text:
Please Select a Room
Customer interaction happens throughout supermarkets and department stores. From checkout lines to dressing rooms, pharmacies to bakeries, good acoustics are key to helping customers and store personnel communicate clearly.
Supermarkets and department stores need a ceiling as versatile as they are. Select a retail ceiling with superior durability to withstand sag and abuse while delivering the sound absorption to make customers comfortable. Strategically placed clouds and canopies above areas like pharmacy pick-up and customer service desks add extra confidentiality.
Mega retail stores are high traffic areas, often with high ceilings, making noise reduction a hot commodity.
Ceiling tiles with superior sound absorption and durability help put a lid on noise while minimising maintenance time and cost.
Showroom ceiling design may need to be unique, yet fit to a tight construction schedule.
Many specialty ceiling tiles are available as standard options- yet you can mix & match them to create your own design and express the personality of your store. Make a statement using strategically placed canopy and baffle ceilings.
Where else can you get sushi, pizza and ice cream in one place? Food courts cater to the tastes of nearly every shopper, making them one of the busiest places in a mall.
Ceiling tiles designed for food prep areas are made with the durability and cleanability to comply with industry standards. Choose from standard acoustic ceiling tiles to wood or metal ceilings, or fun acoustic canopies and baffles. Acoustic options installed over dining areas will help control noise, while specialty options will provide shoppers some eye candy until their next splurge.
As the hub that connects multiple retail areas, concourses are heavily trafficked places. Their large open spaces can get overrun with noise and echo without proper acoustic control and require durable solutions.
Durable metal and wood or wood-effect metal ceilings are great choices in these areas. Added spot acoustic ceiling options like canopy and baffle ceilings are perfect for designing a concourse ceiling that absorbs sound and engages shoppers with a variety of shapes and colours.
A retail reception is a high traffic space that needs to communicate a brand's personality and attract window shoppers to step inside and engage.
Ceilings with balanced acoustic performance will reduce noise while a variety of shapes, colours and materials can help you create a grand entrance shoppers just can't walk by. Retail receptions are great places to showcase canopies and baffles in eye-catching colours.
Boutique and specialty shops are often smaller retail spaces demanding a personal touch. The ceiling can play a role in creating the right environment and help portray the image the retailer is trying to create.
Many specialty ceiling tiles, canopy and baffle ceilings are available as standard options, enabling you to design something out of the ordinary. Mix and match them to create your own design and express the personality of your store.
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text:
Bruce Alton necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 55 diseños de 16 diseñadores freelance.
NunaCash ATM
Our company owns and operates hotels, apartment buildings and restaurants. Within our buildings, we offer private label ATM cash machines for our clients, tenants and people just walking by.
We need a logo/identity for the bank machines that would positioned be on the ATM itself, on a sign above the ATM and on our websites. The logo/identity needs to incorporate the words "NunaCash" and "ATM" (with NunaCash preferably being one word).
The target audience is the general public. They will primarily include hotel guests, restaurant/bar patrons, and general pedestrian traffic in a mall or restaurant.
The NunaCash ATM identity/logo needs to convey two themes or concepts:
First, we need an identity that illustrates strength and legitimacy to our customers and convey the fact that the bank machine has been placed there by a strong institution and not a fly-by-night company. Customers need the confidence that they are safely using their bank card.
Second, the other unique aspect of this project is that the majority of our operations are located in Canada's far north - think of the arctic, snow covered tundra, caribou and glaciers. The first machines will be located in Iqaluit which is the near the Arctic Circle in Northern Canada. While this should not be a central part of the identity, some sort of Northern tie-in would be fine.
So in summary we would like strength, professionalism and the North to be portrayed.
The logo and words ("NunaCash ATM") need to be placed on a rectangular sign (see attached) above the bank machine as well as appropriate for written material and in a smaller format on the machine itself.
The background should be dark blue and the letters yellow (ie be the same as those used in the RBC logo (go to: http://www.rbc.com and see attached)).
As this will be used on a sign, the logo and words must be easily identifiable from 20-30 feet away.
We will need the graphics to be in file formats that can be used to produce signs, webpages and written materials.
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.

subset: commoncrawl


text:
The McCain Cable Bill Can Only Do So Much; Real Change Is Market-Driven
from the it's-innovators-who-need-freedom dept
There's a lot of buzz about Sen. John McCain's proposed Television Consumer Freedom Act (pdf and embedded below), a bill designed to encourage cable companies to unbundle the TV stations they offer, and force the networks to do the same. It also takes away the weak bargaining chip that some networks have attempted to play against Aereo, in which they threaten to pull their broadcasts from the open air, by making them sacrifice broadcast licenses in order to do so.
Everyone on the consumer side agrees that they'd like to have à la carte choices from cable companies, but beyond that there's no shortage of debate as to how effective the bill is likely to be and whether the end result would actually be any better for those consumers. The television market is badly distorted at all levels by monopoly interests and those whiffs of not-quite-collusion by groups of companies with a shared interest in maintaining the status quo, but is this bill capable of overcoming that? And is the practice of bundling really at the heart of the problem, or just a good public face for the deeper issues?
This is hardly the first attempt to stop the practice at either the network or cable provider level. Some courts have already found bundling by cable providers to be legal and not anticompetitive; meanwhile Cablevision is currently pursuing an antitrust suit against Viacom for the network's bundling of stations that it sells to providers. Most of the details of the latter are under seal, but one notable point is Viacom's claim that it already offers channels individually, they just cost way more. If that's true of all Viacom's content, then it wouldn't be affected by McCain's bill anyway, which still permits bundling as long as there is an à la carte option.
And even if it's not true, it just underlines the core problem of this approach: the bill doesn't give networks any reason to make individual channels affordable or desirable. They either already offer an expensive à la carte menu that nobody orders from, or they could easily do so. Moreover, it's not as though the justification for bundling offered by the networks is completely falsified: they can spend more money on niche channels and programs by subsidizing them with the revenue from more broadly popular fare. Of course, it's not as though that justification isn't exaggerated and twisted to suit their needs either, nor is it true that the same fundamental idea couldn't exist without bundling. Networks get more value from niche programs than just transmission fees: they care about audience reach, brand-building, competing with other forms of content, accumulating accolades for prestige shows and even, believe it or not, making good television. There's no reason their businesses could not be structured to continue subsidizing niche programming with popular programming in a slightly less direct manner.
So the final solution, as always, needs to be found in the market — and that's already happening. Basically every single noticeable trend in media consumption habits, not just in television but in music and publishing and every format, points towards a more à la carte world. It's not news that the networks and cable providers have dragged their heels on this in the hope of milking their incumbent position a bit longer, nor is it news that they are privately a lot more freaked out by the cord-cutting movement than their public statements admit. Ultimately, it will be consumers making choices that force these companies to either adapt or perish.
But for that to happen, innovators do need to be able to actually give the consumers those choices. If the market has become so badly distorted that innovators are being locked out, then legal action and new laws are needed. And that's why the aspect of the bill that is likely to be the most effective (not to mention the most interesting) is the way it all seems to come back to Aereo.
The fight that Aereo started sits at the core of almost everything in the bill. Network owners don't like Aereo because they don't want to lose their retransmission fees from cable providers. Cable providers don't like Aereo because they don't want to lose the appeal of the major networks which, despite the ascendence of cable channels, still sit at the core of their service bundles — and because, generally, they don't want cord-cutters to have more options. McCain's bill basically says: Aereo or no Aereo, consumers need choices, and they're going to get them, whether you like it or not.
Is it a worthwhile step? Yes — or, at least, it's hard to see how it could do any harm, even if it does prove ineffectual. Is it the best approach? No. It almost feels like a bet on Aereo's failure. If Aereo were permitted to innovate, rather than being forced to jump through endless technological hoops and still spend more time in court than in the workshop or the boardroom, then the market would already be giving consumers what they want and pushing the networks and cable providers to become more competitive. If there is to be legal reform, it shouldn't be another layer of conditions and caveats on broadcast licenses and the retransmission fee structure that attempts to force the hand of the networks and cable companies, it should be a clarification (and probably a relaxation) of the rules, removing the legal and regulatory uncertainty that holds disruptive startups back. Television doesn't need a Consumer Freedom Act — consumers already have lots of freedom, they just don't have many choices in how they exercise it. The heart of McCain's bill is in the right place, but a Television Innovator Freedom Act is what we really need.
Filed Under: a la carte, bundles, cable tv, innovation, john mccain, policy, technology
Companies: aereo


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We've heard endlessly about the possibility that Mars, the far away red planet, has water, but recently we've gotten closer to a confirmation. Last week NASA revealed that its "Mars Reconnaissance Orbiter [has] revealed possible flowing water during the warmest months on Mars." And, according to an article published in the New York Times, scientists note that "shifting dark streaks on the surface of Mars are signs that water is flowing there today."
Ice has been plentiful on Mars for quite some time but scientists have been looking for evidence of water because it could lead to the possibility of life outside the scope of Earth. While ice is important, "the recipe for life, at least as we know it, calls for liquid water, carbon-based molecules and a source for energy" and "chemical reactions for life come to a halt when water freezes."
The data collected by NASA's Mars Reconnaissance Orbiter is being pored over by Alfred McEwen of the University of Arizona. McEwen notes that "the best explanation for these observations so far is the flow of briny water. We have this circumstantial evidence for water flowing on Mars. We have no direct detection of water."
The observations of the data reveal seasonal discrepancies and that
"some aspects of the observations still puzzle researchers, but flows of liquid brine fit the features' characteristics better than alternate hypotheses. Saltiness lowers the freezing temperature of water. Sites with active flows get warm enough, even in the shallow subsurface, to sustain liquid water that is about as salty as Earth's oceans, while pure water would freeze at the observed temperatures."
While it may be too early to get your hopes up about water or life on Mars, these findings bring us closer than ever to an exciting breakthrough about how we perceive life in the universe.


text:
Orev_corvux necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 50 diseños de 10 diseñadores freelance.
R&W - Raven & Wolf
I am a historian of religion located in Norway and about to live out my dream of launching a small publishing firm - specializing in literature dealing with historical and religious themes. My first publishing task is my own work on Jerusalem - the first and most comprehensive and richly illstraded book on the history of Jerusalem ever published in Norway (in norwegian). I have myself lived several years in the Middle East and I am very fond of the design and architecture found in almost every historical epoch found in this region, especially byzantine and medieval periods. I am very interested in design in general - and my home is like my interests - quite ecclectic and full of esoteric and historical remedies scattered around. I work as a lecturer and a refugee councellor, I love to be outdoors (either mountaineering or kayaking in the sea) and I love to travel the world.
The desired audience is at the moment a segment of the norwegian book-readers of non-fictional litterature, specializing in history/religous ideas. This could also include students of say Middle Eastern Studies. The name of the label is however spelled in English (Raven and Wolf) - both because this is no problem for the norwegian audience, but also since I may go "international" to an english-speaking audience, if I will experience success at home. The segment is small, however, and exclusive. The first edition of the upcoming book will be 3000 books only.
I am looking for a design for my label Raven & Wolf (R&W) which is the name of my publishing firm (and also my two children :-) The logo will adorn upcoming and published books, as well as all other commercial communication on the web and on stationary. I am picturing a design with fonts revealing a somewhat esoteric or antique finishing. The font can be blended into an illustrated design which encompasses a raven (or a raven´s wing) and a wolf (or a full moon?) without this becoming too messy or "cheap". I like it simple, and "dark" - intriguing.
To give you an example of a font that I like, check out the cover of this book: http://en.wikipedia.org/wiki/Jonath…Mr_Norrell
Feel otherwise free to be CREATIVE - I will appreciate ALL attempts being made in this contest! If anyone wants to incorporate an oriental element - making a link to the Middle East/history etc. - feel free!
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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LONDON, Oct. 23 (UPI) -- Britain's Prince William and his wife, Kate, have chosen seven godparents for their 3-month-old son, Prince George, People.com reported.
The baby is to be baptized Wednesday at a small invitation-only ceremony at the Chapel Royal in London's St. James's Palace.
William and Kate selected as the godparents for their first child several friends, as well as Zara Tindall, William's cousin and an Olympic equestrian; Earl "Hugh" Grosvenor, the son one of William's own godparents, the duchess of Westminster; and Jamie Lowther-Pinkerton, the couple's former private secretary.
William's brother, Prince Harry, and Kate's sister, Pippa Middleton, are not among the godparents.
"It was entirely their choice, their personal preference. There was no set number that they had to choose and have gone with seven people," a palace source told People.com. "They wanted to include family and friends and reflect their life on both sides."


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NAME | Description | Description | Attributes | See Also
Directory Server allows you to encrypt individual attributes to protect sensitive information stored in the directory. The encryption does not prevent client applications from reading the attributes. Instead it works at the database index file level to prevent users with access to read database index files from being able to search through the indexes for sensitive information.
For example, before attribute encryption is configured for uid attributes, a user with read access to database index files could easily find out that bjensen is a uid attribute value:
$ strings example_uid.db3 | grep bjensen =bjensen $
Once uid attributes are encrypted, the job is not so easy:
$ strings example_uid.db3 | grep bjensen $
Notice however that encrypted RDN values are not fully hidden. Instead they appear in clear in the DN index:
$ strings example_entrydn.db3 | grep bjensen =uid=bjensen,ou=people,dc=example,dc=com =uid=bjensen,ou=people,dc=example,dc=com $
Default Value
Is readable
Is modifiable
Is multi-valued
Directory Server uses a cipher to encrypt a specified attribute in a given suffix. This property specifies the cipher used.
The following property values are supported:
DES block cipher
Triple-DES block cipher
RC2 block cipher
RC4 stream cipher
Syntax values shown in lower case or partly in lower case are literal values.
Those shown in upper case are syntax types, defined as follows:
A valid attribute type name such as cn or objectClass.
true or false.
A valid distinguished name such as ou=People,dc=example,dc=com.
A duration specified in months (M), weeks (w), days (d), hours (h), minutes (m), seconds (s), and miliseconds (ms), or some combination with multiple specifiers. For example, you can specify one week as 1w, 7d, 168h, 10080m, or 604800s. You can also specify one week as 1w0d0h0m0s.
DURATION properties typically do not each support all duration specifiers (Mwdhms). Examine the output of dsconf help-properties for the property to determine which duration specifiers are supported.
A valid e-mail address.
An IP address or host name.
A positive integer value between 0 and the maximum supported integer value in the system address space. On 32-bit systems, 2147483647. On 64-bit systems, 9223372036854775807.
An interval value of the form hhmm-hhmm 0123456, where the first element specifies the starting hour, the next element the finishing hour in 24-hour time format, from 0000-2359, and the second specifies days, starting with Sunday (0) to Saturday (6).
An IP address or range of address in one of the following formats:
IP address in dotted decimal form.
IP address and bits, in the form of network number/mask bits.
IP address and quad, in the form of a pair of dotted decimal quads.
All address. A catch-all for clients that are note placed into other, higher priority groups.
0.0.0.0. This address is for groups to which initial membership is not considered. For example, for groups that clients switch to after their initial bind.
IP address of the local host.
A valid LDAP URL as specified by RFC 2255.
A memory size specified in gigabytes (G), megabytes (M),kilobytes (k), or bytes (b). Unlike DURATION properties, MEMORY_SIZE properties cannot combine multiple specifiers. However, MEMORY_SIZE properties allow decimal values, for example, 1.5M.
A valid cn (common name).
A three-digit, octal file permissions specifier. The first digit specifies permissions for the server user ID, the second for the server group ID, the last for other users. Each digit consists of a bitmask defining read (4), write (2), execute (1), or no access (0) permissions, thus 640 specifies read-write access for the server user, read-only access for other users of the server group, and no access for other users.
The full path to the file from which the bind password should be read.
A valid, absolute file system path.
A DirectoryString value, as specified by RFC 2252.
An SSL cipher supported by the server. See the Reference for a list of supported ciphers.
An SSL protocol supported by the server. See the Reference for a list of supported protocols.
A time of the form hhmm in 24-hour format, where hh stands for hours and mm stands for minutes.
See attributes(5) for descriptions of the following attributes:
Stability Level
NAME | Description | Description | Attributes | See Also


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Southern Spaces is now offering authors the option of distributing new work published in the journal under a Creative Commons license. Beginning in 2014, in addition to retaining copyright of their work, authors may now elect to license their work under the following Creative Commons licenses.
|Creative Commons loves Open Access, 2014. A derivative work based on an illustration by Jan Ainali. Released under a CC BY SA license by Southern Spaces.
- Using a CC BY (attribution) license, authors allow their work to be freely distributed, copied, and performed, as long as users give credit to the original work. A CC BY license also allows for derivative works. An author might choose this license if she wants to provide the greatest opportunity for reuse.
- Under a CC BY-ND (attribution, no derivatives) license, users are free to copy, display, distribute, or perform the original work with attribution. Users may not make derivative works, such as those "consisting of editorial revisions, annotations, elaborations, or other modifications which, as a whole, represent an original work of authorship."1 An author might choose this license if she wants to retain the exclusive right to make such modifications.
- A CC BY-NC (attribution, non-commercial) license allows for copies, distribution, display, or performances of a work by attribution, but only for non-commercial uses. This license also allows for derivative works. Authors might choose this license if they wish to prohibit commercial publishers from republishing their work without obtaining further explicit permission. Authors should be aware that since much academic publishing is commercial, this license may "discourag[e] or at least slow . . . down [commercial] re-use of [their] content by requiring that people ask . . . permission."2
- The CC BY-NC-ND (attribution, non-commercial, no derivatives) license is the most restrictive choice offered by Southern Spaces. Users may copy, distribute, display, or perform a work, but only for non-commercial purposes. No derivative works are permitted. Authors might choose this license if they wish to encourage greater distribution of their work without permission than would be possible if retaining copyright, but restrict commercial entities from republishing their scholarship, and prohibit all users from making modifications to their work without permission.
Our decision to offer these options is an example of our ongoing evaluation of how to manifest our journal's commitment to open access publishing. By providing greater reuse rights through adopting a Creative Commons license, authors gain the potential to increase the reach and future use of their scholarship.3
Creative Commons licenses also provide an attribution requirement, which is particularly relevant to scholarly publishing but is not included in US Copyright Law.4 Attribution through citations is an important component of scholarly integrity, providing readers with the means to follow a scholar's arguments. Citation counts are also used to assist tenure and promotion committees in assessing a scholar's impact and productivity.5
The publishers of the Public Library of Science (PLOS) have described open access as a spectrum, prompting a move "beyond the deceptively simple question of, 'Is It Open Access?' toward a more productive evaluation of 'HowOpenIsIt?'" Among PLOS's criteria for gauging where a publication lies on the open access spectrum are "reuse" and "copyright." For PLOS, "closed access" means "no reuse rights beyond fair use/limitations and exceptions to copyright (all rights reserved copyright)." PLOS ranks various Creative Commons licenses on its spectrum of openness, characterizing CC BY-ND licenses as midway between open and closed, CC BY-NC licenses as occupying a middle ground, and CC BY licenses as the gold standard for open access.6
Our decision to have authors retain their copyright and give authors the choice among four Creative Commons licenses is based on our desire to balance our commitment to open access with a desire to serve our authors' professional aspirations and respect their choices. Authors may wish to retain some say over who reuses their work, and under what conditions. Some publishers, for example, have stringent requirements about the licensing of previously published works. Retaining copyright can be important for authors who are working on book manuscripts or other projects that may incorporate pieces published elsewhere, especially those authors seeking tenure or promotion. While we encourage the free circulation of information, we believe it is unfair to impose reuse requirements on authors—particularly given the imperatives of "publish or perish" and instability in hiring in higher education.
This new author agreement represents the journal's parallel commitments to open access and to supporting authors of all academic ranks, including those outside the academy. We encourage interested authors to contact us with any questions about our new licensing options, and we look forward to participating in further conversations about open access and author's rights.
See and share the infographic below on Southern Spaces's new author agreement.
- 1. "17 US Code, Chapter 1, Section 101–Definitions," Legal Information Institute, Cornell University Law School, accessed February 10, 2014, http://www.law.cornell.edu/uscode/text/17/101.
- 2. Bethany Nowiskie, "Why, Oh Why, CC-BY?" nowviskie.org, May 11, 2011, accessed February 10, 2014, http://nowviskie.org/2011/why-oh-why-cc-by/.
- 3. At present, there have been no studies on the effects of Creative Commons licensing on future use of scholarship. However, scholars such as informatics professor Dr. Mathias Klang have reported that their Creative Commons–-licensed work has gained more exposure than other publications. See Mathias Klang, "The Advantages of Creative Commons in Academia," SpotOn, October 17, 2012, accessed February 18, 2014, http://www.nature.com/spoton/2012/10/the-advantages-of-creative-commons-in-academia/.
- 4. For more on attribution and US as well as European copyright law, see Christopher Jon Springman, Christopher J. Buccafusco, and Zachary C. Burns, "What's a Name Worth?: Experimental Tests of the Value of Attribution in Intellectual Property," Boston University Law Review 93 (2013): 101–147, http://scholarship.kentlaw.iit.edu/cgi/viewcontent.cgi?article=1732&context=fac_schol.
- 5. New citation analysis tools such as Google Scholar cast an unprecedentedly wide net in identifying sources in which to search for citations, perhaps making requiring attribution—already assumed in traditional scholarly publishing—more consequential. On the use of citation counts and related metrics in tenure and promotion decision-making, see, for example, Henk F. Moed, Citation Analysis in Research Evaluation (Dordrecht, The Netherlands: Springer, 2005). The merits of favoring citation counts in tenure and promotion decisions have long been debated, sometimes charmingly so, as in Eugene Garfield, "Citation Frequency as a Measure of Research Activity and Performance," in Essays of an Information Scientist, ed. Eugene Garfield (Philadelphia: ISI Press, 1977), 406–408.
- 6. "HowOpenIsIt?: Open Access Spectrum (OAS)," Public Library of Science, 2013, accessed February 3, 2014, http://www.plos.org/open-access/howopenisit/.


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|Image credit
2. Even busy people can find time to read. I got stuck into reading this year and loved every minute of it. The best book I read in 2010 was probably 'The Slap' by Christos Tsiolkas, although 'Whitethorn' by Bryce Courtney, The Millenium series by Stieg Larsson and 'The Life of Pi' by Yann Martel are notable mentions.
3. I watch too much TV
4. There is a reason people have those 'films I have seen' widgets in their sidebars. It is actually really hard to remember! I reckon Toy Story 3 was the best film I saw in 2010 (disclaimer: I am yet to see The Social Network, Animal Kingdom or the King's Speech, which I know I will love). Was the Hurt Locker out this year? That was a great film. I also really liked the Green Zone, Inception and Up.
5. It is good to have your email address on your blog. You never know who might want to contact you. CSaM if you are reading this, I cannot comment on your blog (there is a permanent error there) so I haven't been able to say 'hi'. So "Hi" and "Welcome".
6. I have gone beyond 'surviving'.
7. Being unkind to people is unforgivable.
8. You are never too old to be made feel like a 'naughty school girl'.
9. 37 year old women with 4 children can still dance the night away into the wee hours of the morn after too many bevvies with friends. I've still got it!
10. I am a crappy correspondent.
11. Salt-reduced foods also contain a lot less sugar than their salted counterparts.
I am leaving on a jet plane tomorrow morning for Fiji to spend Christmas and New Year there with my family. Squeee!!
I will be back in early January 2011 with more of And then there were four. Until then, you take care and find the joy :)
What did you learn about yourself this year?


text:
Getting a new pair of home knives could be rather exciting. There are several choices on the market to match any spending budget - from $50 to $1000 kitchen knives. One way to find out which producers you can rely is usually to conduct some investigation and look for kitchen kitchen knives rankings so you may not wind up spending money on an issue that is not very really worth your hard earned dollars. Reading item and customer reviews likewise helps a lot in deciding on a new cutlery established that best fits your needs and your budget. best otf knife ever
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Must consider are actually gonna need
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For $50 kitchen knives, the Forschner 3-Part Fibrox set gotten higher home knives scores on OnlyKnives.com. Together with KAI's Komachi sequence, Forschner knives outperform all of the other cutlery from the identical range of prices. For $150 or higher, you have ample for any higher preciseness Shun Classic or Macintosh Professional chef's knife. Also you can accept a Messermeister little establish with the identical selling price. Messermeister's San Moritz Professional Cutlery can certainly rival the better known Wusthof and Henckelds knife sets. best otf spring assisted knife
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In a finances of $300 to $500, you will have the liberty to choose good quality kitchen knives that have regularly gotten higher home cutlery scores such as a 7-Part Shun Classic Set or even a Worldwide 5-Bit Established. Macintosh Specialist cutlery are certainly not available in collections but are cheaper than Shun and World-wide kitchen knives but also solid undertaking.
Macintosh Specialist
For those who have $1000 to enjoy on cutlery, make a good investment on Japanese-manufactured knife collections including Hattori, Misono, Blazen, Glestain, and Nenox all recognized as high quality blade suppliers. Cutlery by these manufacturers use generations-old blade-generating customs and also the latest technology to produce exceptionally sharp kitchen knives. what is the best otf knife for the money
Use generations-old blade-generating customs
- best otf knife brand.
- For $50 knives, the Forschner 3-Item Fibrox established acquired.


text:
Looking to grow your prospect base, build strategic partners, and generate more referrals? Join the Bolingbrook Area Networking Group today and take advantage of the many benefits this industry exclusive LEADS group can provide to your business. Expand your sales team by providing and following up on referral sources.
Guests (including Non-Members) are always welcome to determine if your industry is available. Official B.A.N.G. (Bolingbrook Area Networking Group) registration is available to members of the Bolingbrook Area Chamber of Commerce. Contact us at 630.226.8420 or via e-mail.


text:
Difference between revisions of "PostgreSQL"
m (→Upgrading PostgreSQL: no need for chown if you run the commands as postgres)
(Revert - /var/lib/postgres is owned by root so those commands can not be run as postgres)
|Line 285:
|Line 285:
# systemctl stop postgresql.service
# systemctl stop postgresql.service
mv /var/lib/postgres/data /var/lib/postgres/olddata
postgres /var/lib/postgres/data /var/lib/data/postgres/tmp
[postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
[postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
|Line 306:
|Line 307:
# systemctl stop postgresql.service
# systemctl stop postgresql.service
mv /var/lib/postgres/data /var/lib/postgres/olddata
postgres /var/lib/postgres/data
[postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
[postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
[postgres]$ /opt/pgsql-9.6/bin/pg_ctl -D /var/lib/postgres/olddata/ start
[postgres]$ /opt/pgsql-9.6/bin/pg_ctl -D /var/lib/postgres/olddata/ start
Revision as of 15:15, 23 November 2017
PostgreSQL is an open source, community driven, standard compliant object-relational database system.
This document describes how to set up PostgreSQL. It also describes how to configure PostgreSQL to be accessible from a remote client. Among other applications, PostgreSQL can be substituted for MySQL as part of the LAMP web stack.
- 1 Installing PostgreSQL
- 2 Create your first database/user
- 3 Familiarize with PostgreSQL
- 4 Optional configuration
- 5 Administration tools
- 6 Setup HHVM to work with PostgreSQL
- 7 Upgrading PostgreSQL
- 8 Troubleshooting
Installing PostgreSQL
Install the postgresql package. Then set a password for the newly created postgres user.
Then, switch to the default PostgreSQL user postgres by executing the following command:
- If you have sudo and your username is in
$ sudo -u postgres -i
- Otherwise use su:
$ su # su -l postgres
See sudo(8) or su(1) for their usage.
[postgres]$ in this article.
Before PostgreSQL can function correctly, the database cluster must be initialized:
[postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
- the
--localeis the one defined in the file
- the
-Eis the default encoding of the database that will be created in the future;
- and
-Dis the default location where the database cluster must be stored.
Many lines should now appear on the screen with several ending by
... ok:
The files belonging to this database system will be owned by user "postgres". This user must also own the server process. The database cluster will be initialized with locale "en_GB.UTF-8". The default text search configuration will be set to "english". Data page checksums are disabled. fixing permissions on existing directory /var/lib/postgres/data ... ok creating subdirectories ... ok selecting default max_connections ... 100 selecting default shared_buffers ... 128MB selecting dynamic shared memory implementation ... posix creating configuration files ... ok creating template1 database in /var/lib/postgres/data/base/1 ... ok initializing pg_authid ... ok [...]
If these are the kind of lines you see, then the process succeeded. Return to the regular user using
As root, start and enable
/var/lib/postgres, you will have to edit the service file. If the root is under
home, make sure to set
ProtectHome to false.
Create your first database/user
Become the postgres user. Add a new database user using the createuser command:
[postgres]$ createuser --interactive
Create a new database over which the above user has read/write privileges using the createdb command (execute this command from your login shell if the database user has the same name as your Linux user, otherwise add
-U database-username to the following command):
$ createdb myDatabaseName
Familiarize with PostgreSQL
Access the database shell
Become the postgres user. Start the primary database shell, psql, where you can do all your creation of databases/tables, deletion, set permissions, and run raw SQL commands. Use the
-d option to connect to the database you created (without specifying a database,
psql will try to access a database that matches your username).
[postgres]$ psql -d myDatabaseName
Some helpful commands:
Get help:
=> \help
Connect to a particular database:
=> \c <database>
List all users and their permission levels:
=> \du
Show summary information about all tables in the current database:
=> \dt
Exit/quit the
psql shell:
=> \q or CTRL+d
There are of course many more meta-commands, but these should help you get started. To see all meta-commands run:
=> \?
Optional configuration
Configure PostgreSQL to be accessible from remote hosts
The PostgreSQL database server configuration file is
postgresql.conf. This file is located in the data directory of the server, typically
/var/lib/postgres/data. This folder also houses the other main configuration files, including the
find and
locate are not finding the configuration files.
Edit the file
/var/lib/postgres/data/postgresql.conf. In the connections and authentications section, add the
listen_addresses line to your needs:
listen_addresses = 'localhost,my_local_ip_address' #You can use '*' to listen on all local addresses
Take a careful look at the other lines.
Host-based authentication is configured in
/var/lib/postgres/data/pg_hba.conf. This file controls which hosts are allowed to connect. Note that the defaults allow any local user to connect as any database user, including the database superuser. Add a line like the following:
# IPv4 local connections: host all all my_remote_client_ip_address/32 md5
my_remote_client_ip_address is the IP address of the client.
See the documentation for pg_hba.conf.
After this you should restart
postgresql.service for the changes to take effect.
5432 by default for remote connections. Make sure this port is open and able to receive incoming connections.
For troubleshooting take a look in the server log file:
$ journalctl -u postgresql
Configure PostgreSQL authenticate against PAM
PostgreSQL offers a number of authentication methods. If you would like to allow users to authenticate with their system password, additional steps are necessary. First you need to enable PAM for the connection.
For example, the same configuration as above, but with PAM enabled:
# IPv4 local connections: host all all my_remote_client_ip_address/32 pam
The PostgreSQL server is however running without root privileges and will not be able to access
/etc/shadow. We can work around that by allowing the postgres group to access this file:
setfacl -m g:postgres:r /etc/shadow
Change default data directory
The default directory where all your newly created databases will be stored is
/var/lib/postgres/data. To change this, follow these steps:
Create the new directory and make the postgres user its owner:
# mkdir -p /pathto/pgroot/data # chown -R postgres:postgres /pathto/pgroot
Become the postgres user, and initialize the new cluster:
[postgres]$ initdb -D /pathto/pgroot/data
postgresql.service to create a drop-in file and override the
Environment and
PIDFile settings. For example:
[Service] Environment=PGROOT=/pathto/pgroot PIDFile=/pathto/pgroot/data/postmaster.pid
If you want to use
/home directory for default directory or for tablespaces, add one more line in this file:
Change default encoding of new databases to UTF-8
initdb with
-E UTF8 these steps are not required.
When creating a new database (e.g. with
createdb blog) PostgreSQL actually copies a template database. There are two predefined templates:
template0 is vanilla, while
template1 is meant as an on-site template changeable by the administrator and is used by default. In order to change the encoding of a new database, one of the options is to change on-site
template1. To do this, log into PostgreSQL shell (
psql) and execute the following:
First, we need to drop
template1. Templates cannot be dropped, so we first modify it so it is an ordinary database:
UPDATE pg_database SET datistemplate = FALSE WHERE datname = 'template1';
Now we can drop it:
DROP DATABASE template1;
The next step is to create a new database from
template0, with a new default encoding:
CREATE DATABASE template1 WITH TEMPLATE = template0 ENCODING = 'UNICODE';
Now modify
template1 so it is actually a template:
UPDATE pg_database SET datistemplate = TRUE WHERE datname = 'template1';
Optionally, if you do not want anyone connecting to this template, set
datallowconn to
UPDATE pg_database SET datallowconn = FALSE WHERE datname = 'template1';
Now you can create a new database:
[postgres]$ createdb blog
If you log back in to
psql and check the databases, you should see the proper encoding of your new database:
List of databases Name | Owner | Encoding | Collation | Ctype | Access privileges -----------+----------+-----------+-----------+-------+---------------------- blog | postgres | UTF8 | C | C | postgres | postgres | SQL_ASCII | C | C | template0 | postgres | SQL_ASCII | C | C | =c/postgres : postgres=CTc/postgres template1 | postgres | UTF8 | C | C |
Administration tools
- phpPgAdmin — Web-based administration tool for PostgreSQL.
- pgAdmin — GUI-based administration tool for PostgreSQL.
Setup HHVM to work with PostgreSQL
$ git clone https://github.com/PocketRent/hhvm-pgsql.git $ cd hhvm-pgsql
If you do not use a nightly build, then run this command (verified on HHVM 3.6.1) to avoid compile errors:
$ git checkout tags/3.6.0
Then build the extension (if you do not need an improved support for Hack language, then remove -DHACK_FRIENDLY=ON):
$ hphpize $ cmake -DHACK_FRIENDLY=ON . $ make
Then copy the built extension:
# cp pgsql.so /etc/hhvm/
Add to /etc/hhvm/server.ini:
extension_dir = /etc/hhvm hhvm.extensions[pgsql] = pgsql.so
Upgrading PostgreSQL
Upgrading major PostgreSQL versions requires some extra maintenance.
- Official PostgreSQL upgrade documentation should be followed.
- From version
10.0onwards PostgreSQL changed its versioning scheme. Earlier upgrade from version
9.ywas considered as major upgrade. Now upgrade from version
10.yis considered as minor upgrade and upgrade from version
11.yis considered as major upgrade.
It is recommended to add the following to your
/etc/pacman.conf file:
IgnorePkg = postgresql postgresql-libs
This will ensure you do not accidentally upgrade the database to an incompatible version. When an upgrade is available, pacman will notify you that it is skipping the upgrade because of the entry in
pacman.conf. Minor version upgrades (e.g. 9.0.3 to 9.0.4) are safe to perform. However, if you do an accidental upgrade to a different major version (e.g. 9.0.x to 9.1.x), you might not be able to access any of your data. Always check the PostgreSQL home page to be sure of what steps are required for each upgrade. For a bit about why this is the case, see the versioning policy.
There are two main ways to upgrade your PostgreSQL database. Read the official documentation for details.
For those wishing to use
pg_upgrade, a postgresql-old-upgrade package is available that will always run one major version behind the real PostgreSQL package. This can be installed side-by-side with the new version of PostgreSQL.
When you are ready, upgrade the following packages: postgresql, postgresql-libs, and postgresql-old-upgrade. Note that the data directory does not change from version to version, so before running
pg_upgrade, it is necessary to rename your existing data directory and migrate into a new directory. The new database must be initialized, as described near the top of this page.
# systemctl stop postgresql.service # mv /var/lib/postgres/data /var/lib/postgres/olddata # mkdir /var/lib/postgres/data /var/lib/data/postgres/tmp # chown postgres:postgres /var/lib/postgres/data /var/lib/data/postgres/tmp [postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data'
The upgrade invocation will likely look something like the following. Do not run this command blindly without understanding what it does! Reference the upstream pg_upgrade documentation for details.
[postgres]$ cd /var/lib/data/postgres/tmp [postgres]$ pg_upgrade -b /opt/pgsql-9.6/bin -B /usr/bin -d /var/lib/postgres/olddata -D /var/lib/postgres/data
pg_upgrade will perform the upgrade and create some scripts in
/var/lib/data/postgres/tmp. Follow the instructions given on screen and act accordingly. You may delete
/var/lib/data/postgres/tmp directory once the upgrade is completely over.
Manual dump and reload
You could also do something like this (after the upgrade and install of postgresql-old-upgrade).
- Below are the commands for PostgreSQL 9.6. You can find similar commands in
/opt/for PostgreSQL 9.2.
- If you had customized your
pg_hba.conffile, you may have to temporarily modify it to allow full access to old database cluster from local system. After upgrade is complete set your customization to new database cluster as well and restart
# systemctl stop postgresql.service # mv /var/lib/postgres/data /var/lib/postgres/olddata # mkdir /var/lib/postgres/data # chown postgres:postgres /var/lib/postgres/data [postgres]$ initdb --locale $LANG -E UTF8 -D '/var/lib/postgres/data' [postgres]$ /opt/pgsql-9.6/bin/pg_ctl -D /var/lib/postgres/olddata/ start [postgres]$ pg_dumpall -f /tmp/old_backup.sql [postgres]$ /opt/pgsql-9.6/bin/pg_ctl -D /var/lib/postgres/olddata/ stop # systemctl start postgresql.service [postgres]$ psql -f /tmp/old_backup.sql postgres
Improve performance of small transactions
If you are using PostgresSQL on a local machine for development and it seems slow, you could try turning synchronous_commit off in the configuration. Beware of the caveats, however.
synchronous_commit = off
Prevent disk writes when idle
PostgreSQL periodically updates its internal "statistics" file. By default, this file is stored on disk, which prevents disks from spinning down on laptops and causes hard drive seek noise. It is simple and safe to relocate this file to a memory-only file system with the following configuration option:
stats_temp_directory = '/run/postgresql'
Cannot connect to database through pg_connect()
Install php-pgsql and edit the
php.ini file uncommenting the lines
extension=pdo_pgsql.so and
extension=pgsql.so, then restart


text:
» You are here: Home » Dildos & Dongs » Inflating & Ejaculating » Hung Rider Rex Beige Squirting Dildo
Hung Rider line Rex Beige Dildo. Introducing Rex: he is long, he is thick, he squirts! He is f thick perfectly veined dick with a hefty girth and large squishy balls. Like all Hung Riders, he is body safe, phthalate and latex free. Simply squeeze his balls, place the tip in your liquid of choice, and release to get him full and ready. Ride him hard, then squeeze his balls to release when you are ready. Rex does not mind the rough treatment. Clean up is easy repeatedly fill and release with clean water. Water based lube recommended. Safe and simple cum recipe: mix plain, unsweetened yogurt with a little warm water until it reaches the desired consistency. Specifications: He squirts! Skin safe. Waterproof, non-vibrating dildo. Phthalate free. Latex free. Realistic look and feel. Length 8 inchesInsertable Length 6.5 inches. Width 1.85 inches. Circumference 6.5 inches. Product weight without package 1 pound 2 ounces.
Illinois residents will be charged 8.00% sales tax.
This website is intented solely for viewing and purchasing by an adult audience. If you are under 18 years old (21 years old in some states) we ask you to leave this website. Please do.All models are 18 years of age or older.


text:
mojotoad necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 112 diseños de 32 diseñadores freelance.
The Toadstool
Our company is a technology consultancy that primarily deals with software development. Our typical projects are relatively small in scope, typically involving custom solutions for very specific tasks and problems encountered by our clients. As such, this branding exercise is wide open for ideas, not merely limited to the sleek high-tech look of many technology companies.
The following attributes apply to our ethos: Wise in our ways, Masters of our craft, Playful in life.
Our clients are US-based and tend to be from the non-tech world with a need to solve technology-related problems; for example, law firms requiring help with digital forensics, or perhaps non-profits seeking automation and data harnessing for the enhancement of their online presence.
We tend to already know our clients via social contact and prior experience; projects generally arise during casual conversation; given that, there is no particular need to project a 'stodgy' or overly serious brand, so long as the result is a beautiful design.
A logo that includes "The Toadstool" as part of the design, for use in letterhead and web pages. It would be nice if a graphics-only version were available as well for symbolic branding. An acceptable variation would be just "Toadstool", without the 'The', if including it proves to be problematic from a design perspective.
The following ideas have occurred to us, but we are open to others:
1) Toad. We love toads. Either as sleek and iconic representation that reflects the technological nature of our business, or as a more complex version that embodies the attributes mentioned above, wise, masterful, playful. The result should not be overly cartoonish. And remember, a toad is not a frog! Frogs hop. Toads stroll.
2) Toadstool. A wide-brimmed mushroom (perhaps even integrated as the 'T') seems to have potential.
Some shade of green should be present (earthy green would be nice, but is not strictly required -- if vivid seems to be the way to go, then vivid we go).
Print file format: .ai (CYMK)
Web file format: .jpg and layered .psd (RGB)
No clip art or stock images, please.
We've attached a picture of the owner's pet toad (he is a packman frog, actually, but don't tell him that). It is not necessary to use this image or look in the design, but perhaps it will serve as inspiration.
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


text:
chadberg wrote:Ed Boyer wrote:If I start thousands of sackbut ensembles across the world
Then you'll have greatly amused this sometimes early music performer. Although you've already done that with the notion.
I recently did a gig with a chamber choir and a sackbut ensemble in a church. Now I know we were keeping it a cappella the whole time! Thanks, Ed!


text:
Bob Wilcher necesitaba un nuevo diseño de impreso o envases y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 17 diseños de 7 diseñadores freelance.
Killer B Fitness
Primary Message:
We are a cardio training center. We are not a typical gym. We have the formula that works every time to help people get fit, lose weight and feel great. They get addicted to the results. We have a circuit of 5 cardio machines (Cycleops Power Meter Bicycles, Concept 2 rowers, Life Fitness Ellipticals, VersaClimbers, Vasa Swim Trainers). It's Personal Training without the cost.
Secondary Message
Get more by interval training.
Train smart by heart rate and wattage.
Daily/weekly contests and competitions
Results Guaranteed.
Although the majority of our clients are female aged 35-55 who are looking to lose weight, we want to target males and females from the teens to their late 60's. Our desired audience includes people with all fitness backgrounds and levels.
We want to target all the people who are not seeing results with their current program such as those at the large health clubs.
This must be a 2 sided flyer. On one side it may have a fit guy and girl on machines and on the other side it may say "First Class Free" and have info about Killer B with the logo. These are just ideas. You can be creative.
I've attached some photos, but you may need to photo shop them to get them right. We want a 5 inch by 8 inch flier or something of similar size that can be mass distributed in parking lots and other crowded areas that will attract attention.
Our website is http://www.killerBFitness.com. You can find more out about us there.
We'd like this flier to target those who are looking for results, such as weight loss, improved energy, healthier heart, etc. We want it to appear welcoming, motivational and like it's a new hope for them to get in great shape. We'd definitely like some quality photos that portray a welcoming and fun atmosphere. We'd like it to appeal to clients of all ages - like a family experience.
We are affordable, convenient and produce results. Our fees are listed on the website, but our most attractive pricing for new members is $99/month with a 3 month commitment.
Our MAIN GOAL IS TO TRIPLE our current membership and expand with more locations on a national level. We want people to call us (805) 448-2222 and visit our website at http://www.KillerBFitness.com. Their first class is free.
It may be good to challenge people with a question such as:
Are you getting results with your workouts? Tired of working out and not losing weight? Want to never worry about weight problems again?
Be as creative as you want. Just make me a great flier that attracts attention. We are looking to take this concept to a huge level.


text:
Yesterday the United States Post Office announced that they're getting rid of Saturday delivery of first class-mail. Beginning in August, we'll no longer get letters, cards, bills, magazines, catalogs and junk mail on Saturdays.
Even in this day and age of electronic communication and social media, I love real mail in my real mailbox, and I'm kind of sad that I'll have one less day of it. When my husband was deployed, one of the highlights of my day was the mailbox walk. In that short walk from my front door to the mailbox, my excitement built as I wondered if that would be the day the mailman brought me something with his name on it. The mail run also meant that my daily outgoing letters were on their way downrange, where they would soon become the highlight of my husband's day.
He may not be deployed now, but mail still makes me happy.
On the upside, this new delivery schedule won't be affecting packages, PO box mail or post office hours. According to the USPS website,
"Once implemented during August of 2013, mail delivery to street addresses will occur Monday through Friday. Packages will continue to be delivered six days per week. Mail addressed to PO Boxes will continue to be delivered on Saturdays. Post Offices currently open on Saturdays will remain open on Saturdays."So how is the elimination of Saturday mail going to impact military families? Officials with USPS speculated that it won't make a huge difference, but didn't get back with us with any further information by our deadline. Those love letters you write may take a little bit longer to get to your sweetheart downrange, but because package delivery will remain unchanged, all those care packages we jam pack with love will still reach their destinations in a timely manner.
While some of us still cherish letters, generally speaking, so many military families communicate with faraway loved ones through email, Facebook, Skype, and text messages that the art of the handwritten letter seems to have become almost as archaic as the telegram. So unless the USPS figures out a way to stop all electronic forms of communication on Saturdays, I think we can handle not getting snail mail delivery.
When we asked our Facebook readers what they thought about Saturday mail delivery disappearing, most of the responders said they wouldn't miss it (especially because it means one less day to worry about finding bills in the mailbox). But there were some people, like myself, who will.
So what do you think? Will you miss Saturday mail delivery? How will this affect you as a military family?


text:
Comfy Cozy Laundry Room Door
- Name:
- Comfy Cozy
- Technique:
The glass has been Solid Frost Sandblasted.
Design elements are Clear Glass.
- Specifications:
Comfy Cozy Laundry Room Door - Solid Frost
CLICK GREEN BAR ABOVE TO CUSTOMIZE & BUY!This laundry room door features Sans Soucie's Comfy Cozy. This door can be customized and purchased online! Inside our Glass & Door designer you customize everything about your Glass and Door! Specify your size, choose from 8 wood types and experiment with different designs in different effects, getting instant pricing as you go along! What you see is what you get: your door and glass change LIVE as you make your selections! Design to your hearts content until you come up with just the right look with just the right privacy! Remember: All designs are available in all effects! So if you don't see what you're looking for, just contact us and we'll give you custom pricing, and create the design in whatever effect you need!
• Any Size
• As Glass Insert only or
• Pre-installed in a Door Frame
• Entry and Interior Doors & Glass
• 8 Wood species and Fiberglass Doors
• Shipping is $99, or $199 to some Eastern states
• ETA will vary 3-8 weeks depending on glass and door type
Looking for tips on laundry room design?
Check out these laundry room design tips on Houzz!
Solid Frost effects and Doug Fir doors have the quickest turn-around - 3 weeks to your door step. Specialty Glass effects (2D, 3D and Stained Glass), and our Specialty Woods (all woods except Douglas fir), will require approx. 8 weeks.
Our laundry room door designs are etched in the glass by sandblast glass etching. The design elements such as the border and the text are clear glass, with the background sandblasted frosted opaque. When your laundry room light is OFF, those clear glass areas have a dark look. The lines and shapes are thin enough to obscure the view into the pantry. You can also choose glass that's 100% private for complete obscurity!
Door glass will be tempered 1/8" glass for Solid Frost and 2D Effects. 3D Carving requires a heavier glass to maintain strength and will be 3/8" thick tempered glass. Learn more about glass make up.
Selling both the glass inserts for doors as well as doors with glass, Sans Soucie offers 8 woods as a slab door or prehung in the jamb - any size is available, so if you don't see your size, contact us for a custom quote.
Inside our fun, easy to use online Glass and Door Designer you'll get instant pricing on everything as YOU customize your door and glass! When finished designing, you can place your order online! We're here to answer any questions so please call (877) 331-3397 to speak to a knowledgeable rep! Doors ship worldwide at reasonable prices from Palm Desert, California with delivery between 3-8 weeks depending on door material and glass effect.


text:
- Description
- Material : Eco C-Infinity (100% Ecological Polyester)
Eco C-Infinity is a colourful breakthrough in chlorine resistant fabric technology!
The superior choice for swimmers, C-Infinity has exceptional strength and can retain its durability far beyond other elastane swimwear fabrics. Ideal for frequent pool use for recreational and performance based swimming, alle Funky Trunks & Funkita swimwear is made with Eco C-Infinity.
Eco C-Infinity has:
- High définition colour fastness
- Exceptional chlorine resistance
- Core strenght
- Esasticity
- Shape retention and a soft feel
- Quick drying features and breathhability
- 50+ UV sun protection


text:
Abstract: Dramatic events in human prehistory, such as the spread of agriculture to Europe from Anatolia and the Late Neolithic/Bronze Age (LNBA) migration from the Pontic-Caspian steppe, can be investigated using patterns of genetic variation among the people that lived in those times. In particular, studies of differing female and male demographic histories on the basis of ancient genomes can provide information about complexities of social structures and cultural interactions in prehistoric populations. We use a mechanistic admixture model to compare the sex-specifically-inherited X chromosome to the autosomes in 20 early Neolithic and 16 LNBA human remains. Contrary to previous hypotheses suggested by the patrilocality of many agricultural populations, we find no evidence of sex-biased admixture during the migration that spread farming across Europe during the early Neolithic. For later migrations from the Pontic steppe during the LNBA, however, we estimate a dramatic male bias, with ~5-14 migrating males for every migrating female. We find evidence of ongoing, primarily male, migration from the steppe to central Europe over a period of multiple generations, with a level of sex bias that excludes a pulse migration during a single generation. The contrasting patterns of sex-specific migration during these two migrations suggest a view of differing cultural histories in which the Neolithic transition was driven by mass migration of both males and females in roughly equal numbers, perhaps whole families, whereas the later Bronze Age migration and cultural shift were instead driven by male migration, potentially connected to new technology and conquest.Familial migration of the Neolithic contrasts massive male migration during Bronze Age in Europe inferred from ancient X chromosomes, bioRxiv, Posted September 30, 2016, doi: http://dx.doi.org/10.1101/078360 Update 15/03/2017: "Failure to Replicate a Genetic Signal for Sex Bias in the Steppe Migration into Central Europe"
Friday, September 30, 2016
Male-dominated conquest of Europe by Bronze Age steppe pastoralists
Just in at bioRxiv:
Monday, September 26, 2016
Estonian Biocentre Human Genome Diversity Panel (EGDP)
Published along with Pagani et al. 2016, the EGDP dataset is freely available at the Estonian Biocentre website as VCF and PLINK binary files here. It overlaps at ~550K SNPs with Harvard's Human Origins, and at an impressive ~1.1 million SNPs with the ~1.2 million SNP ancient DNA chip used by the Reich Lab and others. To see what's what, I ran a Principal Component Analysis (PCA) of all of the samples except the Congo Pygmies. I then removed four Siberians that behaved as if they had very recent European ancestry, and reran the PCA. Below are a few screen grabs from the latter analysis. The datasheet is available here. here. Look for the individual IDs with the GS prefix. Using the K7 spreadsheet and nMonte, here's a model for Ashkenazi Jews with some of the new EGDP populations as references, including Avars from the North Caucasus and Arabs from Israel. The Arabs do help to improve the fit, but they're not as important as Samaritans and Tuscans.
Ashkenazi Anatolia_ChL 7.9 Arab_Israel_1 15.65 Avar 0.6 Bashkir 0.05 Cossack 0 Italian_Tuscan 30.45 Polish 11.75 Samaritan 33.6 Uygur 0 distance%=0.2874 / distance=0.002874In any case, that looks like a fairly sensible outcome, considering that it only took me a few minutes to put together. I've seen much worse in scientific literature.
Thursday, September 22, 2016
New rules for comments
All comments posted here must comply with the following rules. Comments that break these rules will be removed. Repeat offenders will be banned.
- no racial or ethnic taunts and insults - do not for any reason speculate about the people posting here - avoid discussions with obvious trolls and/or mentally unstable people* - no conspiracy theories - do some reading here before posting if unfamiliar with the relevant topics - do not discuss or cite any outdated physical anthropology work unless it's just the raw measurement data in the context of discussions about archeology and/or ancient DNA - do not post any illegal or defamatory material - stay on topic unless you have a good excuse for going off topic*Mental illness is not a joke, but it is a reality for a lot of people, so we're bound to see some visitors here occasionally with this problem. If unsure, simply ignore and move on. There is no rule against swearing and name calling, but try to keep things civil. Trolls should be regularly called out for who they are, but keep it short and then move on. See also... Banned commentators list
Wednesday, September 21, 2016
Two pronged AMH colonization of Eurasia. Or not
A robust but healthy debate by proxy between three teams of population geneticists over at Nature today. Emphasis is mine:
Absract: High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations (2, 3, 4, 5) or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history (7, 8, 9) and refuelled the debate on the mutation rate in humans (10). Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record (11), and admixture between AMHs and Neanderthals predating the main Eurasian expansion (12), our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Pagani et al., Genomic analyses inform on migration events during the peopling of Eurasia, Nature, Published online 21 September 2016, doi:10.1038/nature19792 ...
Abstract: Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.Mallick et al., The Simons Genome Diversity Project: 300 genomes from 142 diverse populations, Nature, Published online 21 September 2016, doi:10.1038/nature18964 ...
Abstract: The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama–Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25–40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10–32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama–Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51–72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.Malaspinas et al., A genomic history of Aboriginal Australia, Nature, Published online 21 September 2016, doi:10.1038/nature18299
Thursday, September 15, 2016
R1a and R1b from an early Mongolian tomb
PLoS One has a new paper on a Mongolian imperial tomb dated to 1130–1250 AD, which is the early Mongolian era. Here's the table with the Y-haplogroup results:
Similarly, the high frequency of R1b-M343 in geographic regions associated with the past Mongol khanates including the Golden Horde (from Ural Mountain to Western Siberia, which includes Russia, Ukraine, Belarus, Poland, Azerbaijan, Kazakhstan, and Uzbekistan), Ilkhanate (Iran and neighboring territories including Armenia, Turkey, Georgia, Afghanistan, Syria, and Tajikistan), and Chagatai Khanate (from the Aral sea to the Altai mountain, including Pakistan (Hazara), Uzbekistan, Kazakhstan, Tajikistan, India, and China), strongly suggest a close association between the Y haplotype R1b-M343 and the past Mongol Empire.No, the distribution, frequencies and subclades of R1a or R1b do not show any sort of meaningful correlation with the past Mongol Empire. The most obvious explanation, although not the only possible one, for the presence of R1a and R1b lineages in Mongolian imperial remains are the migrations of the Afanasievo and/or Andronovo people into the Altai region from the Eastern European steppes during the Bronze Age. See here...
Tuesday, September 13, 2016
ISBA7 PalaeoBarn abstracts
The abstract book for this week's meeting is available here. Emphasis is mine. The two abstracts on the genetic shifts in the East Baltic region might look as if they contradict each other, but they don't. What they're suggesting is that the East Baltic was basically home to typical European hunter-gatherers right up until the Late Neolithic, when the Corded Ware people crashed into the area, probably from the steppe via East Central Europe. For more on this topic also see here.
Mitochondrial DNA Analysis of Human Remains from Estonia Pfrengle et al. The transition from hunter-gatherer subsistence to farming is one of the most important processes in human history. In Europe, it has been found to be a result of demic diffusion originating from the Near East. The arrival of the first farmers in Europe lead to an increase of genetic diversity as well as genetic admixture of local hunter-gatherer and the migrating farmers. Previous studies investigating European human history using mitochondrial and genome-wide nuclear data from early farmers and hunter-gatherers have provided detailed insights into the process of admixture and replacement throughout the Neolithic period. However this process has been poorly studied in the Baltic region where archaeological research suggests more extensive scenarios. Here we reconstructed the complete mtDNA of 19 individuals from different archaeological sites of Estonia covering the timespan from the Narva Culture to the Corded Ware Culture and determined their mitochondrial haplogroups. The results show that the typical European hunter-gatherer maternal lineages are represented exclusively in all individuals from until the Middle Neolithic. From the Late Neolithic on, haplogroups that are associated with European Neolithic farmers are detected. The results indicate genetic continuity of foraging cultures of Mesolithic and early Neolithic backgrounds and a late demic diffusion into the territory of Estonia associated with people of the Corded Ware culture. In addition, the generated genetic data are used to gain insights into the demography of burial complexes by sex determination and maternal kinship analysis. The Neolithic Transition at the Edge of Europe Jones et al. In Europe, the Neolithic transition marked the beginning of a period of innovations which saw people move from a mobile lifestyle, dependent on hunting and gathering for survival, to a more sedentary way of life based on food production. This new lifeway, which began in the Near East ~11 kya, spread quickly across the continental interior of Europe predominantly through demic diffusion. While the genetic impact of the Neolithic transition has been well explored in central Europe, its impact on more peripheral regions of the continent has not been as extensively studied. To broaden our understanding of this dynamic phase in European prehistory, we analysed genomes from a 4,000 year temporal transect through the Baltic region spanning from the Late Mesolithic to the Late Neolithic period. We found evidence for connectivity from the Mesolithic to the Neolithic however, we also detected signals consistent with influxes from non-local populations. These influences were distinct from the early farmer admixture which transformed the genetic landscape of central Europe during the Neolithic. Interestingly, dietary stable isotope analyses (δ15N and δ 13C) show that the genetic shifts coincide with diversifications in subsistence strategy. These results suggest that the Neolithic was a period of genetic flux in the Baltic however, the cultural and technological changes observed were largely independent of forager-farmer genetic exchange. Reconstructing population history in East Asia Wang et al. The deep population history of East Asia remains poorly understood compared to that of West Eurasia, due to the lack of ancient DNA data as well as limited sampling of present-day populations especially on the Tibetan Plateau and in southern China. We report a fine scale survey of East Asian history based on genome-wide data from ancient samples in the Amur River Basin, as well as 435 newly reported individuals from 53 populations. Present-day groups can be broadly classified into highly differentiated clusters, corresponding to Amur River Basin, Tibetan Plateau, southern natives and Han Chinese. Populations of the Amur River Basin show a high degree of genetic continuity from seven thousand years ago until today, and are closely related to the strain of East Asian related ancestry present in Native Americans. Tibetan Plateau populations are all admixed, deriving about 5%-10% of their ancestry from an anciently divergent population that plausibly corresponds to the Paleolithic population on the Plateau, and the remaining part from an ancient population that no longer exists in unmixed form but that likely corresponds to expanding farmers from the Middle and Upper Yellow River Basin who also contributed 40-90% of the ancestry of Han Chinese. A total of 10-60% of Han Chinese ancestry derives from southern Native populations, and we show that the type of southern Native ancestry that contributed to Taiwan Island Austronesian speakers is most closely related to present-day speakers of Tai-Kadai languages in southern mainland China. Contextualizing the Tianyuan genome within present and ancient human genomic diversity Yang et al. Recently, many studies have produced an unprecedented number of ancient human genomes, providing insight on human dynamics in many regions, particularly West Eurasia and the Americas. Here, we present genome-wide data from the Tianyuan specimen, dating to ~40,000 years ago. Unlike other ancient genomes studied to date, the Tianyuan genome is the first ancient Upper Paleolithic sample analyzed to have contributed greatly to the East Eurasian ancestral lineage. We compare Tianyuan to several ancient and present day human genomes to better understand both the genetic diversity in the Upper Paleolithic and the similarities and differences between Tianyuan and present day populations. Overall, the addition of genome-wide Tianyuan data provides greater insight into the population history in Eurasia over the last 40,000 years. Capture of ancient genomic DNA of individuals recovered from a Medieval Alemannic gravesite provides evidence for high mobility of fellowships during the 7th century CE. O'Sullivan et al. Whether the historic spread of cultural/language groups such as the Alemanni were migrations or local adoption of culture is still unresolved in archaeology. The Alemanni were a confederation of tribes that inhabited an area, from the third to the 10th century CE, which approximately overlaps with the modern distribution of Alemannic German dialect in Swabia. We present the genomic and isotopic data of eight individuals excavated from a gravesite in Niederstotzingen, Germany of supposed Alemannic origin dated to the 7th century CE. There were two multiple burials at the site suggesting either kinship or fellowship between the individuals. The tombs in the gravesite contained cultural artefacts and weapons indicating close contact of the Alemanni with Longobards and Byzantines. We investigated the genetic affinity of these individuals between each other and to modern West Eurasians. The genetic analysis utilised the targeted enrichment and sequencing of over 1.2 million genetic markers that have known ascertainment. From these data, we found no familial relationship among the individuals in the multiple graves, thus supporting a burial practice based rather on fellowship. All individuals were genetically male. The genetic affinities of the individuals, based on modern genetic distributions, were five Eastern Europeans, two Germans/Austrians and one Southern European. Isotopic data supports that only the Southern European individual was certainly born outside this region. The genetic data appear to correlate with the provenance of the burial artefacts, showing that westward movements and interactions among cultural groups likely occurred in this region during the 7th century CE. Origins and genetic legacy of the first people in Remote Oceania Skoglund et al. The appearance of people associated with the Lapita culture in the South Pacific ~3,000 years ago marked the beginning of the last major human dispersal to unpopulated lands, culminating in the settlement of eastern Polynesia ~1,000-700 years ago. However, the genetic relationship of these pioneers to the long established Papuan peoples of the New Guinea region is debated. We report the first genome-wide ancient DNA data from Asia-Pacific region, from four ~2,900 to ~2,500 year old Lapita culture individuals from Vanuatu and Tonga, and co-analyze them with new data from 356 present-day Oceanians. Today, all indigenous people of the South Pacific harbor a mixture of ancestry from Papuans and a population of East Asian origin that we find to be a statistical match to the ancient Lapita individuals. Most analyses have interpreted the ubiquitous Papuan ancestry in the region today-at least 25%-as evidence that the first humans to reach Remote Oceania and Polynesia were derived from mixtures near New Guinea prior to the Lapita expansion into Remote Oceania. Our results refute this scenario, as none of the geographically and temporally diverse Lapita individuals had detectable Papuan ancestry. These results imply later major human population movements, which spread Papuan ancestry through the South Pacific after the islands' first peopling. An ancient genomic perspective on the horse domestication process Librado et al. The domestication of the horse in the Pontic-Caspian steppes some 6,000 years ago represents one major turning point in human history. With horses, humans could travel for the first time well above their own speed and carry their germs, culture and genes across vast geographic areas. The development of horse-drawn chariots and cavalry also radically changed the history of warfare and was instrumental to the emergence of transcontinental empires. Additionally, beyond the battlefield, farm horses have massively impacted agricultural productivity. The biological changes that accompanied the process of horse domestication are, however, difficult to reconstruct from current patterns of genetic diversity both due to the development of intensively selected and extremely influential breeds during the last two centuries, and the almost extinction of wild horses. Recent developments in ancient DNA research have opened for the characterization of complete genomes, epigenomes and microbiota over long time series. We have applied such approaches to a large panel of horse remains spread across Eurasia and dated to 44,000-200 years ago. This started revealing the genetic structure of horse populations prior to and during early domestication stages as well as the history of genetic changes that accompanied their further transformation in a range of cultural contexts. I will present our latest progress made on an extensive dataset of ancient horse genomes spanning the whole domestication temporal and geographical range. Mobility between the Aegean and the Levant in the Late Second Millennium BCE: inference from ancient DNA of pigs Meiri et al. The Late Bronze and the early Iron Ages (ca. 1450-950 BCE) of the eastern Mediterranean region are characterized by dramatic historical processes. Empires emerged and collapsed, trade connections were established and severed, and at the end of this era socio-political unrest and migration of large groups of people were rife throughout the region. In the 12th century BCE the movements of the so-called "Sea Peoples" affected wide parts of the East Mediterranean. We study the nature of human movements during this period on trade connections, culture and animal husbandry using the ancient DNA of domestic animals, above all pigs. We recently showed that in Israel, European pig haplotypes appeared ca. 900 BCE, and soon after took over the gene pool, with all modern wild boars in Israel carrying European mitochondrial DNA. Here, we broadened the chronological and spatial scopes by studying ancient pig mitochondrial DNA from the southern Levant and Greece. The Near Eastern haplotype Y1 and supposedly Near Eastern haplotype Y2 were discovered in Greece in the mid to late 3rd millennium BCE, while the European haplotypes were found in Israel in the early Iron Age IIA (ca. 900 BCE). We propose that pigs were moved between Europe and Anatolia since the early Bronze Age. Connections between Greece and the southern Levant are observed in the Iron Age, and probably result from the migration of Sea Peoples to the east. These results shed light on networks and movements of people during both times of prosperity and crisis.
Brachycephalization on the western steppe after the Mesolithic
Interesting stuff from the ADNABIOARC team at Scientific Reports today:
Abstract: The Neolithic transition brought about fundamental social, dietary and behavioural changes in human populations, which, in turn, impacted skeletal morphology. Crania are shaped through diverse genetic, ontogenetic and environmental factors, reflecting various elements of an individual's life. To determine the transition's effect on cranial morphology, we investigated its potential impact on the face and vault, two elements potentially responding to different influences. Three datasets from geographically distant regions (Ukraine, Iberia, and the Levant plus Anatolia) were analysed. Craniometric measurements were used to compare the morphology of pre-transition populations with that of agricultural populations. The Neolithic transition corresponds to a statistically significant increase only in cranial breadth of the Ukrainian vaults, while facial morphology shows no consistent transformations, despite expected changes related to the modification of masticatory behaviour. The broadening of Ukrainian vaults may be attributable to dietary and/or social changes. However, the lack of change observed in the other geographical regions and the lack of consistent change in facial morphology are surprising. Although the transition from foraging to farming is a process that took place repeatedly across the globe, different characteristics of transitions seem responsible for idiosyncratic responses in cranial morphology.Cheronet et al., Morphological change in cranial shape following the transition to agriculture across western Eurasia, Scientific Reports, Published online: 13 September 2016, doi:10.1038/srep33316 See also.. Modeling Steppe_EMBA
Thursday, September 8, 2016
ASHG 2016 abstracts
The American Society of Human Genetics (ASHG) 2016 Meeting Online Planner and Abstract Search can be accessed here. Unless I'm missing something, there's surprisingly little ancient genomics stuff this year considering the huge advances in this area recently.
However, Iain Mathieson has an interesting contribution about interactions between Balkan foragers and early Balkan farmers. Reading between the lines, I reckon we can probably expect some R1b in these Balkan ancients. This shouldn't be surprising, however, considering the publication earlier this year of the Ice Age Villabruna genome from present-day northeast Italy, which belonged to R1b and, as pointed out by myself, also showed strong genome-wide ties to ancient Siberians (see here).
Genome-wide ancient DNA from Europe's first encounter of farmers and hunter-gatherers. I. Mathieson.
Oleg Balanovsky has been acting a little strange lately; seemingly going out of his way to fight the Kurgan Indo-European paradigm in various papers and talks. In this poster he underlines the fact that the Yamnaya people from the North Caspian region did not totally vacate their homeland nor moved en masse to Western Europe, but actually left most of their descendants in the North Caspian. OK Oleg, but almost all modern day Europeans, especially those from across Northern and Eastern Europe, do derive a lot of their ancestry from Bronze Age steppe groups closely related to the Yamnaya people of the North Caspian. This will become even more obvious soon with the publication of new ancient data from the Baltic region.
Y-chromosomal sequencing and screening reveal both stability and migrations in North Eurasian populations. O. Balanovsky.
And here we have what appears to be yet another hilariously wrong paper in the making on the population history of South Asia. Why do they mention Anatolia? How about the Arctic Circle? Enough already. Get some goddamn ancient genomes from South Asia and finally do it right.
Genetic variation reveals migrations into the Indian subcontinent and its influence on the Indian society. A. Bose, D.E. Platt, L. Parida, P. Paschou, P. Drineas.
These abstracts also sparked my interest, in a positive way:
Using whole-genome sequencing to shed insight on the complex prehistory of Sardinia. C. Chiang
Y-chromosomal composition of mediaeval and contemporary populations in Norway and adjacent Scandinavian countries: Y-STR haplotypes and the rare Y-haplogroup Q. B. Berger.
A complex history of archaic admixture in modern humans. R. Bohlender, Y. Yu, C. Huff, A. Rogers.
Genomic insights into the population structure and history of the Irish Travellers. E.H. Gilbert.
Friday, September 2, 2016
Ust'-Ishim man x2
Just wanted to see what would happen if I split Ust-Ishim into two homozygous sequences, and ran him in a Principal Component Analysis (PCA) alongside other fully homozygous individuals and composites, both modern day and ancient. In theory this shouldn't be a problem, considering that his genome is of such an incredibly high quality (~42-fold coverage). The datasheets for the PCA below are available here and here. This is the only way that I can think of to run a PCA in which genetic drift specific to the Ust'-Ishim population of ~45K YBP western Siberia has a clear impact. Indeed, lots of interesting things on these plots. Note, for instance, that on the second plot the Afanasievo and Yamnaya-Catacomb composites appear to be attracted to the Caucasus Hunter-Gatherer composite. Also note how unusual the Neolithic Iranians (Iran_EN) appear. here and here. Below are screen caps of angles that appear to recapitulate the geography of Eurasia. See comments below for details. Ancient vs modern day West Eurasian variation
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Un ganador ha sido elegido entre 20 diseños de 8 diseñadores freelance.
My College Options
We provide a platform for high school student to find the right college.
Fun playful poster design needed for high school students:
The goal for this poster is just to create a fun playful teen orientated poster template. This poster is intended for high school guidance counselors to display in their offices to show students the location of colleges in their area. The poster will display a variable map of their region identifying the colleges in their area. For this project just us the sample list and map, the background template is the goal.
Task list
• Logo at the top
• Box with map (sample map image is attached)
• List of schools under the map (List is attached)
• Use the Color palette attached
• The final product should be a layered EPS file


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Now, researchers at the Perelman School of Medicine at the University of Pennsylvania report in Science Translational Medicine a new mouse model of LAM that does replicate those features, producing a way to study disease etiology and develop drugs. What's more, two readily available drugs – an antibiotic and a statin – may help to treat, and maybe reverse, symptoms.
Elena Goncharova, PhD, research assistant professor of Medicine, and Vera Krymskaya, PhD, associate professor of Medicine, Pulmonary, Allergy, and Critical Care Division at Penn, led the study. The team collected TSC2-mutant cells from spontaneous kidney tumors formed in mice. They then "sensitized" those cells by growing them into tumors in immunocompromised mice, excising those tumors, and reinjecting their cells into the tail veins of another set of immunocompromised mice.
Unlike non-sensitized TSC2-deficient cells, the sensitized cells produced multiple lung nodules comprised of smooth muscle-like cells, as in the human disease, as well as destruction of lung tissue and lymphangiogenesis. These nodules also exhibited enhanced activity of an enzyme called matrix metalloproteinase and the loss of elastin, suggesting a potential mechanism for causing that tissue damage. The study also demonstrated for the first time that destruction of lung tissue in LAM is caused by TSC2 deficiency in lung lesions.
TSC1 and TSC2 regulate the mTOR (mammalian target of rapamycin) pathway. As a result, the antibiotic rapamycin is already used therapeutically for pulmonary LAM. But, says Goncharova, the drug appears only to halt cell growth, not induce cell death. When rapamycin is removed, disease progresses. "That showed us that something else was needed to fully treat the disease," she says.
As it turns out, that something else could be a statin.
Statins are well known cholesterol-controlling medications. But they also can inhibit signaling proteins called GTPases, inducing cell death. An earlier study using rapamycin and simvastatin demonstrated that the combination could prevent tumor reoccurrence in a mouse model in which TSC2-mutant tumors were not grown in the lungs, but in the flanks of the animal.
The current study expands that observation, demonstrating that rapamycin plus simvastatin can inhibit the growth of TSC2-mutant tumors in the mouse lung, as well as the resulting tissue damage.
But perhaps more importantly, from a clinical point-of-view, application of the drugs after development of lung nodules and tissue damage could actually reverse tissue damage.
"It's my strong belief that if you want to propose treatment options, you need to reverse or attenuate existing disease. Prevention is not enough," says Goncharova.
As in the earlier study, rapamycin in this study appears to be cytostatic – it halts cell growth; simvastatin induces cell death, and both drugs block matrix metalloproteinases as well. Both drugs are FDA-approved and commercially available.
But before pulmonary LAM patients call their physicians for a prescription, Goncharova stresses that the results were in mice, not humans. Clinical trials are required to test the efficacy of this drug combination in patients. To date, no such trials have been initiated.
"I hope it will be done in the near future," she says.
Other co-authors from Penn include Dmitry Goncharov, Melane Fehrenbach, Irene Khavin, Blerina Ducka, Angela Haczku, and Steven Albelda.
The study was supported by the National Heart, Lung, and Blood Institute (RO1HL71106, RO1HL090829, RO1HL114085), Abramson Cancer Center Core Support Grant (NIH P130-CA-016520-34, P30ES013508, RO1AI072197, RC1ES018505), the American Lung Association (CI-9813-N), the LAM Foundation, and the Auckland Medical Research Foundation.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.


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