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Calorie restriction trial in humans suggests benefits for age-related disease
IMAGE: This graphical abstract depicts the effects of a 2-year calorie restriction (CR) trial in healthy, non-obese humans, which found evidence that prolonged CR enhances resting energy efficiency, resulting in decreased... view more
Credit: Redman et al./Cell Metabolism
One of the first studies to explore the effects of calorie restriction on humans showed that cutting caloric intake by 15% for 2 years slowed aging and metabolism and protected against age-related disease. The study, which will appear March 22 in the journal Cell Metabolism, found that calorie restriction decreased systemic oxidative stress, which has been tied to age-related neurological conditions such as Alzheimer's and Parkinson's diseases, as well as cancer, diabetes, and others.
"Restricting calories can slow your basal metabolism, and if by-products of metabolism accelerate aging processes, calorie restriction sustained over several years may help to decrease risk for chronic disease and prolong life," says lead author Leanne M. Redman, associate professor of Clinical Sciences at Pennington Biomedical Research in Baton Rouge, LA.
CALERIE (Comprehensive Assessment of the Long-Term Effects of Reducing Intake of Energy) was the first randomized controlled trial to test the metabolic effects of calorie restriction in non-obese humans. The second phase of the study reports results from 53 healthy, non-obese men and women between ages 21 and 50 who cut calories by 15% over 2 years and underwent additional measurements for metabolism and oxidative stress. The calorie reductions were calculated individually through the ratio of isotopes absorbed by the participants' molecules and tissues over 2 weeks, a technique that accurately pinpoints a weight-maintenance calorie level.
Those in the calorie restriction group lost an average of almost 9 kg, although they did not follow a particular diet and weight loss was not the study's goal. No adverse effects, such as anemia, excessive bone loss, or menstrual disorders were noted; in fact, both trials led to improvements in mood and health-related quality of life. "We found that even people who are already healthy and lean may benefit from a calorie restriction regimen," Redman says.
In lab animals, calorie restriction lowers core body temperature and resting metabolic rate. Redman emphasized that CALERIE looked at the effects of calorie restriction on aging, not weight loss, where discussions of "fast" or "slow" metabolism most often arise. "We know from mammalian studies that the smaller the mammal, the faster their metabolism and the shorter their longevity," she says.
Many factors, such as antioxidant mechanisms and dietary and biological factors, influence metabolism, Redman says, but current theories hold that a slower metabolism is most beneficial for healthy aging and that organisms that burn energy most efficiently should experience the greatest longevity.
"The CALERIE trial rejuvenates support for two of the longest-standing theories of human aging: the slow metabolism 'rate of living' theory and the oxidative damage theory," she says. The latter ties overproduction of free radicals to oxidative damage to lipids, proteins, and DNA, leading to chronic diseases such as atherosclerosis, cancer, diabetes, and rheumatoid arthritis.
While the number of participants was relatively small and the duration short in the context of a human lifespan, biomarkers of aging were improved in study participants. Next steps include establishing robust biomarkers of human aging and examining the effects of calorie restriction in conjunction with antioxidant foods or substances like resveratrol, which mimic calorie restriction.
This work was supported by the National Institutes of Health (NIH).
Cell Metabolism, Redman et al. "Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging." http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30130-X
Cell Metabolism (@Cell_Metabolism), published by Cell Press, is a monthly journal that publishes reports of novel results in metabolic biology, from molecular and cellular biology to translational studies. The journal aims to highlight work addressing the molecular mechanisms underlying physiology and homeostasis in health and disease. Visit: http://www.cell.com/cell-metabolism. To receive Cell Press media alerts, contact press@cell.com.
DIET/BODY WEIGHT
NUTRITION/NUTRIENTS
Calorie Restriction Graphical Abstract (IMAGE)
http://dx.doi.org/10.1016/j.cmet.2018.02.019
Sperm may offer the uterus a 'secret handshake' American Society for Biochemistry and Molecular Biology
Simulation explores how insects glean compass direction from skylight PLOS
Early mammal fossil reveals the evolutionary origins of having a loose tongue American Association for the Advancement of Science


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An After-Death Experience
Eric Dexheimer March 5, 1998 4:00AM
When Jannette Mayhew popped open the trunk of her car and discovered the bullet-pierced body of her son, she probably thought things couldn't get much worse. But that was before her husband reached into a box he'd been told contained his son's personal effects--but which actually contained the boy's internal organs.
That bizarre turn of events led to a highly unusual lawsuit recently filed by the family in Denver District Court against a local funeral home. The circumstances leading up to the macabre conclusion began just over two years ago, when Fred Mayhew, a mechanic, and his wife, Jannette, a United Airlines employee, sent their 21-year-old son, Mordecai, to Indianapolis. Mordecai had been running with a rough crowd in Denver and getting into trouble, so the Mayhews, who live in Montbello, decided to relocate him to the Midwest in the hopes that he could get a fresh start there.
At first his new life seemed to be going smoothly. Mordecai stayed with relatives and called his mother every Sunday to check in. But on January 9, 1997, he vanished. And although it wasn't unusual for their son to disappear for several days at a time without telling anyone, the Mayhews started to worry when Indianapolis police called on January 23 saying they'd found Mordecai's car but not him.
The car, a black 1996 Chevrolet Impala, had actually been found ten days earlier. According to police records, the vehicle was towed to the Indy Towing Service impound lot. The car had been vandalized, and police suspected that it had been stolen earlier and then abandoned. Police tracked down Jannette through the Impala's registration, which was in her name and listed her Denver address.
As an airline employee, Jannette was able to catch a quick flight out of Denver. She arrived in Indianapolis on the afternoon of January 23 and immediately drove to the impound lot. She was directed by an attendant to her car, which she noted had sustained considerable damage: Several windows were broken and the radio was missing. As she continued surveying the car, Jannette opened the trunk and discovered the dead body of her missing son.
"She was just stunned," says the family's Denver lawyer, Richard Ott Jr. "She was horrified."
Today, just over a year later, Mordecai Mayhew's murder remains unsolved. Ott says he suspects that the case hasn't been given much attention by Indianapolis police because the victim was an out-of-state man with a history of drug dealing. Lieutenant William Reardon, a homicide investigator for the Indianapolis Police Department, denies that this is the case.
Reardon adds that the ten-day span between the time the police towed the car and the time Jannette Mayhew was notified is typical. And he says it is not unusual that the police didn't search the car after impounding it. "We're not going to do a forced entry on a car that clearly belongs to someone," he says.
Following its discovery by his mother, Mordecai Mayhew's body was transported to a local university for an autopsy. The temperature in Indianapolis had been unusually cold for the past several days, so his 200-pound body was frozen solid. John Cavanaugh, a forensic pathologist working for the Marion County coroner's office, remembers that he had to wait nearly one full week for the body to thaw before he could begin his examination.
Despite that inconvenience, Mayhew had been so well-preserved by the cold that determining the cause of his death was a fairly simple matter. He had been shot twice. The first bullet had entered his body from the front, passing through the meaty part of his shoulder and exiting his back. A second shot had entered his body from the back and clipped his heart. This was the shot that killed him. Mayhew's throat had been slashed, too; however, the pathologist observed that the cut wasn't particularly deep, and so he concluded that it probably hadn't been lethal.
In an autopsy, a pathologist makes a long incision down the front of the body and removes the organs, which are examined to determine the exact medical cause of death. Typically, when the pathologist is finished, he puts the organs into a bag, replaces them in the thoracic cavity and closes the cut.
And, says Cavanaugh, who today works in Chattanooga, Tennessee, as a pathologist for the Hamilton County coroner's office, that is exactly what he did. "We put the organs in a biohazard bag and stitched them back up," he recalls.
In addition to aiding the coroner's investigation, the frigid Midwest temperatures of January 1997 had a second beneficial consequence for the grieving Mayhew family. In spite of the length of time between Mayhew's death and the discovery of his body, the cold had kept his remains so well-preserved that an open-casket service was possible. On January 28, following Cavanaugh's autopsy, the body was transported to Indianapolis's Boatright Funeral Home, where Marvin Boatright embalmed it.
When a mortician receives an autopsied body from the coroner's office, he reopens the chest incision to begin the embalming procedure. Generally, the internal organs are embalmed into the corpse. This procedure was not followed in the case of Mordecai Mayhew, however.
Marvin Boatright did not return phone calls. But Ott says that, for some reason, the mortician removed Mayhew's organs from the body and placed them in a separate box rather than back into Mayhew's body. Boatright reportedly labeled the package "internal organs." Even so, pathologist Cavanaugh remains perplexed. "It sounds asinine and foolish," he says. "But," he adds, "that's not my job."
Mordecai Mayhew's remains were placed on a plane to Denver, where the family had planned a service at Caldwell-Kirk Mortuary. The body arrived on the day of the service. It was taken immediately to Caldwell-Kirk in northeast Denver, where the Mayhews and their friends and relatives had gathered to say their goodbyes to Mordecai.
As the family was milling around, waiting for the service to begin, Fred Mayhew, who was standing with his twelve-year-old niece, was approached by a mortuary employee. According to Ott, the Caldwell-Kirk worker presented the niece with a box, which, the worker said, contained Mordecai's "personal effects." Apparently nervous, the niece fumbled the box, and it dropped to the floor.
"Let's go over to the table and open it," Fred Mayhew suggested.
"Of course, he's thinking it's some of Mordecai's things," says Ott. "Like maybe his parka, his wallet, his keys. And he wanted to look at it." Mayhew opened the box, which had a plastic lining, and reached inside.
"Fred Mayhew inserted his arm and hand...and was covered with blood and remains of Mordecai Mayhew," states the family's lawsuit.
"Oh, my God! You're not supposed to see this!" the funeral-home worker allegedly said.
"Fred just froze," Ott says. "He was totally stunned. He just couldn't believe what was happening." Noticing that Mayhew was seemingly in shock and not moving, another Caldwell-Kirk employee gently instructed him to wash his arm and hand.
Jannette Mayhew was standing close by. Within moments she learned what had happened to her husband. "The wake dissolved," says Ott. "There was pandemonium."
The Mayhews declined a request for an interview, and efforts to reach a spokesman for Caldwell-Kirk were unsuccessful. But, says Ott, "Fred has had nightmares ever since this happened. When he talks about this, he still looks at his hand. The whole family has been traumatized. They'll never get over this--there's no way.

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Elizabeth Miller – Implementing Change with Widespread Adoption
This podcast episode is part of our Impact Series, featuring Elevate customers implementing transformative change.
Stakeholders Taking Ownership
This podcast episode is part of our Impact Series, featuring Elevate customers implementing transformative change. Kunoor Chopra, Vice President of Legal Services at Elevate, and Tashmin Ali, a Senior Commercial Attorney with Elevate's Contract Services Business, talk with Elizabeth Miller, Head of Legal Operations at Dolby Laboratories.
[01:00] – With inconsistent coordination and communication between stakeholders – Dolby needed to implement change.
[03:39] – Giving the stakeholders a voice in the process.
[05:55] – Outcomes, value, and results
[08:23] – A dedicated team, teamwork, and collaboration lead to widespread adoption.
[12:56] – The process continues to be enhanced.
[14:50] – The expected long-term impact of change – scalability, improved coordination, and knowledge management.
[17:06] – Stakeholders involved from the beginning have a sense of ownership.
[18:05] – A focus on engagement can go a long way.
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Note: This transcript has been adjusted to improve readability. Transcripts are generated using speech recognition software and human transcribers. The context and more than 95% of the actual transcript have been preserved. We strongly encourage our listeners to listen to the audio.
Nicole Giantonio: Hello, this is Nicole Giantonio, the Head of Global Marketing at Elevate. The podcast episode you're about to hear is part of our Impact Series, featuring Elevate customers implementing transformative change. Kunoor Chopra, Vice President of Legal Services at Elevate, and Tashmin Ali, a Senior Commercial Attorney with Elevate's Contract Services Business, talk with Elizabeth Miller, Head of Legal Operations at Dolby Laboratories. Listen in as they discuss true collaboration and the importance and effect of engaging a broad group of stakeholders when implementing change.
Kunoor Chopra: Thank you so much for joining us, Tashmin and Elizabeth, so great to have you. You both are involved in some fabulous change initiatives at Dolby. Why did Dolby need to implement change?
Elizabeth Miller: We had a few reasons. We had a good process set up on the revenue-generating agreement side. But for our non-revenue-generating agreements, we didn't have a process that everyone was following. We had legal and corporate policies, but they weren't necessarily known to the organization, and they weren't being followed consistently. Agreements were not sent to legal or procurement, or finance for review. Employees might have been signing beyond their spend authorities, and we had little visibility to the volume, risk, or commitments made on the company's behalf. It was just inconsistent coordination and communication between the different stakeholders. In many cases, the stakeholders didn't have any visibility into signed agreements.
KC: Thank you. Often, companies will start to implement change without seriously thinking about the problem they're trying to address. It sounds like you went into this in a more structured way. What was the problem you needed to address or the improvement that you were looking to make?
EM: Primarily, it would be a lack of awareness of our policies and a lack of our ability to enforce our policies. Those were the main things. On top of that, the agreements coming to the legal department for review weren't stored consistently. We have a repository, but it wasn't being used. Also, the review process for agreements wasn't standardized; there were many email exchanges and a time-consuming and inconsistent process for each one.
Tashmin Ali: And to add to that, from Elevate's perspective, a world-class organization like Dolby should have copies of its contracts in one place. While there was a repository, it wasn't used often or properly, or consistently. We wanted to make it easier and clearer for folks within the legal team to store executed contracts in one place. And we wanted to make it easier for business users by establishing a consistent process, an intake form for them to have all their information regarding the deal or a transaction in one place. It is also easier for the reviewers to get automated notifications and review information in one place. Another issue was optimizing the use of legal resources. Dolby is fairly leanly-staffed, and the team needed to spend their time on higher-complexity matters. Without a system in place, there is little understanding of the various non-revenue contract policies and risk profiles associated with engagement; there wasn't an appropriate assignment system. One of the issues we set out to address was to get an appropriate system in place so that Dolby resources were spending their time on matters that truly required their attention.
KC: This sounds like the right person, right task, right location, the right technology, and right process type of solution. An important innovation. When people talk about innovation, they often talk about big-I innovation, some big, shiny object, a massive change. When I think about it, it is about making those changes that will improve how you're working. It sounds like this focused on improving and optimizing the setup of these workstreams. How did you go about implementing change? What did the process and design look like?
EM: I think one of the most successful things that we did was create a cross-functional task force early on, where we involved all the key stakeholders and brought them into the process instead of telling them what the process would be. A lot of us had the same goals. Other departments had policies that they should be reviewing agreements that weren't getting to their desks. Letting them into the process and making them a part of the team helped implement things that they wanted that we might not have been thinking about; it helped with engagement. Even in terms of the people who would be submitting the agreements, bringing them in and saying, "Yes, we're interested in your engagement, and we wanna hear how to make this easier for you." Giving them a voice to help build the process around their needs. We created a lot of engagement where there could have been more resistance to following a new process that didn't exist before.
TA: That also helped from a compliance perspective, getting the key people involved, helping build the process, and ensuring it is followed. When planning for this change, we came up with a comprehensive rollout plan, with a set of requirements and communications by geography. We started in the US with fairly friendly business units that we worked well with and were already starting to establish a contract process. Such groups like Maintenance, the DEWS group, the Human Resources group. Then we slowly rolled out beyond the US to additional regions, going from the US to EMEA, and then APAC to take our shared learnings and early lessons across the geographies and business groups.
KC: It seems like you thought about change management as you were designing out this process. As we all know, the success of any initiative does rely on change management. In terms of this initiative's outcomes and value, what are some results that you've seen today?
EM: The main result is we have a clear, well-adopted process used globally. By well-adopted, I mean there are no loopholes, remarkably. We had gone from a place where we were only receiving a handful of non-revenue agreements, coming to the legal department for review or approval, initially, per month. It's now up to 250 requests a month that don't all need legal review, but they go through the process. Now it's an established process, and all of the stakeholder departments agree on this, and they don't let anybody circumvent the workflow. That in itself increased compliance with our compliance policies, legal policies, IT security policies, and procurement policies. All are being followed.
All of the agreements are housed in a central repository where they're searchable. We could use that data for future agreements, metrics, and benchmarking, seeing what our activities are, and being able to more thoughtful and decide, "What level of risk do we want to take?" Having visibility into, "Where are we spending time and money and committing our resources?" knowing that we can now review, "Is this where we want to be doing those things?" Another huge benefit of these workflow projects is reduced turnaround time, getting completed contracts quicker. It's better for the requester; it's better for the legal resource, helping get work done more quickly and more effectively.
All of the agreements are housed in a central repository where they're searchable. We could use that data for future agreements, metrics, and benchmarking, seeing what our activities are, and being able to more thoughtful and decide, "What level of risk do we want to take?"
Elizabeth Miller
TA: We now have several years of data surrounding non-revenue spending and additional types of spend and things like equipment loans and marketing agreements. We've got a really good sense of the types of contracts that users are entering into on behalf of Dolby, how much they cost the company, what the request's general volume looks like, and how they're broken down business units and by geographies. And as Elizabeth pointed out, how long they take to close. Similar data is collected on NDAs and other agreements where we didn't have even a baseline before; we now have comprehensive data and metrics and benchmarks to measure against.
KC: One of the keys, it sounds like, it's just a collaboration amongst the team. How has that led to the success of the engagement?
EM: It's been a huge factor because we're not getting a lot of resistance from people trying to implement these new processes. Previously, the department was more siloed in how we were operating, managing our requirements, or trying to manage our requirements, maybe not always successfully. The cross-functional collaboration, not only from gathering the engagement as I had mentioned before, but helping everybody feel like we are one company and heading in the same direction, we have similar goals. It's had a ripple effect, not just from one workflow to the next, which it has, we've had many different workflows come out of this first process, and there's more of just a general willingness to collaborate on other unrelated projects. We now have a better partnership with those other teams, and we have better relationships. We all know that we can work together effectively and that we're willing to help each other.
TA: From the Elevate-Dolby collaboration perspective, I think that was critical for the success of these initiatives. Elizabeth and I both, and hopefully, Elizabeth, you can testify to this; we worked as a cohesive team, left arm, right arm. I identified problem areas, stakeholders that needed an extra nudge or internal communication, and Elizabeth quickly and effectively implemented the suggestions I had. She would follow up with them, set meetings, follow up with managers, find inroads into different business units that were a little bit more challenging for us to implement change within. We did work as a team, me targeting folks and Elizabeth taking follow up with those folks. What was critical to the business users is that we were part of a joint legal portals team that wasn't solely Dolby and Elevate. It was one team working cohesively and trying to implement change. I think that a unified voice helped make our message stronger and more impactful.
EM: Absolutely. Tashmin and the other Elevate resources have always been an extension of our team. I think some of the other departments involved in these processes, maybe a little bit less closely. They probably don't know that the Elevate resources are not Dolby employees. I still get emails saying, "Oh, this person on your team," if someone is trying to contact an Elevate resource. They have no way of knowing that they're not a part of the legal department. The way that we've operated on these projects was exactly in line with that. One benefit the relationship has had is that Tashmin handled most project management on the workflows that we've rolled out. This is great because there are things that my team members aren't necessarily either good at or don't have the time to do or just aren't prioritizing. Having dedicated resources to take on these roles and make sure we're not skimping on the communications and the change management helped us because it gave us a complete process, and there weren't pieces falling through the cracks. That likely would have happened without Elevate's support.
Having dedicated resources to take on these roles and make sure we're not skimping on the communications and the change management helped us because it gave us a complete process, and there weren't pieces falling through the cracks.
KC: It's great to hear that the one team concept extended to that broader partnership, Dolby and Elevate. I'm assuming the Dolby stakeholders are happy. You've seen a lot of great results. Do you get any feedback from them on these initiatives?
EM: It depends on which process it is. For some, there was no process before. People didn't have to get anything approved by legal or IT or procurement or finance. They were signing their contracts, and that was done. It is an added step for people who weren't following those policies, a large number. They weren't aware that they weren't following the policies. Now, they are doing things in a standardized way, whereas they could have just signed an email before. I'm sure there is a little bit of aggravation on that part of having to do something that didn't require before. There is also the acknowledgment that we're building this process for them, and we're trying to make it as easy as possible. We're incorporating all the feedback that we receive – as much as possible. I think just the attitude of us being open to feedback and embracing the engagement, whether positive or negative and building that into improvements have gone a long way.
EM: We churned out a handful of workflows, and they've all been in a constant improvement stage ever since. Every month, we have tons of enhancements that we build to all of our workflows, anything that will reduce time, reduce clicks, make the process easier. Other departments have jumped on board, wanting us to collect more data they might need or ask more questions or incorporate some of their initiatives as well. From the other departments who might be reviewing agreements or trying to help implement the process, I would say very positive feedback, for the most part. For the users, it's more mixed in terms of, "Oh, now, I have to follow this process." But there is an appreciation that we are incorporating their feedback; we're trying to make it as easy as possible. Now, there is a standard process, and they know what to do; it's not just searching aimlessly for, "Who do I go to? And what's the next step?"
TA: Our continuing change management policy and the process takes user feedback and incorporates it into continued improvements, giving lots of different opportunities to share experiences, perspectives, and enhancements that we want to see. That goes from the business users to departments like procurement that initially saw this as, "This is another process that I have to follow." They are now giving us ideas for tracking additional questions that would be useful for their department, data around renewals, contracts coming up for expiration, and how our portal might support other supplier initiatives. It's become a platform for that inner department collaboration. In the beginning, it was an additional process or a new process where there was none. It's gone from a barrier to a platform, that's been rewarding to see that transformation.
It's become a platform for that inner department collaboration. In the beginning, it was an additional process or a new process where there was none. It's gone from a barrier to a platform, that's been rewarding to see that transformation.
Tashmin Ali
KC: That's great. The proof will be in the pudding, seeing how this change manifests over time. What are the expected long-term impacts of this change?
EM: One of them is scalability. We went from a process that wasn't enforced to just flooding the legal department with requests. We had to build an easy and scalable process that would let our team manage the volume of requests that they suddenly started receiving. We have confidence in our risk levels, our policy compliance, and a broader comfort level that we know what's out there. We know that our policies are being followed. We have built workflows that don't allow for loopholes, and we've seen improved coordination between departments. The ripple effect of workflow automation – everything from content licenses to website requests – now follows standard processes, and we set up workflows for those. Then there is the knowledge management aspect. We now have a database that gives us awareness of, "What are our commitments? What types of agreements are we signing? Who are we engaging with?" We didn't have that before.
KC: Great. As you were going through this process and this change and this transformation, did you uncover any surprises?
EM: Two main things caught my attention. One is how well the cross-functional teams have collaborated. It's been an amazing partnership with all of the other departments we worked with on this. I can't think of another project where everyone agreed comprehensively and fully supported the process. There was no, "We'll do one or two outside of the system." Having that collaboration and then improving those partnerships with those groups, that was the one main thing that was surprising to me. How well our stakeholders jumped on board. As I mentioned, the volume of ongoing enhancements and additional workflows requested and created, tweaks here and there, there's been broad engagement throughout the company. It's encouraging to see that people are interested, accepting the process, and willing to contribute to making it better.
TA: The sense of ownership that these cross-functional stakeholders have because they've been given opportunities from the very beginning to provide feedback. There's a really strong sense of ownership and commitment to the process. Between legal, procurement, IT, finance, tax, you've got this big group of folks that isn't going to let anything fall through the cracks or go through a loophole. I think it's really powerful—the volume of actual agreements coming through surprised us. We weren't sure whether it would be a trickle of water flowing fast with the first tool. It started with a trickle, and it turned into a much larger volume. We couldn't have anticipated, over time, that we would be in a steady state of 200-250 non-revenue transactions being submitted each month, up from a much smaller number before. That has been surprising and encouraging.
KC: Many of our listeners are in the middle of change projects and looking to innovate. What advice would you give them to help ensure success in their initiatives?
EM: It sounds like we keep stressing this over and over again, but bringing all the key stakeholders in early, making them a part of the task force, gives them a seat at the table in helping design the process. Engage the subject matter experts early. Make sure that their concerns are being considered and built-in. Tashmin, in particular, is fantastic at working with all of the impacted departments, not just who would be on the receiving end but on the end that would be pushing out these requests—working with them, on language, communications, making sure that we're in alignment with the team's leadership on the messages that were being sent out, how they were being worded. Some of the teams care greatly about how messages are communicated and what exact words are used. I think that engagement went a long way, making sure that we're tapping in all the groups. Things that we might not have considered otherwise, even down to the smallest notification messages, having their input on the system generate automated messages.
TA: Thinking carefully about crafting a message and getting everyone's input on that message is more powerful than we realized. As Elizabeth mentioned, some folks will have small tweaks; other times, they'll have massive changes. But when they feel like they've been part of the process of crafting the message, it's very helpful, and that proved useful and continues to be useful.
KC: It seems like it comes down to change management. Thank you so much for sharing the story of your innovation with us. A great conversation, thank you.
EM: Thank you for lending your team to us.
TA: Thanks, Elizabeth, for giving us the platform. It's all about the partnership.
The host of this interview is Elevate's Vice President of Legal Services, Kunoor Chopra, talking with Elizabeth Miller, Head of Legal Operations at Dolby Laboratories, and Tashmin Ali, a Senior Commercial Attorney with Elevate's Contract Services Business.


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LEGAL AID APPLICATION
British Nationality and Right to Abode
This chapter includes:
Introduction to British Nationality
People Born in the UK before 1983
People Born before 1983 but Outside the UK
People Born in the UK after 1982
People Born outside the UK after 1982
Status of an Illegitimate Child
British Citizenship Otherwise by Decent
British Citizenship by Decent
Registration as a British Citizen
Requirements for Naturalisation (Married Person)
Criminality Requirement
Requirements for naturalisation (non-married)
Cancellation/Termination of Citizenship
British National
A British National or a person with the right of abode is entitled to enter the UK without any immigration control. Such a person cannot be removed and deported and can enter whenever he/she likes without any questions asked.
A person is a British National if he was born in the United Kingdom before 1 January 1983 or up to and including 31st December 1982)
A person will also be a British national who was born outside the UK before 1983, and
His/her father was born in the UK; or
His/her father was registered or naturalised as a British citizen in the UK before the child's birth, and
His parents were married, or subsequently, married in a country which recognises such marriage and legitimises the child
If the father became a British National after the birth of the child then this will not make a child British who was born before the father's naturalisation as a British Citizen
A father could only pass on his British nationality acquired in the UK to his legitimate child before 1983
A mother before 1983 could not pass on her British Nationality /citizenship to any child born outside the United Kingdom.
However, Home Office allowed such a child to be registered as a British citizen during the childhood or adulthood of the child
John was born in 1956, in the UK, he is a British National. In 1972 John travelled to Singapore and married Sue, who is not a British National. In 1975, they had a baby girl Jasmin born in Singapore. Jasmin is automatically a British National as she acquires her British Nationality through her father
John was born in 1956, in the UK, he is a British National. In 1972 John Travelled to Singapore and started a relationship with Sue, who is not a British National. In 1975, they had a baby girl Jasmin born in Singapore. John and Sue are not married. Jasmin will not acquire British Nationality as the law only considers a married couple.
Stacy was born in 1961 in the UK, she is a British National. In 1974 Stacy moved to Canada and married Paul, who is not a British National. In 1977, they had a baby girl Lilly born in Canada. Stacy cannot pass her British Citizenship to Lilly. However, Lilly could have applied to register herself as a British National while she was a child or as an adult.
A person will be treated as a British Citizen if he/she was born in the UK after 1982 (from and including 1 January 1983) and at the time of his/her birth either of his parents were
British Citizen, or
Settled Person in the UK (Please refer to Settled Person)
A person will be treated as a British Citizen if he/she was born outside the UK after 1982 (from and including 1 January 1983) and at the time of his/her birth
Either the father or mother was a British National otherwise than by descent by birth in the UK (please refer below for further clarification)
The father or mother was a British National/citizen otherwise than by descent, having been registered or naturalised as British Citizen in the UK before the birth of a Child
If either a child's mother or father acquires British Citizenship after the birth of the child, this does not make the child automatically a British Citizen. The child has to register with Home Office and will have to apply for citizenship
WHO is a Father
A father is a person proven by the production of either a birth certificate which identifies him as father and which is issued by a competent authority, within 12 months of the birth of the child to which it claims to be a father.
A person who provides evidence (DNA test report or Court Order) that he/she is the biological father.
Where an illegitimate child is born in the UK on or after 1st July 2006 is a British Citizen if his Father was either a British National or Settled person at that time.
If a child is born in the UK before 1 July 2006 and his/her father was either a British National or Settled person at that time, such person can apply to Home Office to register as a British citizen, which is at the discretion of Home Office.
Where an illegitimate child is born outside the UK on or after 1st July 2006 will be a British Citizen if such person's father was a British National otherwise than descent or was a register or naturalised as a British Citizen.
Where a person acquires British citizenship by birth in the UK or as a child by registration in the UK or as an Adult by naturalisation in the UK, such person is classified as a British Citizen otherwise than by descent
The practical effect it may have is that such person can automatically pass on British Citizenship to his child who is born Outside the UK
British Citizens by Decent
These are the people who are Born Outside the United Kingdom and acquired British Citizenship by reason of the fact that one or both of their parents is a British Citizen.
The practical effect it may have is that such person cannot automatically pass on British Citizenship to his child who is born Outside UK. It is important to know that some second-generation children can be registered abroad at the British Consulate as British Citizens by further fulfilling conditions. It is a complex area of immigration law, please consult legalally's experienced Immigration Lawyers for further advice if you are a second-generation child.
A child can apply to register as a British Citizen if he was born in the UK after 1982 or after his birth and before attaining the age of 18 years
One of his parents acquired British citizenship or settled status in the UK
Such child remains in the UK for first 10 years of his life and he/she is not absent for more than 90 days in each year during these 10 years, however, certain exceptions do apply to this general rule please consult legalally's experience lawyers for further advice
Naturalisation is a process which allows a foreign national adult who has a settled status to acquire British citizenship.
The Home Secretary has the discretion to grant a certificate to a person who is not a British National
The grant of British Citizenship is not fundamental Human right; however, every applicant has a right to have an application considered fairly
The requirements to obtain a British Citizenship are slightly different for a foreign national who is married to a British citizen or settled
Requirements for naturalisation (Married)
if married to or in a civil partnership with a British citizen
The applicant must be settled at the time of application
Must have been living in the UK for 3 years continuously before applying for naturalisation
Must also be physically present in the UK on the date three years before the application is made
Must not be absent for more than 270 days in total during these qualifying three years and the applicant should also not have spent more than 90 days outside from the UK in the year immediately before the application
Home office may disregard 30 extra days when counting 270 days and 10 extra days when counting for 90 days in the preceding year
The applicant must also have sufficient knowledge of the English language and knowledge of life in the UK
The applicant must also be of a good character. The applicant must disclose all criminal convictions both inside and outside the United Kingdom including Motoring or Road Traffic Offences
An applicant can demonstrate the English language requirements by
Possessing a Home Office approved qualification or by passing a specific language test from a Home Office approved test centre/college
Possessing a Degree which is in line with the guidance of Home office
Or by satisfying that the applicant belonged to a majority English speaking country
Or the applicant has already met the requirement when he/she has made an earlier, successful application for indefinite leave to remain
An applicant can prove knowledge about life in the UK by passing the test commonly referred and known as Life in UK Test.
Impact on Application
4 or more years imprisonment
Application will be refused irrespective of when the conviction occurred
Imprisonment of more than 12 months and less than 4 Years
Application will be refused unless 15 years have been passed since the end of the sentence
Up to 12 months' Imprisonment
Application will be refused unless 7 years have been passed since the end of the sentence
Non- Custodial Sentence
The application will be refused if the conviction occurred in the last 3 years. An applicant has to wait for at least three years from the date of conviction
Where the applicant is neither married to nor in a civil partnership with a British citizen for such applicant the requirements are following
The applicant must have settled in the UK for at least one year before applying for naturalisation
Must have been living in the UK legally for 5 continuous years before applying for naturalisation.
Must also be physically present in the UK on the date 5 years before the application is received by Home office
Must not be absent for more than 450 days in total during these qualifying 5 years and applicant should also not have spent more than 90 days in the year immediately before the application
Must also have an intention to live in the United Kingdom
Home Secretary has the power to cancel or terminate the citizenship of a person who has acquired British Citizenship through naturalisation or by registration, if such a person is involved in the prohibited activities. These include cases which involve National Security, Terrorism, Serious Organised Crime, War Crimes, etc.
Citizenship is a complex area of immigration law. For further information and advice, you can ask the legalally's experienced Immigration lawyer.
While every effort has been made to ensure the accuracy of the information provided in this article, it does not constitute legal advice and cannot be relied upon as such. Each legal case and issue may have unique facts and circumstances, as a result legalally does not accept any responsibility for liabilities arising as a result of reliance upon the information provided. For further help and guidance, you can always rely on and seek advice from our experienced lawyers.
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You know what we love about winter vests? They're cute AND practical—especially for travel. They're lightweight so you don't have to sweat to death in the airport, and, if you buy the right kind, have plenty of pockets for storing iPhones, Chapstick, maybe some tissues, and definitely every manner of item your kids pick up off the ground. These are our picks for the best winter vests for moms.
This winter vest has eight pockets, including a zippered exterior pocket for easy access to your phone or other important items. The ScotteVest NBT for Women is also wrinkle-resistant, making it especially perfect for vacations, and its lightweight material means you can wear it year-round. It comes in black, navy blue, and red.
This lightweight puffer vest offers two exterior pockets and an interior zipper pocket. We love its simple design—and the fact that you can order it in just about every color imaginable! It also comes in a variety of patterns.
Don't want a high-neck vest? The Carhartt Women's Sandstone Mock Neck Sherpa Lined Vest is the answer, with a mock neck area. It offers two front pockets and a zippered pocket at the top, and its faux shearling interior is both stylish and cozy. It comes in five colors: Burl Wood (light pink), Dark Brown, Woodland (green), Crab Apple (hot pink) and Coastline (pale blue).
Looking for a fuzzy vest that can be worn with anything? Check out the ZESICA Women's Sleeveless Zip Up Fuzzy Fleece. This faux fur-lined vest features a zipper closure and two pockets, and comes in four colors: Charcoal, Gray, Blue, and Plum.
The Columbia Women's Morning Light Vest is thick enough to keep you warm, yet light enough that you won't get too hot. Its exterior dries extra fast, making it especially ideal for winter vacations. It has two zippered pockets in the front and comes in five colors: Black/Blue, Camellia Rose (hot pink), Purple, White and Black.
We can't get enough of the Auline Collection Women's Quilted Vest! This vest features a hood, fashionable gold zipper and buttons, and two zippered exterior pockets. It comes in 15 colors and is less than $30!


CBS has officially given the green light to "The Big Bang Theory" spin-off "Young Sheldon", which will chronicle the formative years of Jim Parsons' character, the brilliant but socially awkward Dr. Sheldon Cooper.
Jim Parsons, who's played Sheldon for 10 seasons so far on the hit sitcom, will narrate the half-hour comedy from the character's perspective as an adult, in addition to being an executive producer on the show.
CBS executive Leslie Moonves gave some other hints at a conference last week. Sheldon will have "a very right-wing family, not used to this 10-year old genius living in their midst. It's a terrific script and we have a terrific little kid," Moonves explained.
"Young Sheldon" will debut on CBS later this year as part of the 2017-2018 season.


text:
Sven Lõhmus (born 13 July 1972) is an Estonian pop-composer and lyricist. He is a producer at Moonwalk Studios, a music company featuring Estonian artists.

He has worked with leading artists of Estonia, including Vanilla Ninja (of which he was also manager), Suntribe, Urban Symphony, Grete Paia, Laura Põldvere, and Getter Jaani. In 2003, 2004 and 2010 he won the award for "Best Author" from the "Eesti Popmuusika Aastaauhinnad". He was also the lead singer of two bands, Mr. Happyman and Black Velvet.

Entries in the Eurovision Song Contest
"Let's Get Loud" by Suntribe, Estonia, (Eurovision Song Contest 2005), 20th place (Semi Final)
"Rändajad" by Urban Symphony, Estonia, (Eurovision Song Contest 2009), 6th place
"Rockefeller Street" by Getter Jaani, Estonia, (Eurovision Song Contest 2011), 24th place
"Verona" by Koit Toome & Laura, Estonia, (Eurovision Song Contest 2017), 14th place (Semi Final)

References

External links
moonwalk.ee

Estonian songwriters
1972 births
Living people
Estonian record producers
20th-century Estonian composers
21st-century Estonian composers
20th-century Estonian musicians
21st-century Estonian musicians
Tallinn University alumni

redpajama_set_name: RedPajamaWikipedia


The elder Francona played in the majors for 15 seasons, six with the Indians.
CLEVELAND — Former major leaguer John "Tito" Francona, the father of Cleveland Indians manager Terry Francona, has died. He was 84.
Terry Francona is affectionately called "Tito" after his father.


text:
Stratford School - Hollywood
Client: Stratford Schools
Scope: Renovation
Size: 53,000 SF
Completion: 2016
Project Manager: Mark Hembree, AIA, LEED AP
Stratford Schools, a very successful Northern California private school, teamed up with Berliner Architects to design a new private school in Hollywood – their first school in the burgeoning LA private school market. The existing 53,000 square foot building was renovated to house Pre-K to 8th grade students. Colorful window surrounds were added to give new branding to the building and add a new energy to the adjoining community. In order to meet pro forma enrollment numbers, dedicated exits were added to a mezzanine level for safe exiting of students in Kindergarten–second grade.
The success of the first school in a new market is crucial and the Hollywood campus will provide a solid foundation for future growth of Stratford Schools in the Los Angeles area.


text:
Author: Malcolm Smith
Malcolm Smith is a biologist, former Chief Scientist and Deputy Chief Executive at The Countryside Council for Wales and has been a Member of the Board of The Environment Agency (for England and Wales). He has had numerous features on wildlife, heritage and travel published in a variety of publications and is the author of the acclaimed Life with Birds, a Story of Mutual Exploitation; Back from the Brink and Gone Wild, Stories from a Lifetime of Wildlife Travel.
Back from the Brink by Malcolm Smith
Back from the Brink is an antidote to a world that seems full of stories of wildlife doom and gloom. Amongst all the loss of habitat and the animals and plants that are in spiralling decline, it's easy to forget that there are a huge number of positive stories too; animals threaten... more...
Gone Wild by Malcolm Smith
Often amusing, sometimes romantic or fraught with danger, these 30 short stories are about local people, spectacular places and the special wildlife the author sets out to find. The stories include seeking out Arabian Oryx on the searing plains of the Saudi desert; eiderdown collecting in Iceland... more...
Life with Birds by Malcolm Smith
Life with Birds uncovers the fascinating story of our interdependence with birds. The author weaves an amazing web of inter-relationships, from the Parsi funeral in Mumbai where birds of prey eat the dead; to collecting eider down from nests in Iceland and standing on the once body-strewn battlef... more...
Ploughing a New Furrow by Malcolm Smith
Farmland wildlife has been decimated by intensive crop growing using pesticides, grubbing up hedges, ploughing heathland and draining marshes, etc. With too many sheep grazing our moors, hills and mountains, a range of upland plants, invertebrates and birds has been diminished and the land conver... more...
"Many thanks for dealing with the order so promptly... "
Dianah, UK
"...my Mum was delighted to receive her beautifully wrapped edition of Caithness Archaeology this morning. "
Ann, UK
"...book arrived today thanks. Very well wrapped! "
Martin, UK


text:
Displaying 21 - 30 of 239. Show 10 | 20 | 50 | 100 results per page.
Project acronym BIOMIM
Project Biomimetic films and membranes as advanced materials for studies on cellular processes
Researcher (PI) Catherine Cecile Picart
Host Institution (HI) INSTITUT POLYTECHNIQUE DE GRENOBLE
Summary The main objective nowadays in the field of biomaterials is to design highly performing bioinspired materials learning from natural processes. Importantly, biochemical and physical cues are key parameters that can affect cellular processes. Controlling processes that occur at the cell/material interface is also of prime importance to guide the cell response. The main aim of the current project is to develop novel functional bio-nanomaterials for in vitro biological studies. Our strategy is based on two related projects. The first project deals with the rational design of smart films with foreseen applications in musculoskeletal tissue engineering. We will gain knowledge of key cellular processes by designing well defined self-assembled thin coatings. These multi-functional surfaces with bioactivity (incorporation of growth factors), mechanical (film stiffness) and topographical properties (spatial control of the film s properties) will serve as tools to mimic the complexity of the natural materials in vivo and to present bioactive molecules in the solid phase. We will get a better fundamental understanding of how cellular functions, including adhesion and differentiation of muscle cells are affected by the materials s surface properties. In the second project, we will investigate at the molecular level a crucial aspect of cell adhesion and motility, which is the intracellular linkage between the plasma membrane and the cell cytoskeleton. We aim to elucidate the role of ERM proteins, especially ezrin and moesin, in the direct linkage between the plasma membrane and actin filaments. Here again, we will use a well defined microenvironment in vitro to simplify the complexity of the interactions that occur in cellulo. To this end, lipid membranes containing a key regulator lipid from the phosphoinositides familly, PIP2, will be employed in conjunction with purified proteins to investigate actin regulation by ERM proteins in the presence of PIP2-membranes.
The main objective nowadays in the field of biomaterials is to design highly performing bioinspired materials learning from natural processes. Importantly, biochemical and physical cues are key parameters that can affect cellular processes. Controlling processes that occur at the cell/material interface is also of prime importance to guide the cell response. The main aim of the current project is to develop novel functional bio-nanomaterials for in vitro biological studies. Our strategy is based on two related projects. The first project deals with the rational design of smart films with foreseen applications in musculoskeletal tissue engineering. We will gain knowledge of key cellular processes by designing well defined self-assembled thin coatings. These multi-functional surfaces with bioactivity (incorporation of growth factors), mechanical (film stiffness) and topographical properties (spatial control of the film s properties) will serve as tools to mimic the complexity of the natural materials in vivo and to present bioactive molecules in the solid phase. We will get a better fundamental understanding of how cellular functions, including adhesion and differentiation of muscle cells are affected by the materials s surface properties. In the second project, we will investigate at the molecular level a crucial aspect of cell adhesion and motility, which is the intracellular linkage between the plasma membrane and the cell cytoskeleton. We aim to elucidate the role of ERM proteins, especially ezrin and moesin, in the direct linkage between the plasma membrane and actin filaments. Here again, we will use a well defined microenvironment in vitro to simplify the complexity of the interactions that occur in cellulo. To this end, lipid membranes containing a key regulator lipid from the phosphoinositides familly, PIP2, will be employed in conjunction with purified proteins to investigate actin regulation by ERM proteins in the presence of PIP2-membranes.
Project acronym BIOMOF
Project Biomineral-inspired growth and processing of metal-organic frameworks
Researcher (PI) Darren Bradshaw
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Summary This ERC-StG proposal, BIOMOF, outlines a dual strategy for the growth and processing of porous metal-organic framework (MOF) materials, inspired by the interfacial interactions that characterise highly controlled biomineralisation processes. The aim is to prepare MOF (bio)-composite materials of hierarchical structure and multi-modal functionality to address key societal challenges in healthcare, catalysis and energy. In order for MOFs to reach their full potential, a transformative approach to their growth, and in particular their processability, is required since the insoluble macroscopic micron-sized crystals resulting from conventional syntheses are unsuitable for many applications. The BIOMOF project defines chemically flexible routes to MOFs under mild conditions, where the added value with respect to wide-ranging experimental procedures for the growth and processing of crystalline controllably nanoscale MOF materials with tunable structure and functionality that display significant porosity for wide-ranging applications is extremely high. Theme 1 exploits protein vesicles and abundant biopolymer matrices for the confined growth of soluble nanoscale MOFs for high-end biomedical applications such as cell imaging and targeted drug delivery, whereas theme 2 focuses on the cost-effective preparation of hierarchically porous MOF composites over several length scales, of relevance to bulk industrial applications such as sustainable catalysis, separations and gas-storage. This diverse yet complementary range of applications arising simply from the way the MOF is processed, coupled with the versatile structural and physical properties of MOFs themselves indicates strongly that the BIOMOF concept is a powerful convergent new approach to applied materials chemistry.
This ERC-StG proposal, BIOMOF, outlines a dual strategy for the growth and processing of porous metal-organic framework (MOF) materials, inspired by the interfacial interactions that characterise highly controlled biomineralisation processes. The aim is to prepare MOF (bio)-composite materials of hierarchical structure and multi-modal functionality to address key societal challenges in healthcare, catalysis and energy. In order for MOFs to reach their full potential, a transformative approach to their growth, and in particular their processability, is required since the insoluble macroscopic micron-sized crystals resulting from conventional syntheses are unsuitable for many applications. The BIOMOF project defines chemically flexible routes to MOFs under mild conditions, where the added value with respect to wide-ranging experimental procedures for the growth and processing of crystalline controllably nanoscale MOF materials with tunable structure and functionality that display significant porosity for wide-ranging applications is extremely high. Theme 1 exploits protein vesicles and abundant biopolymer matrices for the confined growth of soluble nanoscale MOFs for high-end biomedical applications such as cell imaging and targeted drug delivery, whereas theme 2 focuses on the cost-effective preparation of hierarchically porous MOF composites over several length scales, of relevance to bulk industrial applications such as sustainable catalysis, separations and gas-storage. This diverse yet complementary range of applications arising simply from the way the MOF is processed, coupled with the versatile structural and physical properties of MOFs themselves indicates strongly that the BIOMOF concept is a powerful convergent new approach to applied materials chemistry.
Project acronym BIONICS
Project Bio-Inspired Routes for Controlling the Structure and Properties of Materials: Reusing proven tricks on new materials
Researcher (PI) Boaz Pokroy
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Summary "In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select. I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials. The three bio-inspired strategies that we will utilize are: (i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase; (ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature; (iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure. The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us (1) to produce single, intricately shaped crystals without the need to etch, drill or polish; (2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase; (3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."
"In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select. I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials. The three bio-inspired strategies that we will utilize are: (i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase; (ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature; (iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure. The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us (1) to produce single, intricately shaped crystals without the need to etch, drill or polish; (2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase; (3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."
Project acronym BOTTOM-UP_SYSCHEM
Project Systems Chemistry from Bottom Up: Switching, Gating and Oscillations in Non Enzymatic Peptide Networks
Researcher (PI) Gonen Ashkenasy
Host Institution (HI) BEN-GURION UNIVERSITY OF THE NEGEV
Summary The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.
The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.
Project acronym C-H ACTIVATION
Project New Concepts for Utilizing a Ubiquitous (Non-)Functional Group - C-H Bond Activation for Increased Efficiency in Organic Synthesis
Researcher (PI) Frank Klaus Glorius
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Summary C-H activations and related reactions can potentially revolutionize the way organic molecules are made and allow a more efficient use of earth's natural resources. Despite the rapid progress of the last couple of years, many problems like limited scope, extreme reaction conditions (temperature, excess of reagents) or low reactivities and selectivities remain in many cases. In this comprehensive proposal containing a number of projects and work packages, we want to develope new C-H activation methods 1) for the efficient synthesis of heterocycles, 2) for the activation of unactivated C(sp3)-H bonds, 3) by employing newly designed Fe-NHC complexes and 4) demonstrating the application of C-H activation for the functionalization of metal-organic frameworks (MOFs). The realization of these goals would render organic synthesis greener and more efficient and would have an impact on the preparation of compounds in academia and industry.
C-H activations and related reactions can potentially revolutionize the way organic molecules are made and allow a more efficient use of earth's natural resources. Despite the rapid progress of the last couple of years, many problems like limited scope, extreme reaction conditions (temperature, excess of reagents) or low reactivities and selectivities remain in many cases. In this comprehensive proposal containing a number of projects and work packages, we want to develope new C-H activation methods 1) for the efficient synthesis of heterocycles, 2) for the activation of unactivated C(sp3)-H bonds, 3) by employing newly designed Fe-NHC complexes and 4) demonstrating the application of C-H activation for the functionalization of metal-organic frameworks (MOFs). The realization of these goals would render organic synthesis greener and more efficient and would have an impact on the preparation of compounds in academia and industry.
Project acronym CARBONFIX
Project Towards a Self-Amplifying Carbon-Fixing Anabolic Cycle
Researcher (PI) Joseph Moran
Host Institution (HI) CENTRE INTERNATIONAL DE RECHERCHE AUX FRONTIERES DE LA CHIMIE FONDATION
Summary How can simple molecules self-organize into a growing synthetic reaction network like biochemical metabolism? This proposal takes a novel synthesis-driven approach to the question by mimicking a central self-amplifying CO2-fixing biochemical reaction cycle known as the reductive tricarboxylic acid cycle. The intermediates of this cycle are the synthetic precursors to all major classes of biomolecules and are built from CO2, an anhydride and electrons from simple reducing agents. Based on the nature of the reactions in the cycle and the specific structural features of the intermediates that comprise it, we propose that the entire cycle may be enabled in a single reaction vessel with a surprisingly small number of simple, mutually compatible catalysts from the recent synthetic organic literature. However, since one of the required reactions does not yet have an efficient synthetic equivalent in the literature and since those that do have not yet been carried out sequentially in a single reaction vessel, we will first independently develop the new reaction and sequences before attempting to combine them into the entire cycle. The new reaction and sequences will be useful green synthetic methods in their own right. Most significantly, this endeavour could provide the first experimental evidence of an exciting new alternative model for early biochemical evolution that finally illuminates the origins and necessity of biochemistry's core reactions.
How can simple molecules self-organize into a growing synthetic reaction network like biochemical metabolism? This proposal takes a novel synthesis-driven approach to the question by mimicking a central self-amplifying CO2-fixing biochemical reaction cycle known as the reductive tricarboxylic acid cycle. The intermediates of this cycle are the synthetic precursors to all major classes of biomolecules and are built from CO2, an anhydride and electrons from simple reducing agents. Based on the nature of the reactions in the cycle and the specific structural features of the intermediates that comprise it, we propose that the entire cycle may be enabled in a single reaction vessel with a surprisingly small number of simple, mutually compatible catalysts from the recent synthetic organic literature. However, since one of the required reactions does not yet have an efficient synthetic equivalent in the literature and since those that do have not yet been carried out sequentially in a single reaction vessel, we will first independently develop the new reaction and sequences before attempting to combine them into the entire cycle. The new reaction and sequences will be useful green synthetic methods in their own right. Most significantly, this endeavour could provide the first experimental evidence of an exciting new alternative model for early biochemical evolution that finally illuminates the origins and necessity of biochemistry's core reactions.
Project acronym CASAA
Project Catalytic asymmetric synthesis of amines and amides
Researcher (PI) Jeffrey William Bode
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Summary "Amines and their acylated derivatives – amides – are among the most common chemical functional groups found in modern pharmaceuticals. Despite this there are few methods for their efficient, environmentally sustainable production in enantiomerically pure form. This proposal seeks to provide new catalytic chemical methods including 1) the catalytic, enantioselective synthesis of peptides and 2) catalytic methods for the preparation of enantiopure nitrogen-containing heterocycles. The proposed work features innovative chemistry including novel reaction mechanism and catalysts. These methods have far reaching applications for the sustainable production of valuable compounds as well as fundamental science."
"Amines and their acylated derivatives – amides – are among the most common chemical functional groups found in modern pharmaceuticals. Despite this there are few methods for their efficient, environmentally sustainable production in enantiomerically pure form. This proposal seeks to provide new catalytic chemical methods including 1) the catalytic, enantioselective synthesis of peptides and 2) catalytic methods for the preparation of enantiopure nitrogen-containing heterocycles. The proposed work features innovative chemistry including novel reaction mechanism and catalysts. These methods have far reaching applications for the sustainable production of valuable compounds as well as fundamental science."
Project acronym CAT4ENSUS
Project Molecular Catalysts Made of Earth-Abundant Elements for Energy and Sustainability
Researcher (PI) Xile Hu
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Summary Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc. Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis. The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc. Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis. The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Project acronym CatASus
Project Cleave and couple: Fully sustainable catalytic conversion of renewable resources to amines
Researcher (PI) Katalin Barta Weissert
Summary Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date. The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are: WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations. The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.
Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date. The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are: WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations. The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.


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If you're thinking about selling your home, then you need to familiarize yourself with the term UPSTAGING! Regardless of whether your home is vacant or occupied with furniture, all sellers should stage their home in order to sell it for the highest price in the shortest period of time.
You only have, on average, 20 seconds to form either a positive or a negative impression in the eyes of a potential buyer once you decide to put your home on the market!!! This is why STAGING your home is SO VITALLY IMPORTANT to a successful sale of your home. Once you put your home on the market it stops being your home and becomes someone else's dream. VISUALLY, all of the colors, spaces, designs, furniture, traffic patterns, and your belongings will form either a favorable or an unfavorable impression. If a buyer experiences the latter, you will lose the sale of your home!
Buyers will submit an offer on a home they can see themselves living in, and STAGING is not about decorating - it's all about how to showcase your home instead of your belongings.
To learn how to get a FREE 1 HOUR STAGING CONSULTATION with one of the areas TOP experts on how to prepare your home to sell for the highest price in the shortest period of time, please fill in the information to the right!


Egg Dying- Chemicals Not Included!
Easy-to-use directions to make multiple colors.
Its that time of year! Easter is soon approaching, and many of us, including myself are going to dye eggs with our children. Traditional egg dye kits are loaded with a plethora of nasty chemicals and artificial dyes, many of which can be harmful to consume.
However, nature-friendly company eco-kids' eco-eggs are all natural, with dyes made only of plant-based ingredients. (Gardenia flower, curcumin, annatto seeds, red radish, red cabbage, and purple sweet potato.) While it isn't quite Easter, I broke out the white eggs and boiling water to try the kit myself! My two sons, Hanz (17) and Riley (8) helped me dye the eggs. The kit included three dye packets: purple, orange, and blue. We mixed the dyes into warm water and got started. Right off the bat we noticed the time that was required to submerge each egg, an average of 5-8 minutes. This could pose an issue with impatient young children, so it might be beneficial to let the eggs sit while they are preoccupied with another activity.
The kit also included a piece of white crayon wax, to allow kids to design any kind of egg they want. Don't let the amount of dyes fool you, the color chart included in the kit helped us make yellow, green, and even brown eggs! After submerging the eggs the colors came out surprisingly well-purple was the most strong, followed by orange, and then blue. However, the process to get a green egg took a few tries, and resulted in a lighter, pastel green. It was challenging to get a solid green egg, as it required a dip in both orange and blue dyes. Another color added to the mix would be helpful, perhaps a red or green, to create a greater option of colors without having to go through the complex process.
We dyed nine eggs total, each having their own unique patterns. Spotted, striped, zig-zag, and classic solid eggs were all included in the mix. We can't wait to eat them even though we have to un-peal these beautiful creations!
The kit also included a wheatgrass growing kit with the intent to display the eggs atop of it. The compressed soil and seeds were included in the main container; a cute, creative, and natural way to display your dyed eggs! Overall, I found this kit to be very simple and easy to use, yet still offered the quality of a traditional, store-bought kit. Would definitely recommend to all of the natural Moms and Dads out there!
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