The price of mistakes in clinical trials

By Guadalupe Astorga

Last January 11, a human clinical trial in phase I caused brain death in one healthy volunteer, while five others were hospitalized. Unfortunately, this is not the only case where healthy volunteers have died or been severely affected.

structure

Structure of Bial’s BIA-10-2474 as described in their Clinical Study Protocol N° BIA-102474-101, and referred to as Compound A in US patent # 20130123493 A1

The molecule (BIA 10-2474) produced by the pharmaceutical company Bial, is an inhibitor of the fatty acid amide hydrolase (FAAH), an enzyme that catabolizes bioactive lipids, including the endocannabinoid anandamide. The drug was developed as a therapy for anxiety and motor disorders associated with Parkinson’s disease, as well as chronic pain in people with cancer and other conditions. Other pharmaceutical companies have previously performed clinical trials to test the analgesic effect of other FAAH inhibitors with no signs of toxicity. However, these studies ended in phase II due to lack of drug effectiveness. Remarkably, the affinity of the inhibitor tested by Pfizer was 14,000 times higher than that of BIA 10-2474. This implies that the specificity of BIA 10-2474 to inhibit the FAAH enzyme is very low. Moreover, the molecular structure of BIA 10-2474 includes a highly reactive imidazole aromatic ring that can bind to other brain enzymes, including 200 other hydrolases with similar structure and whose activity is far from being understood. The investigation, led by the French National Agency for Medicines and Health Products Safety (ANSM), has also shed light on a series of irregularities that occurred during the preclinical trials and were kept secret by Bial, as part of trade secrets. Conceivably the most serious among these is that according to the chemical structure of BIA 10-2474, it is most likely to be an irreversible inhibitor, rather than reversible as the company claims. This implies that even very small concentrations of the drug can irreversibly inhibit, not only the activity of the FAAH enzyme, but also the 200 other hydrolases present in the human brain. Considering this crucial information, it is inconceivable to understand how the trial design could comprise consecutive administrations of high doses of the inhibitor. This piece of evidence seems to be clearly related to the brain damage induced by the drug, as the severely injured volunteers were those who received only the highest doses of the drug. From sixteen groups of eight volunteers administered with increasing doses of BIA 10-2474, only five people were hospitalized after receiving repeated doses of 50 mg (almost the highest tested concentration). According to the ANSM report, this concentration is 10 to 40 times higher than that required to completely inhibit the FAAH enzyme. Indeed, extrapolation of the data taken in animals to humans, suggests that complete inhibition of FAAH is achieved with doses 20 to 80 times smaller than the maximal dose planned to be tested in humans (100mg). Furthermore, even after the first person was hospitalized, the other 5 still received one more dose the next day. The Report of the ANSM states that the mechanism of toxicity of BIA 10-2474 is clearly beyond FAAH inhibition and evidence of this subject needs to be presented by Bial Laboratory in future months.

Another critical piece of information that was kept secret by Bial is the number of animal deaths (including dogs and primates) during the preclinical trial. How could the drug be considered safe and approved to be tested in humans, if closely related animals died? Had the volunteers known this information, would they have taken the risk to test the drug?

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Twenty-four visits to Stockholm: a concise history of the Rockefeller Nobel Prizes

Part XIX: Günter Blobel, 1999 Prize in Physiology or Medicine

By Joseph Luna

Let’s start with a fantastical scene: picture a band of Neolithic humans in a hot air balloon overlooking modern New York City. What would they see and experience? Lacking a vocabulary and a mental model of twenty-first century life, our ancient friends would be awestruck at seeing miniscule specks and strangely ordered structures, lines and squares, in green and gray. Perhaps the occasional yellow rectangle from which specks would enter and exit would catch their attention. Or they might ponder a box with flashing lights, speeding its way across a grid. It’s near impossible to imagine being in their shoes, but it’s easy to envision the excitement as they try to describe and make sense of what they saw.

Günter Blobel

Photo Courtesy of the Rockefeller University

This totally novel experience wasn’t far off from what early cell biologists encountered, as they used the electron microscope (EM) as a sort of hot-air balloon to discover the cities inside cells. By the mid-1960s, they had plotted the geography of all sorts of cellular worlds, had given names to energy-making blobs and recycling vesicles, and with the help of radioactive amino acid labeling, had a basic sense of where proteins were made and where they ended up. But big questions remained such as how did a protein know where it needed to go? For a discipline built on EM observations from high above, this was a challenging question to answer, but it captivated a young German post-doc enough to dream as if he landed his hot air balloon and walked among molecules, where the view was much clearer.

Günter Blobel arrived in George Palade’s laboratory in 1967, shortly after completing his PhD at the University of Wisconsin at Madison. He joined a dynamic group of researchers who had stumbled upon an odd observation concerning the protein factories of the cell, its ribosomes: proteins destined to remain inside the cell were often made from a pool of freely cytoplasmic ribosomes, whereas proteins meant to be exported from the cell quickly associated with ribosomes attached to the endoplasmic reticulum (ER). How a new protein made this decision to stay in the cytoplasm or go to the ER was a mystery.

Within a few years, and overwhelmingly without much evidence, Blobel and a colleague (and Rockefeller University alum) named David Sabatini formulated what became known as “the signal hypothesis” that might explain how proteins got sorted to their proper locations. It represented a truly imaginative and startlingly precise leap, as if one could envision a five digit postal code and a stamp authentication system simply by watching mail trucks from space. Blobel and Sabatini proposed that ER destined proteins contained a special stretch of amino acids that acted like a signal that became apparent the moment the protein was being made at a ribosome. This signal sequence, located at the head of a protein, would be recognized by a factor (or factors) that would, in turn guide the synthesizing ribosome to the ER, where the protein in question could finish being born as it translocated across the ER membrane. Once properly sorted into the ER, the signal sequence was no longer needed and could be removed by an enzyme, even while the protein was still being made. Once finished, the protein could then go and do its job.

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The Lowline

By Aileen Marshall

lowline-light-collector-demo-960x639

Photo Courtesy of Dan Barasch via Kickstarter.com

Have you heard of the Lowline? No? Well maybe because it doesn’t fully exist yet. And no, it’s not under the Highline, although its name was inspired by it. It will be an underground park in an abandoned trolley terminal under Delancey Street. The park will use new solar technology to redirect sunlight underground to grow plants and light the park.

The Williamsburg Bridge Trolley Terminal opened in 1908 on Delancey Street.  Trolleys went back and forth to Brooklyn across the aforementioned bridge.  The station extends three blocks underground from Essex Street to Clinton Street, and has interesting architectural features, such as cobblestones and a 15-foot ceiling. It closed in 1948 and has been sitting empty ever since.

Then in 2009 architect James Ramsey, who used to work at NASA developing optics for satellites, heard about it.  He discussed it with his friend Daniel Barasch, a strategist for Google.  Ramsey thought he could use fiber optics to collect and redirect sunlight underground to make it into a park. They made a proposal to the city.

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Aileen Marshall/NATURAL SELECTIONS

Two feasibility studies were started in 2011. One was by HR&A Advisors, a real estate, economic and energy consulting firm. The other was from the engineering firm Arup. Both came up with positive findings, indicating that it would be helpful to the community. Since 2012 the Lowline organization has run a program called Young Designers. They offer educational programs to local schools and other groups, using the lab for lessons in science, technology, engineering and design.

By 2012, the pair had raised $150,000 on Kickstarter to build a laboratory exhibit of the solar technology that would be used in the Lowline. As of 2015, the Lowline organization has raised $155,000 to build the park. The exhibit lab uses what Ramsey calls “remote skylights,” the technology that would be used in the park. An above-ground parabolic disk collects sunlight, then a concentrator increases the light 30-fold and filters out the hotter rays. Protective tubes send light to a central distribution point via fiber optic cables, then to an aluminum canopy in the lab. That, in turn, reflects the light into the lab. This illuminates the lab and allows the plants to grow. Since it is reflected sunlight, it contains the full spectrum of sunlight, including the wavelengths needed for photosynthesis. Optic technology allows the outdoor disk to follow the sun during the day and maximize the amount of sunlight it collects. Mirror boxes would toggle the light between electric and sunlight to allow for variations, such as cloudy days.

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Manhattan Spring and Summer Fun

By Susan Russo

Museum_of_Math

Photo Courtesy of the National Museum of Mathematics

Consider these (mostly) FREE events in NYC Parks, many falling between June and October:

At Bryant Park (between Fifth and Sixth Avenues, from 40th to 42nd Streets) check out http://bryantpark.org/ for days and times of events. For adults and kids, there are games to play, such as chess, checkers, mah jongg, and board games, plus active sports, which include petanque (much like bocce or lawn bowling), ping-pong, and a putting green. Under a tent is the outdoor “Reading Room,” stocked with books and magazines for all ages. In addition, there’s an “Art Cart” in June, August, and September, with free supplies to use and artworks to take home. The park has three restaurants, food stands, and crafts and souvenir shops. There are coffee, pastry and deli shops all along 40th Street. If it’s too hot or it rains and the outdoor Reading Room is full, duck into the magnificent main library building, http://www.nypl.org/locations/schwarzman (for open hours), which has a very large but comfortable Children’s Library (with books, CDs, and DVDs for kids, and seven PC terminals), as well as a beautiful Map Room, a great shop, and a small café. And the youngest ones will thrill to the many, many inviting stairs to climb.

Madison Square Park (between Madison and Fifth Avenues, from 23rd to 26th Street) http://madisonsquarepark.org/

In addition to a great playground and a “water wheel,” there are concerts, workshops in horticulture, and outdoor art for all ages, and, for kids, story times and “Art in the Park.” There is also a large outdoor plaza with tables and seating. Vendors are set up all around the park. (If it rains, I’ve heard good things about the Museum of Math at the north end of the Park (11 East 26th Street) http://momath.org/.

imagination playground

Photo Courtesy of NYC Parks

Their website says it has “a special emphasis on activities for 4th through 8th graders,” but it’s expensive – free for toddlers, $9 for children, students, and seniors, and $15 for adults.)

Besides local parks in Manhattan there are “Art Parks,” playgrounds for kids with works they can climb on:

“The Tom Otterness Playground – Silver Towers” on 42nd Street between 11th and 12th Avenues;

“The Real World” in Rockefeller Park between Chambers and Warren Streets in Lower Manhattan;

“The Imagination Playground” at the South Street Seaport at Berling Slip on John Street between Front and South Streets.

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Culture Corner

Sacred and Profane Images in Venice and Padua

By Bernie Langs

CC_Bernie2The laws and edicts are laid out in the Old Testament in exacting terms specifying the ornaments, utensils and measurements for these objects utilized in the holy temple and for the division of spaces designated as sacred from those places for mortals. The biblically assigned priestly caste was left to minister the negotiation between man and God. Only he could physically enter the area behind the curtain or veil beyond the altar separating the congregation from the Holy Spirit.

The Jewish religion prohibits graven images of God, forbidding representational sculptures or paintings of biblical stories and heroes. There are examples of Jewish burial tombs and other remains that had been decorated with the symbols for rituals and life in the ancient world that were later mutilated or chiseled away by disapproving rabbis as a reminder of these edicts. Early Christian images, after co-opting ideas from those previously of service to ancient Roman and Greek gods or from secular life, accelerated into the early medieval time with flourishes of astounding profundity and beauty. Lives were lost over the iconoclast notion that to pictorially represent Christ and the Holy Spirit was a dangerous trespass on the immaculate and omniscient ideal since no picture could or should imitate or approximate the Divine.

At the culmination of the middle ages and into the early and High Renaissance there was no holding back the master illuminators, sculptors and painters in Italy and in the northern areas of Europe. Great religious art peters out by the mid-seventeenth century at which time there was no longer room for innovation and the power that such images had previously attained was lost.

Today we live in a time of hyper self-awareness. As many people abandon notions of a God who is aware of mankind’ actions and is capable of direct intervention in human affairs, there remains a void to be filled for a higher purpose in life. From some perspectives, a desirable end of ritualistic and avid dogmatic doctrine might relieve a great deal of worldly tensions since fanatics and zealots hold strong so-called inspired revelations. Equally profound and illuminating might be a more objective and scientific study of those in the past who, in the written word or through the plastic arts, drew inspiration on the notions and ideas of their times of what was holy and greater than human endeavor. Some might find interest in a religion that reluctantly winks at the thought of a Primary Mover and nothing else, yet still finds fascination in what was revealed by others who had taken a different, mystical path as they groped for understanding a higher purpose.

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56-Downed-Up Charges

By George Barany, Christopher Adams, Martin Herbach, and Alex Vratsanos

George Barany is a Rockefeller alum (1977) currently on the Chemistry faculty of the University of Minnesota–Twin Cities. Christopher Adams is a graduate student in mathematics at the University of Iowa, Martin Herbach is a retired computer scientist living in Silicon Valley, and Alex Vratsanos is studying business and psychology at Kutztown University in Pennsylvania.  For more information, including a link to the answer, visit here (http://www.chem.umn.edu/groups/baranygp/puzzles/twittercharges/). More Barany and Friends crosswords can be found here (http://www.chem.umn.edu/groups/baranygp/puzzles/).

Across

June2016NaturalSelectionsGRID1. Jeanne d’Arc, e.g.: Abbr.
4. Number of freedoms, to FDR
8. Mexican motel (and one-time Yankee catcher Jorge)
14. Punching tool
15. Recommend emphatically, as money to fight Zika
16. Beat Murdoch at his own game?
17. My follower in 1968?
18. Genuine, in Germany
19. Homophone for homophobe “Lyin’ Ted”
20. Hungarian short-haired dog
22. Narrow waterway
24. Metric weights: Abbr.
25. Live, as an interview
26. Self-important bureaucrat from “The Mikado”
28. Senator Sherrod (since 2007) or Scott (who lost to 3-Down in 2012)
30. Hide-hair connection
31. Disapproving sound
34. Goes too far
37. One-under bridge, in the Pledge of Allegiance
39. Staff member?
40. Turkish name that means “desire”
42. One-named Irish Grammy winner
43. Goddess with a spear and a national capital named for her
45. Seaweed product with a reduplicative name
47. Like FDR’s Deal
48. ___-cone
50. Minuteman Davis, memorialized through an iconic French sculpture
51. Sarah Palin, e.g.
54. Apple’s instant messaging software
57. Historic introduction?
58. Hit CBS procedural with three spinoffs
59. Star in Aquila
60. Mexican beer brand
62. Harmony, so to speak
64. Sch. in Monroe whose alumni include Bubby Brister, Tim McGraw, and Ben Sheets (anagram of NUL)
65. First game
66. “___ Smile Be Your Umbrella”
67. Highgate (London) or Père-Lachaise (Paris): Abbr.
68. With 56-Down, 3-Down’s Twitter antagonist
69. Decorative pitcher
70. Clairvoyance, e.g.

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Quotable Quote

john-adams21“It is to be a school of Political Prophets I Suppose — a Nursery of American Statesmen…I am making of it annual, for Sending an entire new set every year, that all the principal genius’s may go to the University in Rotation — that we may have Politicians in Plenty. Our great Complaint is the scarcity of Men fit to govern Such mighty Interests, as we are clashing in the present Contest — a scarcity indeed! For who is Sufficient for these Things? …You and I have too many Cares and occupations and therefore We must recommend it to Mrs Warren and her Friend Mrs Adams to teach our Sons the divine Science of the Politicks: And to be frank, I suspect that they understand it better than we.”

-John Adams, who had been appointed to serve as a delegate to the First Continental Congress, in a letter to James Warren, a legislator in the Massachusetts General Court, who was also to serve (June 25, 1774).

Life on a Roll

Musical Fountains Show in Versailles

By Elodie Pauwels

ElodiePauwels_Apollo_fountain1Imagine the magnificent Palace of Versailles under a clear blue sky. Imagine spring has just sprung. Imagine strolling in that environment, going from one statue to a pond, then turning left to discover a mysterious alley. Suddenly, as if by magic, classic music is played, and water is turned on at each fountain in the vicinity of the Palace. Welcome to the musical fountains show, every weekend afternoon from Spring to Fall! Here is my favorite: the Apollo fountain, representing Apollo on his chariot. More pictures are available on my photo blog: http://elodiepphoto.wordpress.com/ElodiePauwels_Apollo_fountain2

Twenty-four visits to Stockholm: a concise history of the Rockefeller Nobel Prizes.

Part XVIII: Robert Bruce Merrifield, 1984 Prize in Chemistry

By Joseph Luna

By the time Bruce Merrifield sat down to write in his lab notebook in May 1959, a scientific puzzle had been twirling in his head for quite some time. What he wrote next summarized a Nobel-worthy problem and offered a bold but totally unproven solution, all in three sentences. It turned out to be an impeccably succinct opening salvo, not just for a research career, but for an entire field.

“There is a need for a rapid, quantitative, automatic method for the synthesis of long chain peptides. A possible approach may be the use of chromatographic columns where the peptide is attached to the polymeric packing and added to by an activated amino acid, followed by removal of the protecting group and with repetition of the process until the desired peptide is built up. Finally the peptide must be removed from the supporting medium.”

To unpack this a bit: Merrifield spotted the need to take amino acid building blocks and string them together to form a peptide of his choosing (or if a really long peptide, a whole protein). His idea in essence was to use a solid support to get an amino acid to hold still, so that he could methodically link amino acids together sequentially. Finally, the immobilized chain of amino acids, the peptide, could be released and studied.

At a time when molecular biology was just getting off the ground, Merrifield’s understated first sentence belies a history of protein chemistry already more than half a century old, as well as his own frustration at making the small peptides he was interested in studying. After joining Wayne Wooley’s research group as a post-doc at Rockefeller in 1949, Merrifield applied his biochemistry training by isolating and characterizing “strepogenins” a catch-all term for small peptides that stimulated bacterial growth. The standard practice was to isolate these peptides from a biological source, but this approach almost always generated scholarly (aka vicious) pushback: it was very difficult to rule out contamination. If a compound could be crystalized as a means of isolating it to “purity”, most biochemist naysayers would generally be assuaged.

Chemists, however, were an entirely different breed of naysayer. They would only be convinced by chemical synthesis of a pure compound, characterized at each intermediate step as a measure of quality, and where, by definition, no biological contaminant could be introduced since no life form (other than the chemist’s hands) was required. For this reason, most biochemists weren’t really considered chemists: they merely isolated and characterized what they thought were active compounds, but they could very well be fooling themselves. Justus von Leibig’s famous chemical dictum “Tierchemie ist Schmierchemie” (Biochemistry is sloppy chemistry) stung hard for the better part of a century.

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Searching the Nobel Prize

By Susan Russo

There is a wealth of enjoyment in exploring Nobel Prize information online. There are videos, such as a documentary of the four 2012 Laureates’ discoveries in medical research; Mother Teresa’s and Elie Wiesel’s speeches after their awards of their Peace Prizes; and a 1994 interview with John Nash (prize in Economic Sciences), including his views of the movie A Beautiful Mind, based on his life and work. Another category, “Nobel Laureate Facts”, delivers statistics on the number of total prizes throughout the years, the number of women’s prizes “so far”, ages of the awardees, and the reasons that two awardees, Jean-Paul Sartre and Le Duc Tho, declined their prizes. Other current special features appear about Albert Einstein, Marie Curie, Malala Yousafzai, and Rabindranath Tagore. There is even a section called “Educational Games”, which includes “Save the Dog” about diabetes, “Bloodtyping”, “A Drooling Game” about conditioned learning, and “All about Laser.” In another link, the Director of the Norwegian Nobel Institute describes the process of nominations for the Peace Prize.

My favorite section, however, is listening to the Nobel podcasts, short interviews giving us the viewpoints of the awardees in their own words.  A recent interviewee was Rockefeller’s own Roderick MacKinnon. There are two separate interviews with May-Britt Moser and Edvard Moser, 2013’s dual awardees in Medicine. May-Britt Moser talks about “pure joy” for herself, and “inequality in science”, while her husband Edvard speaks of the value of “partnership” and recalls “childhood memories.” Mario Molina, awardee in Chemistry in 1995, discusses “climate change” and the role of “human activity” and says, “The risks are unacceptable.”  In 2006, Roger Kornberg (Chemistry) admits that most of his “ideas are wrong.” John Mather, a NASA scientist (Physics, 2006) thinks that if there is water on Mars, there is likely to be life in some form. Elizabeth Blackburn (2009 Physiology or Medicine), whose discoveries show how telomeres transform in aging, says, “We just know so much and yet we know so little.” We hear from Randy Schekman, whose award in 2013 was in Physiology or Medicine, arguing for open access in scientific publications.  And George Smoot (Physics, 2015) lauds the fact that “science today is a truly global enterprise.”  Some Nobel Prize winners admit that they were surprised by their awards. One, John O’Keefe (2013, Physiology or Medicine), prefers being in the lab, saying, “I’m a bench scientist.” And Alice Munro, who won the prize in Literature in 2013, describes her reaction as, “Bewildering but very pleasant.” In all the podcasts I’ve heard, the awardees reflect an excitement in their work, and most display a spirited optimism for the future. All in all, “meeting” these people online is thought-provoking and inspirational, at least to this listener.

Culture Corner

Six Perfect Songs

By Bernie Langs

I enjoy listening to music of all genres and styles and truly appreciate the efforts of not only good composition and musicianship, but of superlative production in the recording studio. On a visceral, emotional, tactile and maybe even soulful level, I have many favorite tunes that I deem perfect. These are songs I’ve never tired of hearing after years of listening to them. I would include such pop songs as diverse as Midnight Confessions by The Grass Roots that was a hit in 1968, Billie Jean, the Michael Jackson mega-hit with stellar production by Quincy Jones, and the live version by The Cream of I’m So Glad, which boasts a ripping solo by Eric Clapton, which I consider the best in all of live rock recordings. I could make the case for many songs as “perfect”, but I’ve chosen the following six to make remarks on:

SIx: Whole Lotta Love by Led Zeppelin. Jimmy Page, guitarist of Led Zeppelin, has spoken of his obsessiveness in getting imaginative production sounds for his instrument in the studio, but even more importantly of the band’s consistent search for great “riffs.” And the clever, engaging riffing history of this monster band began with the very first notes of their first big hit, Whole Lotta Love and culminated with the ascending guitar notes that makes a later song Kashmir a spiritually inviting mystical journey. Whole Lotta Love has front man Robert Plant singing at full throttle impassioned best. The abstract middle-break instrumental, with fading in and out head-play sounds, was unprecedented at the time. Drummer John Bonham has a great rollout of that interlude, which is followed by the piercing wail of Page’s axe, which in turn segues back to the original riff. Brilliant!

Five: Heroes by David Bowie. Bowie fans will forever be intrigued by his Berlin period, when he retreated in the 1970s to that Cold War city to change artistic direction and wax philosophical. The album Heroes has a fabulous unity of thought and it’s a disturbing one in which Bowie ruminates about the state of human emotion and its quasi-surreal future. The album production by Brian Eno, with assistance from Tony Visconti, is a perfect fit for Bowie’s dark mood. Never before had synthesizers been utilized so fabulously in the rock music genre, melding perfectly with the structure of Bowie’s dense and revelatory songs. The album’s title song, “Heroes,” isn’t just a Cold War simultaneous desperate lament and solitary moment-in-time celebration. It boasts technical musicianship unmatched by any of Bowie’s and Eno’s contemporaries. Decades after most rock music is forgotten, they’ll still be studying David Bowie.

Four: Adagietto of the 5th Symphony by Gustav Mahler. This movement of Mahler’s 5th is simply the most beautiful theme in music history. Theorist Theodor Adorno called passages of Mahler’s symphonies “songs” so Mahler’s passage here fits neatly in this list crowded with rock songs. I first heard the Adagietto at the IBM Gallery of Art, where it was played in an auditorium during the Gallery’s exhibition on the ancient, volcanically obliterated city of Pompeii. Images of the destroyed city and its artifacts were displayed in a slide show in the darkened theater to the sounds of Mahler’s emotionally-charged song. Adorno’s point that Mahler never completely repeats entire themes as practiced by his predecessors, holds true in this case. The passage’s sad strings often do mournfully restart, but Mahler tweaks the presentation as if developing the yearning thoughts. The crescendo is forceful, and, unlike many of Mahler’s themes, resolves beautifully. One finds oneself longing for—what is it? Love? An unattainable soul mate? Understanding? For a better world? It’s all there in this perfect “song.”

Four: Jumpin’ Jack Flash, Street Fighting Man, Honky Tonk Women by the Rolling Stones. Yes, I know that’s three songs. Released in quick succession from 1968 to 1969, only Street Fighting Man was imbedded on an album (Beggar’s Banquet). All three have what’s missing in much of today’s pop and rock music: ingenious melodies, unique guitar riffs (by Keith Richards), entertaining lyrics, and roughshod emotion all tarted up in within tight production. Mick Jagger sings his living guts out, Charlie Watts drives the pounding beat home, and bassist Bill Wyman patiently picks his moments to emerge from the mix to take us all on a ride. The lyrics range from catchy and clever to novelistic in the case of Jumpin’ Jack Flash, which tells the improbable tale of an unlikely protagonist “born in a crossfire hurricane” climaxing with his drowning, where he is “washed up and left for dead.” Top shelf Stones.

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New York State of the Mind

This month Natural Selections interviews Raquel Hernandez-Solis Research Assistant, Gilbert Laboratory

Interview by Guadalupe Astorga

How long have you been living in the New York area? 

NYSOM

Photo Courtesy of Raquel Hernandez-Solis

Two years, and I also lived here for three months during the Rockefeller SURF program (Summer Undergraduate Research Fellowship).

Where do you currently live?  Which is your favorite neighborhood?

I live in my favorite neighborhood which is Astoria, Queens; it’s a wonderful place. It has the New York vibes and also a bit of L.A., which I love.

What do you think is the most overrated thing in the city? And underrated? 

I was going to say the most overrated thing is Shake Shack, but now I know it has also expanded to L.A.

I think Williamsburg is also overrated; it has lost a bit of the charm, even 3 years ago.
Underrated, I think Astoria Park, it has a beautiful view over the bridge and you can run on the track, there’s always someone selling fruit in carts.

What do you miss most when you are out of town? 

I miss the feeling of being able to do anything very quickly. I miss being only a 15 minute train ride from my dance class or my favorite restaurant. I love the convenience of the city.

Has anything (negative or positive) changed about you since you became one of us “New Yorkers”?

I have gotten a bit more cautious because I had some break-in incidents, but I have not lost my sense of exploration. When I first got here I used to get off the train in a random station to explore the neighborhood, and I have not lost that, but I do feel that I have gotten a bit more cautious.

If you could change one thing about NYC, what would that be?

I would change smoking laws in the streets, that’s my least favorite thing in the city. I feel that the cigarette smoke that I smell on my way to work is too much.  

What is your favorite weekend activity in NYC?

In the summer I really like looking at the free dance and cultural activities in my Time Out magazine. Last summer I saw the ballet Hispanico for free at Lincoln Center and also different concert venues outside.

 What is the most memorable experience you have had in NYC?  

My most memorable experience was to be able to perform in the Barclays Center, last summer, and feel like Beyoncé for a night, walking on the floor of the center and seeing thousands and thousands of people, it was the really cool.

Bike, MTA or walk it???

I love the MTA, and I’m starting to expand my horizons with the bus system. I think it’s very convenient because it takes you where the subway cannot.

If you could live anywhere else, where [would] might that be? 

I would like to live in Mexico for a little bit, not only to reconnect with my family down there; but I would also love the opportunity to do folklorico dance there for an extended period of time.

Do you think of yourself as a New Yorker?

I think so. My heart has changed from Los Angelino to New Yorker. I’m 75% New Yorker now.

 

For Your Consideration

By Jim Keller

As we begin our fifth year of uncovering and examining the content that will eventually form the enigma that is the Academy Awards race, I thought it would be interesting to switch things up and break down my films of interest list by release date, festival appearance and production status. After all, outside of the pedigree attached to each film, these are the only available parameters to measure the Oscarability of each film, sight unseen. The early part of the Oscar race (from January until the Telluride Film Festival in August) is a moving target. The awards stops along the way, such as the Sundance, South by Southwest, and Cannes film festivals, can be equated to the change of seasons: their arrival is inevitable, but their impact is uncertain. This makes spit balling what may come down the slippery slope of the Oscar pike a dicey proposition. For one, a lot of the films lack distribution or have soft release dates, making it easy for studios to push their release to the following year. Second, the films discussed here haven’t been screened, so it’s impossible to know the genre they fit into. All we have to go on is the log line, the talent attached, and a little intuition. In this sense, one could say this parallels how we size up politicians, but I digress.

Last year, FYC’s Crystal Ball Edition covered only two out of eight 2016 Best Picture nominees. With that, I give you films of interest, set to debut this year, which could wind up in this year’s Oscar conversation.

Films to Compete for the Palme d’Or at the Cannes Film Festival: May 11-22

Photo Courtesy of Amazon Studios

Photo Courtesy of Amazon Studios

The Neon Demon (director: Nicolas Winding Refn, status: Completed, release date: June 2016):

Why you might like it: It’s a horror/thriller about an aspiring model (Elle Fanning) who moves to Los Angeles, only to have her youth and vitality devoured by a group of beauty-obsessed women who will stop at nothing to get what she has.

Why I’ve got my eye on it: It’s the third film from the director whose first film Drive competed for the Palme in 2011 and won him the Best Director prize. While his last film Only God Forgives was a critical flop, there’s no reason to believe that he can’t learn from past mistakes. Fanning has become a prolific actress and seems well-suited for a young ingénue role.

Photo Courtesy of The Weinstein Company

Photo Courtesy of The Weinstein Company

Loving (director: Jeff Nichols, status: Post-production, release date: November 2016):

Why you might like it: The drama tells the true story of Richard and Mildred Loving (Joel Edgerton and Ruth Negga), an interracial couple who were sentenced to prison in Virginia in 1958 for getting married.

Why I’ve got my eye on it: After the second year of #OscarsSoWhite, there are several films cropping up this year featuring prominent roles for minorities (and even a second one about an interracial marriage, see below). This second 2016 offering from Nichols, is one such film. Given Nichols’ track record to date and the prime release date, this could be an awards player for Best Picture, Director, actor and actress.

The Last Face (director: Sean Penn, status: Completed, release date: 2016):
Why you might like it: A director of an international aid agency in Africa (Charlize Theron) meets a relief aid doctor (Javier Bardem) amidst a political/social revolution, together they face tough choices surrounding humanitarianism and life through civil unrest.

Why I’ve got my eye on it: Penn’s last film, 2007’s Into the Wild, earned high critical acclaim and went on to land a Supporting Actor nomination for Hal Holbrook. Theron and Bardem are always ones to watch: Theron won Best Actress in 2004 for Monster and was nominated again in 2006 for North Country, and Bardem was nominated for Best Actor in 2001 for Before Night Falls, he won Best Supporting Actor in 2008 for No Country for Old Men, and was last nominated for Best Actor for 2010’s Biutiful. While the two are a formidable duo, its French actress Adèle Exarchopoulos who I’m most excited to see after her remarkable turn in 2013’s Blue is the Warmest Color. As of now, the film lacks distribution and may be one of those pushed to 2017.

Films Likely to Appear at the Telluride Film Festival: September 2-5

The Birth of a Nation

The Birth of a Nation

The Birth of a Nation (director: Nate Parker, status: Completed, release date: October 2016):

Why you might like it: Nat Turner (Parker), a former slave in America, leads a liberation movement in 1831 to free African-Americans in Virginia, which results in a violent retaliation from whites.

Why I’ve got my eye on it: This is one of my most anticipated films of the year and the second of those featuring prominent roles for minorities. It is also directed by the African-American Parker, who stars in the film. It premiered this year at Sundance; where it won the Audience Award and Grand Jury Prize in the U.S. Dramatic Competition. Fox Searchlight Pictures bought worldwide rights to the film in a $17.5 million deal, the largest deal to be made at the fest to date. Look for this one as a Best Picture contender.

Billy Lynn’s Long Halftime Walk (director: Ang Lee, status: Post-production, release date: November 2016):

Why you might like it: Based on the novel of the same name by Ben Fountain, this drama concerns infantryman Billy Lynn (newcomer Joe Alwyn) who recounts a Thanksgiving Dallas Cowboys halftime show that he and his squad members made an appearance during in the final hours before the soldiers returned to Iraq.

Why I’ve got my eye on it: Lee was nominated for Best Director in 2001 for Crouching Tiger, Hidden Dragon, and he won in 2006 for Brokeback Mountain, and in 2013 for Life of Pi, a film with a staggering visual achievement. He has confirmed that Billy Lynn will be shot 120 frames per second, the highest frame rate for a film to date. The film also features Kristen Stewart, who has been flirting with Academy recognition with stellar supporting turns in 2014’s Still Alice and Clouds of Sils Maria.

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Purple Reign

By DEANE MORRISON AND GEORGE BARANY

George Barany is a Rockefeller alum (1977) currently on the Chemistry faculty of the University of Minnesota–Twin Cities. Deane Morrison, a distinguished science writer, is his U of M colleague. For more about this specific puzzle, including a link to the answer, visit here. More Barany and Friends crosswords can be found here.

Across

1.___ coil (electrical device invented in1891)PrinceTributeGrid
6.Aussie greeting, often followed by “mate”
10.Ballplayer’s headgear
13.They keep the wheels turning
14.Song title shared by “The Sound of Music” and “West Side Story”
15.Put away groceries?
16.Facility whose large glass pyramid would glow purple whenever this puzzle’s
honoree was present
18.Obstacle
19.Band boosters
20.Theater chain that merged with AMC in 2006
21.Get bushed
22.___ moss
24.Concise in speech
26.Billboard’s #1 single of 1984
30.Fish stick?
31.Scott Turow autobiographical bestseller of 1977
32.Get ready to drive, in golf
36.“___ U”
38.Number of Grammies won, as well as pronunciation of a #3 top 40 hit, by this
puzzle’s honoree
41.Small force
42.Classified, as blood
44.Land of Esau’s descendants
46.DDE’s wartime command
47.Prince’s followers
51.Big wind
54.Go ___ great length
55.Willing partner
56.Grieve
59.Coffee, tea, or beer
62.No-win situation
63.Song that begins with a spoken eulogy to “this thing called life”
65.Bobbie Gentry wrote one to Billy Joe
66.The ___ Project (“Sleeper”)
67.Quibblers split them
68.Nothing but the bottom of the ___
69.Some mil. awards
70.Old lab heaters named after a volcano

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“The Answers My Friend …”

By ROBERT MARK AND GEORGE BARANY

George Barany is a Rockefeller alum (1977) currently on the Chemistry faculty of the University of Minnesota–Twin Cities. Robert Mark is a native New Yorker currently teaching in Thailand, and a long-time admirer of this puzzle’s theme.  For more information, including a link to the answer, visit here. More Barany and Friends crosswords can be found here. More Barany and Friends crosswords can be found here.

Across

1.Two-person log cutter
7.Stetson or sombrero, e.g.
10.Battery terminal
15.Symbol for viscosity or index of refractionAnswersMyFriendpuzGrid
18.One way to serve curry
19.Small amounts, as ofcream
20.Filleted
21.Actor Beatty or Sparks
22.Biff, in the past, present, and “Future”?
25.___ alai
26.Jumbo follower
27.Hawaiian beach ball?
28.Ricochet
29.Between all and none
30.Reassurance to celllist Yo-Yo?
34.Direct recruiting pitch from an iconic Uncle?
36.Tenth-century pope, better remembered in crosswords than in the history books (anagram of name of a certain rodent)
37.Took ___ for the worse
39.1990’s Indian P.M.
40.Director Tarantino
43.New York tribe, city, or lake
46.Like the walls at WrigleyField
50.One that, according to Higgins, hardly ever happens in Hertford, Hereford, and
Hampshire?
52.They’re just this side of paradise?
54.Common street or tree
55.Clinch, as a deal
57.E w e’s m a t e
58.Near-Miss. state?
59.German candy brand
63.Malaysian palm
66.Humiliate
69.Place for prison guards?
76.Apple implement
77.Pasta, in product names
78.Off course, of course
79.Point of no return?
82.___ Paulo, Brazil
83.Word with dash or happy
86.Prof ’s e-mail address ender
87.Chiropractor’s diary?
93.Local, at times?
97.Don Draper’s domain
98.Gets game
100.Aggravate
101.“Norma ___”
103.Actors Dillon and Damon
105.Grps. of Boy or Girl Scouts
106.He’s a card
111.Annie Leibovitz, to her fans?
116.X, Y, or Z
117.Collect data or data collector
119.Acronym in the news for gravitational wave detection
120.Start of Massachusetts’ motto
121.Criticize, slangily
122.Admire Jagger or Richards on social media?
126.They may amend xword clues
127.Rubber seal
128.Grievance, slangily
129.Caught, as a butterfly
130.Susan of “The Partridge Family” and “L.A. Law”
131.Ministers
132.NYC subway line
133.Tool box item

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Quotable quote

Commonplace miracle:
that so many commonplace miracles happen…
A miracle, just take a look around:
the world is everywhere.
An additional miracle, as everything is additional:
the unthinkable
is thinkable.

Maria Wislawa Anna Szymborska, 1923 – 2012, Nobel Prize for Literature 1996

Life on a Roll

By Qiong Wang

Rome is a living open museum. Every road leads there. It is impossible to tell stories about an ancient city like Rome. You just don’t know where to start. The squares, the fountains, the statues, the cathedrals, the ruins and the monuments… It is “La Grande Bellezza”, the great beauty. Rome wasn’t built in one day; neither is the visit to Rome. I tried to capture its beauty from the perspective of the locals using my camera. One picture doesn’t do it justice at all.FullSizeRender

 

FullSizeRender_1IMG_3634

 

 

 

 

 

 

 

 

 

 

 

 

Growing vegetables in small spaces

By Guadalupe Astorga

image 1

Top Left: Hydroponic research in Epcot Center, Orland/Antony Pranata,CC. Top Rigt: Hydroponics/Frank Fox, CC /Bottom panels: Our Windowfarms Project

One of today’s global issues concerns the supply of fresh food to people in cities. While the carbon footprint for transporting fruits and vegetables from the areas where they are produced, to the consumers’ tables can reach high levels for longer distances, local production and consumption have several advantages. A number of new initiatives make it possible to take advantage of urban spaces to grow fresh vegetables in your own city or apartment.

In cities where the space is dominated by concrete construction, urban agriculture has shed new light into public and private spaces, promoting community interactions and the development of organic alternatives to intensive crop farming.

Different projects have taken over rooftops and unused spaces in New York City, not only to grow fresh vegetables for distribution in the local community, but also to offer a sustainable model for urban agriculture in open spaces.

Other interesting alternatives involve hydroponic cultures, which offer a very efficient way to grow different types of organic plants with no need of big spaces. In recent years, several hydroponic techniques have exploded and evolved in a plethora of varieties developed by enthusiastic farmers who have openly shared their knowledge on the internet, making videos with detailed tutorials and instructions for beginners and experienced farmers. Hydroponics are not expensive or complicated, can be started at any time of the year, and you can control what you eat.

image 2

Left panel: Hydrosock Version/Jim Flavin; Right panel: Hydroponics principle/iamozone, CC

In an example of these collaborative initiatives, also born in New York City, hydroponic vertical gardens are designed for our apartment windows, and people around the world have shared their experiences to create new innovative and esthetic designs. You will need a bit of creativity and enthusiasm to make this project in your apartment, but it is certainly worth it.

A more convenient and simpler alternative to get started wih hydroponics in your own apartment at minimal cost is the Hydrosock Version, proposed by Jim Flavin (Fig. 1, left panel). This handy design is the easiest version of hydroponics; it does not need an air pump to oxygenate the water, nor expensive or specialized materials. The roots get oxygen as the water level decreases in the reservoir. The principle is shown in Fig. 1 right panel.

I encourage you to make this simple hydroponic system at home for high yields of vegetable production and little cost. This is the proper time of the year to start if you want to harvest delicious vegetables for this summer.

You will just need:

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