Daily Archives: July 3, 2016

Rohtek Automation

Posted: July 3, 2016 at 12:14 pm

ROHTEK LLC is a specialized automation distributor company principally serving the aerospace and defense industries. Our goal is to help our customers achieve greater productivity and results leveraging our highly reliable automation control systems, accessories, and technical support. Simply put: ROHTEK LLC will provide the support and easy-to-use automation systems to our customer base to achieve immediate positive impact in their productivity.

Our Human Machine Interface (HMI) products also known as Operator Interface Terminals (OIT) are compatible and able to connect via Ethernet or using the serial ports with most Programmable Logic Controllers (PLCs) including Allen Bradley, Fuji, Hitachi, Schneider Electric, Panasonic, Omron, Siemens, Toshiba and Mitsubishi. This attribute, combined with our world-class reliability and easy-to-use software interfaces makes us the best solution for any existing automation line.

Our Fatek PLC products and training devices are a professional line of controllers focused on small, high-quality and high-functionality micro PLC controllers. With a tradition of high quality and break-through engineering innovation since 1992 our Fatek PLCs are increasingly reaching market share in high-reliability applications in Europe and North America.

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Rohtek Automation

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The Automation Conference

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Thank you to our attendees, GE Digital, Kepware Technologies, our tabletop exhibitors and sponsors for helping to create a sold-out event. We hope to see you all next year!

The Automation Conference & Expo is the leading peer-to-peer educational and networking event for industrial automation professionals. As an attendee, youll learn why todays automation innovations are critical for your operation. This years knowledge exchange took place May 24-25 at the Chicago Marriott OHare, offering technology end-users the ability to:

- get tips on automation implementation from industrys leading companies - choose from over two dozen educational sessions - network with experts and automation thought leaders - access practical insights from experienced practitioners

Our program is designed for automation professionals in the process industries, discrete manufacturing and packaging, and includes general and track sessions; in-depth Technology Workshops and tabletop exhibits, staffed by solutions experts.

The 2016 conference program explored todays hottest manufacturing trends and challenges:

Our pre-conference event, Machine Technology Day, covered these issues:

Download our event brochure

Who should attend:

To receive event alerts, please contact Ashley Friedman.

Learn more about collaborative robotics at this year's Automation Conference & Expo. Demands from a range of industries are driving the rapid development of cage-free robots that work alongside humans. Heres a look at some of the latest developments.Read more

Next gen HMIs and PackML will be featured at this years event. Heres a recent article about how OEMs balance flexibility with familiarity in the human machine interface and the value of PackML. Read more

The Automation Conference & Expo 2016 (AC&E) will explore trends and technologies that drive increased efficiency, profits and safety for manufacturers across all industries. Practical applications of IIoT, collaborative robotics, cybersecurity and other technologies will be featured May 24-25 in Chicago.Read more

Its only been about four years now since the concept of the Internet of Things (IoT) really began to pick up steam. Read more

If you are a U.S. manufacturer, you already know this fact: skilled people are hard to find. From production line workers, to skilled trade people, technicians, and engineers, finding the right skillsets to support your production is a significant challenge... Read more

The Organization for Machine Automation and Control (OMAC) is offering a PackML Workshop in conjunction with Machine Technology Day, May 23 in Chicago. This half-day training focuses on distinct PackML implementation tasks for packaging end-users, integrators, and OEMs.Read more

Annual industrial automation conference, May 24-25 in Chicago, offers discounted registration rate for women in manufacturing.Read more

"Networking opportunities were tremendous."

"This is a formidable conference. Great presentations, event organization and the right number and quality of attendees."

"Great conference-well worth it thank you!"

"Great chance to meet with a wide variety of people in the automation industry."

"Networking opportunities were very good due to the quality of attendees."

"Chance to meet other professionals and discuss the common issues we all feel."

"Real world examples...hearing about others' successes and failures."

"Learned the latest developments, found trends and future directions."

"Love this event."

Thanks to our TAC sponsors, who help fund this educational scholarship, awarded during The Automation Conference.

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The Automation Conference

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WinAutomation – Smart Macro Recorder, Web Automation …

Posted: at 12:14 pm

WinAutomation is a powerful and easy to use Windows based platform for building Software Robots.

Software robots are apps that live in your computer and can be instructed to do whatever a real user does. Teach them to perform effortlessly any of your tasks, leveraging WinAutomation Macro and Web Recorders.

Automate any desktop application. WinAutomations superb Macro Recorder will set your computer on autopilot.

Automate Web Sites and Web Apps.WinAutomations intelligent Web Recorder automates any web process effortlessly.

Automating easier than playing with toy bricks with the Visual Robot Designer and its point and click interface.

Automate anything on-demand. Have your Software Robots created by experts.

This is the most advanced and incredible software out there! I have spent thousands of dollars on software that doesnt come close to what this product does [] Truly amazing and I cant say enough! Its simply the BEST!

Jackie Foigelman http://www.CertifiedInterpretersInc.com

After comparing WinAutomation to other options on the market it became very clear that this solution is far superior. Its intuitive interface and great video tutorials helped us get started quickly [] Thanks for the great service!

Ben Kuhl http://www.FetterGroup.com

I have worked in IT for 15 years. With a few exceptions have never had this level of support. This product has and will save us countless hours [] I tried other products and can say this is far more flexible, intuitive, and feature rich.

Will Resendes Merced College

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WinAutomation - Smart Macro Recorder, Web Automation ...

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Automation Solutions – Home

Posted: at 12:14 pm

For nearly 20 years, Automation Solutions has been an integral partner to manufacturers building automated machinery in the Northwest, providing systems integration, programming, UL508 control panels, and field support. We have helped manufacture thousands of machines that have been sent all over the world into every conceivable industry. We stand behind and support every machine we have ever built.

We are also proud to be a full line stocking distributor for the components that we trust to use in the assemblies that bear our name and reputation. We are more than an integrator, and more than a distributor; we offer a value-added process.

Bringing the perspectives of integrator and distributor together means that we are not just selling components from a sales sheet, but we're offering the components that we use day-in and day-out to satisfy the needs of our long-term OEM and end user customers. We know the strengths and limitations of each of these components and are pleased to offer that experience to our distribution customers.

As a long-term supplier to machine builders, Automation Solutions has to stand behind everything we build and every component we sell. We have more to risk than a single component sale; we have to ensure that the system works properly, is delivered on time, and will keep performing for years to come.

Let us help you with your machine or factory automation requirements, and we guarantee that you will be fully satisfied with the results.

Robert "Kip" Johnston President Automation Solutions

April 22, 2016 GREEN FLEET INDUSTRY CHOSEN AS A FEATURED EXHIBITOR FOR THE 2016 HANNOVER MESSE GUIDED TOUR

March 31, 2016 AUTOMATION SOLUTIONS JOINS LARGEST EVER U.S. BUSINESS DELEGATION TO 2016 HANNOVER MESSE TRADE SHOW

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Automation Solutions - Home

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System Integration | Industrial Automation

Posted: at 12:14 pm

Custom Automated Industrial Control Solutions

No matter how unique your manufacturing or production needs, we are committed to designing and engineering a custom-automated control solution specific to that industrya solution that will reduce your costs and give your business the competitive edge it needs to succeed.

Todays ever-changing industrial controls technologies offer new and innovative ways to approach automation and control issues. To take advantage of these new technologies, you need a partner who understands how to apply them to your needs. From concept to commissioning, we are committed to developing, building, and maintaining quality industrial control automation systems that assist you in meeting your companys production goals.

Current economic conditions dictate that your operation must produce product as efficiently and reliably as possible. Industrial Automation will work closely with you to develop new systems, or to cost-effectively enhance the capabilities of existing machines to meet your requirements. Our experience with robotics, PLCs, touch screens, SCADA/HMI systems, machine vision, pneumatic, hydraulic and motion control, process control systems and other automation solutions can be put to work for your company to help solve your most difficult challenges. We will reduce downtime & waste, improve quality, increase efficiency and productivity, enhance safety, and reduce energy costs.

Industrial Automation has been an industrial controls systems integrator since 1990. We have served a variety of industries throughout the United Statesfrom agriculture to water systemsby designing and engineering custom automated control solutions specific to each individual industry. Through the combined experience of our technical staff and business partners we can design and build a custom automated control solution that will increase the safety, quality, productivity, and efficiency of your operations. We are committed to developing a solid, custom solution that will meet and exceed your expectations.

We provide 24/7/365 service for your controlled process that is second to none. When your systems are downyou are losing money. We understand this. Our experience in many industries allow us to get you back on-line fast. We provide remote or on-site troubleshooting and support for your industrial process controls and equipment. Contact Us for assistance.

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System Integration | Industrial Automation

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Riverside Automation – Machine Controls

Posted: at 12:14 pm

Cost Effective Automation Solutions

At Riverside Automation in Rochester, NY, we build automated machines that are fully customized to the exact specifications and needs of our clients. Every job starts with a question or an obstacle and ends with an automated machine capable of building, inspecting, or testing your product. Our shop draws clients from a wide range of industries across the globe and is proud to offer a quick turn around using state of the art CAD/CAM technology and on-site engineering.

We have been a leader in the design and build of special machines controls and tooling for over 33 years and follow our projects from initial concept all the way through installation. Our team of mechanical and electrical engineers, electricians, mechanics, and tool makers has the experience and is committed to creating a machine that will give you an edge over the competition.

Our extensive experience in a wide variety of industries, including automotive, optical, material handling and packaging, refrigeration, consumer products, and more, means we can help bring your business to the next level. We would be honored to speak with you about your next project and are confident in our ability to design and build a quality piece of equipment at a competitive price.

Whether you need sub-assembly machines, testing of a final product, or automated inspection, we have the capability to build the machine that is right for you. Contact us today to see how we can help. We would love to give you a tour of the facilities or walk you through our process.

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Riverside Automation - Machine Controls

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Automation: The Car Company Tycoon Game Windows – Mod DB

Posted: at 12:14 pm

This one has been a little more slow and complex to develop than expected, but after a long 3 months (4 really, but one was taken up with our first holiday in 4 years!) B1414 is now live for everyone. This update brings more complete car design aspects, along with car designer scenarios and a much improved user interface. There are also quite a few more new car bodies to base your designs from.

The next few months will be dedicated to some fairly unexciting but very important work, ready for release on Steam. We'll be making major improvements aimed at making Automation more polished, easier to learn, and all around more professional looking. More improvements to UI and the process of model designing will make it much more logical and simple to design a big range of models based on one particular car. Pop-ups/Tooltips will be added for many thing, and tutorial videos will be done/redone covering every techincal part of the game. We'll also be aiming to add a bunch of improved multiplayer modes, including Lap Time and Rally Stage Time challenge modes, with the ability to set your scores over the a few days, so you don't need to all be online together to compete.This update will be the first one to release on Steam, which is an exciting milestone, and will hopefully bring in more sales allowing us to bring further people on to work on car body art and other new content, And after this update is out of the way, it's finally time to start work on the Tycoon aspect of things!

Car Designer Features & Changes Added Mid Engine Cars Suspension Easy Mode Added Quality Sliders and dependencies for all car designer tabs Adjustable Rim Offsets Added Multilink Suspension Added the first automatic gearboxes Reliability and Environmental Resistance stats Passenger Space and Cargo Space stats Production Units, Costs and Service Costs stats Offroad and Utility stats Rebalanced Sportiness, Tameness, Comfort, Prestige and Safety calculations 9 Car Designer Scenarios Rebalanced material properties Many new part year dependencies Limited Cars to a Maximum of 2 wings, and 2 lips Added tire profile year limitation Base safety will stop progressing 10 years after a body first unlocks Bodies sorted by Year. Newest at the top Revised the Bottoming Out calculations to be less harsh Wings/Lips no longer punch holes in the body shell

Car Designer Fixes Fixed the crash caused by using MPH + dragging the top speed slider to top for high-revving engines (finally!) Fixed the Yaw Rate graph cut off when using mph as a unit for speed Fixed Certain cars not being able to complete a lap Fixed the proper gear delay being used on the test track Fixed Front Longitudinal AWD engine placement issues Fixed the sensitivity of resizing various fixtures, making it more responsive Fixed steamroller bug where wheels would become comically wide New Car Bodies Large 60s Coup 2 Large 70's Coups Large 90's Coup Large 60s Sedan Large 00's Sedan Small 80s Supercar Small 10s Supercar Large 10s Supercar

UI & Sound Completely reworked UI and UI flow Car Design Wizard for the whole car design process All new UI sounds Ambient sounds Added test track soundsNew Car & Engine Manager Temporary changed the Platform/Model game mechanic Many more stats on the three different testing pages Updated graphs Updated test track UI Manual start for car testing on testing page Engine Designer Fixes / Rebalances Reduced power gain when riching up fuel mixture Octane rating in VVL systems uses the lower cam setting Added bypass valve year limitation Fixed the your engine was created in a previous version message bug Fixed bore and stroke having two decimals too few using imperial units Fixed a bug where loading a VVL engine set the wrong lower cam setting Fixed an engine loading bug that caused the block config lua error

General Things Changed MTBF to Reliability for less confusion New scenario scoring system implemented for car designer scenarios Fixed various aerodynamics calculations and exploits Changed all Man Hours to Production Units Added Console can be accessed by pressing tilde (~). Commands are help(), HideBuildings(), ShowBuildings(). Changed to saving screenshots as PNG. If you turn off FXAA, and use the HideBuildings() command, you can take pictures of engines/cars on a transparent back-drop. Useful for taking screenshots of Engines and Cars with no backdrops. Fixed the tutorial video sound cutting off after a minute Thumbnails are now deleted when you delete the model / engine it belongs to Many more little fixes

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Automation: The Car Company Tycoon Game Windows - Mod DB

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Second Amendment Basics | Law Center to Prevent Gun Violence

Posted: at 12:09 pm

A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear Arms, shall not be infringed. The Second Amendment to the US Constitution

Does the Second Amendment prevent effective gun regulations? What is the right to bear arms? Second Amendment litigation has become a critical battleground since the U.S. Supreme Court held, in District of Columbia v. Heller, that the Amendment guarantees an individual right to possess a firearm in the home for self-defense. This decision created a radical shift in the meaning of the Second Amendment, but it doesnt prevent smart gun regulations. In fact, since Heller, courts nationwide have found a wide variety of firearms laws constitutional because they can help prevent gun deaths, injuries, and crimes in communities across the country.

The Law Center not only tracks the extensive Second Amendment litigation currently happening nationwide, but also analyzes the trends, to bring you the latest developments in the courts.

Learn more about the 2008 DC vs Heller decision.

Learn more about the 2010McDonald v. City of Chicago decision.

In 2008, the U.S. Supreme Court singlehandedly inserted the judicial system into the ongoing national debate over gun laws in America. In a 5-4 decision inDistrict of Columbia v. Heller, the Court invalidated the District of Columbias handgun ban and firearm storage law, stating for the first time that the Second Amendment protects a responsible, law-abiding citizens right to possess an operable handgun in the home for self-defense.

Heller was unquestionably a radical decision, overturning the Courts previous ruling that the Second Amendment was tied to state militia service. For almost seventy years, lower federal and state courts nationwide had relied on that pronouncement to reject hundreds of Second Amendment challenges.

The Heller decision immediately drew strong criticism from a wide array of legal scholars, historians, advocates and legislators, including a particularly scathing rebuke from respected conservative judge Richard Posner, who noted that, The only certain effect of the Heller decision will be to increase litigation over gun ownership.

In fact, new litigation started almost immediately. The day that Heller was announced, plaintiffs filed a lawsuit challenging the City of Chicagos handgun ban, with a second suit filed the next day. Other suits emerged soon after, escalating once the Supreme Court confirmed that the Second Amendment also applied to state and local laws in 2010s McDonald v. City of Chicago decision. After that case, the number of lawsuits challenging gun laws nationwide skyrocketed.

Thankfully, despite the explosion of litigation, courts across the country have rejected the overwhelming majority of Second Amendment challenges initiated since Heller. Gun rights advocates and criminal defendants across the country have sought to expand the Second Amendment to invalidate almost every gun law on the books today. In siding with us and the majority of Americans who support sensible gun laws, courts are finding that smart laws arent just constitutionaltheyre also critical to keeping our communities safe from gun violence.

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The Cost of Sequencing a Human Genome

Posted: at 12:07 pm

The Cost of Sequencing a Human Genome

Advances in the field of genomics over the past quarter-century have led to substantial reductions in the cost of genome sequencing. The underlying costs associated with different methods and strategies for sequencing genomes are of great interest because they influence the scope and scale of almost all genomics research projects. As a result, significant scrutiny and attention have been given to genome-sequencing costs and how they are calculated since the beginning of the field of genomics in the late 1980s. For example, NHGRI has carefully tracked costs at its funded 'genome sequencing centers' for many years (see Figure 1). With the growing scale of human genetics studies and the increasing number of clinical applications for genome sequencing, even greater attention is being paid to understanding the underlying costs of generating a human genome sequence.

Accurately determining the cost for sequencing a given genome (e.g., a human genome) is not simple. There are many parameters to define and nuances to consider. In fact, it is difficult to cite precise genome-sequencing cost figures that mean the same thing to all people because, in reality, different researchers, research institutions, and companies typically track and account for such costs in different fashions.

A genome consists of all of the DNA contained in a cell's nucleus. DNA is composed of four chemical building blocks or "bases" (for simplicity, abbreviated G, A, T, and C), with the biological information encoded within DNA determined by the order of those bases. Diploid organisms, like humans and all other mammals, contain duplicate copies of almost all of their DNA (i.e., pairs of chromosomes; with one chromosome of each pair inherited from each parent). The size of an organism's genome is generally considered to be the total number of bases in one representative copy of its nuclear DNA. In the case of diploid organisms (like humans), that corresponds to the sum of the sizes of one copy of each chromosome pair.

Organisms generally differ in their genome sizes. For example, the genome of E. coli (a bacterium that lives in your gut) is ~5 million bases (also called megabases), that of a fruit fly is ~123 million bases, and that of a human is ~3,000 million bases (or ~3 billion bases). There are also some surprising extremes, such as with the loblolly pine tree - its genome is ~23 million bases in size, over seven times larger than ours. Obviously, the cost to sequence a genome depends on its size. The discussion below is focused on the human genome; keep in mind that a single 'representative' copy of the human genome is ~3 billion bases in size, whereas a given person's actual (diploid) genome is ~6 billion bases in size.

Genomes are large and, at least with today's methods, their bases cannot be 'read out' in order (i.e., sequenced) end-to-end in a single step. Rather, to sequence a genome, its DNA must first be broken down into smaller pieces, with each resulting piece then subjected to chemical reactions that allow the identify and order of its bases to be deduced. The established base order derived from each piece of DNA is often called a 'sequence read,' and the collection of the resulting set of sequence reads (often numbering in the billions) is then computationally assembled back together to deduce the sequence of the starting genome. Sequencing human genomes are nowadays aided by the availability of available 'reference' sequences of the human genome, which play an important role in the computational assembly process. Historically, the process of breaking down genomes, sequencing the individual pieces of DNA, and then reassembling the individual sequence reads to generate a sequence of the starting genome was called 'shotgun sequencing' (although this terminology is used less frequently today). When an entire genome is being sequenced, the process is called 'whole-genome sequencing.' See Figure 2 for a comparison of human genome sequencing methods during the time of the Human Genome Project and circa ~ 2016.

An alternative to whole-genome sequencing is the targeted sequencing of part of a genome. Most often, this involves just sequencing the protein-coding regions of a genome, which reside within DNA segments called 'exons' and reflect the currently 'best understood' part of most genomes. For example, all of the exons in the human genome (the human 'exome') correspond to ~1.5% of the total human genome. Methods are now readily available to experimentally 'capture' (or isolate) just the exons, which can then be sequenced to generate a 'whole-exome sequence' of a genome. Whole-exome sequencing does require extra laboratory manipulations, so a whole-exome sequence does not cost ~1.5% of a whole-genome sequence. But since much less DNA is sequenced, whole-exome sequencing is (at least currently) cheaper than whole-genome sequencing.

Another important driver of the costs associated with generating genome sequences relates to data quality. That quality is heavily dependent upon the average number of times each base in the genome is actually 'read' during the sequencing process. During the Human Genome Project (HGP), the typical levels of quality considered were: (1) 'draft sequence' (covering ~90% of the genome at ~99.9% accuracy); and (2) 'finished sequence' (covering >95% of the genome at ~99.99% accuracy). Producing truly high-quality 'finished' sequence by this definition is very expensive; of note, the process of 'sequence finishing' is very labor-intensive and is thus associated with high costs. In fact, most human genome sequences produced today are 'draft sequences' (sometimes above and sometimes below the accuracy defined above).

There are thus a number of factors to consider when calculating the costs associated with genome sequencing. There are multiple different types and quality levels of genome sequences, and there can be many steps and activities involved in the process itself. Understanding the true cost of a genome sequence therefore requires knowledge about what was and was not included in calculating that cost (e.g., sequence data generation, sequence finishing, upfront activities such as mapping, equipment amortization, overhead, utilities, salaries, data analyses, etc.). In reality, there are often differences in what gets included when estimating genome-sequencing costs in different situations.

Below is summary information about: (1) the estimated cost of sequencing the first human genome as part of the HGP; (2) the estimated cost of sequencing a human genome in 2006 (i.e., roughly a decade ago); and (3) the estimated cost of sequencing a human genome in 2016 (i.e., the present time).

The HGP generated a 'reference' sequence of the human genome - specifically, it sequenced one representative version of all parts of each human chromosome (totaling ~3 billion bases). In the end, the quality of the 'finished' sequence was very high, with an estimated error rate of <1 in 100,000 bases; note this is much higher than a typical human genome sequence produced today. The generated sequence did not come from one person's genome, and, being a 'reference' sequence of ~3 billion bases, really reflects half of what is generated when an individual person's ~6-billion-base genome is sequenced (see below).

The HGP involved first mapping and then sequencing the human genome. The former was required at the time because there was otherwise no 'framework' for organizing the actual sequencing or the resulting sequence data. The maps of the human genome served as 'scaffolds' on which to connect individual segments of assembled DNA sequence. These genome-mapping efforts were quite expensive, but were essential at the time for generating an accurate genome sequence. It is difficult to estimate the costs associated with the 'human genome mapping phase' of the HGP, but it was certainly in the many tens of millions of dollars (and probably hundreds of millions of dollars).

Once significant human genome sequencing began for the HGP, a 'draft' human genome sequence (as described above) was produced over a 15-month period (from April 1999 to June 2000). The estimated cost for generating that initial 'draft' human genome sequence is ~$300 million worldwide, of which NIH provided roughly 50-60%.

The HGP then proceeded to refine the 'draft' and produce a 'finished' human genome sequence (as described above), which was achieved by 2003. The estimated cost for advancing the 'draft' human genome sequence to the 'finished' sequence is ~$150 million worldwide. Of note, generating the final human genome sequence by the HGP also relied on the sequences of small targeted regions of the human genome that were generated before the HGP's main production-sequencing phase; it is impossible to estimate the costs associated with these various other genome-sequencing efforts, but they likely total in the tens of millions of dollars.

The above explanation illustrates the difficulty in coming up with a single, accurate number for the cost of generating that first human genome sequence as part of the HGP. Such a calculation requires a clear delineation about what does and does not get 'counted' in the estimate; further, most of the cost estimates for individual components can only be given as ranges. At the lower bound, it would seem that this cost figure is at least $500 million; at the upper bound, this cost figure could be as high as $1 billion. The truth is likely somewhere in between.

The above estimated cost for generating the first human genome sequence by the HGP should not be confused with the total cost of the HGP. The originally projected cost for the U.S.'s contribution to the HGP was $3 billion; in actuality, the Project ended up taking less time (~13 years rather than ~15 years) and requiring less funding - ~$2.7 billion. But the latter number represents the total U.S. funding for a wide range of scientific activities under the HGP's umbrella beyond human genome sequencing, including technology development, physical and genetic mapping, model organism genome mapping and sequencing, bioethics research, and program management. Further, this amount does not reflect the additional funds for an overlapping set of activities pursued by other countries that participated in the HGP.

As the HGP was nearing completion, genome-sequencing pipelines had stabilized to the point that NHGRI was able to collect fairly reliable cost information from the major sequencing centers funded by the Institute. Based on these data, NHGRI estimated that the hypothetical 2003 cost to generate a 'second' reference human genome sequence using the then-available approaches and technologies was in the neighborhood of $50 million.

Since the completion of the HGP and the generation of the first 'reference' human genome sequence, efforts have increasingly shifted to the generation of human genome sequences from individual people. Sequencing an individual's 'personal' genome actually involves establishing the identity and order of ~6 billion bases of DNA (rather than a ~3-billion-base 'reference' sequence; see above). Thus, the generation of a person's genome sequence is a notably different endeavor than what the HGP did.

Within a few years following the end of the HGP (e.g., in 2006), the landscape of genome sequencing was beginning to change. While revolutionary new DNA sequencing technologies, such as those in use today, were not quite implemented at that time, genomics groups continued to refine the basic methodologies used during the HGP and continued lowering the costs for genome sequencing. Considerable efforts were being made to the sequencing of nonhuman genomes (much more so than human genomes), but the cost-accounting data collected at that time can be used to estimate the approximate cost that would have been associated with human genome sequencing at that time.

Based on data collected by NHGRI from the Institute's funded genome-sequencing groups, the cost to generate a high-quality 'draft' human genome sequence had dropped to ~$14 million by 2006. Hypothetically, it would have likely cost upwards of $20-25 million to generate a 'finished' human genome sequence - expensive, but still considerably less so than for generating the first reference human genome sequence.

The decade following the HGP brought revolutionary advances in DNA sequencing technologies that are fundamentally changing the nature of genomics. So-called 'next-generation' DNA sequencing methods arrived on the scene, and their effects quickly became evident in terms of lowering genome-sequencing costs; note that these NHGRI-collected data are 'retroactive' in nature, and do not always accurately reflect the 'projected' costs for genome sequencing going forward).

In 2015, the most common routine for sequencing an individual's human genome involves generating a 'draft' sequence and comparing it to a reference human genome sequence, so as to catalog all sequence variants in that genome; such a routine does not involve any sequence finishing. In short, nearly all human genome sequencing in 2015 yields high-quality 'draft' (but unfinished) sequence. That sequencing is typically targeted to all exons (whole-exome sequencing) or aimed at the entire ~6-billion-base genome (whole-genome sequencing), as discussed above. The quality of the resulting 'draft' sequences is heavily dependent on the amount of average base redundancy provided by the generated data (with higher redundancy costing more).

Adding to the complex landscape of genome sequencing in 2015 has been the emergence of commercial enterprises offering genome-sequencing services at competitive pricing. Direct comparisons between commercial versus academic genome-sequencing operations can be particularly challenging because of the many nuances about what each includes in any cost estimates (with such details often not revealed by private companies). The cost data that NHGRI collects from its funded genome-sequencing groups includes information about a wide range of activities and components, such as: reagents, consumables, DNA-sequencing instruments, certain computer equipment, other equipment, laboratory pipeline development, laboratory information management systems, initial data processing, submission of data to public databases, project management, utilities, other indirect costs, labor, and administration. Note that such cost-accounting does not typically include activities such as quality assurance/quality control (QA/QC), alignment of generated sequence to a reference human genome, sequence assembly, genomic variant calling, or annotation. Almost certainly, companies vary in terms of which of the items in the above lists get included in any cost estimates, making direct cost comparisons with academic genome-sequencing groups difficult. It is thus important to consider these variables - along with the distinction between retrospective versus projected costs - when comparing genome-sequencing costs claimed by different groups. Anyone comparing costs for genome sequencing should also be aware of the distinction between 'price' and 'cost' - a given price may be either higher or lower than the actual cost.

Based on the data collected from NHGRI-funded genome-sequencing groups, the cost to generate a high-quality 'draft' whole human genome sequence in mid-2015 was just above $4,000; by late in 2015, that figure had fallen below $1,500. The cost to generate a whole-exome sequence was generally below $1,000. Commercial prices for whole-genome and whole-exome sequences have often (but not always) been slightly below these numbers.

Innovation in genome-sequencing technologies and strategies does not appear to be slowing. As a result, one can readily expect continued reductions in the cost for human genome sequencing. The key factors to consider when assessing the 'value' associated with an estimated cost for generating a human genome sequence - in particular, the amount of the genome (whole versus exome), quality, and associated data analysis (if any) - will likely remain largely the same. With new DNA-sequencing platforms anticipated in the coming years, the nature of the generated sequence data and the associated costs will likely continue to be dynamic. As such, continued attention will need to be paid to the way in which the costs associated with genome sequencing are calculated.

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Last Updated: June 6, 2016

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Maximum life span – Wikipedia, the free encyclopedia

Posted: at 12:06 pm

Maximum life span is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between life and death, provided circumstances that are optimal to that member's longevity.

Most living species have at least one upper limit on the number of times cells can divide. This is called the Hayflick limit, although number of cell divisions does not strictly control lifespan (non-dividing cells and dividing cells lived over 122 years in the oldest known human).

In animal studies, maximum span is often taken to be the mean life span of the most long-lived 10% of a given cohort. By another definition, however, maximum life span corresponds to the age at which the oldest known member of a species or experimental group has died. Calculation of the maximum life span in the latter sense depends upon initial sample size.[1]

Maximum life span contrasts with mean life span (average life span, life expectancy), and longevity. Mean life span varies with susceptibility to disease, accident, suicide and homicide, whereas maximum life span is determined by "rate of aging".[2] Longevity refers only to the characteristics of the especially long lived members of a population, such as infirmities as they age or compression of morbidity, and not the specific life span of an individual.

The longest-living person whose dates of birth and death were verified to the modern norms of Guinness World Records and the Gerontology Research Group was Jeanne Calment, a French woman who lived to 122. Reduction of infant mortality has accounted for most of the increased average life span longevity, but since the 1960s mortality rates among those over 80 years have decreased by about 1.5% per year. "The progress being made in lengthening lifespans and postponing senescence is entirely due to medical and public-health efforts, rising standards of living, better education, healthier nutrition and more salubrious lifestyles."[3] Animal studies suggest that further lengthening of human lifespan could be achieved through "calorie restriction mimetic" drugs or by directly reducing food consumption. Although calorie restriction has not been proven to extend the maximum human life span, as of 2014, results in ongoing primate studies have demonstrated that the assumptions derived from rodents are valid in primates as well [Reference: Nature 01.04.2014].[4]

No fixed theoretical limit to human longevity is apparent today.[5] "A fundamental question in aging research is whether humans and other species possess an immutable life-span limit."[6] "The assumption that the maximum human life span is fixed has been justified, [but] is invalid in a number of animal models and ... may become invalid for humans as well."[7] Studies in the biodemography of human longevity indicate a late-life mortality deceleration law: that death rates level off at advanced ages to a late-life mortality plateau. That is, there is no fixed upper limit to human longevity, or fixed maximal human lifespan.[8] This law was first quantified in 1939, when researchers found that the one-year probability of death at advanced age asymptotically approaches a limit of 44% for women and 54% for men.[9]

It has also been observed that the VO2max value (a measure of the volume of oxygen flow to the cardiac muscle) decreases as a function of age. Therefore, the maximum lifespan of an individual can be determined by calculating when his or her VO2max value drops below the basal metabolic rate necessary to sustain life - approximately 3 ml per kg per minute.[10] Noakes (p.84) notes that, on the basis of this hypothesis, athletes with a VO2max value between 50 and 60 at age 20 can be expected "to live for 100 to 125 years, provided they maintained their physical activity so that their rate of decline in VO2max remained constant."

A theoretical study suggested the maximum human lifespan to be around 125 years using a modified stretched exponential function for human survival curves.[11]

Small animals such as birds and squirrels rarely live to their maximum life span, usually dying of accidents, disease or predation. Grazing animals accumulate wear and tear to their teeth to the point where they can no longer eat, and they die of starvation.[citation needed]

The maximum life span of most species has not been accurately determined, because the data collection has been minimal and the number of species studied in captivity (or by monitoring in the wild) has been small.[citation needed]

Maximum life span is usually longer for species that are larger or have effective defenses against predation, such as bird flight, tortoise shells, porcupine quills, or large primate brains.

The differences in life span between species demonstrate the role of genetics in determining maximum life span ("rate of aging"). The records (in years) are these:

The longest-lived vertebrates have been variously described as

With the possible exception of the Bowhead whale, the claims of lifespans >100 year rely on conjecture (e.g. counting otoliths) rather than empirical, continuous documentation.[citation needed]

Invertebrate species which continue to grow as long as they live (e.g., certain clams, some coral species) can on occasion live hundreds of years:

Plants are referred to as annuals which live only one year, biennials which live two years, and perennials which live longer than that. The longest-lived perennials, woody-stemmed plants such as trees and bushes, often live for hundreds and even thousands of years (one may question whether or not they may die of old age). A giant sequoia, General Sherman is alive and well in its third millennium. A Great Basin Bristlecone Pine called Methuselah is 4,845 years old (as of 2014) and the Bristlecone Pine called Prometheus was a little older still, at least 4,844 years (and possibly as old as 5,000 years), when it was cut down in 1964. The oldest known plant (possibly oldest living thing) is a clonal Quaking Aspen (Populus tremuloides) tree colony in the Fishlake National Forest in Utah called Pando at about 80,000 years.

"Maximum life span" here means the mean life span of the most long-lived 10% of a given cohort. Caloric restriction has not yet been shown to break mammalian world records for longevity. Rats, mice, and hamsters experience maximum life-span extension from a diet that contains all of the nutrients but only 4060% of the calories that the animals consume when they can eat as much as they want. Mean life span is increased 65% and maximum life span is increased 50%, when caloric restriction is begun just before puberty.[37] For fruit flies the life extending benefits of calorie restriction are gained immediately at any age upon beginning calorie restriction and ended immediately at any age upon resuming full feeding.[38]

A few transgenic strains of mice have been created that have maximum life spans greater than that of wild-type or laboratory mice. The Ames and Snell mice, which have mutations in pituitary transcription factors and hence are deficient in Gh, LH, TSH, and secondarily IGF1, have extensions in maximal lifespan of up to 65%. To date, both in absolute and relative terms, these Ames and Snell mice have the maximum lifespan of any mouse not on caloric restriction (see below on GhR). Mutations/knockout of other genes affecting the GH/IGF1 axis, such as Lit, Ghr and Irs1 have also shown extension in lifespan, but much more modest both in relative and absolute terms. The longest lived laboratory mouse ever was a Ghr knockout mouse on caloric restriction, which lived to ~1800 days in the lab of Andrzej Bartke at Southern Illinois University. The maximum for normal B6 mice under ideal conditions is 1200 days.

Most biomedical gerontologists believe that biomedical molecular engineering will eventually extend maximum lifespan and even bring about rejuvenation.[citation needed]Anti-aging drugs are a potential tool for extending life.[39]

Aubrey de Grey, a theoretical gerontologist, has proposed that aging can be reversed by Strategies for Engineered Negligible Senescence. De Grey has established The Methuselah Mouse Prize to award money to researchers who can extend the maximum life span of mice. So far, three Mouse Prizes have been awarded: one for breaking longevity records to Dr. Andrzej Bartke of Southern Illinois University (using GhR knockout mice); one for late-onset rejuvenation strategies to Dr. Stephen Spindler of the University of California (using caloric restriction initiated late in life); and one to Dr. Z. Dave Sharp for his work with the pharmaceutical rapamycin.[40]

Accumulated DNA damage appears to be a limiting factor in the determination of maximum life span. The theory that DNA damage is the primary cause of aging, and thus a principal determinant of maximum life span, has attracted increased interest in recent years. This is based, in part, on evidence in human and mouse that inherited deficiencies in DNA repair genes often cause accelerated aging.[41][42][43] There is also substantial evidence that DNA damage accumulates with age in mammalian tissues, such as those of the brain, muscle, liver and kidney (reviewed by Bernstein et al.[44] and see DNA damage theory of aging and DNA damage (naturally occurring)). One expectation of the theory (that DNA damage is the primary cause of aging) is that among species with differing maximum life spans, the capacity to repair DNA damage should correlate with lifespan. The first experimental test of this idea was by Hart and Setlow[45] who measured the capacity of cells from seven different mammalian species to carry out DNA repair. They found that nucleotide excision repair capability increased systematically with species longevity. This correlation was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein[46]). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. The association between nucleotide excision repair capability and longevity is strengthened by the evidence that defects in nucleotide excision repair proteins in humans and rodents cause features of premature aging, as reviewed by Diderich.[42]

Further support for the theory that DNA damage is the primary cause of aging comes from study of Poly ADP ribose polymerases (PARPs). PARPs are enzymes that are activated by DNA strand breaks and play a role in DNA base excision repair. Burkle et al. reviewed evidence that PARPs, and especially PARP-1, are involved in maintaining mammalian longevity.[47] The life span of 13 mammalian species correlated with poly(ADP ribosyl)ation capability measured in mononuclear cells. Furthermore, lymphoblastoid cell lines from peripheral blood lymphocytes of humans over age 100 had a significantly higher poly(ADP-ribosyl)ation capability than control cell lines from younger individuals.

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