancer, diabetes, and more. Did you ever imagine that humans could be related enough to a fruit fly to use them to learn more about human disease?
I never knew about it before. I was mesmerised to find out at the exhibition at St. James. That was very interesting!
– How did you feel when interacting with the art: climbing the DNA staircase, or entering the echo-proofed room in Strait Street?
It was an amazing experience, not just as a regular person attending the event but also as film maker while on the job.
– Have you ever been to a festival of its kind in Malta or abroad before?
It was a first for me, and was very impressed about how professional the event was.
– Did you expect to see something more from the festival? Is there anything you would like to see at the festival next year?
Well, from my point of view it may be no surprise to hear me say: more music.
– How would you describe the audience of the Science in the City Festival?
People of all ages and from all walks of life were there — it was certainly an event for everyone!
– Do you think that art can be used to explain science?
Yes it can, Science in the City proved that.
– How does science play its part in your own life?
I am very into IT, computers, software, gadgets and electronic music/visual. Technology is all around me and with me everyday, and forever evolving and improving.
