text:
Financial Services and Real Estate
COLUMN-Got any copper to spare? Please send to China: Andy Home
By Andy Home
(The opinions expressed here are those of the author, a columnist for Reuters)
* Global exchange stocks of copper: tmsnrt.rs/1WGa8t2
LONDON, Feb 23 (Reuters) - Note to global copper producers. If you have any surplus metal and you're not already doing so, please send it to China.
The country is currently sucking up copper at a faster rate than even during the boom years of rampant infrastructure spend.
Quite evidently, reports of the death of the Chinese manufacturing sector may have been slightly exaggerated.
But there is also no doubt that China is embarked on a massive stock-building exercise.
The most visible part of this phenomenon has been the surge in inventory registered with the Shanghai Futures Exchange (SHFE), which now comfortably exceeds that in the London Metal Exchange's (LME) global warehouse network.
SHFE stocks have just hit a historic high. LME stocks are at a one-year low and still falling.
Such a mass relocation of inventory may be broadly price neutral but on current trends is going to generate very divergent outcomes in terms of market structure.
IMPORTS UP...
January's imports of refined metal may have been down on December but that month's tally of 423,000 tonnes was the highest on record.
On a year-on-year basis last month's net imports of 315,000 tonnes were up almost 16 percent.
Moreover, January's net figure dwarfs average monthly rates of 256,000 tonnes in 2009, 239,000 tonnes in 2010 and 223,000 tonnes in 2011, three years of frenetic Chinese construction activity as Beijing sought to offset the impact of the Global Financial Crisis.
True, there may be some distortion arising from the timing of the Lunar New Year holidays in China but this trend of super-strong imports has been running for several months. Last year's imports of 3.68 million tonnes were also a record high.
Imports of copper concentrates, meanwhile, are also running at an extremely fast pace.
The first time monthly imports of the raw material exceeded 1.0 million tonnes (bulk weight) was in September 2013 and it was a fairly rare occurrence until last year.
January's tally of 1.17 million tonnes marked the sixth straight month of seven-figure tonnages.
Higher concentrate imports should, all other things being equal, translate into lower demand for imports of refined metal.
All other things, however, are far from equal.
...STOCKS UP...
The simple explanation for why imports continue to boom is that the arbitrage has for some time remained largely import-positive.
But what are the drivers keeping that arbitrage open and fuelling China's undiminished appetite for imports?
Chinese copper usage may have lost a lot of its growth momentum as the country's real estate bubble gradually deflates and the broader manufacturing sector loses its previous white heat, but it hasn't imploded.
Moreover, Chinese smelters' reaction to low prices, a combination of production cuts, reduced commercial sales and distress sales to the government stockpile manager, the State Reserves Bureau, may have created a temporary shortage of commercially available metal.
But it is also clear that much of what is currently entering the country is piling up in inventory.
SHFE stocks have increased by almost 100,000 tonnes since the start of January and at a current 276,904 tonnes are at record highs.
There are also some 400,000 tonnes of copper sitting in the statistical shadows of Shanghai's bonded warehouse zone.
There is also, it is probably fair to say, a lot more still lying in even greater statistical darkness in mainland warehouses.
And that's not even counting the stuff that is being held by the secretive State Reserves Bureau, the true heart of statistical darkness when it comes to Chinese copper stocks.
In part, such stock-building is a normal reaction to low prices. China is still a net consumer of copper and like any buyer will be incentivised to accumulate inventory during periods of price troughs.
An added incentive may be coming from expectations of further yuan devaluation, which would make dollar-denominated metal more expensive.
Of course there's no point in accumulating inventory if you expect your own customer demand to collapse.
If there's a positive from these figures in terms of the state of the Chinese manufacturing engine, it's that many Chinese players are keeping the faith that things are only going to be get better, or at least not appreciably worse.
Graphic on global exchange stocks of copper:
tmsnrt.rs/1WGa8t2
...BUT NOT ON THE LME
It's not the first time SHFE stocks have exceeded those held by the LME but the last time was in 2005, a year of chronically low stocks when LME inventory fell below 30,000 tonnes.
And the differential with the SHFE was never more than a couple of thousand tonnes back then.
It is currently over 70,000 tonnes and that's just at a headline basis.
Stripping out the amount of metal earmarked for physical load-out, available LME stocks are actually a lot lower than the headline total of 203,700 tonnes.
After another 7,750 tonnes of net new cancellations yesterday, available LME stocks, or "open tonnage" as its known in LME parlance, stands at just 162,300 tonnes.
Both headline and open tonnage stocks have been trending lower since the start of this year, in sharp contrast to what's happening in China.
Such divergence in Shanghai and LME stocks trends has happened before but rarely so starkly.
And while that may not in itself mean much for the outright copper price, it does have significance in terms of respective spread structures.
The SHFE is currently trading in contango. The LME is currently trading in backwardation with cash prices commanding a premium over forward prices.
That LME backwardation looks fairly benign right now. The benchmark cash-to-three-months spread CMCU0-3 was valued at a modest $3.50-per tonne backwardation at Monday's official close.
That may be due to an absence of any dominant position holder, although one entity has been popping in and out of the LME's market positioning reports for some time.
History suggests, however, that LME open tonnage is approaching levels where the spreads can get stormy, particularly if there are significant short positions to be rolled, as seems likely given the recent outright price action.
A more acute backwardation may disrupt the flow of copper into China but until it does, surplus metal is still heading to the market of first resort.
Editing by David Evans


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Aparthotel Attica 21, C/ Milena Jesenska, 40-60, Sabadell.
Hotel Don Candido, Rambleta del Pare Alegre 98, Terrassa.
Hotel La Florida, Ctra Vallvidrera al Tibidabo 83-93, Barcelona.
Majestic Hotel & Spa, Passeig de Gràcia, 68 Barcelona.


text:
The 4 biggest myths about female orgasm, according to a sex therapist
By Suzannah Weiss
You might've heard of the orgasm gap — the tendency for men in our society to orgasm more than women. You may not have heard, though, that some women — five to 10 percent, according to one meta-analysis — have never had an orgasm. Sex therapist Vanessa Marin's online course Finishing School is hoping to change that. Through recorded talks, a workbook, and group calls, Marin teaches women who have never orgasmed or have trouble orgasming how to identify and dismantle their orgasmic blockages.
Since I've had the pleasure (no pun intended) of taking the course, I know that one of the biggest blockages Marin addresses is the internalization of myths about the female orgasm. "I want you to recognize that all these things you believe about your orgasm don't belong to you," she tells her students. "They were put there by an anti-sex, anti-woman society."
Hopefully, you know that certain ideas about the female orgasm — like that it normally happens through intercourse — are myths, but Marin addresses some lesser-known misconceptions. Here are some that you might find surprising.
Myth #1: Some women can't orgasm
It's true that some women have not orgasmed yet, but Marin too often sees this fact treated as evidence that some women cannot orgasm. "There has never been evidence that certain women are physically incapable of orgasming," she says in her course. If you haven't orgasmed, Marin urges against viewing your body as the problem. It's more likely that you simply have not yet learned how to orgasm — in fact, you may have been actively discouraged from exploring your body and sexuality. These are problems with our society, not problems with your body.
Myth #2: Female orgasms are more complicated than male ones
Along the same lines, the orgasm gap is often attributed to inherent characteristics of the female body — namely, that vulvas are supposedly more complicated and less orgasmic than penises. But the main reason it seems that way is that men have gotten more practice, according to Marin. Due to societal double standards, men typically masturbate earlier and more frequently than women. But it actually takes them a month to a year on average to learn how to orgasm. And once women learn to orgasm, most can get there pretty reliably. Sex researcher Shere Hite reported in The Hite Report that 95% of women she studied who masturbated could orgasm "easily and regularly, whenever they wanted." Female genitalia is amazing and should be celebrated for what it can do, not denigrated for what it supposedly cannot do.
Myth #3: You should instinctively know how to orgasm
One reason so many women haven't orgasmed is that they're expected to automatically know how and learn virtually nothing, according to Marin. Then, they feel ashamed for not knowing, which makes them scared to even try. Or, since they haven't figured it out like everyone else supposedly has, they believe they're incapable.
But the truth is, while some people experience their first orgasms accidentally or through their own experimentation, many need to learn — and that's OK! Advice online and in magazines can be frustratingly vague, but courses like Finishing School, sites like OMGYes, books like Laurie Mintz's Becoming Cliterate, workshops at sex toy shops like Good Vibrations, apps like Lioness, and sessions with a sex therapist can all help you figure it out.
Myth #4: Female orgasms are always intense
Based on the screams and ecstatic faces of many porn stars and actresses, you may believe female orgasm is always an out-of-this-world experience. But many of Marin's clients find that their first orgasms are so subtle, they're not even sure if they're orgasming. Some wonder, "Was that it?" The truth is, orgasms exist on a spectrum from giant earthquakes to tiny rumbles, according to Marin. Your first ones especially may be mild. But the fortunate thing is, they get better as time goes on. Besides, orgasms are like chocolate: Even when they're bad, they're still good.
Angry about these destructive messages you've been given about your body? Use that anger as motivation to pursue your pleasure unapologetically, no matter what the patriarchy tells you. As Marin tells her students, "I want you to get fired up to prove all of these dumb female orgasm myths wrong."
/Shutterstock.com

redpajama_set_name: RedPajamaCommonCrawl


Did you know that more than 60% of all confirmed data breaches involve the leveraging of weak, stolen, or default passwords?
One of your practice's frontline defenses for avoiding the phishing attacks and other cybercriminal schemes is effective password management. How well are you managing yours? Take this short (and fun) quiz to find out.
Strong passwords are too complicated to remember. It's fine to use passwords that are short and easy.
Easy passwords are easy to crack. Believe it or not, the most popular passwords in the United States are still "password" and "12345." These weak passwords offer little security and are simply dangerous. Instruct your team to create strong passwords that contain a mix of letters, cases, and symbols. If you're concerned about not remembering passwords, uses a password-management program like LastPass, which saves passwords securely and provides access to them on any device.
Another option to use a passphrase, using a combination of letters and symbols. For example, "Fido" is an insecure password and easy to guess if it's your pet's name. But My1$tPetWasFid0 follows strong password guidelines and is more secure.
A. Is a really bad idea.
B. Is essential to getting any work done if you are over 40.
C. Is a nice way to help new employees get to know you.
I still see sticky notes regularly in the practices I visit. And there is always at least one staff member's desk with multiple, colored, sticky notes containing his or her password in plain sight. This is not good cyber hygiene. Conduct a walk around the office and remove all sticky notes and other evidence of passwords in plain sight. Do it today; we'll both sleep better tonight.
B. If you forget the password, your coworker can remind you.
C. It's never ok to share passwords.
When it comes to data security, sharing is never ok. A practice in the East used only passwords for the entire team: "doctor" and "nurse." Although this is an extreme case, passwords are shared with some regularity in many practices. Beyond the cybersecurity concerns, sharing passwords has professional liability issues because they render electronic medical record (EMR) audit trails useless. It's impossible to identify the person who reviewed or entered information if passwords are shared.
Compliance issues are also triggered by password sharing. There's no sure way to determine whether patient privacy is maintained if it's unclear which user is accessing them.
The bottom line is passwords are like underwear…don't share them and change them often. Anyone caught sharing passwords should be disciplined.
4. When should a practice disable the passwords of employees who leave?
A. By the end of the week after the employee is gone.
B. When my kid is home from college; he handles stuff like that in our computer system.
C. Immediately after you have terminated the employee, or the employee has left the premises on good terms.
D. We're supposed to disable passwords?
Staff turnover is a given. So have a plan for terminating user IDs and passwords in all systems immediately after the employee leaves. Often, this step is delayed or forgotten, leaving passwords active for potential access. Put credential disabling at the top of your employee-departure checklist.
5. If you aren't using a password manager, the best way way to remember a complicated strong password is to use the same one for multiple accounts.
Humans are creatures of habit. According to a survey by LastPass and Lab42, 59% of us "mostly" or "always" use the same password for everything.
And only 55% said they would change their password if their account was hacked. Startling, but true.
Make sure you and your team are not part of the 55%. Insist on strong passwords. Store them in a password manager. And don't use the same password for every account.


After two years, now, of living with my heart situation I guess I've become pretty accustomed to it and don't pay it any never mind outside of the occasional impact to my diet or physical output; minor that they are.
However, as normal as it may be to me, it's still certainly not normal to others; specially when these others, such as my friends I'm staying with here in Seattle, have already had another friend nearly die on them after having a heart attack. So I guess, from the other room, it's totally plausible she'd hear "OH MY HEART!" and be... concerned.


text:
export { AST_NODE_TYPES, AST_TOKEN_TYPES, TSESTree, } from '@typescript-eslint/typescript-estree/dist/ts-estree';
export { ParserServices } from '@typescript-eslint/typescript-estree/dist/parser-options';
//# sourceMappingURL=ts-estree.d.ts.map

redpajama_set_name: RedPajamaGithub


Now that you have completed your studies and graduated with a certificate / diploma or an honorable associate's degree in the field of phlebotomy, you are officially a phlebotomy technician.
Due to the extensive courses you have taken and the skills you have learned, you are more than qualified to provide proper phlebotomy care. Now is the time to gather all that you have learned and the skills you have acquired, in order to apply such knowledge to real-world situations.
This is the time to increase your level of confidence and use your professionalism to seek job opportunities as a phlebotomist. During the planning stages of looking for such an opportunity, it is priority to prepare a good resume.
A good resume should be highlighting your skills, education and professional experience. Each highlight should be relevant to the position in which you are seeking: phlebotomy technician. If you recently graduated from a training program and have no professional work experience, it is important to highlight experience gained from your externship. Such a resume would help to open the doors of opportunity. Once you are done with that, common interview questions should be prepared and rehearsed prior to and immediately after scheduling an interview.
During the job hunting process, there are many places to search in hope of finding employment as a phlebotomy technician. If you view the classified section of newspapers, online or in print, there are tons of job openings listed. Of the many ads that are there, you are sure to find job openings for phlebotomy technicians. Other places to search include online job sites such as Indeed.com, Monster.com and CareerBuilder.com.
These job sites are flooded with employment opportunities, as hundreds of new jobs are posted daily. Once you have scanned through all the postings and have found opportunities that interest you, the next step is to schedule an interview.
While speaking with potential employers on the phone in hopes of obtaining an interview, effective communication is priority. During this process, it is important to put your best foot forward, as first impressions are lasting impressions. Although communication by phone is not face-to-face, communication at this stage is equally important, as it could lead to an interview for the desired position as a phlebotomy technician. Making use of correct grammar, while speaking slowly and clearly, are effective ways to communicate.
It is always recommended to have an air of confidence, as this will show through your speech. Such characteristic will send a positive message to the potential employer and lead him or her to believe that your job qualities are outstanding. This unspoken message should surely get you to the interview table. A bullet list concerning phone etiquette is noted below. Use this reference often to master such skills.
Speak slowly and clearly: You want to make sure your words are heard and understood.
Use proper grammar: You want to make sure your message is clearly understood.
Be professional: Do not eat or drink while speaking on the phone.
Speak confidently: Speak with a positive attitude and self-assurance; this message will be well-received.
Speak in a quiet environment: Schedule an interview in an environment that is free of background noise and speak in low traffic areas.
Avoid interruptions: Allow a potential interviewer to complete a statement or question before commenting or responding.
Use clarification: Once an interview is scheduled, repeat important information such as the date, time and place of the interview; this will help to avoid the possibility of miscommunication.
Obtain important information: It is important to obtain the interviewer's first and last name in addition to the correct spelling and pronunciation. This will help to eliminate embarrassing moments of misspelling the interviewer's name on an application or mispronouncing his or her name during the greeting process.
Once you have succeeded in impressing the potential interviewer via phone, it is now time to make a favorable impression face-to-face. While attending an interview, it is always in your best interest to put your best foot forward. Although this is equally true when scheduling an interview, there are some differences.
During a face-to-face interview, the interviewer or potential employer sees the entire package. At this point, he or she makes the connection between your communication skills and a physical picture of who you are. Your communication skills are now placed with an identifiable image. As such, this allows an interviewer to quickly assess who you are and determine if you are the right person for the job.
In order to send a positive message, it is important to dress appropriately, act confidently and maintain a level of professionalism at all times. By doing so, this sends a message to the potential employer that you are deeply interested in obtaining a position within his or her company or organization. A bullet list concerning the skills and techniques necessary to have a successful interview is referenced below. Use this reference often and master the topics noted.
Sell yourself: If you are shy, this is not the time to possess such characteristic. If you are a person with confidence, use this to your advantage. Speak highly of the skills you have acquired throughout your phlebotomy training. Tell of your experience during your externship and impress the interviewer with examples of your venipuncture skills. Sound enthusiastic concerning your role as a future phlebotomist with the interviewing company.
Dress appropriately: No hats, caps, sneakers, jeans or excessive jewelery. Certain hats, however, may be worn due to religious references.
Arrive early: This allows time to mentally and physically prepare yourself for the interview, if applicable. This also allows time to complete an application or list references prior to the scheduled appointment.
Make eye contact: Making eye contact sends a message of confidence. This air of confidence lends itself to credibility; this is important in every interview.
Show recognition: Greet the interviewer by last name. This shows a level of respect and acknowledgment concerning the position held by the interviewer. Everyone loves to be respected and acknowledged.
Provide complete answers: Answer all questions thoroughly; do not leave room for assumptions. Give the exact information you want the interviewer to know.
Research: It is always important to do a little research concerning the company with which you will have an interview. The knowledge gained will allow you to ask questions relevant to the company. Your ability to ask questions concerning a company's history will show your interest in the company and the position of phlebotomy technician.
Be exactly who you are: Show your true personality, if appropriate. Smile, speak positively, be grateful and assertive. Walk, talk and act with a disposition of confidence. Such characteristic provides an insight concerning your future role as a phlebotomy technician.
Present an outstanding resume: The information on your resume provides an insight to your quality and skills. The style and quality of paper used will provide an insight concerning who you are as a person.
Now that you have received a list to master the skills necessary for phone etiquette and a list of skills needed to land the job, it is now necessary to familiarize yourself with interview questions. As you seek jobs, it would be to your advantage to know some of the common questions asked during an interview. Knowing such questions beforehand will allow you the opportunity to review them and prepare proper responses.
1. How did you become interested in phlebotomy?
As a young child, I have always had an interest in healthcare. As I have attended many medical appointments in the past, I have always been fascinated with the medical terms used by phlebotomy technicians and the use of phlebotomy equipment. I was always amazed to see how phlebotomists performed venipuncture procedures. I have always had the desire to become a phlebotomist.
2. Are you comfortable with venipuncture procedures?
I am extremely comfortable with venipuncture procedures. During my phlebotomy courses, I received extensive training concerning the collection of blood. My training involved step-by-step instructions ranging from where and how to tie a tourniquet, to choosing the correct needle type and size in addition to finding the perfect vein. Additionally, the in-class training and real-life experience I received from my externship allows me to be extremely comfortable with the collection of blood.
3. How much phlebotomy experience do you have?
My phlebotomy experience extends from the three month training I received from my phlebotomy courses and my 40 hours of training during my externship. Additional experience comes from the 3 month volunteer work I provided for various hospitals and outpatient draw sites.
4. Why should I hire you as a phlebotomist?
By hiring me as a phlebotomy technician, I will be an asset to your healthcare staff. Once hired, I will bring my knowledge of the venipuncture process and experience of working with various populations. My skills of working with people will bring repeat patients who expect to receive high-quality healthcare.
5. What qualities would you bring to the job?
As a certified, skilled phlebotomist, one of the most important qualities I will bring to the job is professionalism. I will treat all colleagues and patients with the respect they deserve. Patients will receive quality healthcare regardless of their nationality or economic status. I will treat each patient as a person by engaging in small conversation to provide a feeling of relaxation throughout the blood collection process.
6. How would you identify a patient?
As a professional phlebotomist, it is my responsibility to correctly identify patients at all times. This will help to eliminate any errors and the possibility of malpractice, due to the delivery of healthcare to the wrong patient. To correctly identify a patent, I will ask for critical information concerning the patient's full name, date of birth and address. The provided information will be compared to the healthcare records o file.
7. What would be the best part of the job?
The best part of being a phlebotomist would be doing what I love best: Providing quality healthcare and assisting patients when possible. The service all patients deserve.
8. What would be the worst part of the job?
As a phlebotomist, the worst part of my job would be the inability to make patients feel comfortable. As a healthcare professional, it would be my responsibility to gain the trust of my patients.
9. How would you describe a typical day as a phlebotomist?
A typical day as a phlebotomist include gathering patient files and organizing work stations. When a patient arrives, I will introduce myself and ask questions concerning the patient's first and last name, date of birth and address. This information will be used to compare the information on file. Before blood is withdrawn, non-sterile gloves will used to open an alcohol pad, a band-aid and a sterile gauze. The necessary equipment will be displayed. Once the patient is asked which arm is preferable for the process, I will inform the patient of each step and prepare him or her for the actual withdrawal of blood. A tourniquet will be applied to the patient, palpation of the veins will take place and the site to be injected will be sterilized. Once the blood is collected in the vacutainer , the sample will sent to the lab for various tests.
10. How do you find a vein?
Once a tourniquet is tied, I would use the palpation method to find a suitable vein.
11. What if you have difficulty finding a vein?
If I have difficulty finding a median cubital vein, I would check the cephalic vein. If difficulty persists, after checking both arms, I would palpate the dorsal vein for withdrawal. Withdrawing blood from the hand would be the last resort.
12. What would you do if you saw an unpleasant interaction between a colleague and a patient?
If I observed an unpleasant interaction between a colleague and a patient, I would pleasantly ask my colleague if he or she needed assistance. Hopefully my presence and assistance would turn a negative experience into a positive one.
13. Why do you want to work here?
I have chosen to work here because my research indicates high-quality care performed at this facility. I would like to work among the best in the field of phlebotomy.
14. Do you have a problem working with the young or elderly?
I do not have a problem working with either population. My phlebotomy training and experience provides me with the skills and patience to work with all populations.
I am a pleasant individual with an out-going personality. I am reliable, professional and dedicated.
Seeking a position as a phlebotomy technician involves great preparation. Mastering the skills of phone etiquette and the skills necessary to land a job are critical in the preparation process. Once these skills are mastered, you are sure to land the job of your dreams and make use of your phlebotomy diploma / degree.
I found this extremely helpful!!
I thought this was very helpful and I will be adding it to the list of other possible interview questions they may ask.
I have an interview soon and wanted to know what questions will be asked I must say the above has helped me where it has given me an insight in case I'm asked these question I'm going for this job and I really hope I get it abit Nevous blank minded but I hope it all goes well as I have been out of employment for a long time.
Oh wow extremely helpful thank u so much.
This is so helpful, I was able to get a well based idea on how to answer the questions and what questions to expect.
Thank you. This is helpful but do theye ask the same questions if you're going to a phlebotomy learnership interview?


With technology finding its way into more and more aspects of our everyday lives, it was only a matter of time before our homes got some tech-savvy upgrades.
For decades we have been prompted to live in tighter, more efficient and "greener" homes. And for decades, the definition of "greener" has evolved along with our sensibilities.


Situated on the west end of Santa Rosa Island in Pensacola Beach is the Gulf Islands National Seashore and Portofino Island Resort & Spa, offering vacation condominium rental homes with a perfect balance of indulgence surrounded by natuesl beauty. Ideally located between the Gulf of Mexico and Santa Rosa Sound, Portofino's protected shoreline offers endless opportunities for recreation and relaxation on the beautiful emerald green waters of Pensacola Beach Florida.
On your next Florida beach vacation, make plans to explore the sand, surf and sky as you hike, bike or kayak along the shoreline. Dine on some of the Gulf Coast's freshest seafood, savory steaks and other surperb cuisine at one of Portofino's restaurants. Awaken your senses with pampering spa treatments. From the moment you arrive, Portofino's professional staff will spoil you as you enjoy one of nature's unspoiled playgrounds.


text:
> Robert, son of Gregory steward of Coldingham
Robert, son of Gregory steward of Coldingham
Total number of associated factoids: 150
Transaction factoids (1) Relationship factoids (73) Title factoids (14) Witnesses factoids (62)
1239 Resignation of lands in Coldingham Sealer 3/159/1 (ND, App. no. 272)
undated Son of Robert, son of Gregory steward of Coldingham (Familial relationship) object (relationship) 3/156/1 (ND, App., no. 309)
undated Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/150/6 (ND, App., no. 276)
undated Son of Gregory of Coldingham (Familial relationship) subject (relationship) 3/61/1 (ND, App., no. 213)
undated Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/478/13 (ND, App., no. 330)
X 9 Dec. 1223 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/488/10 (ND, App., no. 183)
X 1233 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/341/1 (ND, App., no. 302)
X 1234 Son of Gregory of Coldingham (Familial relationship) subject (relationship) 3/56/1 (ND, App., no. 318)
X 6 Oct. 1245 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/441/2 (ND, App., no. 368)
X circa 1247 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/500/2 (ND, App., no. 391)
X 1249 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/488/20 (ND, App., no. 257)
X 1249 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/201/2 (ND, App., no. 376[*])
1200 X 1235 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/368/1 (ND, App., no. 271)
1212 X 1221 Son of Robert, son of Gregory steward of Coldingham (Familial relationship) object (relationship) 3/512/1 (ND, App., no. 320)
1220 X 1229 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/488/22 (ND, App., no. 187)
Mar. 1234 X 1244 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/499/7 (ND, App., no. 401)
1239 Son of Gregory of Coldingham, steward (Familial relationship) subject (relationship) 3/159/1 (ND, App. no. 272)
1239 X 1242 Son of Gregory of Coldingham (Familial relationship) subject (relationship) 3/62/4 (ND, App., no. 339)
undated Dominus (Lord/Sir) 3/153/2 (ND, App., no. 381)
undated steward 3/156/1 (ND, App., no. 309)
undated steward of Coldingham 3/162/1 (ND, App., no. 356)
1248 X 1290 steward of Coldingham 3/210/3 (ND, App., no. 308)
12 Dec. 1248 Dominus (Lord/Sir) 3/478/12 (ND, App., no. 364)
1255 X 1281 steward 3/153/3 (ND, App., no. 280)
circa 1260 X 1272 steward 3/499/13 (ND, App., no. 398[*])
Sunday 29 Dec. 1280 steward of Coldingham 3/156/2 (ND, App., no. 273)
undated Obligation relating to land to be held by hereditary right in the villa of Lamberton 3/442/3 (ND, App., no. 350)
undated Gift of a half-ploughgate of land in the villa and territory of Renton (BWK) 3/153/1 (ND, App., no. 380)
undated Gift of a toft and croft in villa of Ayton, with pits, and 18 acres on the plain 3/61/1 (ND, App., no. 213)
undated Charter granting half-ploughgate of land in Renton (BWK) 3/153/2 (ND, App., no. 381)
undated Charter in respect of one and a half acres in Coldingham and one and half acres of land between Flaxiwelles and Kelloclawe 3/150/6 (ND, App., no. 276)
undated Gift of seven acres in Ayton 3/66/1 (ND, App., no. 202)
unavailable Gift of David of Quixwood's whole land in the villa of Oldcambus and outside, in exchange for 60 acres in the territory of Coldingham, etc. 3/488/10 (ND, App., no. 183)
undated Sale of Stephen son of Waltheof and his issue 3/478/13 (ND, App., no. 330)
undated Quitclaim of all the cultivated land near Hallecroft 3/150/3 (ND, App., no. 312)
undated Gift of land above Pilmuir and half acre at head of that land 3/160/1 (ND, App., no. 323)
X 1233 Sale of house in the villa of Coldingham, with a toft and croft and 2 acres of land in the territory of Coldingham, for 3 marks of silver 3/341/1 (ND, App., no. 302)
X 1233 Quitclaim of all land held within and without the villa of Coldingham 3/365/1 (ND, App., no. 315)
X 1233 Quitclaim of Adam son of Thurkil to the prior of Coldingham for 3 silver marks 3/499/1 (ND, App., no. 337)
X 1234 Sale of land in villa of Coldingham (BWK) 3/56/1 (ND, App., no. 318)
X 1234 Gift of half a toft in the villa of Lamberton 3/232/1 (ND, App., no. 352)
X 6 October 1245 Gift of land in Prenderguest with houses, for 47 marks 3/531/1 (ND, App., no. 366)
X 6 October 1245 Confirmation of a sale by William of Scremerston to the prior of Coldingham 3/441/2 (ND, App., no. 368)
X 6 October 1245 Confirmation of gift made by William son of Robert of Scremerston to Coldingham Priory of land at Prenderguest 3/531/2 (ND, App., no. 367)
X circa 1247 Gift of 13 acres and one rood in the territory of Great Reston 3/500/2 (ND, App., no. 391)
X 1248 Gift of 5 acres of land in Fleurs in the territory of Coldingham (BWK) 3/150/5 (ND, App., no. 314)
X 1249 Quitclaim of the the homage and service of Henry, brother of Patrick of Dunning, owed for land in Renton 3/201/2 (ND, App., no. 376[*])
X 1249 Quitclaim of lands, buildings and tofts in the vill of Coldingham 3/283/6 (ND, App., no. 296)
X 1249 Gift of 5 roods of land near Benerig 3/488/20 (ND, App., no. 257)
X 1249 Gift of one and a half acres of land in the territory of Coldingham near the sea 3/488/17 (ND, App., no. 247)
X 1249 Quitclaim of a half-ploughgate in the villa of Oldcambus 3/55/4 (ND, App., no. 191)
X 1249 Gift of a third of the toft which belonged to Matania and a third of the toft belonging to Ewoc, and 4 acres of land in North Lamberton 3/331/5 (ND, App., no. 349)
X 1249 Gift of 1 acre of land above Hallydown (in Coldingham, BWK) 3/488/21 (ND, App., no. 258)
X 1249 Gift of a half-ploughgate of land in Little Reston in return for a half-ploughgate 3/499/11 (ND, App., no. 400)
X 1249 Resignation of unjustly held lands in Great Reston 3/500/3 (ND, App., no. 389)
X 1249 Confirmation of gift of one and a half acres of land in the territory of Coldingham, near the sea, under the cliff of 'Sabul' 3/488/26 (ND, App., no. 248)
X 1249 Quitclaim of a house and curtilage in Coldingham 3/155/1 (ND, App., no. 277)
X 1249 Gift of two oxgangs of land in villa of Ayton, with toft and croft 3/65/1 (ND, App., no. 219)
X 1249 Gift of 3 roods of land near 'Ebbecnol' 3/488/18 (ND, App., no. 249)
X 1250 Gift of 30.5 acres of land in the territory of Great Reston 3/500/4 (ND, App., no. 390)
X 1255 Grant to feuferme of land in Prestrikel and Coldingham 3/150/2 (ND, App., no. 304)
1200 X 1235 Gift of land in the territory of Coldingham 3/368/1 (ND, App., no. 271)
1212 X 1220 Gift of half and acre to light the altar of Coldingham 3/150/1 (ND, App., no. 311)
1212 X 1221 Sale of land in Coldingham 3/512/1 (ND, App., no. 320)
1220 X 1229 Renewal of David of Quixwood's gift of land in villa of Oldcambus 3/488/22 (ND, App., no. 187)
March 1234 X 1244 Gift of 9 acres in the territory of Little Reston 3/499/7 (ND, App., no. 401)
March 1234 X 1244 Gift of the homage and service Patrick son of Uhtred with all the lands he had from the donation of Adam of Reston 3/499/8 (ND, App., no. 402)
March 1234 X 1244 Gift of a toft and croft to light altar where the mass of the Blessed Virgin Mary is daily celebrated 3/418/1 (ND, App., no. 290)
March 1234 X 1244 Gift of a toft and croft in Little Reston to maintain lights on St Mary's altar in the church of Coldingham 3/499/4 (ND, App., no. 395)
1239 X 1242 Gift of an oxgang of land in Prenderguest 3/440/1 (ND, App., no. 371)
1239 X 1242 Confirmation of the gift of David of Quixwood to the fabric of the church of Coldingham, of 3 perches of land in Coldingham 3/488/23 (ND, App., no. 252)
1239 X 1242 Gift of the whole plough-land of Leycroft 3/478/9 (ND, App., no. 224)
1239 X 1242 Quitclaim of right and claim in Henry son of Dolfin, Walter his son, and their retinue, and in Robert son of Osulf, his sons, and their retinue 3/62/4 (ND, App., no. 339)
1239 X 1242 Gift of an acre and a half above 'Duueknol' for the building of the church of St Mary at Coldingham 3/488/14 (ND, App., no. 253)
1242 X 1244 Gift of an acre and a half of land with pertinents in the territory of Coldingham 3/488/16 (ND, App., no. 254)
22 September 1244 X 12 December 1248 Confirmation of the sale of all his land 3/335/1 (ND, App., no. 373)


Readyhedge Ltd - growers & suppliers of quality instant hedging and screening.
Readyhedge is a wholesale nursery growing high quality instant hedging and screening plants.
The Readyhedge range of instant hedging is grown in 1m troughs and is ready spaced for ease of planting. This unique product is ideally suited to landscape contracts and domestic gardens alike.
Some examples of other products in our instant hedging and screening range include pleached trees, espalier fruit, high and low screening panels.
Hedging plants from 1m to 4m are available in containers or rootball/bareroot in the winter.


The Inspire Her: Women's Empowerment and Transformation Programme is for women of all ages (14+) who are ready to see real, significant and impacting changes in their lives.
This 1 day Programme will inspire, and motivate you to transform, as you learn, develop and put the principles of success into practice.
The day will be hosted by Success Coach and Motivational Speaker Simone Bell, and Progression Coach and Inspirational Speaker Francesca McDowall.
Claim your FREE Tickets today, and bring your mum, friends, sisters and daughters. There is something very powerful that happens when women gather together, and we know that you will be shifted to your next level.
Do I have to wear business clothes?
You will have a lunch break, where you can go and purchase your own lunch at the bar or in the local facilities. Tea and coffee will also be available for you to purchase at the bar.
Unfortunately, not, so hopefully you will have enough time to find suitable childcare, as the event is suitable for 14 years up. However, if you have a babe in arms, or are a breastfeeding mum you would be welcome to bring your little one.
Yes, the venue has free parking facilities. It is also on a bus route if you are taking public transport.
Is this a one off event?
Book your ticket, attend and you can find out more of what we have planned for you.
Pen, paper or a device to take notes on. In addition cash or cards as there will be an opportunity to purchase books and other resources.


text:
Josef Ludwig Ressel (ur. 1793  w Chrudimiu, zm. 1857 w Lublanie) – czeski wynalazca, z zawodu inżynier leśnik. W 1827 roku otrzymał patent na śrubę napędową statku. W 1829 roku zastosował drewnianą śrubę własnej konstrukcji na statku Civetta.

Przypisy

Bibliografia
 Encyklopedia PWN, Tom 3, Warszawa 1991, s. 155.

Czescy wynalazcy
Leśnicy
Urodzeni w 1793
Zmarli w 1857

redpajama_set_name: RedPajamaWikipedia


Having a print-to-mail mail recovery plan provides businesses with essential peace of mind, knowing they can continue to send critical customer communications in the event of a business disruption. These crucial customer communications support normal business operations throughout a company's life cycle and, most importantly, can directly affect the bottom line. With so much at stake, it's important that we as a critical communications recovery provider deliver a customer experience that reassures our customers that their recovery plans are sound and thoroughly tested.
When we engage with new customers, our first goal is to learn as much as we can about their print and mail applications and processes. Through initial phone calls, testing, change management processes, hosting visits to our facilities and, in turn, visiting theirs, we gather the necessary information to be as prepared as possible to replicate their production environment if and when we are called into action.
When it comes to overall disaster recovery planning, the biggest issue we see is failing to include all critical print applications and volumes in the recovery plan. It is important to have all applications tested and detailed in the recovery plan to prevent any hiccups should a disruption occur. Nearly all declaration assistance we have provided to our customers in our 18-year history has included applications and volumes that were not included in the recovery plan. While we have been able to accommodate these requests, start-up was slower for these unexpected applications since they had not been previously tested. And, if we were supporting other declarations, equipment usage might prevent us from completing these untested applications according to the customer SLAs.
When it comes to testing your recovery plan, the biggest point of failure is not realizing the full spectrum of resources required to print. While some customers provide data files with all resources embedded, others do not. When resources are provided separately there is always the risk of a missing resource or two that will prevent us from completing a successful print test.
Because we've seen these issues first-hand, we have developed a tried and true process for onboarding new customers. This process usually happens at the same time contract negotiations are taking place with the sales and legal departments. Our Client Solutions Account Managers plan several calls with the customer to review data, transmission, print, insert and mail requirements. These specifications are used for initial testing as well as general customer information. Technical calls between our network teams can also take place to set up the transmission lines the customer requires to send us their data files. Once all details are known, a Proof of Concept test is completed to confirm our ability to meet all requirements to our customer's complete satisfaction.
Mail-Gard's philosophy has always been to focus on "how can we make it easy for our customers to do business with us?" We understand the people charged with putting a company's disaster recovery plan in place have full-time responsibilities that go beyond implementing a successful recovery plan. Knowing that, and with years of experience behind us, we work with our customers to create a successful plan and provide a customer experience that gives them the peace of mind they desire.


Checksum error in the encrypted file Setup-1.bin. Corrupt file or wrong password.
I have installed the game fine but there is no icon for me to use to launch the game can anyone please help?
senha do jogo para extrair?
Lots of seeders so download was fast. Scanned all files, everything came up clean. Installer worked perfectly, and I'm playing it right now no issues!
The torrent link is not working. It is showing some error of different ISP. please upload a different link.
Says it has a checksum error in Setup-1.bin. I'm positive all parts were downloaded properly and not one is broken. Any fix?
Okay, solved the checksum error. Now the setup crashes randomly in between giving a CLR20r3 error.
The torrent file is not found. Can you reupload it?
Please upload the torrent link. It seems to be down.
I've a problem running the game. I've downloaded it alright, UnRAR with Win RAR and mounted it with WinISO. Then the setup runs alright too but when all is ended, I cannot find the .exe that launchs the game.
Thank you in advance for solving my problem !
This game can by play with directx 10?


text:
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Project acronym AUTOCOMPLEMENT
Project The role of complement in the induction of autoimmunity against post-translationally modified proteins
Researcher (PI) Leendert TROUW
Host Institution (HI) ACADEMISCH ZIEKENHUIS LEIDEN
Call Details Consolidator Grant (CoG), LS7, ERC-2016-COG
Summary In many prevalent autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) autoantibodies are used as diagnostic and prognostic tools. Several of these autoantibodies target proteins that have been post-translationally modified (PTM). Examples of such modifications are citrullination and carbamylation. The success of B cell-targeted therapies in many auto-antibody positive diseases suggests that B cell mediated auto-immunity is playing a direct pathogenic role. Despite the wealth of information on the clinical associations of these anti-PTM protein antibodies as biomarkers we have currently no insight into why these antibodies are formed. Immunization studies reveal that PTM proteins can induce antibody responses even in the absence of exogenous adjuvant. The reason why these PTM proteins have 'autoadjuvant' properties that lead to a breach of tolerance is currently unknown. In this proposal, I hypothesise that the breach of tolerance towards PTM proteins is mediated by complement factors that bind directly to these PTM. Our preliminary data indeed reveal that several complement factors bind specifically to PTM proteins. Complement could be involved in the autoadjuvant property of PTM proteins as next to killing pathogens complement can also boost adaptive immune responses. I plan to unravel the importance of the complement–PTM protein interaction by answering these questions: 1) What is the physiological function of complement binding to PTM proteins? 2) Is the breach of tolerance towards PTM proteins influenced by complement? 3) Can the adjuvant function of PTM be used to increase vaccine efficacy and/or decrease autoreactivity? With AUTOCOMPLEMENT I will elucidate how PTM-reactive B cells receive 'autoadjuvant' signals. This insight will impact on patient care as we can now design strategies to either block unwanted 'autoadjuvant' signals to inhibit autoimmunity or to utilize 'autoadjuvant' signals to potentiate vaccination.
In many prevalent autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) autoantibodies are used as diagnostic and prognostic tools. Several of these autoantibodies target proteins that have been post-translationally modified (PTM). Examples of such modifications are citrullination and carbamylation. The success of B cell-targeted therapies in many auto-antibody positive diseases suggests that B cell mediated auto-immunity is playing a direct pathogenic role. Despite the wealth of information on the clinical associations of these anti-PTM protein antibodies as biomarkers we have currently no insight into why these antibodies are formed. Immunization studies reveal that PTM proteins can induce antibody responses even in the absence of exogenous adjuvant. The reason why these PTM proteins have 'autoadjuvant' properties that lead to a breach of tolerance is currently unknown. In this proposal, I hypothesise that the breach of tolerance towards PTM proteins is mediated by complement factors that bind directly to these PTM. Our preliminary data indeed reveal that several complement factors bind specifically to PTM proteins. Complement could be involved in the autoadjuvant property of PTM proteins as next to killing pathogens complement can also boost adaptive immune responses. I plan to unravel the importance of the complement–PTM protein interaction by answering these questions: 1) What is the physiological function of complement binding to PTM proteins? 2) Is the breach of tolerance towards PTM proteins influenced by complement? 3) Can the adjuvant function of PTM be used to increase vaccine efficacy and/or decrease autoreactivity? With AUTOCOMPLEMENT I will elucidate how PTM-reactive B cells receive 'autoadjuvant' signals. This insight will impact on patient care as we can now design strategies to either block unwanted 'autoadjuvant' signals to inhibit autoimmunity or to utilize 'autoadjuvant' signals to potentiate vaccination.
Max ERC Funding
Start date: 2017-09-01, End date: 2022-08-31
Project acronym AVATAR
Project Integrating Genomics and Avatar Mouse Models to Personalize Pancreatic Cancer Treatment
Researcher (PI) Manuel HIDALGO MEDINA
Host Institution (HI) HOSPITAL UNIVERSITARIO DE FUENLABRADA
Call Details Advanced Grant (AdG), LS7, ERC-2014-ADG
Summary The prognosis of patients with metastatic pancreatic cancer (PDAC) is very poor. Recent studies have started to elucidate the genetic landscape of this disease to show that PDAC is a genetically complex, unstable, and heterogeneous cancer. However, in-depth analysis of individual patient genomes couple with personalize Avatar mouse models is providing highly effective therapeutic opportunities for the individual patient. Thus, metastatic PDAC appears a candidate disease to implement a genomics-base, personalized treatment approach. In this project, we will conduct an open label, multicenter, randomized phase III study in patients with standard of care resistant metastatic pancreatic cancer aiming to test the hypothesis that an integrated personalized treatment approach improves survival compare to a conventional treatment. Patients randomized to the personalize treatment arm will undergo a biopsy of a metastatic lesion to perform a targeted genome analysis using next generation sequencing. In addition, we will generate a personalize Avatar mouse model from the same patient. We will employ sophisticated bioinformatic analysis as well as mining of drug response-genetic databases to select, for each individual patient, candidate therapeutic targets that will be experimentally tested in the patient´s Avatar model to select the most effective regimen that will ultimately applied to the patient. In addition, based on the genomic data, we will design an individualized monitoring plan for each patient using BEAMing technology to monitor circulating levels of mutated genes. Furthermore, with a discovery goal, we will perform in depth genomic analysis of metastatic PDAC lesions in this cohort of clinically well-annotated patients with Avatar mouse models for therapeutic validation. Overall we expect this work will contribute to our understanding of PDAC and will favourably impact the treatment of this dismal cancer.
The prognosis of patients with metastatic pancreatic cancer (PDAC) is very poor. Recent studies have started to elucidate the genetic landscape of this disease to show that PDAC is a genetically complex, unstable, and heterogeneous cancer. However, in-depth analysis of individual patient genomes couple with personalize Avatar mouse models is providing highly effective therapeutic opportunities for the individual patient. Thus, metastatic PDAC appears a candidate disease to implement a genomics-base, personalized treatment approach. In this project, we will conduct an open label, multicenter, randomized phase III study in patients with standard of care resistant metastatic pancreatic cancer aiming to test the hypothesis that an integrated personalized treatment approach improves survival compare to a conventional treatment. Patients randomized to the personalize treatment arm will undergo a biopsy of a metastatic lesion to perform a targeted genome analysis using next generation sequencing. In addition, we will generate a personalize Avatar mouse model from the same patient. We will employ sophisticated bioinformatic analysis as well as mining of drug response-genetic databases to select, for each individual patient, candidate therapeutic targets that will be experimentally tested in the patient´s Avatar model to select the most effective regimen that will ultimately applied to the patient. In addition, based on the genomic data, we will design an individualized monitoring plan for each patient using BEAMing technology to monitor circulating levels of mutated genes. Furthermore, with a discovery goal, we will perform in depth genomic analysis of metastatic PDAC lesions in this cohort of clinically well-annotated patients with Avatar mouse models for therapeutic validation. Overall we expect this work will contribute to our understanding of PDAC and will favourably impact the treatment of this dismal cancer.
Project acronym BARCODE
Project The use of genetic profiling to guide prostate cancer targeted screening and cancer care
Researcher (PI) Rosalind Anne Eeles
Host Institution (HI) THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL
Summary "Prostate cancer is the commonest solid cancer in men in the European Community. There is evidence for genetic predisposition to the development of prostate cancer and our group has found the largest number of such genetic variants described to date worldwide. The next challenge is to harness these discoveries to advance the clinical care of populations and prostate cancer patients to improve screening and target treatments. This proposal, BARCODE, aims to be ground-breaking in this area. BARCODE has two components (1) to profile a population in England using the current 77 genetic variant profile and compare screening outcomes with those from population based screening studies to determine if genetics can target screening more effectively in this disease by identifying prostate cancer that more often needs treatment and (2) genetically profiling men with prostate cancer in the uro-oncology clinic for a panel of genes which predict for worse outcome so that these men can be offered more intensive staging and treatment within clinical trials. This will use next generation sequencing technology using a barcoding system which we have developed to speed up throughput and reduce costs. The PI will spend 35% of her time on this project and she will not charge for her time spent on this grant as she is funded by The University of London UK. The research team at The Institute Of Cancer Research, London, UK is a multidisciplinary team which leads the field of genetic predisposition to prostate cancer and its clinical application and so is well placed to deliver on this research. This application will have a dramatic impact on other researchers as it is ground –breaking and state of the art in its application of genetic findings to public health and cancer care. It will therefore influence the work being undertaken in both these areas to integrate genetic profiling and gene panel analysis into population screening and cancer care respectively."
"Prostate cancer is the commonest solid cancer in men in the European Community. There is evidence for genetic predisposition to the development of prostate cancer and our group has found the largest number of such genetic variants described to date worldwide. The next challenge is to harness these discoveries to advance the clinical care of populations and prostate cancer patients to improve screening and target treatments. This proposal, BARCODE, aims to be ground-breaking in this area. BARCODE has two components (1) to profile a population in England using the current 77 genetic variant profile and compare screening outcomes with those from population based screening studies to determine if genetics can target screening more effectively in this disease by identifying prostate cancer that more often needs treatment and (2) genetically profiling men with prostate cancer in the uro-oncology clinic for a panel of genes which predict for worse outcome so that these men can be offered more intensive staging and treatment within clinical trials. This will use next generation sequencing technology using a barcoding system which we have developed to speed up throughput and reduce costs. The PI will spend 35% of her time on this project and she will not charge for her time spent on this grant as she is funded by The University of London UK. The research team at The Institute Of Cancer Research, London, UK is a multidisciplinary team which leads the field of genetic predisposition to prostate cancer and its clinical application and so is well placed to deliver on this research. This application will have a dramatic impact on other researchers as it is ground –breaking and state of the art in its application of genetic findings to public health and cancer care. It will therefore influence the work being undertaken in both these areas to integrate genetic profiling and gene panel analysis into population screening and cancer care respectively."
Project acronym BARCODE DIAGNOSTICS
Project Next-Generation Personalized Diagnostic Nanotechnologies for Predicting Response to Cancer Medicine
Researcher (PI) Avraham Dror Schroeder
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS7, ERC-2015-STG
Summary Cancer is the leading cause of death in the Western world and the second cause of death worldwide. Despite advances in medical research, 30% of cancer patients are prescribed a medication the tumor does not respond to, or, alternatively, drugs that induce adverse side effects patients' cannot tolerate. Nanotechnologies are becoming impactful therapeutic tools, granting tissue-targeting and cellular precision that cannot be attained using systems of larger scale. In this proposal, I plan to expand far beyond the state-of-the-art and develop a conceptually new approach in which diagnostic nanoparticles are designed to retrieve drug-sensitivity information from malignant tissue inside the body. The ultimate goal of this program is to be able to predict, ahead of time, which treatment will be best for each cancer patient – an emerging field called personalized medicine. This interdisciplinary research program will expand our understandings and capabilities in nanotechnology, cancer biology and medicine. To achieve this goal, I will engineer novel nanotechnologies that autonomously maneuver, target and diagnose the various cells that compose the tumor microenvironment and its disseminated metastasis. Each nanometric system will contain a miniscule amount of a biologically-active agent, and will serve as a nano lab for testing the activity of the agents inside the tumor cells. To distinguish between system to system, and to grant single-cell sensitivity in vivo, nanoparticles will be barcoded with unique DNA fragments. We will enable nanoparticle' deep tissue penetration into primary tumors and metastatic microenvironments using enzyme-loaded particles, and study how different agents, including small-molecule drugs, proteins and RNA, interact with the malignant and stromal cells that compose the cancerous microenvironments. Finally, we will demonstrate the ability of barcoded nanoparticles to predict adverse, life-threatening, side effects, in a personalized manner.
Cancer is the leading cause of death in the Western world and the second cause of death worldwide. Despite advances in medical research, 30% of cancer patients are prescribed a medication the tumor does not respond to, or, alternatively, drugs that induce adverse side effects patients' cannot tolerate. Nanotechnologies are becoming impactful therapeutic tools, granting tissue-targeting and cellular precision that cannot be attained using systems of larger scale. In this proposal, I plan to expand far beyond the state-of-the-art and develop a conceptually new approach in which diagnostic nanoparticles are designed to retrieve drug-sensitivity information from malignant tissue inside the body. The ultimate goal of this program is to be able to predict, ahead of time, which treatment will be best for each cancer patient – an emerging field called personalized medicine. This interdisciplinary research program will expand our understandings and capabilities in nanotechnology, cancer biology and medicine. To achieve this goal, I will engineer novel nanotechnologies that autonomously maneuver, target and diagnose the various cells that compose the tumor microenvironment and its disseminated metastasis. Each nanometric system will contain a miniscule amount of a biologically-active agent, and will serve as a nano lab for testing the activity of the agents inside the tumor cells. To distinguish between system to system, and to grant single-cell sensitivity in vivo, nanoparticles will be barcoded with unique DNA fragments. We will enable nanoparticle' deep tissue penetration into primary tumors and metastatic microenvironments using enzyme-loaded particles, and study how different agents, including small-molecule drugs, proteins and RNA, interact with the malignant and stromal cells that compose the cancerous microenvironments. Finally, we will demonstrate the ability of barcoded nanoparticles to predict adverse, life-threatening, side effects, in a personalized manner.
Project acronym BEAT
Project The functional interaction of EGFR and beta-catenin signalling in colorectal cancer: Genetics, mechanisms, and therapeutic potential.
Researcher (PI) Andrea BERTOTTI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TORINO
Summary Monoclonal antibodies against the EGF receptor (EGFR) provide substantive benefit to colorectal cancer (CRC) patients. However, no genetic lesions that robustly predict 'addiction' to the EGFR pathway have been yet identified. Further, even in tumours that regress after EGFR blockade, subsets of drug-tolerant cells often linger and foster 'minimal residual disease' (MRD), which portends tumour relapse. Our preliminary evidence suggests that reliance on EGFR activity, as opposed to MRD persistence, could be assisted by genetically-based variations in transcription factor partnerships and activities, gene expression outputs, and biological fates controlled by the WNT/beta-catenin pathway. On such premises, BEAT (Beta-catenin and EGFR Abrogation Therapy) will elucidate the mechanisms of EGFR dependency, and escape from it, with the goal to identify biomarkers for more efficient clinical management of CRC and develop new therapies for MRD eradication. A multidisciplinary approach will be pursued spanning from integrative gene regulation analyses to functional genomics in vitro, pharmacological experiments in vivo, and clinical investigation, to address whether: (i) specific genetic alterations of the WNT pathway affect anti-EGFR sensitivity; (ii) combined neutralisation of EGFR and WNT signals fuels MRD deterioration; (iii) data from analysis of this synergy can lead to the discovery of clinically meaningful biomarkers with predictive and prognostic significance. This proposal capitalises on a unique proprietary platform for high-content studies based on a large biobank of viable CRC samples, which ensures strong analytical power and unprecedented biological flexibility. By providing fresh insight into the mechanisms whereby WNT/beta-catenin signalling differentially sustains EGFR dependency or drug tolerance, the project is expected to put forward an innovative reinterpretation of CRC molecular bases and advance the rational application of more effective therapies.
Monoclonal antibodies against the EGF receptor (EGFR) provide substantive benefit to colorectal cancer (CRC) patients. However, no genetic lesions that robustly predict 'addiction' to the EGFR pathway have been yet identified. Further, even in tumours that regress after EGFR blockade, subsets of drug-tolerant cells often linger and foster 'minimal residual disease' (MRD), which portends tumour relapse. Our preliminary evidence suggests that reliance on EGFR activity, as opposed to MRD persistence, could be assisted by genetically-based variations in transcription factor partnerships and activities, gene expression outputs, and biological fates controlled by the WNT/beta-catenin pathway. On such premises, BEAT (Beta-catenin and EGFR Abrogation Therapy) will elucidate the mechanisms of EGFR dependency, and escape from it, with the goal to identify biomarkers for more efficient clinical management of CRC and develop new therapies for MRD eradication. A multidisciplinary approach will be pursued spanning from integrative gene regulation analyses to functional genomics in vitro, pharmacological experiments in vivo, and clinical investigation, to address whether: (i) specific genetic alterations of the WNT pathway affect anti-EGFR sensitivity; (ii) combined neutralisation of EGFR and WNT signals fuels MRD deterioration; (iii) data from analysis of this synergy can lead to the discovery of clinically meaningful biomarkers with predictive and prognostic significance. This proposal capitalises on a unique proprietary platform for high-content studies based on a large biobank of viable CRC samples, which ensures strong analytical power and unprecedented biological flexibility. By providing fresh insight into the mechanisms whereby WNT/beta-catenin signalling differentially sustains EGFR dependency or drug tolerance, the project is expected to put forward an innovative reinterpretation of CRC molecular bases and advance the rational application of more effective therapies.
Project acronym bECOMiNG
Project spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management
Researcher (PI) Niccolo Bolli
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Summary As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Project acronym Bio-ICD
Project Biological auto-detection and termination of heart rhythm disturbances
Researcher (PI) Daniël Antonie PIJNAPPELS
Summary Imagine a heart that could no longer suffer from life-threatening rhythm disturbances, and not because of pills or traumatizing electroshocks from an Implantable Cardioverter Defibrillator (ICD) device. Instead, this heart has become able to rapidly detect & terminate these malignant arrhythmias fully on its own, after gene transfer. In order to explore this novel concept of biological auto-detection & termination of arrhythmias, I will investigate how forced expression of particular engineered proteins could i) allow cardiac tissue to become a detector of arrhythmias through rapid sensing of acute physiological changes upon their initiation. And how after detection, ii) this cardiac tissue (now as effector), could terminate the arrhythmia by generating a painless electroshock through these proteins. To this purpose, I will first explore the requirements for such detection & termination by studying arrhythmia initiation and termination in rat models of atrial & ventricular arrhythmias using optical probes and light-gated ion channels. These insights will guide computer-based screening of proteins to identify those properties allowing effective arrhythmia detection & termination. These data will be used for rational engineering of the proteins with the desired properties, followed by their forced expression in cardiac cells and slices to assess anti-arrhythmic potential & safety. Promising proteins will be expressed in whole hearts to study their anti-arrhythmic effects and mechanisms, after which the most effective ones will be studied in awake rats. This unexplored concept of self-resetting an acutely disturbed physiological state by establishing a biological detector-effector system may yield unique insight into arrhythmia management. Hence, this could provide distinctively innovative therapeutic rationales in which a diseased organ begets its own remedy, e.g. a Biologically-Integrated Cardiac Defibrillator (Bio-ICD).
Imagine a heart that could no longer suffer from life-threatening rhythm disturbances, and not because of pills or traumatizing electroshocks from an Implantable Cardioverter Defibrillator (ICD) device. Instead, this heart has become able to rapidly detect & terminate these malignant arrhythmias fully on its own, after gene transfer. In order to explore this novel concept of biological auto-detection & termination of arrhythmias, I will investigate how forced expression of particular engineered proteins could i) allow cardiac tissue to become a detector of arrhythmias through rapid sensing of acute physiological changes upon their initiation. And how after detection, ii) this cardiac tissue (now as effector), could terminate the arrhythmia by generating a painless electroshock through these proteins. To this purpose, I will first explore the requirements for such detection & termination by studying arrhythmia initiation and termination in rat models of atrial & ventricular arrhythmias using optical probes and light-gated ion channels. These insights will guide computer-based screening of proteins to identify those properties allowing effective arrhythmia detection & termination. These data will be used for rational engineering of the proteins with the desired properties, followed by their forced expression in cardiac cells and slices to assess anti-arrhythmic potential & safety. Promising proteins will be expressed in whole hearts to study their anti-arrhythmic effects and mechanisms, after which the most effective ones will be studied in awake rats. This unexplored concept of self-resetting an acutely disturbed physiological state by establishing a biological detector-effector system may yield unique insight into arrhythmia management. Hence, this could provide distinctively innovative therapeutic rationales in which a diseased organ begets its own remedy, e.g. a Biologically-Integrated Cardiac Defibrillator (Bio-ICD).
Project acronym BIO-IRT
Project Biologically individualized, model-based radiotherapy on the basis of multi-parametric molecular tumour profiling
Researcher (PI) Daniela Thorwarth
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Summary High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume. This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT. During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT. In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription. Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
High precision radiotherapy (RT) allows extremely flexible tumour treatments achieving highly conformal radiation doses while sparing surrounding organs at risk. Nevertheless, failure rates of up to 50% are reported for head and neck cancer (HNC) due to radiation resistance induced by pathophysiologic factors such as hypoxia and other clinical factors as HPV-status, stage and tumour volume. This project aims at developing a multi-parametric model for individualized RT (iRT) dose prescriptions in HNC based on biological markers and functional PET/MR imaging. This project goes far beyond current research standards and clinical practice as it aims for establishing hypoxia PET and f-MRI as well as biological markers in HNC as a role model for a novel concept from anatomy-based to biologically iRT. During this project, a multi-parametric model will be developed on a preclinical basis that combines biological markers such as different oncogenes and hypoxia gene classifier with functional PET/MR imaging, such as FMISO PET in combination with different f-MRI techniques, like DW-, DCE- and BOLD-MRI in addition to MR spectroscopy. The ultimate goal of this project is a multi-parametric model to predict therapy outcome and guide iRT. In a second part, a clinical study will be carried out to validate the preclinical model in patients. Based on the most informative radiobiological and imaging parameters as identified during the pre-clinical phase, biological markers and advanced PET/MR imaging will be evaluated in terms of their potential for iRT dose prescription. Successful development of a model for biologically iRT prescription on the basis of multi-parametric molecular profiling would provide a unique basis for personalized cancer treatment. A validated multi-parametric model for RT outcome would represent a paradigm shift from anatomy-based to biologically iRT concepts with the ultimate goal of improving cancer cure rates.
Project acronym Bio-Phononics
Project Advanced Microfluidics & Diagnostics using Acoustic Holograms – Bio-Phononics
Researcher (PI) Jonathan Cooper
Host Institution (HI) UNIVERSITY OF GLASGOW
Summary This proposal seeks to develop a novel technique for fluid and particle manipulations, based upon exploiting the mechanical interactions between acoustic waves and phononic. The new platform involves generating surface acoustic waves (SAWs) on piezoelectric chips, but, unlike previous work, the ultrasonic waves are first coupled into a phononic lattice, which is placed in the path of the ultrasonic wave. The phononic lattice comprises a miniaturised array of mechanical elements which modulates the sound in a manner analogous to how light is "patterned" using a hologram. However, whilst in an optical hologram, the pattern is created by exploiting the differences in refractive indices of the elements of the structure, here the ultrasonic field is modulated both by the elastic contrast between the elements in the array, as well as by the dimensions of the array and its surrounding matrix (including the size and pitch of the features within the array). The result of passing the acoustic wave through a phononic crystal is the formation of new and complex ultrasonic landscapes. As part of the proposed work we aim to understand the physics of this technology and to exploit its development in a range of medical devices. We will show that by using phononic crystals it is possible to create highly controllable patterns of acoustic field intensities, which propagate into the fluid, creating pressure differences that result in unique flow patterns to enable a new platform for including biological sample processing, medical diagnostics, drug delivery and blood clotting devices – all on low cost disposable devices. Different frequencies of ultrasound will interact with different phononic structures to give different functions, providing a toolbox of different functions. Just as in electronics, where discrete components are combined to create circuits, so we propose to combine different phononic lattices to create fluidic microcircuits with important new applications.
This proposal seeks to develop a novel technique for fluid and particle manipulations, based upon exploiting the mechanical interactions between acoustic waves and phononic. The new platform involves generating surface acoustic waves (SAWs) on piezoelectric chips, but, unlike previous work, the ultrasonic waves are first coupled into a phononic lattice, which is placed in the path of the ultrasonic wave. The phononic lattice comprises a miniaturised array of mechanical elements which modulates the sound in a manner analogous to how light is "patterned" using a hologram. However, whilst in an optical hologram, the pattern is created by exploiting the differences in refractive indices of the elements of the structure, here the ultrasonic field is modulated both by the elastic contrast between the elements in the array, as well as by the dimensions of the array and its surrounding matrix (including the size and pitch of the features within the array). The result of passing the acoustic wave through a phononic crystal is the formation of new and complex ultrasonic landscapes. As part of the proposed work we aim to understand the physics of this technology and to exploit its development in a range of medical devices. We will show that by using phononic crystals it is possible to create highly controllable patterns of acoustic field intensities, which propagate into the fluid, creating pressure differences that result in unique flow patterns to enable a new platform for including biological sample processing, medical diagnostics, drug delivery and blood clotting devices – all on low cost disposable devices. Different frequencies of ultrasound will interact with different phononic structures to give different functions, providing a toolbox of different functions. Just as in electronics, where discrete components are combined to create circuits, so we propose to combine different phononic lattices to create fluidic microcircuits with important new applications.
Project acronym BIOCCORA
Project Full biomechanical characterization of the coronary atherosclerotic plaque: biomechanics meets imaging
Researcher (PI) Jolanda Wentzel
Host Institution (HI) ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Myocardial infarction is responsible for nearly 40% of the mortality in the western world and is mainly triggered by rupture of vulnerable atherosclerotic plaques in the coronary arteries. Biomechanical parameters play a major role in the generation and rupture of vulnerable plaques. I was the first to show the relationship between shear stress – one of the biomechanical parameters - and plaque formation in human coronary arteries in vivo. This accomplishment was achieved by the development of a new 3D reconstruction technique for (human) coronary arteries in vivo. This reconstruction technique allowed assessment of shear stress by computational fluid dynamics and thereby opened new avenues for serial studies on the role of biomechanical parameters in cardiovascular disease. However, these reconstructions lack information on the vessel wall composition, which is essential for stress computations in the vessel wall. Recent developments in intravascular image technologies allow visualization of one or more of the different plaque components. Therefore, advances in image fusion are required to merge the different plaque components into one single 3D vulnerable plaque reconstruction. I will go beyond the state-of-the art in image based modeling by developing novel technology to 3D reconstruct coronary lumen and vessel wall, including plaque composition and assess biomechanical tissue properties allowing for full biomechanical characterization (shear stress and wall stress) of the coronary plaque. The developed technology will be applied to study 1) vulnerable plaque progression, destabilization and rupture, to improve identification of risk on myocardial infarction and 2) predicting treatment outcome of stent implantation by simulating stent deployment, thereby opening a whole new direction in cardiovascular research.
Myocardial infarction is responsible for nearly 40% of the mortality in the western world and is mainly triggered by rupture of vulnerable atherosclerotic plaques in the coronary arteries. Biomechanical parameters play a major role in the generation and rupture of vulnerable plaques. I was the first to show the relationship between shear stress – one of the biomechanical parameters - and plaque formation in human coronary arteries in vivo. This accomplishment was achieved by the development of a new 3D reconstruction technique for (human) coronary arteries in vivo. This reconstruction technique allowed assessment of shear stress by computational fluid dynamics and thereby opened new avenues for serial studies on the role of biomechanical parameters in cardiovascular disease. However, these reconstructions lack information on the vessel wall composition, which is essential for stress computations in the vessel wall. Recent developments in intravascular image technologies allow visualization of one or more of the different plaque components. Therefore, advances in image fusion are required to merge the different plaque components into one single 3D vulnerable plaque reconstruction. I will go beyond the state-of-the art in image based modeling by developing novel technology to 3D reconstruct coronary lumen and vessel wall, including plaque composition and assess biomechanical tissue properties allowing for full biomechanical characterization (shear stress and wall stress) of the coronary plaque. The developed technology will be applied to study 1) vulnerable plaque progression, destabilization and rupture, to improve identification of risk on myocardial infarction and 2) predicting treatment outcome of stent implantation by simulating stent deployment, thereby opening a whole new direction in cardiovascular research.
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Residents in Bastrop oppose Trump's end to DACA program
Andy Sevilla
asevilla@statesman.com
Natalia DePaz says her heart breaks for some members of her family as well as for about 800,000 people who have benefited from an Obama-era immigration program that the Trump administration said it was rescinding.
U.S. Attorney General Jeff Sessions announced Sept. 5 that the Trump administration was rescinding and phasing out the Deferred Action for Childhood Arrivals program, which allows undocumented immigrants who were brought into the U.S. as children to get temporary work permits and avoid deportation.
"It breaks my heart to know that they're struggling through that and they're unaware of what could happen to them and what the next steps are," DePaz said of immigrants now left in limbo after Session's announcement. "I don't agree with anything of what Trump decided to do to just to get it out and give certain amount of time for Congress to make a new law."
DePaz was one of nearly 30 residents who lined the Old Iron Bridge in Bastrop last week wielding signs in support of DACA and protesting Trump's move to rescind the immigration program.
"I would want (Trump) to understand that DACA is very important for a lot of people, and immigrants are who make up this country," DePaz said. "Everybody is an American. It doesn't matter who you are, it doesn't matter where you come from, you have rights and you deserve those rights."
Smithville resident Ginger Redden, who helped organize the Sept. 20 rally in Bastrop, said that from an early age her parents, who went to segregated schools, ingrained in her to treat everybody fairly, that everyone was equal.
"These are basic principles that I was raised with — and it seemed like they had been progressing for quite a long time — and lately it's like you've been given permission to be a jerk to everyone and this is not how I grew up," Redden said. "I feel like we've come a long way in terms of rights for women, LGBTQ rights, and now all of that feels like it's falling back. And it's frightening. This is not the America where I grew up and believe in."
In a Sept. 5 memo, the Department of Homeland Security said people who currently have permits under the DACA program will not have them rescinded. Instead, they will be allowed to expire after two years.
Sessions said Obama "deliberately sought to achieve what the legislative branch specifically refused to authorize on multiple occasions" with the executive order that created DACA.
"If we are to further our goal of strengthening the Constitutional order and rule of law in America, the Department of Justice cannot defend this overreach," Sessions said.
Trump said in a statement that the plan is to phase out DACA, allowing for "a window of opportunity for Congress to finally act." On Twitter, he said he was looking forward to working with Democrats and Republicans to reform immigration "in a way that puts hardworking citizens of our country 1st."
White House officials have said immigrants with DACA permits that expire on or before March 5 are allowed to seek renewals by Oct. 5.
An ABC News/Washington Post poll released Monday showed 86 percent of Americans support a right to residency for undocumented immigrants who arrived in the country as children.
"We care about our friends and neighbors and the young people in our communities," Redden said. "We are saying, 'Hey, this is not OK, this is not the America we were raised in and we're going to speak up about it."
DePaz and several students at the Colorado River Collegiate Academy formed a Young Democrats club to empower youth to speak up on important issues like DACA.
"DACA is a prime example of an issue that is urgent for our youth to speak up for because there are students and other people in our community who are affected by it," the new student group said in a statement.