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Discovering the HIV/AIDS Drug "Cocktail" in an Equation
David Ho is the Scientific Director & CEO of the Aaron Diamond AIDS Research Center. Ho’s laboratory has focused on the pathogenesis of HIV infection. Most recently, his group has made substantial strides in the development of vaccines for HIV, as well as in the development of innovative prevention strategies. Ho also serves as head of the China AIDS Initiative, an alliance of Chinese and international organizations dedicated to helping China accelerate its response to HIV/AIDS.
David Ho: In terms of the most important scientific discovery to come out of my group there was an acute moment, an eureka moment so to speak, and this was in 1994. By that time my colleagues and I had been immersed in AIDS research already and we realized that for any given patient with HIV infection his or her viral load or the amount of virus in the blood tends to remain rather constant over time. We had been thinking about that, why does it remain constant? And gradually we realized that it was a what we call a dynamic equilibrium, that is the amount of the virus being made is approximately equal to the amount of virus being cleared, so it was a steady state. And then the eureka moment came when we had the opportunity to administer new drugs to HIV-infected people. And within weeks of doing so we collected the data and it showed that viral load actually dropped precipitously. And of course that is a great outcome for the patient and for the doctor, but the question that we posed was "Why does it drop and why does it drop in that acute manner?"
This is where my quantitative background in physics applied; we realized that we could actually write that out mathematically in a straightforward differential equation that an AP high school student would be able to do. From there, fitting the data and doing the calculation we were able to come up with the idea. We were using the drugs to block virus infection and production and therefore the precipitous decline reflected the fact that the virus was constantly being cleared at a very rapid rate. So using that quantitative background we were able to calculate what the turnover of virus was all the time in a given infected person and that number turned out to be enormously large, so the virus was just replicating away at a rapid clip.
And from there we also knew that HIV changes every time it replicates, so high replication rate meant high error rate and therefore HIV was able to mutate very quickly. We could then do the additional calculation to show that if you treat this virus with one or two drugs at a time the virus is predictably going to mutate and escape from the action of the drugs. But at the same time we could also calculate what it would take to corner the virus so it’s not able to escape. Those calculations suggested to us that three or more drugs would do the trick. So we knew that by 1995 and launched a series of experiments in patients using what is now called a cocktail therapy of three drugs or more. And immediately within weeks we saw the good result. But we wanted to wait to see if the results could be sustained and it was only by middle of 1996 we realized that we were able to keep the virus below detection level for a good year and that opened up the door for what is called combination therapy today.
Question: When did you first know that you wanted to be a scientist?
David Ho: I’m not sure there was one moment that sparked my interest in math and sciences. I think as far as I could recall I have always had some interest in these areas. I certainly remember being a very curious child and perhaps that is a precursor to pursuing science, but I think there is also quite a bit of family influence that affected me gradually and that has to do with having a number of important family members who pursue science or engineering, including my father and a very important uncle. Their interest in technology and in sciences I think had a great deal of influence on my decision ultimately to pursue science.
Question: How intense was your early education in science and math?
David Ho: In terms of the math education in Taiwan, it was quite intense. So the math that I had learned by sixth grade served me pretty well until about eighth or ninth grade here in the U.S. In terms of science education we didn’t have that much formal science in Taiwan and I began to be exposed to that in the later years in middle school and of course in high school and so I think I was first grounded in math and then gradually shifted into the sciences. That is what I remember.
Question: How did your early education influence your career?
David Ho: My career did not go as planned. Initially as I said my interest was in physics, but through my college education I saw the coming of new biology and the promises of biomedical research, so I shifted my interest from physics to life sciences and ultimately went to medical school with the idea that I would somehow pursue medical research. And my real focus in medicine did not come until sometime later when I was doing my clinical training when I first encountered patients with what we now call AIDS and that sparked a real interest in me and I have pursued that kind of research ever since 1982.
Question: Why did you get interested in infectious diseases?
David Ho: I was initially interested in cardiology, but gradually I realized infections affect many, many people throughout the world and many of the infections are actually manageable or treatable and we can make an impact. In particular, I was interested in new infections that plague the world and when I was doing my medical training there were a number of new infections that emerged, including what we call Legionnaires’ disease and Lyme disease today. But as I was finishing medical training I encountered some of the earliest cases of HIV/AIDS and I realized that was a fascinating scientific challenge in terms of trying to understand what was the underlying cause, but I did not realize that it would become a major public health problem until sometime later.
Question: What were your initial thoughts when you saw some of the first cases of AIDS?
David Ho: I was doing my chief medical year as chief resident in internal medicine in the west side of Los Angeles when the very first case was a young homosexual man who presented to the hospital with a multitude of problems all of which suggest that his immune system was not functioning very well and that was curious to me because he was not getting any chemotherapy or radiation or any drugs that would suppress the immune system. It was immediately clear that we were looking at something new because such a case was never described in the textbooks. Then he was treated for his acute problems, but only to die a few weeks later. And then another case that was quite similar came in, and another and another. In rapid succession we had five such cases and it was too much of a coincidence to observe this. We realized that something was going on with a common theme and from their medical history it was pretty clear that it was a transmissible disease and the search was on to hunt down that microbe that was the underlying cause.
The pioneering HIV/AIDS researcher used high school math in creating a drug "cocktail" to combat the worldwide epidemic.
Emotional intelligence is a skill sought by many employers. Here's how to raise yours.
- Daniel Goleman's 1995 book Emotional Intelligence catapulted the term into widespread use in the business world.
- One study found that EQ (emotional intelligence) is the top predictor of performance and accounts for 58% of success across all job types.
- EQ has been found to increase annual pay by around $29,000 and be present in 90% of top performers.
You're always in control of your breath.
- Anxiety is triggered environmentally and emotionally, but a physiological response quickly follows.
- Calming breathing techniques help to tamp down the physiological response of anxiety.
- The following four exercises are known to help calm anxiety and develop focus.
Stressed? Use This Breathing Technique to Improve Your Attention and Memory, with Emma Seppälä<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="ac308f8ef7490814bcb4c1841725cf35"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/NrJZu6bGyHg?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><h3>Alternate Nostril Breathing</h3><p>Emma Seppälä, science director at Stanford Center For Compassion And Altruism Research And Education, says American culture values intensity yet undervalues calmness. We never shut off. While intensity has its place, every animal in nature inherently knows the necessity of rest in order to store up energy for when it's actually needed. Americans are careless with our energy reserves, which is why so many of us are chronically tired, overworked, and stressed out. </p><p>Seppälä knows that breathing changes our state of mind. She recommends a popular yogic breathing technique, <em>nadi shodhana</em>, also known as alternate nostril breathing. </p><p>Place the index and middle fingers of your right hand on your forehead. Use your thumb to close your right nostril while inhaling through the left nostril, then close the left nostril with your ring finger and exhale through your right nostril. Repeat this for at least two minutes, then sit quietly for another minute or two, breathing normally. </p><p>There are many variations of this technique. My favorite is a four-cycle breath: inhale for a count of four through one nostril, retain your breath for a count of four, exhale for four, hold your breath out for four. If you're new to this breathing technique, retention might initially create more anxiety than it relieves, so try the basic inhale-exhale pattern until you can last for at least five minutes before moving onto breath retentions.</p>
Mind Hack: Combat Anxiety with This Breathing Technique<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="0cd55bb6ac6c7dd5daab3c29b7a82843"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/7xalaT2FwS8?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><h3>Power Breath</h3><p>Game designer and author of "Superbetter," Jane McGonigal, recommends the Power Breath: exhale for twice as long as you inhale. She says this will shift your nervous system from sympathetic to a parasympathetic tone—you'll calm down. Simply sit comfortably, close your eyes, and begin by inhaling for a count of four and exhaling for a count of eight. </p><p>This is also a popular yoga breathing technique. As with <em>nadi shodhana</em>, it can initially kick up rather than diminish anxiety. If you find long exhales challenging, begin by inhaling and exhaling at an even rate: a count of four in both directions. Then try to slowly increase your exhale to a count of five, six, and so on. Longtime practitioners can inhale for a count of four and exhale for a count of 50. As with any muscle, you can train your breathing. The benefits are immense. </p>
Breathing Techniques to Help You Relax<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="56511aaa4d1c06cc65077b8daf7670fb"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/RHpTR2wRc8c?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><h3>Focus Word Breathing</h3><p>Lolly, a Mind-Body Specialist at the University of Maryland Heart Center, offers what she calls Focus Word Breathing. Traditionally, this is known as Mantra meditation. Choose a word that has meaning to you—<em>calm</em>, <em>grace</em>, <em>ease</em>—and repeat it during every inhalation and exhalation. As your mind wanders, the word becomes a sort of flagpole that you've mentally planted to bring you back to this moment. </p><p>As a former sufferer of anxiety disorder, I remember how important my thoughts were when having a panic attack. The power of the physiological symptoms increased when I dwelled on negative thoughts. This spiral felt like being sucked into a vortex. By contrast, when I was able to redirect my thinking, the symptoms lessened. </p><p>Mantra meditation never completely worked during an attack. By that point, my physiology had been hijacked. But as a regular practice, this breathing technique is powerful. Think of it as training for the big game of life. You teach yourself to focus on beneficial words. Your attention goes where thinking leads you, but you also have control of your thoughts. By integrating a mantra with breathing, you're priming your mind to focus at will.</p>
How to do Viparita Karani (Legs Up the Wall) w/ AnaMargret Sanchez<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="6ebcd48808f1ef73d5d35b9b4f58e8e8"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/YHxoiq1YivE?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><h3>Deep Belly Breathing</h3><p>This exercise is commonly used by yoga instructors to bring their students into Corpse Pose (Savasana). Place your hands over your stomach while lying down and focus your attention there. Take deep, even breaths into your hands. As with the last technique, focus your mind there. Relax the muscles at your extremities: your toes, fingers, and forehead. Allow yourself to melt into the floor. </p><p>I love doing this breath while in <em>Viparita Karani</em>, otherwise known as Legs Up the Wall posture. The video above explains how to enter this pose; a blanket or pillow under your lower back makes the posture comfortable. Once there, I practice deep belly breathing. This technique always calms me down. I've recommended it to friends suffering from insomnia; they all responded with positive anecdotal feedback. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank" rel="noopener noreferrer dofollow">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer dofollow">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer dofollow">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Get 11 hours of proven techniques on candlestick, day trading, and investment.
- Becoming a successful trader involves learning the psychology tricks of the trade.
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Evolution doesn't clean up after itself very well.
- An evolutionary biologist got people swapping ideas about our lingering vestigia.
- Basically, this is the stuff that served some evolutionary purpose at some point, but now is kind of, well, extra.
- Here are the six traits that inaugurated the fun.
The plica semilunaris<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgwMS9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTYxMTgyMzg1NX0.ZY8qmhtoZfbRMAqrNnmbgyk7GLabglx_9lBq3PKcy7g/img.png?width=980" id="99882" class="rm-shortcode" data-rm-shortcode-id="68e8758894b0359c6ef61b2c158832b2" data-rm-shortcode-name="rebelmouse-image" />
The human eye in alarming detail. Image source: Henry Gray / Wikimedia commons<p>At the inner corner of our eyes, closest to the nasal ridge, is that little pink thing, which is probably what most of us call it, called the caruncula. Next to it is the plica semilunairs, and it's what's left of a third eyelid that used to — ready for this? — blink horizontally. It's supposed to have offered protection for our eyes, and some birds, reptiles, and fish have such a thing.</p>
Palmaris longus<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgwNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMzQ1NjUwMn0.dVor41tO_NeLkGY9Tx46SwqhSVaA8HZQmQAp532xLxA/img.jpg?width=980" id="879be" class="rm-shortcode" data-rm-shortcode-id="970e9c15f3c3d846dde05e2b2c6ebf12" data-rm-shortcode-name="rebelmouse-image" />
Palmaris longus muscle. Image source: Wikimedia commons<p> We don't have much need these days, at least most of us, to navigate from tree branch to tree branch. Still, about 86 percent of us still have the wrist muscle that used to help us do it. To see if you have it, place the back of you hand on a flat surface and touch your thumb to your pinkie. If you have a muscle that becomes visible in your wrist, that's the palmaris longus. If you don't, consider yourself more evolved (just joking).</p>
Darwin's tubercle<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NjgxMi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0ODUyNjA1MX0.8RuU-OSRf92wQpaPPJtvFreOVvicEwn39_jnbegiUOk/img.jpg?width=980" id="687a0" class="rm-shortcode" data-rm-shortcode-id="b38a957408940673ccc744f0f6828d18" data-rm-shortcode-name="rebelmouse-image" />
Darwin's tubercle. Image source: Wikimedia commons<p> Yes, maybe the shell of you ear does feel like a dried apricot. Maybe not. But there's a ridge in that swirly structure that's a muscle which allowed us, at one point, to move our ears in the direction of interesting sounds. These days, we just turn our heads, but there it is.</p>
Goosebumps<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMxNC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNzEyNTc2Nn0.aVMa5fsKgiabW5vkr7BOvm2pmNKbLJF_50bwvd4aRo4/img.jpg?width=980" id="d8420" class="rm-shortcode" data-rm-shortcode-id="f735418322b34382dcd882299c9ccc48" data-rm-shortcode-name="rebelmouse-image" />
Goosebumps. Photo credit: Tyler Olson via Shutterstock<p>It's not entirely clear what purpose made goosebumps worth retaining evolutionarily, but there are two circumstances in which they appear: fear and cold. For fear, they may have been a way of making body hair stand up so we'd appear larger to predators, much the way a cat's tail puffs up — numerous creatures exaggerate their size when threatened. In the cold, they may have trapped additional heat for warmth.</p>
Tailbone<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMxNi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMDMzMDc3N30.p9BEtkf3-PV3EtDSQMUGUeopsimiCHUagx97P4f8IBw/img.jpg?width=980" id="e8ab8" class="rm-shortcode" data-rm-shortcode-id="0063ce99bdd22fbebe1279244b87935c" data-rm-shortcode-name="rebelmouse-image" />
Coccyx. Image source: decade3d-anatomy online via Shutterstock<p>Way back, we had tails that probably helped us balance upright, and was useful moving through trees. We still have the stump of one when we're embryos, from 4–6 weeks, and then the body mostly dissolves it during Weeks 6–8. What's left is the coccyx.</p>
The palmar grasp reflex<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xOTA5NzMyMC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNjY0MDY5NX0.OSwReKLmNZkbAS12-AvRaxgCM7zyukjQUaG4vmhxTtM/img.jpg?width=980" id="8804c" class="rm-shortcode" data-rm-shortcode-id="45469ca5ee5f43433a782f7d4ac0a440" data-rm-shortcode-name="rebelmouse-image" />
Palmar reflex activated! Photo credit: Raul Luna on Flickr<p> You've probably seen how non-human primate babies grab onto their parents' hands to be carried around. We used to do this, too. So still, if you touch your finger to a baby's palm, or if you touch the sole of their foot, the palmar grasp reflex will cause the hand or foot to try and close around your finger.</p>
Other people's suggestions<p>Amir's followers dove right in, offering both cool and questionable additions to her list. </p>
Fangs?<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Lower mouth plate behind your teeth. Some have protruding bone under the skin which is a throw back to large fangs. Almost like an upsidedown Sabre Tooth.</p>— neil crud (@neilcrud66) <a href="https://twitter.com/neilcrud66/status/1085606005000601600?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Hiccups<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Sure: <a href="https://t.co/DjMZB1XidG">https://t.co/DjMZB1XidG</a></p>— Stephen Roughley (@SteBobRoughley) <a href="https://twitter.com/SteBobRoughley/status/1085529239556968448?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Hypnic jerk as you fall asleep<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">What about when you “jump” just as you’re drifting off to sleep, I heard that was a reflex to prevent falling from heights.</p>— Bann face (@thebanns) <a href="https://twitter.com/thebanns/status/1085554171879788545?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script> <p> This thing, often called the "alpha jerk" as you drop into alpha sleep, is properly called the hypnic jerk,. It may actually be a carryover from our arboreal days. The <a href="https://www.livescience.com/39225-why-people-twitch-falling-asleep.html" target="_blank" data-vivaldi-spatnav-clickable="1">hypothesis</a> is that you suddenly jerk awake to avoid falling out of your tree.</p>
Nails screeching on a blackboard response?<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Everyone hate the sound of fingernails on a blackboard. It's _speculated_ that this is a vestigial wiring in our head, because the sound is similar to the shrill warning call of a chimp. <a href="https://t.co/ReyZBy6XNN">https://t.co/ReyZBy6XNN</a></p>— Pet Rock (@eclogiter) <a href="https://twitter.com/eclogiter/status/1085587006258888706?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Ear hair<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Ok what is Hair in the ears for? I think cuz as we get older it filters out the BS.</p>— Sarah21 (@mimix3) <a href="https://twitter.com/mimix3/status/1085684393593561088?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Nervous laughter<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">You may be onto something. Tooth-bearing with the jaw clenched is generally recognized as a signal of submission or non-threatening in primates. Involuntary smiling or laughing in tense situations might have signaled that you weren’t a threat.</p>— Jager Tusk (@JagerTusk) <a href="https://twitter.com/JagerTusk/status/1085316201104912384?ref_src=twsrc%5Etfw">January 15, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Um, yipes.<blockquote class="twitter-tweet" data-conversation="none" data-lang="en"><p lang="en" dir="ltr">Sometimes it feels like my big toe should be on the side of my foot, was that ever a thing?</p>— B033? K@($ (@whimbrel17) <a href="https://twitter.com/whimbrel17/status/1085559016011563009?ref_src=twsrc%5Etfw">January 16, 2019</a></blockquote> <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>
Are there innate differences between female and male brains?
People have searched for sex differences in human brains since at least the 19th century, when scientist Samuel George Morton poured seeds and lead shot into human skulls to measure their volumes.