Harnessing nature to beat cancer

first_imgEvery year, more than 18 million people around the world are told, “You have cancer.” In the U.S., nearly half of all men and more than one-third of women will develop some kind of cancer during their lifetimes, and 600,000-plus die from it annually. Despite the billions of dollars and countless new treatments that have been thrown at it since President Richard M. Nixon declared “war” on the disease in 1971, cancer refuses to be beaten.Why does it remain such a formidable foe? After all, it’s been known since Nixon’s day that unrepaired genetic damage can cause cells to grow uncontrollably, which is viewed as cancer’s root cause. But this understanding has not pointed the way to an obvious treatment. Research into cancer biology has revealed it to be one of the most complex and insidious human diseases for a variety of reasons.Lung cancer cells (red) invading human lung tissue (blue). Credit: Wyss Institute at Harvard UniversityFirst, cancer can be caused by any number of factors, from viral infections to exposure to carcinogenic chemicals to simple bad genetic luck. One patient’s lung cancer might be caused by an entirely different constellation of mutations than another’s, and a drug that targets a certain mutational profile benefits only a subset of patients. Furthermore, cancer cells often spontaneously develop new mutations, limiting the effectiveness of genetically targeted drugs.Second, cancer is caused by malfunction of the body’s own cells, so it is hard to design drugs that will target only cancerous cells while sparing healthy ones.Third, while genetic mutations can drive cancer formation, cancers can stop growing and remain dormant for years, suggesting that there are more factors at play than gene mutation alone.And finally, cancer has a number of different “tricks” that allow it to hide from the body’s highly vigilant immune system, letting it grow undetected and unchecked until, often, it is too late.Cancer treatment regimens through the 19th and 20th centuries were largely limited to an aggressive triumvirate of surgery, radiation, and chemotherapy, all of which carry traumatic side effects and can bring patients to the brink of death in the name of saving their lives. As our knowledge of the disease has grown more nuanced over the decades, a paradigm shift has happened in the field, centered on the recognition that attacking a complex disease with blunt tools is not the most effective approach. A surge of new therapeutic strategies — including immunotherapy, nanotechnology, and personalized medicine — is giving hope to patients for whom traditional treatments have failed and offering the potential of long-lasting cures.Scientists at the Wyss Institute for Biologically Inspired Engineering with expertise in fields ranging from molecular cell biology and immunology to materials science, chemical engineering, mechanobiology, and DNA origami are at the forefront of several of these novel approaches. Their research, united by the common principle of emulating nature, has the potential to make existing treatments better, create new ones, and even prevent cancer from starting in the first place.Better drug delivery is in our bloodChemotherapy has been the backbone of cancer treatment for the past half-century, because it infuses drugs into the bloodstream to kill rapidly dividing cancer cells all through the body. However, since chemotherapy systemically targets all fast-growing cells, it can also damage the intestines, bone marrow, skin, hair, and other parts of the body, and in some cases must be given at such a high dose that it nearly kills the patient in the course of treatment. Efforts to make chemotherapy drugs less toxic have included encapsulating them in nanoparticles that release them only when they reach their intended location, but less than 1 percent of nanoparticle-encapsulated drugs actually reach their targets, as the human liver and spleen aggressively filter them out of the blood. “If we can deliver a chemical signal to monocytes via a nanoparticle backpack that keeps them in the ‘on’ state after they differentiate into macrophages, they could be much more effective at attacking a tumor rather than becoming part of it.” — Samir Mitragotri Samir Mitragotri, a core faculty member at the Wyss Institute, decided to apply chemical engineering to the problem of keeping drugs in the bloodstream long enough to do their jobs. The first thing he faced was that red and white blood cells circulate through the blood several times a day, seemingly escaping detection and destruction by the liver and spleen.“I thought, ‘If these cells are naturally not cleared from the bloodstream, maybe we can use them to help the nanoparticles stay there as well, rather than creating some new and expensive disguise to protect the nanoparticles,’” said Mitragotri, the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).Mitragotri’s lab found that nanoparticles attached to red blood cells are indeed ignored by the liver and spleen in mice, and the nanoparticles are sheared off and deposited into tissues when the blood cells make the particularly tight squeeze through the tiny capillaries that deliver blood to organs. By injecting blood-cell-bound nanoparticles into a blood vessel directly upstream of whole human lungs, the researchers were able to get 41 percent of them to accumulate in the lung tissue — a far cry above the usual 1 percent.“Simply by changing which blood vessel we inject the nanoparticles into, we can deliver a much higher dose of a drug to its intended organ, and rely on the body’s natural clearing mechanism to get rid of any particles that don’t reach the target. We can even get some nanoparticles to target the brain,” Mitragotri said.Despite its bad reputation, chemotherapy is unlikely to be going anywhere soon, as research has found that new therapies work best when given in combination with chemotherapy. But technologies such as blood-cell-bound nanoparticles could help reduce the dose that must be administered and increase chemotherapy’s efficacy, improving the quality of life for cancer patients worldwide.,Mitragotri has also found success applying this nanoparticle “backpack” strategy to white blood cells called monocytes, which differentiate into immune cells called macrophages that fight diseases including cancer. Not only are monocytes able to carry their nanoparticle drug loads with them as they infiltrate tissues (which could help deliver drugs to tumors deep inside organs), but the nanoparticles could one day be used to control the monocytes themselves.“One of the sneaky things tumors can do is turn macrophages off in a similar way that they turn other immune cells off, such that up to half of a tumor can be made of dormant macrophages,” Mitragotri explained. “If we can deliver a chemical signal to monocytes via a nanoparticle backpack that keeps them in the ‘on’ state after they differentiate into macrophages, they could be much more effective at attacking a tumor rather than becoming part of it.”Creating a safe space for immune cellsBy exploring how controlling immune cells might help kill cancer, Mitragotri is dipping his toes into the burgeoning immuno-oncology movement, which reasons that modifying a patient’s immune system (which is already designed to hunt down and kill malfunctioning cells) so it can overcome cancer’s evasive tactics is better than trying to design a novel drug for every kind of known cancer. The FDA has approved a number of immunotherapy approaches in recent years, including “checkpoint inhibitor” drugs that take the brakes off immune cells that have been inactivated by cancer cells, and T-cell therapies, which involve removing a patient’s T cells, engineering them to attack the cancer, multiplying them, and infusing them back into the body.A newer tactic, cancer vaccines, attempts to modify a patient’s immune system from within so that it not only attacks existing tumors, but also creates an immune “memory” to destroy future cancerous growths. However, engineering that process to take place completely within the body has proven to be a challenge. The only cancer vaccine the FDA has approved so far was Provenge, in 2010. It was a commercial failure due to its hefty $93,000 price tag and complicated, days-long treatment process that required multiple infusions.But one person was enthralled rather than disappointed by Provenge’s public failure: David Mooney, a founding core faculty member of the Wyss and the Robert P. Pinkas Family Professor of Bioengineering at SEAS. “My lab has had a longstanding interest in cell-based therapies for diseases like cancer. We thought the concept of training the body’s own immune system to fight cancer was really beautiful, but we wondered if there was a way we could simplify it by moving that whole process into the body instead of doing parts of it in a lab, like Provenge required.”The body has a natural training ground in the form of its lymph nodes, which harbor immune cells called dendritic cells that become activated and initiate an immune response when they detect evidence of an invading pathogen from the lymph vessels. Cancer cells, however, secrete immunosuppressive signals that can disrupt this process. A materials scientist and chemical engineer by training, Mooney realized that if he could construct and implant an artificial lymph node made from a material that was distinct from the rest of the body (and therefore protected from cancer’s influence), it might provide a safe haven in which to activate dendritic cells, which would then unleash the immune system’s attack on the cancer.His lab has done just that, creating a cancer vaccine in the form of a spongy disk about the size of an aspirin tablet that is implanted into a patient and biodegrades once it has done its work. Essentially an artificial lymph node, the vaccine contains signals that attract dendritic cells and activate them with proteins found on the patient’s tumor cells. The activated dendritic cells then travel to the closest lymph node, where they train other types of immune cells to recognize and destroy the tumor. This may provide the additional benefit of protecting against recurrences of the cancer — even in another location — since the trained T-cells can proliferate and circulate through the body looking for the same kind of tumor cells to attack and destroy.,Dramatic responses in cancerous mice that received the vaccine spurred Mooney and his collaborators at the Dana-Farber Cancer Institute (DFCI) to start a phase 1 clinical trial with support from both institutes, to see if it had the same effect in human patients. This kind of study is usually undertaken by hospitals and pharmaceutical companies, but rarely inside academia. In traditional pharmaceutical and biotech environments the process of getting such an innovation into clinical trials usually takes six or seven years, in this case the vaccine was tested in its first patient just three years after initial publication of its development. The results attracted the attention of the drug giant Novartis, which licensed the technology from the Wyss Institute in 2018 and took the reins for future clinical trials, with plans to develop the concept into a treatment for multiple kinds of cancer.“The Wyss Institute was just starting, and we knew we wanted to focus on translating discoveries from the lab to the clinic,” said Mooney. “So we saw the cancer vaccine not only as a treatment with real potential to help lots of patients, but also as an opportunity to create a path for moving novel therapies out of academia and into the real world faster. There is no way I could have run a clinical trial out of my laboratory, so being able to build a team inside the Wyss to do the experiments and manufacturing needed for the FDA application, and partnering with DFCI to organize and run the clinical trial, was really what allowed us to get to the point where we’re implanting the vaccines in cancer patients so quickly.”One such patient, profiled in a recent Boston Globe article, remains cancer-free nearly two years after being vaccinated for advanced melanoma. But Mooney is not content to rest on his laurels. “Cancer is a complex disease, and it’s unlikely there will be a single answer for all people and all kinds of cancer, so we need to keep exploring different approaches,” he said.One of these approaches is a partnership with another Wyss faculty member, William Shih, who has long been interested in how his research on DNA molecules that self-assemble into defined 3-D structures — also known as DNA origami — can improve the precision with which cancer therapy is delivered. Shih and Mooney are working on a joint project to see if DNA origami–based nanostructures can be incorporated into the cancer vaccine to enhance its ability to create a sustained immune response.“When dendritic cells are activated, either in a lymph node or in the cancer vaccine, they have a decision to make: Do they initiate an antibody response, where antibodies are produced that bind to a specific pathogen and mark [the cancer cells] for destruction, or do they initiate a T-cell response, where they send T cells to destroy the pathogen directly?” explained Shih, a professor of biological chemistry and molecular pharmacology at DFCI and Harvard Medical School (HMS). “We want to nudge them toward the T-cell response, because it’s a more effective way to kill cancer cells.”Shih’s DNA origami nanostructures take advantage of the fact that DNA is a very stable and predictable compound thanks to the strong bonds between its four chemical bases. By constructing strands of DNA whose sequences of bases along their length are precisely known, Shih and his lab have been able to design 3-D DNA structures that effectively build themselves like automated Lego blocks, and whose properties can be tuned down to the nanoscale.For the cancer vaccine, Shih’s lab has designed a DNA “cask” structure that presents a densely packed, precisely arranged display of ligands, or molecules that bind to other molecules, which are usually found on pathogens like bacteria or viruses and are recognized by the body’s immune system as foreign. These ligands essentially produce a danger signal recognized by dendritic cells, and can make them choose to initiate a T-cell immune response more often than an antibody response. “Our initial data suggest that the precise patterning of ligands we’re able to achieve with DNA origami make a big difference in activating the dendritic cells the way we want them to be activated,” Shih said. “We have this miracle [vaccine]. Let’s make it better.”A Neighborhood Watch for cancerImmunology is all the rage for treating cancers after they occur, but every cancer arises from what was once a normal cell. What if we could tease out exactly what promotes the development of cancer and find a way to reduce the chances it will form in the first place? That’s a tall order, as hundreds of substances are known to cause cancer, hundreds more are suspected but unproven carcinogens, and other factors such as lifestyle and genetics all conspire to damage our DNA.But some causes play an outsized role in cancer’s development, such as chronic inflammation, which is associated with nearly 25 percent of all human cancers. Research being undertaken by the Wyss Institute’s founding director, Donald Ingber is now investigating the possibility of treating the inflammation of the connective tissue and blood vessels that surround and support organs (known collectively as the stroma) rather than directly attacking tumors themselves.Healthy lung tissue (red) surrounds cells that express markers typically found on both cancerous and healthy cells (green and yellow) in a Lung Cancer Chip, indicating that the relationship between normal and cancerous cells is more complex than originally thought. Credit: Wyss Institute at Harvard University“Understanding how stromal tissues can influence the development of cancer has intrigued me personally since the time I was a graduate student,” said Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital and a professor of bioengineering at SEAS. “We and others have shown that changes in the physical structure and composition of the stroma can promote cancer formation and, conversely, that putting cancerous cells into a healthy stromal environment can suppress tumor growth, suggesting that targeting the tumor microenvironment could lead to new cancer-reversal therapies.”Ingber is part of a global research team tackling this problem from multiple angles as part of Cancer Research UK’s Grand Challenge, a competition it won earlier this year. Key to the project is Ingber’s organ chip technology, which allows researchers to carry out human organ–level experimentation in vitro. Each organ chip is a microfluidic culture device containing hollow microchannels that can be lined with living human epithelial and stromal cells, which experience physical conditions similar to those found in the body, including blood flow, breathing motions in the lung, peristalsis in the intestine, and so forth. The Wyss Institute has created organ chips that faithfully mimic the lung, kidney, intestine, bone marrow, brain, and more, allowing researchers to grow tumor cells within the natural microenvironments found in the body and then test treatments without exposing animals or patients to potentially harmful conditions.“Our organ chips have shown us time and time again that in order for organ cells to function normally, they have to be provided with the right microenvironment,” said Ingber. “For this project, we will build models of different stages of cancer progression using cells isolated from human patients to understand how interactions between stromal cells and organ-lining cells change as inflammation-associated cancers form, as well as develop new ways to combat this response.”By combining organ chips with bioinformatics and machine-learning approaches, the team hopes to identify new stromal-targeted treatments that can restore inflamed tissue to its healthy form, thereby preventing cancer progression, or induce cancerous or precancerous tissues to revert to a more normal state. By studying human cancer progression in vitro, the team also hopes to discover new diagnostics that can be used to identify the small subset of patients with inflammation-associated premalignant conditions, such as Barrett’s esophagus or ulcerative colitis, that might progress to cancer.“Treating cancer is ultimately going to need to be a multifaceted approach, because the disease itself is so multifaceted,” Ingber said. “The Wyss Institute was founded on the basis of bringing people together from different disciplines to tackle big problems in medicine through communication and collaboration among experts with a broad range of different perspectives. Doing that within the Wyss Institute has led to advances like organ chips, and doing that at a larger scale, such as with the Grand Challenge, allows whole institutions to put their resources together and drive real change for millions of patients living with devastating diseases like cancer worldwide.”Whether targeting blood cells, the immune system, or stromal tissue, all of these projects are guided by the principle of using existing biological elements as the basis for new therapies, rather than trying to invent new cures from scratch.“The human body is a marvel of biological engineering that has been tuned over millions of years to be able to fight off threats and heal itself,” said Ingber. “When we can recognize its inherent abilities and work with them rather than against them, we are taking full advantage of all the experimentation that evolution has already done for us. We believe this type of interdisciplinary, bio-inspired approach can help create more new treatments for cancer and other complicated diseases much more effectively than traditional drug development strategies.”last_img read more

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Tort and lobbying issues make noise but little changes

first_img June 15, 2005 Senior Editor Regular News Tort and lobbying issues make noise but little changes Tort and lobbying issues make noise but little changes Expect bills on both topics to be introduced next year Gary Blankenship Senior Editor Two issues with potentially wide-ranging effects on many Florida Bar members were high profile battles in the legislature this year, but when the dust had settled, not much had changed.But those involved in the disputes over lobbying disclosure legislation and attempts to change tort laws say both are likely to be back before lawmakers in their 2006 Regular Session.The Florida Bar, which is restricted on the legislative actions it can take, did not take lobbying positions on either issue. But many lawyers closely watched the tort and lobbying conflicts as they could affect many practices around the state.Many observers also saw the issues as linked, with Senate President Tom Lee, R-Brandon, championing more disclosure for lobbyists and House Speaker Allan Bense, R-Panama City, favoring more protections for businesses in defending tort actions. And because of the failure of the upper and lower chambers to agree, the lobbying bill and the bills making the most serious tort changes died on the last day of the session.Rep. Dudley Goodlette, R-Naples, isn’t so sure there was such a solid connection.“The fact of the matter is the House in any event did pass a bill that dealt with the subject matter of lobbying reform, but did not go as far as the Senate president wanted to go [in the bill originally passed by the upper chamber and sent to the House],” he said. “Therefore, the Senate did not take it up and pass it.”Tort reform, on the other hand, was a hodge-podge of priorities of the House leadership and individual bills by House members.“I think that the speaker of the House is a businessman and the members of the House are free to file six bills,” Goodlette said. “Many of the members of the House had an interest in tort reform or litigation reform measures.”Bills requiring more medical proof of injury before filing, such as asbestos claims and giving electric utilities greater protection when streetlights fail, which were Bense’s priorities, did pass, he said, while another bill giving business owners greater protections from suits by victims of crimes committed on their property, also the speaker’s priority, failed, as did many other member-sponsored bills. Lobbying The lobbying bill proved to be a contest of the public’s right to know versus traditional privacy privileges. And it was particularly ticklish for lawyer/lobbyists.“I think it would have been important for the press and public to see what the real impact of money in that political process is,” said Ben Wilcox, head of the Florida Chapter of Common Cause, and a supporter of Lee’s lobbying proposals. “We’re not really getting an accurate picture with what is required now for lobbyist disclosure.”Wlicox noted there were some criticisms that the Senate bill could cause problems, including some claims that if one lawyer in a firm did lobbying, then every attorney in that firm could be forced to reveal what clients paid, even for lawyers who did no lobbying and for clients who hired the firm for nonlobbying work.“I realize that in the first draft of the bill, that scenario was raised as a potential problem,” Wilcox said. “I believe that problem could be dealt with; I saw it more as a red herring.“I’m hoping that Sen. Lee will come back and take another shot at it. Maybe we can have a dialogue with lobbyists who were open to the changes. Maybe we can come forward with some compromise legislation that will move the state forward and be comparable to what other states require.”Tallahassee attorney and lobbyist Wade Hopping said it wasn’t so much that he objected to having to report more information to the state on his lobbying activities, but that he thought much of the information that would have been required by the Senate was either confusing, impractical, or useless.“I wish there were more give-and-take on the mechanics,” he said. “I respect the right of the legislature to fix the policies, but many, many times, on many pieces of legislation, it’s not what the legislature wants to do, but how they do it. I would hope there would be more dialogue on how to do it.”Hopping said problems he saw included that reporting periods were changed, and the annual regular sessions would be split into two separate reporting periods. That would make it difficult to compile the information lawmakers said they were trying to make more available to the public, he said.There was also a lack of clarity about determining what was important information. Hopping said sometimes his and other firms are hired to do both legal and lobbying work for a client, and determining where the line falls can be done, but it might waste time and resources.Likewise there may not be a direct relationship between what a client pays and what a lawyer-lobbyist earns, Hopping said. At his firm, his compensation comes from a pool into which all of the firm’s fees go and from which are paid its expenses and overhead. Thus, a lobbying client paying a hefty fee to the firm for Hopping’s services might have little if any direct impact on Hopping’s final compensation. He noted that only five of the 37 attorneys at his firm do significant lobbying, although a few others are registered but primarily provide expert testimony at legislative hearings.“How much does the public have a right to know and what form should that be so it’s useful in making decision?,” Hopping asked. “The other part is what do they have a right to know about my compensation?”Among the differences between the House and Senate final versions of the lobbying bill were:• The Senate would require lobbyists to report individual expenditures for food and beverages and for whom the expenditure was made; the House deleted that provision.• The Senate would require reporting all contributions to a political party, which in turn could be forwarded to a legislator as an indirect gift. The House deleted that provision.• The House required reporting only categories of income by lobbyists unless the dollar compensation exceeded $150,000 per semiannual reporting period. The Senate required exact dollar reporting of a lobbyist’s compensation from an employer if the total compensation exceeded $45,000 in a quarterly reporting period.• The Senate would have the auditor general audit 3 percent of all lobbying firms annually, while the House version did away with the auditing requirement.• The House would require semiannual reporting, while the Senate would mandate quarterly reporting.• The Senate would require a lobbyist submitting a report to certify it is complete and accurate, while the House would require certification that it is complete and accurate to the best of the filer’s knowledge. Tort Bills Alexander Clem, president of the Academy of Florida Trial Lawyers, said the deluge of tort bills — most of which did not pass — came from both legislative leaders and a variety of business interests. He speculated those interest groups are rushing to push business-friendly tort bills before the 2006 elections, and while the House, Senate, and governor’s mansion are all controlled by Republicans. Clem argued that more laws aren’t needed.“The state of Florida and its citizens have been tort-reformed to death over the past 10 years,” he said. “There has not been any demonstrable need for any further restrictions or elimination of the people’s constitutional right to pursue redress when they’ve suffered catastrophic injuries.”But George Meros, who has lobbied on tort issues for years, said the legislature is slowly “making common sense reforms” and restoring fairness to the tort arena. He says more needs to be done.“There remains areas of inequity in Florida law that other states have reformed and it is high time we reformed,” Meros said. “Joint and several liability needs to be fully repealed, and the other areas that were at issue in this session I’m sure will be discussed and at issue next year.”Meros said “significant progress” was made this year in the areas of class actions, slip and fall, and product liability matters — all of which will be revisited next year.Of the bills that did pass, one gives power companies more protection from suits related to streetlight failures. Those companies will now have 60 days after they are notified to fix such a problem before they would be liable for damages, Clem said.Likewise, another bill gives asbestos companies greater protection, by requiring those exposed to asbestos show an injury before being allowed to file suit, Meros said.“What this bill will do is require a screening to show actual physical injury,” Meros said, adding those exposed to asbestos who do not show physical impairment now, but show physical impairment in the future, will still be able to sue and the statutes of limitations will be tolled until evidence of impairment is detected.Another bill that didn’t pass would have given business property owners greater protections from lawsuits from victims of crime committed on their properties. Clem said a major sticking point was business owners wanted the criminal listed as a defendant on the jury verdict form, but lawmakers failed to go along with that provision. Meros said the holdup was due to a misunderstanding that the bill would have immunized property owners or that it somehow would have a negative impact on crime prevention.Bills aimed at restricting lawsuits based on product liability and class actions claims also failed, in part, Clem said, because the agriculture industry and others realized they would have to pursue such claims in federal court, making those actions more expensive and time-consuming.Other failed bills would have given radiologists more protection from lawsuits, limited damages for teaching hospitals, and given nursing homes some protections if they guaranteed a certain minimum liability standard.Clem said the academy also saw as part of the tort battles legislation to implement amendments 7 and 8 approved by voters last November. The former gives patients and potential patients more access to adverse incident reports and other medical records, while the latter requires removing the license of any doctor found to have committed three acts of malpractice. The legislation to carry out those amendments “gutted” their intent, Clem said, adding, “Our expectation is we do go to court to reinstate amendments 7 and 8.”“Florida lawyers ought to look at the reality of it rather than the spin,” Meros said. “Look at it from the perspective of do the reforms make good common sense, are they fair. And, if so, we as lawyers should always advance the social interest of making our laws fairer and more predictable to the common person, regardless of whether we are financially impacted by it.”last_img read more

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HTML5 Does Have A Mobile Future: Mozilla’s Chris Heilmann Goes Mythbusting

first_img2012 may well be remembered as the year when application developers turned against HTML5. Which will be ironic, as HTML5 has evolved more in 2012 than in any other year since it became a reality. But with companies like Facebook dropping HTML5 in favor of native mobile apps, the hype cycle around the standard has turned. Some developers have become disappointed and disillusioned with HTML5. They have come to believe the myths that HTML5 may be, ultimately, untenable.Chris Heilmann, principle developer evangelist at Mozilla, aims to bust some of the negative myths that have cropped up around HTML5. In a recent blog post, Heilmann gives an impassioned and pragmatic breakdown of the so-called myths surrounding HTML5. He touches on contentious issues of performance, monetization, developer tools and debugging, offline use and capabilities. For the most part, Heilmann’s argument is not wrong. His crux is that HTML5 is of the Web and for the Web – and that the Web is everywhere. He leans heavily on the “write once, run everywhere” principle and the problems of “native” apps that are optimized to perform and monetize through a closed application-store model. The HTML5 vs. Native app argument isn’t new of course, but Heilmann effectively counters many of today’s most popular misconceptions around HTML5 – discoverability, user experience, performance and monetary viability for developers.This isn’t an academic argument. In the long run, the emergence and evolution of HTML5 affects where mobile users get their mobile apps and the perception of how they perform. For the most part, users do not care how their apps were built, as long as they work. But how developers view these choices can change the course of how apps are made, where consumers find them and the tools that app creators choose to use for building for mobile devices. MonetizationPundits like to say that HTML5 app developers are not able to monetize their apps. Heilmann, correctly, disproves this as a general theory. “Saying that HTML5 has no monetization model is like saying the Web can not be monetized (which is especially ironic when this is written on news sites that show ads),” Heilmann wrote. There is a nasty little secret hidden here that applies to all app developers, mobile or otherwise: Most apps make no money. For every runaway success (Angry Birds et al.) there are probably a thousand apps that languish with few users and/or no hope of making money. Between iOS, Android, Windows Phone and BlackBerry, there are approximately 1,580,000 (or so) apps – and 80% of them make next to nothing. Only the top 10% considered successful. The Web is a similar landscape. For every Google, there are companies like Microsoft that lose millions every quarter on their online properties. The concept is not that HTML5 cannot be monetized, but rather that it is very difficult to make big money in mobile in general.Performance & CapabilitiesHeilmann contends that HTML5 can perform just as well as native apps, except that closed mobile operating systems do not allow hardware acceleration and integration through the browser to outside apps. This is true – and one reason that Facebook decided to turn away from HTML5.Fundamentally, the concept of “write once, run everywhere” is easy to achieve in HTML5. It is more difficult to achieve, “write once, perform well everywhere.” HTML5 apps for Web and mobile are often targeted towards a specific platform, such as a certain browser. When those apps are not running on that browser, the performance suffers.The problem is not a matter of whether or not the HTML5 app can perform, but rather that of user experience. Facebook’s HTML5-first vision for mobile meant that the core of its app was built around its mobile m.facebook.com site and then “wrapped” for native stores such as iOS and Android. Many users complained that the Facebook mobile application was nearly unusable on some smartphones, especially for Android users on older devices. Mozilla shows off WebAPIs earlier this yearBut the onus for HTML5 performance and capabilities really has little to do with the HTML5 development community (presuming a developer’s code is well done, of course) but rather the individual mobile operating systems. It’s the operating system and platform providers who need to open up hardware integration and acceleration so that HTML5 developers can tune to them. This lack of cooperation between the OS providers and HTML5 is a key reason that Mozilla is creating its own operating system, the Firefox OS (formerly “Boot2Gecko”) which will be completely Web-based and deployed internationally in 2013. As for capabilities, Mozilla is recreating many of the custom features of native apps – such as camera, contacts, calendar etc. – with its WebAPI initiatives, which tie a smartphone browser to hardware features. Mozilla Has An AgendaIt is understandable that Heilmann is intense in his support of HTML5. The capabilities of the technology stack mixed with the obstacles it faces create all the ingredients for an impassioned plea.But Heilmann has an agenda here. Mozilla started in the late 1990s to counteract the Microsoft Internet Explorer monopoly. That battle has now switched to mobile, with HTML5 the primary weapon in Mozilla’s arsenal. So Mozilla has to rally the troops against the closed platforms. The continued existence of Mozilla depends upon an open Web. As the Web goes mobile, the closed nature of operating systems like Apple’s iOS and its App Store threaten Mozilla to its core. The fact is that HTML5 is not for everybody. Some developers will gladly take the advantage of the native approach and its closed ecosystem… and laugh all the way to the bank. Then again, native is not for everybody, especially for media brands or large enterprises that cannot or will not invest in the developer resources to create a native app for every platform. Will Mobile OS Makers Play Along?Heilmann makes a significant point in noting how closely the future of HTML5 is tied to the goodwill of the native operating systems. “The main reason why HTML5 is not the obvious choice for developers now is the above mentioned lockout when it comes to hardware. An iOS device does not allow different browser engines and does not allow HTML5 to access the camera, the address book, vibration, the phone or text messaging. In other words, everything that makes a mobile device interesting for developers and very necessary functionality for Apps,” Heilmann wrote. There is no certainty that the native platforms will move an inch to support pure HTML5 apps (unwrapped for native performance) outside of their own purposes. For Apple specifically, there is little incentive to do so. That’s why it makes sense for companies like Mozilla to take its future into its own hands with projects like Firefox OS. Yet there is no guarantee that Firefox smartphones will sell well – and it is impossible to monetize without attracting eyeballs.When it comes to mobile users, the goal is for none of this to matter. If I want use Firefox OS or HTML5 apps, I need to trust that those apps will work as well as the native versions I am already used to from the closed app store models. Consumers should not even have to know if an app is native or HTML5 Web-based at all. The goal is to trust that any app, no matter how it is made, will work well on your device. With the complex relationship between the mobile operating systems, native app creation and the Web, there is no guarantee of that right now. That has to change. Outside of the specific Mobile Web App vs. Native App argument and the uncertainties it creates, there is a growing place in app development for HTML5 in the near and long term. The biggest problem – user experience – is conquerable. It will just take more cooperation among the various players to achieve.Top image from HexGL racer by Thibaut Despoulain. dan rowinski Tags:#HTML5#Mozilla Related Posts What it Takes to Build a Highly Secure FinTech …center_img Why IoT Apps are Eating Device Interfaces Role of Mobile App Analytics In-App Engagement The Rise and Rise of Mobile Payment Technologylast_img read more

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No plans to retire from ODIs, says Sachin Tendulkar

first_imgHe might be skipping ODIs with regularity but Sachin Tendulkar says he does not plan to quit the format altogether just yet and will continue as long as he enjoys the game.Sachin’s 100 tons in picturesTendulkar, who has played just two ODI series after the World Cup last year, most recently opted out of the tour of Sri Lanka later this month, fuelling speculation about his future in the format.But the 39-year-old star batsman insisted that he rarely gets affected by what is speculated about him.”It’s not what XYZ think, it’s what I feel and I feel as long as I am enjoying and I feel like being part of it, I’ll continue (playing ODIs),” he told a news channel.”I felt I shouldn’t be part of the Twenty20 squad in 2007 and I had been asked (to stay on) but I felt I should not be part of Twenty 20 squad because the team did well. When I get that feeling in one-day cricket may be I would take that decision,” he said.Tendulkar said he decided to opt out of Sri Lanka tour as he wanted to spend time with his children.”I just wanted to spend time with my family, as simple as that. I spoke to the BCCI and requested them. To be able to spend time with my children is also important.”Because once we go back they will go to their schools then you won’t get quality time which any family man expects from his family and that is something which will keep me going for next 10 months,” he said.advertisementlast_img read more

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Womens Tennis Is Still Anyones Game Just Look At The French Open

FiveThirtyEight Embed Code More: Apple Podcasts | ESPN App | RSS | Embed The women’s side of the French Open has seen plenty of upsets. Only three of the 10 top-ranked players made it through the third round, with high-profile competitors such as No. 1 Naomi Osaka and No. 10 Serena Williams among them. After her loss to 20-year-old American Sofia Kenin, Serena Williams, who has battled persistent injuries this season, was asked if she still would have entered the Open had she known the outcome. She said she would never have believed that she would be out in the third round. We’ll look at how Serena’s expectations fair against the growing parity in women’s tennis and how sharply this contrasts with the predictable cast of characters on the men’s side.The MLB draft is underway, and as Diamondbacks GM Mike Hazen describes the experience, “the draft is very risky — it has always been risky.” The Hot Takedown team breaks down how this draft differs from other major sports, plus the strategies and trends exhibited in the early rounds.Finally, our Rabbit Hole of the Week looks at the Women’s College World Series. A dive into the key players and their professional pursuits lands us deep into the surprising world of Olympic demonstration sports.Here’s what we’re looking at this week:Justine Henin, the last “Queen of Clay.”Last year, our colleague Tom Perrotta wrote about the increased parity in women’s tennis, and it’s never felt more timely.ESPN’s Jeff Passan breaks down the convoluted MLB draft.Some MLB hopefuls are opting to play abroad rather than participate in the draft.Rachel Garcia’s impressive performance in the semifinals against the University of Washington.You won’t want to miss these videos of skijorning and korfball. read more

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Sika realizes dream after donning scarlet and gray

It’s pretty fitting that a guy like senior offensive lineman Scott Sika would be from a town called Strongsville, Ohio. But not just for the obvious reasons one would expect. Sika was able to walk on to the Ohio State team because of his heart and work ethic. But he is a pretty strong guy, too. Putting on the scarlet jersey and silver helmet was a lifelong dream for Sika. Nearly every member of his family went to OSU. He remembers watching every Buckeye game on Saturdays when he was growing up with his father, who went to optometry school at OSU. “He’s been a big influence in my life. He’s one of the main reasons why I chose to walk on too, because he would always tell me ‘you could play here,’ but you always have doubts in the back of your mind,” Sika said. “But once you get here you realize, as they say, fathers know best. Just his influence has helped me.” Choosing to walk on to OSU’s team did not come without any risks. He would not be guaranteed a scholarship, like he had been offered from smaller programs. Nor would he be guaranteed any playing time. But Sika never had a problem focusing on the positives. “I couldn’t pass up the chance. I really wanted to go to college here. Why not give it a try and play. It’s turned out really well for me,” he said. Sika said the rigors of playing for the scout team were difficult at first, but he always maintained a team-first mentality. “When I started I knew I was going to be on the scout team. Basically I’m here to help the team. Granted, I wish I could play as much as possible, but I’m just doing what I have to do to help the team,” Sika said. “It’s coaches’ decision, whether it’s playing scout team or playing with the twos, I just do what I do and I’ve enjoyed it.” While Sika’s father, brother, sister and mother all attended OSU, his uncle wore navy and maize as a football player for the Michigan Wolverines. “It was pretty ironic,” he quipped. “We always gave each other a hard time. Every week he says he roots for us, aside from when we play Michigan obviously. We go at it, but the last couple years I’ve easily had the upper hand and he hasn’t been able to say much. It’s a fun relationship, we go back and fourth but he just wants the best for me.” The memories of multiple BCS games, including a couple National Championship games and the Rose Bowl, will stay with Sika, But he said aside from all the obvious big stages he’s seen, it’s been the relationships he’s built with his teammates that he’ll remember most. Sika will be graduating with a degree in sports management. He plans on using everything he’s learned as a football player at OSU and the connections he’s made to help him in the professional world. But no matter what, he’ll always remember the feeling he had when he first realized he was a Buckeye. “It was surreal,” he said. “As I tell a lot of people, you don’t really understand it when you’re doing it. Sometimes you sit back and say to yourself ‘wow, I’m playing for the second ranked team in the nation.’ “You get to play where Orlando Pace and Eddie George played. It’s just an honor and you don’t realize it when you’re here but once you’re gone … it’s just memories and I’m so thankful to have had an opportunity.” read more

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Ohio State mens volleyball takes 2 against Grand Canyon

Freshman outsider hitter Miles Johnson (13) attempts to spike the ball during a match against Grand Canyon Feb. 21 at St. John Arena. OSU won, 3-0.Credit: Jonathan McAllister / Lantern photographerThe Buckeyes were successful at their chance for revenge against the Grand Canyon Antelopes, finishing with a clean sweep.The No. 14 Ohio State men’s volleyball team took down Grand Canyon 3-0 (25-18, 25-21, 25-20) Saturday and 3-0 (25-18, 31-29, 25-23) Friday in Columbus.The Buckeyes (7-6. 4-2) were preparing their offense all week prior to the match against the Antelopes (6-9, 0-6), said coach Pete Hanson. OSU put the offensive practice to work and averaging 45 kills during the two matches against Grand Canyon.“If the offense is producing at a very high level, it can erase some of your bad spots that you are trying to cover up … If we can get our offense to play at a steady level, we are going to have the chance to be successful night in and night out,” Hanson said.During Saturday’s match, redshirt-freshman middle blocker Driss Guessous had a match-high 11 kills for OSU and finished the match with a .474 attack percentage. Freshman outside hitter Miles Johnson added nine kills and two solo blocks, while junior middle blocker Dustan Neary and redshirt-junior opposite Andrew Lutz each totaled eight kills. Freshman setter Christy Blough had a match-best 37 assists and chipped in two solo blocks and two kills.Senior middle blocker Jonathan Newton said winning the match came down to stopping the Antelopes early.“We knew that to be able to control the game, we had to stop their (Grand Canyon) momentum from the beginning,” Newton said.Lutz led the squad with 13 kills Friday, while Johnson added a career-best 11. Guessous and junior outside hitter Michael Henchy finished with nine and eight kills, respectively. Blough had a match-best 40 assists Friday night.Henchy said Saturday the Buckeyes are on the cusp of reaching the level of play they have been striving to acheive.“We are coming more and more into form and we’re not too far away from being a great team,” Henchy said.OSU is set to close out its five-match home stand as it hosts No. 13 Ball State Wednesday. The No. 14 Buckeyes and the Cardinals are scheduled to face off at 7 p.m. in St. John Arena. read more

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Mens volleyball Ohio State advances to conference semis

Ohio State senior setter Christy Blough sets the middle for redshirt sophomore Blake Leeson against Quincy on April 15 at St. John Arena. Credit: Aliyyah Jackson | Lantern reporterThe No. 2 Ohio State men’s volleyball team (28-2, 17-0 MIVA) is headed to the Midwestern Intercollegiate Volleyball Association (MIVA) Semifinals after downing Quincy University (7-22, 2-14 MIVA) in straight sets. After meeting three times, Saturday’s win was OSU’s first sweep of the Quincy Hawks this season.In OSU’s shortest match of the season, OSU’s offense was aided in large part by junior outside hitter Nicolas Szerszen. Szerszen, who was named MIVA Player of the Year on Tuesday, led the team with 13 kills on 19 errorless attempts. “I think that Nic Szerszen playing like the player of the year kind of really helped us step up and win it in three,” senior middle blocker Driss Guessous said. “I think when he has a good game, it’s a lot easier for all of us to play better.”After stringing together four straight points to begin the first set, the Buckeyes controlled the lead throughout the set. The Hawks were only able to score back-to-back points on one occasion in the first frame, losing 14-25.The Hawks struggled to get points on offense, with the team hitting at a rate of .045 in the set. On the other side of the net, the Buckeyes had a .522 attacking efficiency. Senior opposite Miles Johnson and Szerszen combined to give the Buckeyes three aces in the set. “I commended Nicolas after the match,” head coach Pete Hanson said. “I thought Nicolas was the guy who set the tone in that regard that he just played, I thought, a relentless match tonight.”Much like the first set, the Hawks never saw a lead in the second set, trailing by as much as six points midway through the second set. A 5-1 run helped the Hawks battle back make the score 13-15, but they ultimately fell to the Buckeyes 20-25.In the second set, the Buckeyes improved their attacking rate to .526 and stuffed the Hawks on six occasions. Senior setter Christy Blough accounted for two blocks on his own. The Hawks hit better in the second set as well with the team improving to a .263 hitting rate.“What we talked about in the locker room or what I asked them to do was to play as hard and with as much energy as we could from the time the whistle blew to the time the play was over,” Hanson said. “Whether we made a mistake or not was kind of immaterial, but it was about our effort. It was about our commitment to making a lot of plays.”After a short intermission, OSU led 11-3 with Quincy’s only points coming from Buckeye service errors. The rest of the set mirrored the beginning and OSU took the third frame 25-15.The Hawks were unable to find an answer on offense in their final set of the season. The team paired six kills with six attacking errors. OSU, on the other hand, had 13 kills and two attacking errors to close out the match.With the win, the Buckeyes move on to the MIVA Semifinals and face either No. 11 Ball State University or No. 12 Loyola University, Chicago. First serve is at 7 p.m. on Wednesday in St. John Arena. read more

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Italys winless streak continues

first_imgThe Italian football national football team extended their winless streak to five games after their 1-1 draw against Ukraine in an international friendly on Wednesday night.The Azzurri, fielding an experimental line-up, produced a fine first half display but couldn’t secure the victory as Andriy Shevchenko’s Ukraine earned a well-deserved away draw.Italy head coach, Roberto Mancini made changes to the team that 1-0 to European champions Portugal during last month’s UEFA Nations League game in Lisbon.The former Manchester City manager started the game with the attacking trio of Juventus’ Federico Bernardeschi, Lorenzo Insigne of Napoli and Fiorentina’s Federico Chiesa, and would have been impressed with their first half display, as the combined to create a number of chances but couldn’t find a way past Andriy Pyatov in Ukraine’s goal before half time.Bernardeschi got the ball roiling for the former world champions when his low strike found its way past Pyatov to hand the Italians the lead in the 55th minute.Cristiano Ronaldo, JuventusSerie A Betting: Match-day 3 Stuart Heath – September 14, 2019 Considering there is a number of perfect starts so early in the Serie A season, as well as a few surprisingly not-so perfect ones….However, the joy of the Italian supporters was short lived, as Ruslan Malinovskyi levelled seven minutes later with a low shot which Italy goalkeeper Gianluigi Donnarumma appeared to see late. The visitors almost took the lead when Malinovskyi hit the crossbar with a curling free kick.The game took a short break in the 43rd minute for one minute’s applause in memory of the 43 people who lost their lives when a motorway bridge collapsed in the city on Aug. 14.“We deserved to score a couple of goals tonight, we have to improve on this aspect and continue on this path,” said Mancini, according to ESPN.“We need to be more incisive.”last_img read more

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Nuno We can cope without Boly

first_imgWolves boss Nuno Espirito Santo believes his squad can cope without Willy Boly who saw red in their 3-0 defeat at Manchester City on Monday.Boly was sent off in the 19th minute for a reckless challenge on Bernardo Silva at the Etihad on Monday night.The defender has played every minute of Premier League football this season and replacing him for their clash with Leicester on Saturday might prove tricky for Nuno, but he’s confident the team can adapt without him.Premier LeaguePremier League Betting: Match-day 5 Stuart Heath – September 14, 2019 Going into the Premier League’s match-day five with a gap already beginning to form at the top of the league. We will take a…“What I find, when a squad is short of player numbers, they have to have the mentality to cope with those kinds of moments, and we have it,” he told the club’s website.“We are completely comfortable with the decision that we’re going to have to make and are completely confident that it will work out.“It’s versatility, it’s about being versatile. When you know the idea of the team, you are capable to deal with different positions, but there is no such thing of developing a player in various positions, what you have to do is work on where you want your players to compete.”last_img read more

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