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Snake-Like Intelligent Robot in Development

Jie Fu and Cagdas Onal

Jie Fu, left, and Cagdas Onal hold an earlier snake-like soft robot (Worcester Polytechnic Institute)

19 October 2017. An engineering team is creating a self-powered robot that can travel independently like a snake through uneven and cluttered surfaces, such as disaster sites. Worcester Polytechnic Institute in Massachusetts recently received a $400,000 award from National Science Foundation to develop this system.

The three-year project is led by Worcester Tech robotics engineering professors Cagdas Onal and Jie Fu seeking a robotic system that can navigate through messy, real-life environments filled with rough, uneven, and damaged surfaces filled with obstacles and clutter. The researchers envision a soft, segmented device that moves like a snake, with the intelligence to visualize, interpret, and adapt to its surroundings.

“The goal of this project is to have a snake-like robot with the autonomy to navigate through its environment without close supervision,” says Fu in a university statement. “In search-and-rescue scenarios, you’d want a robot you can rely on to go into areas inaccessible by humans and provide critical information about conditions there and about who needs to be rescued first.”

The device is expected to have a series of modules made of soft silicone rubber, each with its own motors, sensors, and control units that allow the system to move on its own. The modules would be connected into an integrated system, directed by two sets of algorithms. One group of algorithms will control the basic motions of the modules, responding to stimuli in the immediate environment.

In some cases, Onal explains, the device could use objects in its environment to move ahead. “A snake, for instance,” says Onal, “could move by wrapping part of its body around a rock so it can push against it and propel itself better. If it’s in a pipe or a maze-like structure, it might push off the walls to be able to move around an obstacle.”

The second set of algorithms will provide high-level planning and control, including coordinating the movements of individual modules in the device. The algorithms would make it possible for the device to learn from the accumulated experience of the device, translated into models for encountering future tasks.

“If I put the robot in the sand and then on gravel, it would exhibit different behaviors,” adds Fu. “On the higher level we can introduce learning-based mechanisms so the robot will learn the best way to move based on the environment it’s in and based on what it needs to achieve in that environment.”

While the Worcester Tech team expects its device to be used primarily in emergency situations like natural disasters, the researchers believe the system has lessons for industry, particularly in designing interactions between humans and robots. Unlike most robots, this device seeks out physical contact with its surroundings, which can result in robotics better designed for interactions with humans, and improve the ability of workers and robots to collaborate.

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Lilly, CureVac Partner on RNA Cancer Drugs in $1.8B Deal

RNA illustration

RNA illustration (University College London, Flickr)

18 October 2017. Drug maker Eli Lilly and Company and biotechnology company CureVac AG agreed to develop a series of cancer immunotherapies based on CureVac’s messenger RNA technology. The deal, if completed in full, could bring CureVac, in Tübingen, Germany, as much as $1.8 billion.

CureVac’s technology adapts messenger RNA, nucleic acids related to DNA that leave the cell nucleus and go to cells’ protein-making components. Those cell components synthesize human proteins by reading and translating the genetic code in messenger RNA into the appropriate amino acids for that protein. The company’s platform is based on research by Ingmar Hoerr in the 1990s, one of CureVac’s founders, who discovered a way of controlling RNA that was previously considered too unstable for use as a treatment or vaccine.

For cancer immunotherapies, CureVac says its RNActive technology delivers messenger RNA molecules as a vaccine, encoded for antigens that stimulate immune responses to specific tumors. The target neoantigens — those not previously encountered by the immune system — take up the messenger RNA molecules, then depending on the type of cancer, stimulate a mix of T-cells that directly destroy cancer cells, or help along the immunotherapy process.

Much of CureVac’s pipeline is now devoted to cancer immunotherapies, addressing prostate cancer and non-small cell lung cancer. The non-small cell lung cancer therapies, in an early-stage clinical trial and preclinical studies, are already licensed to Boehringer Ingelheim, as reported by Science & Enterprise in September 2014. The prostate cancer therapy is in intermediate-stage trials.

Under the agreement, Lilly, based in Indianapolis, and CureVac will collaborate on development of up to 5 cancer vaccines based on RNActive. CureVac is responsible for design of the messenger RNA therapies, as well as formulation and manufacture of the products for clinical trials. Lilly will identify the 5 targets for development, and be responsible for their subsequent clinical stages and commercialization. CureVac retains the option of co-marketing the vaccines in Germany.

CureVac is receiving an immediate payment of $50 million, plus an equity investment from Lilly of €45 million ($53 million). If all 5 cancer immunotherapy products are realized by the partnership, CureVac could earn $1.7 billion in developmental and commercial milestones, as well as royalties on product sales.

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Phone App Screens for Postpartum Depression

Woman with smartphone

(kaboompics.com/Pexels)

18 October 2017. A new smartphone app helps detect depression among women who recently gave birth, and optionally gathers data for continued research on the disorder. The app, called the MGH Perinatal Depression Scale, or MGHPDS, is a creation of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, affiliated with Harvard Medical School.

Postpartum depression is a disorder that can affect women after child birth, characterized by feelings of extreme sadness, anxiety, and exhaustion. Symptoms can range from crying frequently or for no apparent reason and feelings irritability or restlessness, to anger and rage, and frequent headaches or other pains. While postpartum depression likely results from a number of physical and emotional causes, the quick drop in estrogen and progesterone hormones in the mother’s body leads to chemical changes that could trigger mood swings. Interrupted sleep patterns after giving birth can also contribute to exhaustion and depression in the mother.

In a March 2017 article in the publication Ob.Gyn.News, Center for Women’s Mental Health director Lee Cohen called postpartum depression, or PPD, “the most common complication in modern obstetrics,” yet with few women diagnosed with the condition receiving effective care. Cohen, also a professor of psychiatry at Harvard Medical School, cited a review of 32 studies of depression during pregnancy and after child birth which report an average of 14 percent with depression during pregnancy and 16 percent after giving birth. Yet, many of the women diagnosed with depression do not receive treatment, and relatively few — 5 percent during pregnancy and 3 percent after birth — end up well.

The Perinatal Depression Scale app — “perinatal” refers to the period during pregnancy and immediately after birth — seeks to screen more systematically for the disorder by taking advantage of smartphone technology. The app asks women age 18 to 45 during pregnancy and up to 12 weeks following birth to complete questionnaires about mood, anxiety, sleep and stress. Among the instruments in the app is the Edinburgh Postpartum Depression Scale, a 10-item scale used most often to screen for the disorder. But the app also asks about other symptoms associated with postpartum depression, such as sleep disturbance, anxiety, and perceived stress.

The app is free and downloaded from the iTunes App Store; only an iPhone version is available. Users of the app are asked to consent to sharing their responses to the questionnaires with researchers at Mass. General, to refine and better focus the data-gathering instruments. A second version of the app is in development and scheduled for release late next year.

“It is our hope,” says Cohen in a Mass. General statement, “that as screening for PPD becomes increasingly common across the U.S. and globally, easy-to-use tools like the MGHPDS, which can be readily used on smartphones and other digital devices, will lead to more accurate screening of perinatal mood and anxiety disorders and to improved clinical outcomes for patients.”

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Scientifically-Proven Ways to Make Your Employees Happier

– Contributed content –

18 October 2017. Making your employees happy is an important goal for any company. It’s a kind thing to do and makes your company more ethical, but it also encourages your employees to care more. If you want them to work better and harder, you need to make them care about their work. The problem is, how do you know what will really make them happy and which so-called solutions are just the latest trends that don’t really work. The answer is to turn to science, to find the things that are proven to make employees happier. You can look at business studies, as well as psychological theories and phenomena.

Journey-reward graphic

(Gerd Altmann, Pixabay)

Have clear expectations and rewards

Learning about human behavior is a great way to work out how to make your employees happy. One useful theory is the valence instrumentality-expectancy theory. It says that people behave according to expected outcomes or their value. In the workplace, you can think about this in terms of having clear expectations and rewards for your employees. They can feel a lot happier if they know what’s expected of them, and you know what they expect of you, and how they’re going to benefit when their task is completed. Consider setting out clear guidelines to clarify expectations and rewards.

Allow remote working

Remote working is becoming more and more popular now that it’s so easy to stay connected. According to a study in the Harvard Business Review, people working at home are not only happier, but they can be more productive too. A lot of bosses worry about letting people work at home, thinking that they’re allowing them to slack off. But remote staff can be productive because they’re given more control over their time. They have to take responsibility for their work, and they still need to meet deadlines and be available when they’re needed.

Hiring freelancers graphic

(Wikimedia Commons)

Consider flexible working

Work-life balance is extremely important to many people. A study by the Corporate Executive Board found that employees with a good work-life balance worked 21% harder than others. Apart from remote working, flexible schedules are also helpful to improve work-life balance. You can require employees to work a certain number of hours but be more flexible with when they can start and finish work. Or you could even say they can work whatever schedule they life, as long as they’re completing their work to a high standard.

Allow for career progression

If you want to make your employees happy long-term, you need to give them reasons to stick around. One of the biggest reasons for them to leave is that they feel they can’t go anywhere within your company. A study by Glassdoor found that for every additional 10 months that an employee can’t progress, they are 1% more likely to leave after finally getting promoted. While not everyone can keep moving up the ranks, creating a clear path for ambitious people to follow could make a big difference in employee retention.

Before you start buying your employees gym memberships or taking them on vacation, find the ways you can make them happier from day-to-day.

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First Trial of Alzheimer’s Drug Underway

Brain illustration

(DARPA.gov)

17 October 2017. The first clinical trial is underway of a therapy for stopping the progression of Alzheimer’s disease that purports to rebuild neural connections in the brain. The trial, sponsored by M3 Biotechnology Inc. in Seattle, is testing in humans for the first time its small-molecule drug code-named NDX-1017.

Alzheimer’s disease is a progressive neurodegenerative disease affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta peptides, as well as misfolded tangles of proteins inside brain cells known as tau. The Alzheimer’s Association says some 5.4 million individuals in the U.S. have the disorder, of which 5.2 million are age 65 or older. By 2050 that number is expected to increase to 16 million.

M3 Bio says NDX-1017 addresses receptors of proteins known as hepatocyte growth factors that stimulate growth of cells and tissue in several organs in the body. Among the functions provided by hepatocyte growth factors are self-repair of injured organs and protection against inflammation. In the case of NDX-1017, these properties are directed to the repair and protection of neurons, or nerve cells, in the brain.

The early-stage clinical trial is enrolling 92 individuals to test NDX-1017’s safety, tolerability, and chemical activity in the body. NDX-1017, given as injections under the skin, will be tested against a placebo among younger healthy adults, age 18 to 45, and older healthy individuals, age 60 to 75. The research team is testing single and multiple doses of the treatments at ascending levels, looking primarily for signs of adverse effects for up to 20 days. However, the team is also assessing concentrations of NDX-1017 in blood plasma over 48 hours and the length of time the drug remains in the blood.

M3 Bio began in 2013, while company co-founder and CEO Leen Kawas was a postdoctoral research associate in pharmacology and toxicology at Washington State University in Pullman. The company’s R&D is supported by grants from Alzheimer’s Drug Discovery Foundation and Dolby Family Ventures, as well as $12 million in equity raised in the company’s first venture funding round, according to the Seattle Times. Alzheimer’s Drug Discovery Foundation and Dolby Family Ventures, along with the W-Fund that supports tech start-ups in Washington State are also funding the clinical trial.

“Current drugs on the market for Alzheimer’s patients offer only symptomatic relief,” says Kawas in a company statement, “whereas we anticipate NDX-1017 will slow, halt and potentially restore lost function. The preclinical studies suggest we are on the right path, and we are excited to advance a much-needed brain regenerative therapy to alleviate the suffering of millions afflicted by the disease, and their families, around the world.”

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Univ. Spin-Off Reports Cancer Immunotherapy Advance

For-Robin lab

Kate Rittenhouse-Olson, left, with company scientist Diala Ghazal. (Douglas Levere, University at Buffalo)

17 October 2017. A highly targeted synthetic antibody, developed by a university spin-off enterprise, was shown to destroy human breast cancer cells grafted in lab mice. The findings reported by the company For-Robin Inc. in Williamsville, New York, appear in the September 2017 issue of the journal Neoplasia. For-Robin founder and president Kate Rittenhouse-Olson plans to discuss the findings next week at the BioNetwork Partnering Summit in Laguna Niguel, California.

For-Robin is developing immunotherapy treatments for breast cancer that address the Thomsen-Friedenreich glycoantigen, absent or masked by carbohydrates in normal tissue, but present in several human cancers, including breast, colon, bladder, and prostate. The company licensed research by Rittenhouse-Olson, then a University at Buffalo microbiologist, that led to creation of an antibody called JAA-F11, designed to bind on and stop the growth of human cancer cells with Thomsen-Friedenreich antigens on their surface.

In the paper, the researchers tested a humanized form of JAA-F11 antibody, engineered to prevent rejection by the immune system, in lab cultures and mice. The results show in lab cultures the humanized antibody kills cells from both breast and lung cancer tumors. In mice grafted with human breast tumors, the antibody stopped the growth of these tumors, both working alone and combined with maytansine, a cancer-killing compound. The authors report the antibody also prevented tumor cells from binding with blood vessel cells to help prevent spread of the cancer, and non-cancerous cells were unaffected by the treatments.

The researchers believe the JAA-F11 antibody both alone and configured as an antibody drug conjugate, designed to more precisely deliver chemotherapy drugs to reduce adverse effects of conventional chemotherapy, can treat multiple types of breast cancer. Among these variations is triple-negative breast cancer that expresses no estrogen, progesterone, or HER2 receptors used as targets for other breast cancer treatments.

Rittenhouse-Olson recently left her professorship in microbiology to devote full time to For-Robin Inc. The company is more than a commercial venture to Rittenhouse-Olson. The enterprise is named for her sister Robin that died of breast cancer at age 31. As reported by Science & Enterprise in May 2015, the company received a $2 million Small Business Technology Transfer grant from National Cancer Institute for preclinical development of the JAA-F11 antibody.

“What we are focused on now,” says Rittenhouse-Olson in a university statement, “is fundraising and preparing for human clinical trials, which will include scaling up production of our antibody under controlled conditions that meet the requirements of the U.S. Food and Drug Administration.”

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Online Game Harnessed to Combat Foodborne Toxins

Maize with aflatoxin

Maize with aflatoxin molds (National Institute of Environmental Health Sciences)

16 October 2017. A consortium of companies and university labs is recruiting participants in an online computer game to design synthetic proteins to neutralize a toxin that contaminates food crops. The project aims to design a protein that degrades aflatoxins, a naturally occurring poison that affects food stocks, particularly in the developing world, and known to cause liver cancer.

Aflatoxins are molds produced by fungi, which are generally eliminated early in the supply chain by regulatory authorities in the developed world, but in limited resource areas can poison food stocks, including basic staples like maize and nuts. The molds are highly toxic to animals and humans, and as a result can be passed along to humans by livestock eating contaminated feed. University of California in Davis, one of the participants in the initiative, cites data that show aflatoxins cause some 90,000 cases of liver cancer a year, along with stunted growth and immune system disorders.

The initiative is recruiting participants in FoldIt, an online protein folding game, to design a synthetic protein that best degrades and neutralizes aflatoxins. FoldIt is a game platform where individuals compete to assemble amino acid building blocks into complex proteins. Participants design their amino acid assemblies into chains, with folds in the chains made to achieve specific shapes that in turn achieve specific purposes. FoldIt games are sometimes used, as in this case, to crowdsource solutions for protein folding problems, with imagination and problem-solving ability as important as scientific knowledge to craft a solution.

In addition to UC-Davis, participants in the project include Northeastern University in Boston and University of Washington in Seattle that developed the FoldIt platform. Also taking part are the Partnership for Aflatoxin Control in Africa, food products company Mars Inc., and life science devices and products company Thermo Fisher Scientific.

Participants in the FoldIt game will be given an enzyme with the potential to neutralize aflatoxins by degrading a key protein structure called a lactone ring. In its current state, however, the enzyme is ineffective. FoldIt participants are asked to restructure the enzyme to interact with aflatoxin molecules to degrade the lactone ring, and thus reduce the molecules’ toxicity.

“While aflatoxin has been a known issue for decades,” says UC-Davis biochemist Justin Siegel in a university statement, “advances in computation and biotechnology, coupled with the imagination of players from around the world, may finally result in a solution to this pressing problem.” Siegel adds that, “No single organization can tackle a problem this large, but the uncommon collaboration between the groups coming together here will enable us to not only discover a potential solution, but translate it in a way that has real impact.”

The first round of the Aflatoxin Challenge is now underway, with feedback provided as the puzzles become more complex. Siegel’s lab, supported by Mars Inc. will review the entries to find the most promising designs. Thermo Fisher Scientific is providing its gene synthesis services to encode the top designs. All FoldIt player designs will be available in the public domain, and will not be submitted for intellectual property protection.

Siegel tells more about the initiative in this audio interview with Scientific American.

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Roche, Biotech to Discover New Antibiotics

Klebsiella pneumonia bacteria

Klebsiella pneumonia bacteria (CDC.gov)

16 October 2017. A biotechnology company that discovers new drugs through detailed genomic analysis is partnering with drug maker Roche to find new treatments for bacterial infections that resist current antibiotics. The collaboration with Roche is expected to bring Warp Drive Bio in Cambridge, Massachusetts as much as $387 million over the course of the agreement.

Warp Drive Bio is a five year-old company discovering new drugs that address disease-causing proteins considered too difficult to treat with conventional small-molecule drugs or biologic therapies alone. These protein targets, says the company, are either inside cells making them inaccessible to biologics, or do not have particular features needed to bind with small molecule drugs.

Among Warp Drive Bio’s tools is a technique it calls genome mining that searches for molecular targets inside microbes hidden to conventional lab analytical methods. The company says it compiled a database of 4 million gene clusters derived from 135,000 microbial strains, queried by its own search engine to reveal targets expressed by these genomic signatures. These new targets, says the company, make it possible to develop synthetic molecules with new mechanisms for attacking bacteria. Warp Drive Bio says it is evaluating more than 100 previously undiscovered classes of antibiotic candidates not yet analyzed for their potential impact on human health.

Roche identifies new treatments for antibiotic resistance as one of its core research objectives. The agreement gives Roche an exclusive, worldwide license to develop and commercialize undisclosed classes of new antibiotics identified by Warp Drive Bio through its genomic mining techniques. The collaboration is specifically going after gram-negative drug-resistant bacteria. “Gram” refers to a classification for bacteria where the microbes either retain (gram-positive) or shed (gram-negative) a test stain on their protective cell coatings.

Centers for Disease Control and Prevention says each year some 2 million people in the U.S. develop infections resistant to antibiotics, resulting in at least 23,000 deaths. Gram-negative bacteria are resistant to multiple drugs and are increasingly resistant to most available antibiotics, says CDC. These bacteria have built-in abilities to find new ways to be resistant and can pass along genetic materials that allow other bacteria to become drug-resistant as well. Gram-negative infections include those caused by Klebsiella, Acinetobacter, Pseudomonas aeruginosa, and E. coli bacteria.

Warp Drive Bio is receiving an initial payment of $87 million covering option fees and preclinical research. The company is also eligible for up to $300 million in future development, regulatory, and sales milestones of products that result from the collaboration, as well as royalties on sales of those products. Warp Drive Bio, however, will retain the rights to other classes of antibiotics discovered in the project, but not developed by Roche.

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Flashback: Drug Pricing Reform Even Big Pharma Might Like

Science & Enterprise is taking a break From 2 to 13 October. Until then, we will re-run some of our recent special reports. Our regular posts will return on 16 October.

Pills and dollar bill

(TBIT/Pixabay)

2 May 2016. At a press event in Washington, D.C. last week, Representative Lloyd Doggett of Texas, a champion of lower prescription drug prices, took aim at drug companies and their business practices. “An unaffordable drug is 100 percent ineffective,” Doggett told an audience at Center for American Progress on 26 April. He noted that 9 out of 10 drug makers spend more on marketing than R&D, with Americans spending 12 times more on drugs than people in Ireland, where some American drug companies are trying to escape for lower corporate tax rates.

Doggett, a senior Democrat on the House Ways and Means Committee, was keynote speaker at a panel discussion of a report from Center for American Progress, a progressive think tank in Washington, D.C. Like Doggett, CAP’s report — titled Enough is Enough — called for action by Congress and the executive branch to bring more transparency to drug pricing, and to create pricing models based more on value to the patient than maximizing revenues to the drug companies. The federal government, said CAP’s report and a panel of experts to discuss its findings, can play a larger role in bringing down drug prices, from exercising its buying power through Medicare and Medicaid, as well as leveraging its support for basic life sciences research.

The pharmaceutical industry in the U.S. has a long track record of successfully heading off actions by governments, either by cutting advantageous deals or through lobbying. But calls for doing something meaningful about escalating drug prices are getting louder and angrier, with the industry now left largely alone to fight its legislative battles. And new technologies could make the industries current economic model as outmoded as Life magazine and the Sears catalog.

High prices causing unfilled prescriptions

The panel, chaired by Ezekiel Emanuel, vice-provost at University of Pennsylvania and long-time proponent of health care reform, included Marilyn Tavenner, CEO of America’s Health Insurance Plans, Debra Whitman, chief public policy officer at AARP, and Joshua Ofman, vice-president for for global value, access, and policy at biopharmaceutical company Amgen. Tavenner joined the health insurance industry group in July 2015 after serving in 2013-14 as Administrator of Centers for Medicare and Medicaid Services, in the U.S. Department of Health and Human Services.

The entire panel, including Amgen’s Ofman, the sole industry representative, agreed high drug prices were a problem and cause for concern. Whitman cited recent surveys by AARP of Americans age 50 and over showing more and more difficulty paying for prescription drugs, including 1 in 3 respondents who did not fill a prescription mainly because of its cost. In addition, three-quarters (76%) of American seniors want government to do more to bring down drug prices, about the same percentage of Americans overall cited in CAP’s report that say drug prices are too high.

The panel discussed several proposals in the CAP report and elsewhere to bring more transparency to drug prices, employ comparative effectiveness research to assess the relative value of different treatments, encourage bulk-sale negotiations with government and large insurers, apply success-based outcome models to justify higher prices for drugs, and limit out-of-pocket cost-sharing in health insurance plans. Other ideas included limits on patent lifetimes and bans on pay-for-delay schemes where drug companies pay makers of generic drugs to delay issuing substitutes with lower prices.

Liberal policy wonks at think tanks aren’t the only people pushing these proposals. Many of these same ideas were expressed in an article signed by 118 cancer specialists in July 2015 in the journal Mayo Clinic Proceedings, and in March 2016 by the American College of Physicians in an article in Annals in Internal Medicine. These statements suggest large segments of the physician community aren’t buying the industry’s arguments.

Amgen’s Ofman pushed back on many of these proposals, noting that the costs for developing new drugs are high because the nature of disease is difficult and complex, with Amgen itself spending $4 billion a year on R&D. Thus measuring the value of drugs is also difficult and complex, particularly when bringing in the needs of special populations, like the disabled or children. Applying a single value formula to drug prices, said Ofman, becomes in effect a cost-control, which would have serious market repercussions.

In addition, Ofman pointed out negotiations by insurance plans can bring down costs for some customers, but hospitals still charge full price for non-insured patients. Moreover, Ofman argued, value should be calculated over the drug’s lifetime, including its generic period. Ofman’s arguments resulted in the other panel members accepting, at least in principle, that the issue does not lend itself to easy answers.

Continue reading Flashback: Drug Pricing Reform Even Big Pharma Might Like

Taking a Break

Airliner taking off

(Matthew Grapengieser, Flickr)

2 October 2017. Science & Enterprise is taking a two-week break. During this time, we will repost stories with our special reporting in recent months. Our regular reporting will resume on Monday, 16 October.

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