"The future is already here ? it's just not very evenly distributed," wrote William Gibson. He's right. Luckily, the future is mostly in my attic workshop. I've been lucky enough to have access to a Form 1 3D printer for the past week and have come away with a better sense of the platform, the way forward of 3D printing in general and Form 1 in particular. In short, the Form 1 is one of the simplest and most usable printers I've ever used and, barring a few minor peccadilloes, it is well worth the hype -- and price tag.
New compound excels at killing persistent and drug-resistant tuberculosisPublic release date: 17-Jun-2013 [ | E-mail | Share ]
Contact: Mika Ono mikaono@scripps.edu 858-784-2052 Scripps Research Institute
LA JOLLA, CA June 17, 2013 An international team led by scientists at The Scripps Research Institute (TSRI), the Howard Hughes Medical Institute and Albert Einstein College of Medicine of Yeshiva University has identified a highly promising new anti-tuberculosis compound that attacks the tuberculosis (TB) bacterium in two different ways.
"These findings represent an effort to help solve one of the major global health crises of our timethe resurgence of TB and its dangerous drug-resistant strains," said Peter G. Schultz, the Scripps Family Chair Professor of Chemistry at TSRI, who was senior author of the study with William R. Jacobs, Jr., member of the Howard Hughes Medical Institute and professor of microbiology & immunology and of genetics at Albert Einstein College of Medicine.
"In cell cultures and in mice, this compound showed powerful activity against ordinary active TB bacteria, non-replicating TB bacteria and even extensively drug-resistant TB strains," said Feng Wang, a member of the Schultz lab at TSRI and first author of the study with Dhinakaran Sambandan of the Jacobs lab and Rajkumar Halder of the Schultz lab.
The paper appears in this week online ahead of print in an Early Edition of the Proceedings of the National Academy of Sciences.
Global Health Crisis
Although isoniazid and rifampin, the two front-line TB drugs, came into use in 1952 and 1967 respectively, new TB infections still occur at the rate of roughly one per second. At any moment about a third of the existing human population is infectedmostly with inactive, latent TB, although active TB still kills over one million people each year. Russia, Africa, China and Southeast Asia have been especially hard hit by the epidemic.
Increased urbanization, public health complacency and immunity-weakening HIV have been major enablers of TB's spread in recent decades. But the bacterium that causes TBMycobacterium tuberculosis (Mtb)also happens to be unusually well adapted for persisting in humans. Among other strategies, it frequently reverts to a dormant, non-replicating state and also creates attack-resistant cell colonies called biofilms, which contain a high proportion of non-replicating TB.
Compared to ordinary, fast-replicating TB, these other forms of TB are much less susceptible to existing drugs. Effective TB therapy thus requires months to years of regular dosing. But many patients quit before completing such long courses of treatment and end up incubating drug-resistant TB strains. Some strains are now "extensively drug-resistant" (XDR) and virtually untreatableand usually fatal.
Killing the Persisters
"The big challenge here has been to find a drug that clears TB infection more quickly, which means it has to be effective against both replicating and non-replicating TB," said Wang, now also a scientist at the California Institute for Biomedical Research (CALIBR), a non-profit organization founded by Schultz for the early-stage development of new medicines.
Most existing TB drugs work poorly against non-replicating TB, having been developed principally for their ability to kill actively replicating TB. Wang therefore set up a different kind of screening testone to detect compounds that block TB's persistence-related ability to form biofilms.
Because experiments with live TB require a special (level 3) biosafety facility, Wang used a related but non-disease-causing mycobacterium for his initial, high-throughput test. Screening a diverse library of 70,000 compounds, he quickly found one, dubbed TCA1, that stood out for its ability to inhibit mycobacterial biofilms.
Tests in Jacobs's biosafety level 3-certified laboratory confirmed that TCA1 also has powerful activity against TB. "Surprisingly, it turned out to kill both non-replicating and replicating TB," Wang said.
In cell culture tests, TCA1 on its own killed more than 99.9% of ordinary, actively replicating TB bacteria within three weeks, and in combination with isoniazid or rifampin, could kill 100% within that period. TCA1 also showed strong effectiveness against drug-resistant TB strains, removing all signs of one common strain within a week when combined with isoniazid. Against a highly fatal "super-bug" strain from South Africa, which resists all conventional TB drugs, the new compound on its own had a kill rate of more than 99.999% within three weeks.
As expected, TCA1 also showed potent effects against non-replicating TB. Tests in mice confirmed TCA1's effectiveness and suggested that the combination of TCA1 and isoniazid could be more powerful than existing drug regimens. TCA1 showed no sign of toxicity or adverse side effects in cell culture and mouse experiments, and also showed almost no tendency to induce drug resistance in TB.
A Complex Mechanism
Working with the laboratories of Gurdyal S. Besra and Klaus Ftterer at the University of Birmingham, UK, Katarina Mikusova at Comenius University in Slovakia, and Kai Johnson at Ecole Polytechnique Fdrale de Lausanne (EPFL) in Switzerland, the team next did structural and biochemical analyses to determine how the new compound kills Mtb so efficiently.
The researchers found it works in an apparently unique way, largely by targeting two Mtb enzymes, one supporting TB replication and the other TB dormancy and persistence. "I don't know of any other antibiotic that kills replicating bacteria through one pathway and non replicating bacteria through another, as this one does," Wang said.
Now funded by the Global Alliance for TB Drug Development, Wang and his colleagues are working to devise improved variants of TCA1. "We already have analogs of TCA1 that are more potent and look very promising as TB drug candidates," said Wang.
Assuming that preclinical tests are completed successfully, he added, the group hopes to find a pharmaceutical company partner to sponsor clinical trials in TB patients.
###
Contributors to the study, "Identification of a small molecule with activity against drug-resistant and persistent tuberculosis," also included Jianing Wang, Insha Ahmad, Pengyu Yang and Yong Zhang of TSRI; Sarah M. Batt of University of Birmingham; Brian Weinrick, John Kim and Morad Hassani of Howard Hughes Medical Institute and Albert Einstein College of Medicine; Stanislav Huszar of Comenius University (Slovakia); Claudia Trefzer of EPFL; Zhenkun Ma, Takushi Kaneko and Khisi E. Mdluli of the Global Alliance for Tuberculosis Drug Development; Scott Franzblau of the University of Illinois; and Arnab K. Chatterjee of CALIBR.
The study was funded in part by the National Institutes of Health (grants AI26170 and A10-97548), the European Community's Seventh Framework Programme (260872), the Global Alliance for TB Drug Development and the Albert Einstein College of Medicine Center for AIDS Research (AI051519).
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
New compound excels at killing persistent and drug-resistant tuberculosisPublic release date: 17-Jun-2013 [ | E-mail | Share ]
Contact: Mika Ono mikaono@scripps.edu 858-784-2052 Scripps Research Institute
LA JOLLA, CA June 17, 2013 An international team led by scientists at The Scripps Research Institute (TSRI), the Howard Hughes Medical Institute and Albert Einstein College of Medicine of Yeshiva University has identified a highly promising new anti-tuberculosis compound that attacks the tuberculosis (TB) bacterium in two different ways.
"These findings represent an effort to help solve one of the major global health crises of our timethe resurgence of TB and its dangerous drug-resistant strains," said Peter G. Schultz, the Scripps Family Chair Professor of Chemistry at TSRI, who was senior author of the study with William R. Jacobs, Jr., member of the Howard Hughes Medical Institute and professor of microbiology & immunology and of genetics at Albert Einstein College of Medicine.
"In cell cultures and in mice, this compound showed powerful activity against ordinary active TB bacteria, non-replicating TB bacteria and even extensively drug-resistant TB strains," said Feng Wang, a member of the Schultz lab at TSRI and first author of the study with Dhinakaran Sambandan of the Jacobs lab and Rajkumar Halder of the Schultz lab.
The paper appears in this week online ahead of print in an Early Edition of the Proceedings of the National Academy of Sciences.
Global Health Crisis
Although isoniazid and rifampin, the two front-line TB drugs, came into use in 1952 and 1967 respectively, new TB infections still occur at the rate of roughly one per second. At any moment about a third of the existing human population is infectedmostly with inactive, latent TB, although active TB still kills over one million people each year. Russia, Africa, China and Southeast Asia have been especially hard hit by the epidemic.
Increased urbanization, public health complacency and immunity-weakening HIV have been major enablers of TB's spread in recent decades. But the bacterium that causes TBMycobacterium tuberculosis (Mtb)also happens to be unusually well adapted for persisting in humans. Among other strategies, it frequently reverts to a dormant, non-replicating state and also creates attack-resistant cell colonies called biofilms, which contain a high proportion of non-replicating TB.
Compared to ordinary, fast-replicating TB, these other forms of TB are much less susceptible to existing drugs. Effective TB therapy thus requires months to years of regular dosing. But many patients quit before completing such long courses of treatment and end up incubating drug-resistant TB strains. Some strains are now "extensively drug-resistant" (XDR) and virtually untreatableand usually fatal.
Killing the Persisters
"The big challenge here has been to find a drug that clears TB infection more quickly, which means it has to be effective against both replicating and non-replicating TB," said Wang, now also a scientist at the California Institute for Biomedical Research (CALIBR), a non-profit organization founded by Schultz for the early-stage development of new medicines.
Most existing TB drugs work poorly against non-replicating TB, having been developed principally for their ability to kill actively replicating TB. Wang therefore set up a different kind of screening testone to detect compounds that block TB's persistence-related ability to form biofilms.
Because experiments with live TB require a special (level 3) biosafety facility, Wang used a related but non-disease-causing mycobacterium for his initial, high-throughput test. Screening a diverse library of 70,000 compounds, he quickly found one, dubbed TCA1, that stood out for its ability to inhibit mycobacterial biofilms.
Tests in Jacobs's biosafety level 3-certified laboratory confirmed that TCA1 also has powerful activity against TB. "Surprisingly, it turned out to kill both non-replicating and replicating TB," Wang said.
In cell culture tests, TCA1 on its own killed more than 99.9% of ordinary, actively replicating TB bacteria within three weeks, and in combination with isoniazid or rifampin, could kill 100% within that period. TCA1 also showed strong effectiveness against drug-resistant TB strains, removing all signs of one common strain within a week when combined with isoniazid. Against a highly fatal "super-bug" strain from South Africa, which resists all conventional TB drugs, the new compound on its own had a kill rate of more than 99.999% within three weeks.
As expected, TCA1 also showed potent effects against non-replicating TB. Tests in mice confirmed TCA1's effectiveness and suggested that the combination of TCA1 and isoniazid could be more powerful than existing drug regimens. TCA1 showed no sign of toxicity or adverse side effects in cell culture and mouse experiments, and also showed almost no tendency to induce drug resistance in TB.
A Complex Mechanism
Working with the laboratories of Gurdyal S. Besra and Klaus Ftterer at the University of Birmingham, UK, Katarina Mikusova at Comenius University in Slovakia, and Kai Johnson at Ecole Polytechnique Fdrale de Lausanne (EPFL) in Switzerland, the team next did structural and biochemical analyses to determine how the new compound kills Mtb so efficiently.
The researchers found it works in an apparently unique way, largely by targeting two Mtb enzymes, one supporting TB replication and the other TB dormancy and persistence. "I don't know of any other antibiotic that kills replicating bacteria through one pathway and non replicating bacteria through another, as this one does," Wang said.
Now funded by the Global Alliance for TB Drug Development, Wang and his colleagues are working to devise improved variants of TCA1. "We already have analogs of TCA1 that are more potent and look very promising as TB drug candidates," said Wang.
Assuming that preclinical tests are completed successfully, he added, the group hopes to find a pharmaceutical company partner to sponsor clinical trials in TB patients.
###
Contributors to the study, "Identification of a small molecule with activity against drug-resistant and persistent tuberculosis," also included Jianing Wang, Insha Ahmad, Pengyu Yang and Yong Zhang of TSRI; Sarah M. Batt of University of Birmingham; Brian Weinrick, John Kim and Morad Hassani of Howard Hughes Medical Institute and Albert Einstein College of Medicine; Stanislav Huszar of Comenius University (Slovakia); Claudia Trefzer of EPFL; Zhenkun Ma, Takushi Kaneko and Khisi E. Mdluli of the Global Alliance for Tuberculosis Drug Development; Scott Franzblau of the University of Illinois; and Arnab K. Chatterjee of CALIBR.
The study was funded in part by the National Institutes of Health (grants AI26170 and A10-97548), the European Community's Seventh Framework Programme (260872), the Global Alliance for TB Drug Development and the Albert Einstein College of Medicine Center for AIDS Research (AI051519).
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
The park that was the center of defiance against the rule of Turkish Prime Minister Recep Tayyip Erdogan has been cleared by riot police after more than two weeks of protests. As thousands of demonstrators try to regroup in Taksim Square, smaller skirmishes between police and protesters have broken out in other parts of Istanbul.
Here's a gallery of images from the past two weeks of protests and pushback in Turkey.
Follow AP photographers and photo editors on Twitter: http://apne.ws/15Oo6jo
FILE - In this Oct. 4, 2012 file photo, television personality Kim Kardashian poses for photographers at the red carpet during the 40th anniversary of Cosmopolitan magazine in Spanish in Mexico City. Kardashian reportedly gave birth to a baby girl Saturday, June 15, 2013 in Los Angeles. (AP Photo/Marco Ugarte, File)
FILE - In this Oct. 4, 2012 file photo, television personality Kim Kardashian poses for photographers at the red carpet during the 40th anniversary of Cosmopolitan magazine in Spanish in Mexico City. Kardashian reportedly gave birth to a baby girl Saturday, June 15, 2013 in Los Angeles. (AP Photo/Marco Ugarte, File)
LOS ANGELES (AP) ? It looks to be a baby girl for Kim Kardashian and her rapper boyfriend Kanye West. Or does it?
The couple was keeping silent Sunday in the wake of multiple reports that Kardashian has given birth over the weekend, about a month premature.
But Kardashian's sister Khloe appears to have let a rather cryptic cat out of the bag on Twitter.
"I can not even begin 2describe the miracle that is now apart of our family. Mommy/baby are healthy &resting. We appreciate all of the love," she tweeted Sunday.
She quickly followed with a second tweet: "More info will come when the time is right! Thank you all for understanding! We love you all dearly! Overwhelmed with love right now."
Kardashian mom Kris Jenner linked to both tweets on her Twitter account. She was scheduled to be a presenter at Sunday night's Daytime Emmy Awards.
The reality TV star's pregnancy was almost as anticipated as the royal pregnancy of Kate Middleton, who is due in mid-July. That's about the time the Kardashian baby had been due.
The 32-year-old has often been photographed since announcing she was pregnant, opting to continue to wear designer clothing. She told The Associated Press in April that she eventually embraced being an expecting mom after getting past "the awkward phases and stages."
The couple had initially kept the baby's gender a secret, but the sex was revealed earlier this month during one of Kardashian's doctor appointments on "Keeping up with the Kardashians."
News of the birth has been swaddled in unusual secrecy. Representatives for West and Kim Kardashian did not respond to emails and calls from The Associated Press, nor did any representatives for family members, friends and professional associates. And all of the weekend media reports on the birth were attributed to anonymous sources.
In a recent interview with The New York Times, West said he didn't like talking about his family or the arrival of his child.
"Like, this is my baby. This isn't America's baby," he said.
Earlier, we posted a blog about the recent publication in Climbing Magazine on Training for Off-Width Climbing written by local Missoula rock climber, Pamela Pack, with guidance by Alpine?s Leah Versteegen. Part I of the two part series published in May 2013 reviewed the basic foundation of a training cycle to prepare a climber for the grueling sport of off-widths. Part II, released in the June 2013 edition of Climbing Magazine, is on the shelves now. Check it out!
I want to highlight a specific area of Pamela?s training program, stabilization. At Alpine Physical Therapy, we put a lot of emphasis on stabilization training, for the core of course, but also the hips and lower extremities, shoulder girdle and upper extremities. Understanding core stability is an aspect of training that is important for everyone, but becomes absolutely necessary for elite athletes such as Pamela. After suffering dislocating ribs, herniated discs in her lumbar spine, a torn rotator cuff, torn MCL?the list goes on, optimal stability and biomechanics are allowing Pamela to continue her pursuit of tackling the most difficult off-width climbs imaginable.
For more information on Alpine?s sports performance outreach for climbers, visit our clinic webpage on the topic by?clicking here.
?
As part of her article on training for off-width?s Pamela describes the role of Pilates in her program:? ?One of your greatest challenges may be working around injuries. If you are injured, addressing that should be a priority. Trying to get stronger around an injury means other areas are overcompensating, and you?ll never truly heal yourself and be full-body strong. In my experience, Pilates has been the single most effective form of injury prevention and rehabilitation. Shoulder, back, hip, and other pain/damage require more stabilization work to get your entire body back to full strength, and Pilates can create deep core stability while maintaining flexibility and mobility.?
Pamela attributes much of her success climbing to the detailed workouts that have been developed specific to her sport by a combination of exercise specialists during the off-season in Missoula. While Leah has guided her overall rehabilitation and training program, Samantha Schmidt at Alpine PT and Samantha Glaze at The Core Studio have taken her to the next level in stabilization training with fine-tuned mechanics and isolated stability utilizing Pilates and Core Align. Well done ladies.
PARIS (AP) ? The Paris Air Show, which opens for business on Monday, brings hundreds of aircraft to the skies around the French capital, the usual tense competition between aircraft manufacturers Boeing and Airbus, and a slew of innovations large and small. Here's what to look for over the show:
BATTLE OF THE WIDE-BODIES
The much-anticipated Airbus A350 flew for the first time on Friday, launching a new air race between the European plane maker and Boeing for long-haul wide-body aircraft.
Boeing has dominated the market so far, but troubles with the lithium ion batteries in its 787 Dreamliner are giving customers a reason to give a close look at Airbus' first all-new plane in eight years. The CEO of Airbus parent EADS, Tom Enders, has said he expects a "few hundred" new orders. Boeing executives, meanwhile, downplayed the air show's importance for orders, noting that the two companies have historically split the commercial aircraft market.
A year ago, at the Paris Air Show's sister event in Britain, Boeing beat Airbus for the number of orders announced. The U.S. company took in $37 billion in orders and commitments, well above Airbus' $16.9 billion.
But the announcements during the air shows are not always a reliable indicator of business since prices are often negotiated down heavily and big orders don't always coincide with the event.
The race for the title of biggest plane maker is as tight as ever. Over the whole of 2012, Airbus delivered 588 planes. That was a record, but one Boeing beat with 601 deliveries, the first time since 2003 it came out on top.
NO HANDS ON DECK
They have swooped into wildfires to take temperatures and tracked animals across Africa. They have guided a fuel tanker to safety through icy waters. Drones are increasingly being used for non-military purposes and are expected to feature prominently at the Paris Air Show.
There are still tough restrictions on their flight for safety reasons, but while the Federal Aviation Authority works on new rules, the makers of drones will aim to show off innovation and technical prowess at the show. Eurocopter, a company based in France, will showcase new technology that can transform a manned helicopter into one that flies without a pilot.
EVEN IN PARIS, SEQUESTRATION TAKES TOLL
American fighter jets aren't taking to the skies above Paris, nor will they be seen on the ground, for the first time in more than two decades thanks to the U.S. government's spending cuts - the infamous 'sequestration'.
The U.S. pavilion remains the largest, but the event will be less of a sales showcase for latest military hardware and more a place for suppliers to meet up with potential customers.
Russia, on the other hand, is looking to make a splash by presenting fighter jets and military helicopters at the show for the first time since 2001. The Sukhoi manufacturer will showcase its Su-35, a twin-engine multipurpose fighter, for the first time outside Russia. Britain and France also will have fighter jets on display.
"It's two different trends between commercial aircraft and defense," said Eric Bernardini, a consultant for AlixPartners who follows the aerospace industry.
EVERY LITTLE BIT COUNTS
Less flashy but just as important for the industry will be the myriad technological innovations that parts suppliers will come to Paris to present. The biggest issue? The cost of fuel.
The price of jet fuel has more than tripled worldwide since 2003 ? a trend both jet manufacturers and airlines expect to continue. Electric- or solar-powered commercial flights are wildly improbable and biofuels aren't yet economically viable, so airlines are looking to improve mileage any way possible.
For long-haul flights, that means more carbon-fiber in airplane bodies and other design tweaks, such as electric motors for taxiing. For passengers, it means no end in sight on extra baggage fees.
___
Follow Lori Hinnant at: https://twitter.com/lhinnant
Local resident Michael Schaaf knew something was wrong when his day-to-day worries began to interfere with his life. After consulting with a doctor, he decided to seek help for his generalized anxiety disorder (GAD) at Loyola University Medical Center.
Schaaf?s doctor, Aparna Sharma, says it?s important to remember that anxiety is a normal human emotion that aids in survival. However, when it becomes excessive and interferes with everyday life, people need to seek professional help.
Often, individuals with generalized anxiety experienced something traumatic as a child. Sharma says a coping mechanism, is to worry about trivial, day-to-day matters because these serve as a distraction from the real emotions at play. Memories may be traumatic and are often difficult to deal with.
According to the National Institute of Mental Health, there are two main kinds of treatment for GAD. Cognitive behavior therapy can be used to change how the patient thinks, behaves, and reacts to certain situations. Medication is another alternative and typically patients are prescribed either anti-depression or anti-anxiety medications. As always, it?s important to talk with a doctor before obtaining any medication.
Sharma says that other solutions can as simple as doing enjoyable, relaxing activities such as reading, journaling, or exercising. If you or someone you know may have GAD, it?s important to seek professional help and know that anxiety is curable.
Tags: Anxiety, CLTV, featured, generalized anxiety disorder, Jane Monzures, Loyola University, Loyola University Medical Center, Mental Health, stress, WGN, worry
"The future is already here ? it's just not very evenly distributed," wrote William Gibson. He's right. Luckily, the future is mostly in my attic workshop. I've been lucky enough to have access to a Form 1 3D printer for the past week and have come away with a better sense of the platform, the way forward of 3D printing in general and Form 1 in particular. In short, the Form 1 is one of the simplest and most usable printers I've ever used and, barring a few minor peccadilloes, it is well worth the hype -- and price tag.
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Public release date: 17-Jun-2013
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