text:
HD competition Sex Tube- When girls are competing, you have to see it
8:00Its time for the ZZ Universe Competition The passion is building and the milliondollar questions are piling up Which competitor has the sweetest booty
8:02Admirable team fuck scene with pornstars Sara Jay Sarah Vandella Spicy J 3 breasty curves were playing outside on the grass being naked A man came and
0:0518yo babysitters playing sex games
0:05gentle anal games with brutal rod
6:07Ravishing nineteen year old Ashlynn Leigh accepts a challengeif this babe can keep her raiment on that babe wins giant money But James Deen and his fe
6:23Saoirse Ronan jerk off challenge
6:01Penny Pax and Anikka Albright take a break from town life and take a hike in the woods but they dont know that James Deen is spying on them awaiting t
4:26Billy got stuck doing a giant presentation at work that his boss was supposed to do But during the time that his boss took the afternoon off to go sit
7:00Real sophomore harlots in bj contest lapping up dongs
13:00Games with carrot
8:01This week we surprise u with some gripping and laughable competitions This slender brunette hair doesnt know this man but this does not prevent '
0:05College students playing erotic games
12:01Hanna and Vera are 2 marvelous lesbians They practice lesbo games for a lengthy time but this day they wanted to receive smth in their wet cracks and
4:26Sophie Dee is a breasty nurse and that babe has a particular power this babe can cure everyone out of drugs merely using her biggest tits This fellow
3:04Miss infant over and above Miss Hat HOTNESS - Spring Break Skin To collect G-string Contest
7:02Malya is a real milf and she can't live without to have fun with juvenile boyz in adult games Right now she's swallowing a delightsome jock
3:02It begins with a kiss in the saunaand 2 of our large DDFBustycom superstars Katarina and Carnal Jane are off into an erotic rencounter in the sauna Ha
1:49Bella Moretti Kacie Starr and Katie St Ives are competing which one can give the more good fellatio
3:01Hungarian girl Mia Stone would accompany Eve Gal on her memorable lesbo journey Foot fetish is a recent detail they include in their vehement lesbo ga
7:32It is like agreeable Erica Fontes and Victoria Volt are competing to watch which one of 'em is plan to make his manhood harder faster They are gr
2:30Mother besides Daughter sucking off Contest 02
6:39CFNM euro milfs tugging competition
4:26Juvenile babysitter goldenhaired chick wishes to acquire extramoney for her work This defiant pair suggested her to have fun in their avantguarge game
25:13Sasha Grey - BringUm teenager 23
8:01Priya and Xander are one as well as the other fighting for the same position at the company they one as well as the other work in The One And The Othe
0:03Subtitled CMNF ENF Asian reverse brilliance gap game
8:00Karina Heart has the most good natural melons in this game and this babe have fun with 'em all the time
2:00Mother plus Daughter blowjob Contest
2:30Mother more than that Daughter headjob Contest #02
8:01The superlatively good game of exposed Twister ever to receive filmed on movie is here for u to have a fun it Come scrutinize the glamorous lissome bo
8:01Gorgeous Nikki Sexx is the hottie of your dreams This Babe completely adores anal games Her resilient butt gap takes biggest darksome object inside as
8:01turned-on Rose Monroe is the number 1 ass of the Year 2 14. this cutie knows a really unusual way to say thanks to contest assistants Jordan Ash toget
8:02Juelz is a pornstar but is that babe a porn legend Can that babe dom the solo scene The model on hottie The large dong Shell get to have fun the game
12:01Sophie Lynx has the most good ass in the game and she can't live without to use glass toys in her anal opening
2:30Mother together with Daughter blowyoral-service Contest 02
6:04Alan Stafford is playing a game of poker with Mark Davis and Mr Pete and when this guy loses all cash that guy bets his wife Cherry Torn That Guy lose
8:01Our hawt porn begins show for the kids how to have fun real party games and along the way some weenies acquire sucked and drilled on Even some muff re
4:26Becca Blossoms is marvelous frustrated in how Sammie Spades sucks her paramours dick Becca joins their raunchy game in order to improve it on the blow
0:05Sugary legal age teenager willing for a perverted game
8:01Suzanne Kelly is a beautiful brunette hair who likes to engulf weenies previous to letting 'em dive in her pussy and Voodoo will receive his chan
6:02Sara Jay is set up by her spouse to take part in perverted sex games with an ally and his resigned wife Kait Snow One As Well As The Other wives acqui
10:01This blonde chick named Tiffany likes to have fun with her ally in adult games Moreover they are doing it in the forest where nobody can watch them Ju
Top rated hd sex sites:
Wife Sex Movie
Sex Hub HD
Porn Gladiator
Horny Elephant
My Wife Sex
Xxx Videos
amateur sex clip
XNXX Rate
Sex Movies
Porno Tube HD
Adult Movies
Home Porn
home sex hostel
Gold Jizz
Tube York Porn
6:00Argentina is one of the hottest sweethearts in the game and that babe truly craves to smack a hard knob in her face hole and pussy This massage turned
8:01Bruce Venture is having a favourable day right now since Gracie Glam is one of the hottest hotties in the game This Guy bonks her like no one else and
0:05Real nonprofessional group in party game
5:01Ftv chicks Masturbation contest enters upon Romi along with Raylene
0:07Deepthroat contest in a college dorm room
8:01Trinity St Clair doesnt wanna miss anything that's why she's so slow and attentive to the cocksucking part of this raunchy game Pretty Soon
3:02Bewitching juvenile honey Cherry Jul is a giant fan of a football game This Babe dons the football uniform and positions expertly on camera Pretty Soo
7:02Monster pecker is a long shot 'coz Callie Cobra
5:31Sweet Latin Babe cuties with priceless forms of bodies Miya Monroe and Nadia Night are having contest which of 'em is blowing better The fellow t
0:05In Nature's Garb amateurs masturbate for group game
16:57legal age teenagers At A Spring Break G-string Contest
8:01Abbie Cat is a super sexy breasty milf whose sex appetite is quite insatiable and she likes all kind or role game playing Luckily Danny D has brought
4:26Pair of hawt wicked youthful lesbos are playing truthordare That is an astonishing begin for vehement and unfathomable lesbo fuck Check out that clip
8:04genre getting laid contest thanks to young babes
4:26This interview with an entire crowd of wild lesbo pornstars looking for a chance to acquire it on with every other will be a very hawt one See 'e
3:29Subtitled oriental nudist CMNF outside sample stretching
5:05This game of undress blackjack with Alyssa Reece Celeste Star and Molly Cavalli is guaranteed to be a hawt one Especially when Molly herself loses and
8:01Wild momma Reena Sky is here for todays update Shes been without the game for a while but shes back and willing to make u suck large fucking loads She
4:26Theres no way this lesbo game of truth or dare with several topnotch lesbo porn stars participating will be a boring one The mommies want to have some
8:00This enjoyment redneck game with pumpkins is intend to have one rather unexpected outcome The favourable winner will receive sucked off by Lylith Lave
0:21Turkish Pornstar Sibel Kekili Shae From Game Of Thrones Compilation
8:01Those 3 frisky angels JC Simpson Molly Cavalli and Nevaeh have arranged the real casino party and played several card games getting the stripped breas
5:08Those ribald hotties like sports Breasty sexy goldenhaired and elegant gentle brunette hair are playing basket ball nude outdoors near their college e
6:04japanese damsels in unexplainable fucking contest
6:56Pissing contest for the reason that turned-on lesbians
7:00Lickerish and wicked sex doll Lili Lamour in fine nylons can't live without anal games
0:02obscenely brutal anal games with jism
5:00Pressley Carter prefers to have fun in various games and in nasty ones too Moreover that babe desires to be pounded hard this day and thats why her al
0:03Subtitled CFNM eager Oriental ramrod guessing game show threatening
8:01Home team has lost this game but 2 lewd cheerleaders Courtney Cummz and Alexis Ford are here to support their trainer with oral pleasure and some grea
5:01Anal games with actually sexually excited bitches Cameron Canada licking and puts her tongue intro Maia Daviss anal hole definitely she can't liv
6:00garden gay girl climax contest
1:44German hotties break in a pissing contest
0:05Brutal bum games of hawt lesbos
8:03Avril Hall and Malena Morgan begins with ardent French giving a kiss and when their charming slits become indeed wet honeys begins their main game of
10:03They all got drunk and when one of angels offered to have some great orgy Nobody was afresh and trying it for the 1st time So beauties fondle every ot
8:07Leighton Meester Jerk off toss-up
5:31Chastity Lynn and Kristina Rose are the hottest lesbian babes in the game for sure In this movie scene u can watch how slutty they are and this time t
17:00Truth or dare
8:02Brannon Rhodes Missi Daniels their girlfriends and boyfriends are having nifty bang enjoyment in a VIP zone of the club See anything what takes place
1:08Squirt Competition
4:26Billy is a surfer who had an accident during his latest contest and was sore all over This Chab decided to acquire a Nuru massage to watch of it would
8:01In this movie of everyones beloved reality television show Specie Talks we watch models talked into a gazoo contest where they compare snatches to det
8:02Chanel is one of the superlatively good volleyball payers in the team Johnny comes to the game and is stunned with her wild figure This Guy invites Ch
2:42Carmella BingJustin Magnum and Phoenix Marie have fun with greater quantity than the ball at this football game Football and sex great Its what each p
5:02See as this young hawt redhead and her blond mother figure bond in daybed with a little game of truthordare Not surprisingly garments disappear quickl
6:01Rainia Belle is one of the hottest women in the game and that babe takes his hard 10Pounder like a real pro Her arse is just screaming for sex and thi
7:04Lesbo latex fetish game with Angelica Heart and Latex Lucy would make u impressed The beauty in latex costume of cat is getting arse spanked previous
4:31Sweetheart Foxxx can't live without stylish studs and their dicks But that babe has a pecker also and sometimes it's longer This time Vin De
4:26Billy is a surfer who had an accident during his latest contest and was sore all over This Chab decided to receive a Nuru massage to watch of it would
27:29Chunky ebon bitches Sabrina Love Farrah Fox compete
8:00Alyssa Lynn is one of the hottest milfs in the game and Johnny Sins is the dude who copulates her like a real pro That Guy copulates her so hard that
5:02Excellent beauties are playing outdoors with bubbles and their asses Afterwards they proceed the game inside solely this time they are getting fully n
1:40:13The darksome chavette
0:05Nonprofessional hazing legal age teenagers exposed games
10:14Eva Angelina Keanni Lei and Tricia Oaks are competing to become the queen of blowbang and so far they appear to be tied Have A Fun watching 'em a
7:01Take a look at 2 delightful lesbo whores Antonya and Salome playing sexy fisting games
2:39young Miss HOTNESS - Spring Break Skin To gain panties Contest
6:06in any event since I saw my classmate in moist t-shirt contest with
5:01Alyssa Branch experiences the emotional uplift and craves u to feel the same That Babe plays the games with her body and tries to be as tender with he
0:05College games fucking fast lesbs
5:02Elis Diamonds sweet attitude to lesbo sex is a valuable thing to behold How this babe plays in lesbo games and forces partners to fall on their knees
0:05College games copulating fast lesbian babes
4:26Mr Pete was siting at home and playing computer games Sudenly came priceless marvelous teacher Alyson Westley That Babe was very hot and they started
5:09Angels actually enjoying playing in pool billiard They will have fun this game and then cuties wanna fuck right on the billiard table So fucking hot C
6:05Seda And Violet Monroe are made to compete for the opportunity to stay as a servant in James Deens Manor The One And The Other gals wrestle for knob a
5:02Shyla Jennings Dani Daniels and Molly Cavalli are enjoying a game of golf and they look truly wonderful whilst wearing these sexy miniskirts in the op
3:01Leanne Crow shows us how to be distracted during a game of pool as that babe invites us to see her have fun in her brassiere and panties That hotty wi
8:00Heres a little lesson in game See as bored juvenile and inexperienced Veronika is talked into showing her consummate little tanned blond boobies to ki
8:01Weve got an interracial threesome featuring 3 blondeif u count the resident deepdicker and one exquisitely hawt Japanese broad I Love it And so will y
5:02The games of Olympia and Zaya are surely not the goodiegoodie sort that other beauties as juvenile and enchanting as 'em play Those 2 brunettes a
???Touch her boobies during baseball game
6:05Sweet twenty year old Megan Murray is about to cross her comfort zone line with James Deen This Chab chains her to the wall and makes her crouch in th
19:152 astonishing whores are playing lesbo games
7:01Have A Fun 2 flamboyant voluptuous hotties Cathy Heaven and Tigerr Benson playing hawt lesbo games
8:00Those seducing and hawt lesbos Eva Karera and Kendra Craving have incredible big globes that sexily bounce whilst one as well as the other milfs have
0:06Fat doxy acquires nailed in the bath
2:30Mother plus Daughter headjob Contest 02
Top rated hd sex tubes:
Hot Porn Files
One Porno Tube
Busty Cats
You jizz tube
Beez Tube
Gonzo hamster
homemade girls
PornHDHub .XXX
Best sexo
Homemade Blowjob
hamster sex
Hd Tube Movies .XXX
homemade couples
Homemade Reality
homemade fuck
Picked Movies
Top rated porn categories
Visit these Free Porn Tubes
- 1. Wife Sex Movie
- 2. Sex Hub HD
- 4. Porn Gladiator
- 5. Horny Elephant
- 6. My Wife Sex
- 7. nu-bay.com
- 8. Xxx Videos
- 9. sweetteengirls.com
- 10. amateur sex clip
- 11. XNXX Rate
- 12. Sex Movies
- 13. Porno Tube HD
- 14. fullhqporn.com
- 15. Adult Movies
- 16. Home Porn
- 17. home sex hostel
- 18. Gold Jizz
- 19. homemadesex.xxx
- 20. Tube York Porn
- 21. Hot Porn Files
- 22. One Porno Tube
- 23. hdhub.xxx
- 24. Busty Cats
- 25. You jizz tube
- 26. Beez Tube
- 27. Gonzo hamster
- 28. homemade girls
- 29. PornHDHub .XXX
- 30. Best sexo
- 31. Homemade Blowjob
- 32. xhamsterhd.xxx
- 33. hamster sex
- 34. Hd Tube Movies .XXX
- 35. homemade couples
- 36. hometuber.com
- 37. Homemade Reality
- 38. homemade fuck
- 39. amateur-homemade.com
- 40. Picked Movies
- 41. pussysmile.com
- 42. Anal xxxx
- 43. homemademovies.xxx
- 44. gigporntube.com
- 45. homemade sex
- 46. amateursextube.xxx
- 47. Russian Porn tube
- 48. teenxxxtubes.com
- 49. watchmygf.xxx
- 50. youngporncom.com
- 51. Extreme Tube Movies
- 52. HDPornVideo .XXX
- 53. pornmovieshd.xxx
- 54. teenslutsplash.com
- 55. tubevideoshd
- 56. New Youporn
- 57. young-porn-videos.com
- 58. Young Orchids Tube
- 59. pornohdv.com
- 60. xnxxhd.xxx
- 61. adult amateur porn
- 62. Anal Sex Tubes
- 63. ayoungtube.com
- 64. Best Videos Xxx
- 65. i Sexy Tube
- 66. newtube
- 67. Nude Teen Porn
- 68. Porn Tube
- 69. teen-blowjob-tube.com
- 70. theyteens.com
- 71. Time Less Porn
- 72. sexmovetube.com
- 73. xxxin.xxx
- 74. 18teenpornox.com
- 75. 8teenfuckmovies.com
- 76. busty cats
- 77. Ero Sex Tube
- 78. Full X Hamster
- 79. Gonzo Lobster
- 80. hot-teenagers.com
- 81. Mad Vagina
- 82. xhamster
- 83. New Keez Porn
- 84. Nip Videos
- 85. Orgasmic Pages
- 86. seeteenfuck.com
- 87. teensex.to
- 88. tuba nuba
- 89. tube nube
- 90. Tubeum Porn Tube
- 91. tubuz
- 92. vid tube .xxx
- 93. wteenporn.com
- 94. Xhamster Galore
- 95. younghdsex
- 96. dosexvideo.com
- 97. 100 Porn Tube
- 98. 18 Teen Porno Tube
- 99. amateur porn
- 100. 1st Porn Tube
- 101. TV Porn
- 102. 7 XXX Tube
- 103. 8 xxx tube
- 104. Absolute Sex
- 105. Young Sex
- 106. Ahme FuckMe
- 107. Free Porno XO
- 108. All Hard Sex Tube
- 109. All XNXX
- 110. Alma Tube
- 111. Amateur xxxtube
- 112. amateur nudes
- 113. Amoral Videos
- 114. analsexteenshd
- 115. Teen Anal Sex
- 116. Beautiful girl sex
- 117. Big porn tube
- 118. Busty Cats
- 119. BustyCats .TV
- 120. College Teen Sex
- 121. Hot Fuck
- 122. Dark Categories
- 123. Defloration Porn Tube
- 124. Dick Porn Tube
- 125. dita tube
- 126. Doggystyle Anal Sex
- 127. Don Tube Porn
- 128. Dream XXX Tube
- 129. Drive Porn Tube
- 130. Extreme Fuck Tube
- 131. Free XXX Movies
- 132. freehomemadetube.xxx
- 133. freesextubes.xxx
- 134. fresh porn tube
- 135. Fucking Beaver
- 136. fuckingteenpussy.com
- 137. Fuckin Silly
- 138. gfporn.xxx
- 139. Go hd porn
- 140. Grade UP Tube
- 141. Handy Hardcore
- 142. hardcoreteenporni.com
- 143. hdfuck.xxx
- 144. Hd porn films
- 145. HDPornTube
- 146. hdpussy.xxx
- 147. hdteensexmovies.com
- 148. hdworld.xxx
- 149. homemadefuck.xxx
- 150. homemadepornvideos.xxx
- 151. homeporntube.xxx
- 152. hometeenmovs.com
- 153. hornynakedteens.com
- 154. Free Anal
- 155. hothd.xxx
- 156. Huge Sex TV
- 157. keezhdmovies.xxx
- 158. Lara Movies
- 159. Lara Porn
- 160. lb video
- 161. Lustful Hand
- 162. Mad Sex Tube
- 163. Me Jerk
- 164. Monsta Tube
- 165. naked amateurs
- 166. Young Teen
- 167. onlineteenporn.com
- 168. onlyteenclips.com
- 169. perfect girls
- 170. Pimp Tube
- 171. Porn-OK
- 172. pornb.xxx
- 173. pornhdmd.xxx
- 174. Porno Sisters
- 175. Pretty Nu TV
- 176. private home movies
- 177. Royal Adult
- 178. Rus Chicks
- 179. seeteenanalsex.com
- 180. Spermy Porn
- 181. Spydder Tube
- 182. stolen gf porn
- 183. teen-anal-tube.com
- 184. teen-sexy-girls.com
- 185. teenassestube.com
- 186. teencouplesporn.com
- 187. teenporn3
- 188. teenporntubea.com
- 189. teenpornvideoshq.com
- 190. teensex18y.com
- 191. teensex7.com
- 192. Teen Sex Vids
- 193. teensexvideoo.com
- 194. teentitsvideos
- 195. Tetty Tube
- 196. Top XNXX
- 197. HD Tube8
- 199. Tubeum


text:
Why Foley Scandal Is Biggest Issue In Mid-Terms
Here's what Mark Foley's former opponent -- and almost surely the next congressman from Foley's district -- said yesterday:
"It's clear from all of the reports coming in from across the country that the Republican leadership team has been well aware of this problem with the pages for well over a year. It looks to me that it was more important to hang on to a seat and hold on to power, than to take care of our children."
Tim Mahoney's words say it all -- and it's an issue that, unlike, say, health care and the war, will cut straight to the bloodstream of middle America, like political heroin. The GOP is toast and Dennis Hastert's days as speaker are numbered.
Get the This Week's Top Stories Newsletter
Every week we collect the latest news, music and arts stories — along with film and food reviews and the best things to do this week — so that you'll never miss New Times Broward-Palm Beach's biggest stories.
In Case You Missed It
Upcoming Events
Nova Southeastern University Sharks Volleyball
TicketsWed., Jul. 27, 1:00pm
Florida Launch vs. Rochester Rattlers
TicketsSat., Jul. 30, 7:30pm
Florida Launch
Sat., Jul. 30, 7:30pm
Fight Time PRO MMA
TicketsFri., Aug. 12, 8:00pm
Popular Stories
Sponsor Content

subset: commoncrawl


text:
PEG, poly-ethylene-glycol; PLA2, phospholipase A2; s-PLA2, secretory phospholipase A2
Paper submitted on the occasion of The European Lipid Science Award 2011
The physical properties of the lamellar lipid-bilayer component of biological membranes are controlled by a host of thermodynamic forces leading to overall tensionless bilayers with a conspicuous lateral pressure profile and build-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes. In particular, the average molecular shape and the propensity of the different lipid and protein species for forming non-lamellar and curved structures are a source of structural transitions and control of biological function. The effects of different lipids, sterols, and proteins on membrane structure are discussed and it is shown how one can take advantage of the curvature-stress modulations brought about by specific molecular agents, such as fatty acids, lysolipids, and other amphiphilic solutes, to construct intelligent drug-delivery systems that function by enzymatic triggering via curvature.
Practical applications: The simple concept of lipid molecular shape and how it impacts on the structure of lipid aggregates, in particular the curvature and curvature stress in lipid bilayers and liposomes, can be exploited to construct liposome-based drug-delivery systems, e.g., for use as nano-medicine in cancer therapy. Non-lamellar-forming lysolipids and fatty acids, some of which may be designed to be prodrugs, can be created by phospholipase action in diseased tissues thereby providing for targeted drug release and proliferation of molecular entities with conical shape that break down the permeability barrier of the target cells and may hence enhance efficacy.
Our picture of lipid membranes has come a long way since Gorter and Grendel in 1925 formulated the lipid-bilayer hypothesis 1–3. Most textbook models of membranes are still based on the celebrated fluid-mosaic Singer–Nicolson model from 1972 4–6, although we have in recent years seen significant amendments to this model, not least fuelled by the finding of lipid membrane domains in both model membranes and cells 7–12 and the subsequent "raft rush" 13–17. The science of lipidology has now become an established discipline, acknowledging that lipids organize in space and time and display emergent physico-chemical properties that are beyond the chemical nature of the individual molecules and which collectively control membrane function 8.
Recently, lipidomics has followed as a new science in the omics-sequel, characterized by an explosion in detailed data for lipid profiles of tissues, cells, and subcellular components 18. The focus is now swinging toward enumerating individual lipid species, determining their identity, and quantitating their amount. Time is ripe to marry the two disciplines, both in order to take lipidomics beyond the stage of "stamp collection" 8 and in order to incorporate into the lipidology approach the new knowledge about the individual lipid species. I will illustrate my viewpoint in the present mini-review by discussing the use of the old concepts of lipid shape and membrane curvature in the context of trans-membrane structure, membrane permeability, and enzymatic action. I will go on to demonstrate how insights into lipid shape and membrane curvature can be translated into technological applications within nano-medicine and drug delivery mediated by liposomes. In particular I will show how lipids may serve as prodrugs, pro-enhancers, and pro-permeabilizers within liposomal drug delivery in cancer therapy 19, 20.
Curvature is a key concept in biology 21–24 although in many cases overlooked by the life-science community. Curvature is a so-called emergent property that arises as a consequence of the complex and collective behavior of a large number of molecules. Typically, curvature is a dynamic entity that fluctuates due to entropic forces, and in the case of membranes it varies in time due to transient interactions between the membrane and other cellular components, such as proteins, solutes, as well as vesicles and other membranes. In fact the entire cell, its membranes, organelles, and transport systems are subject to stabilizing and destabilizing forces that couple to curvature. An example is shown in Fig. 1 in the case of intra-cellular trafficking and the dynamical morphogenesis and maintenance of the Golgi apparatus 25.
Of the four main classes of macromolecules which make up all types of biological systems: the carbohydrates, the fats, the proteins, and the nucleic acids – the fats, e.g., the lipids, distinguish themselves as molecules that in contrast to the three other classes are not polymers bound by covalent forces. Carbohydrates are poly-saccharides, proteins are poly-peptides, and nucleic acids are poly-nucleotides. The lipids do not form polymers under natural conditions, both rather self-assemble into macromolecular aggregates in water in the form of superstructures like micelles and lipid bilayers as illustrated in Fig. 2. Of these structures, the closed lipid bilayer in the form of a unilamellar vesicle or liposome is a structure of fundamental importance for life since it is a model of the lipid-bilayer component of cell membranes 26–31. A detailed visualization of the spontaneous formation of an ensemble of self-assembled liposomes in a suspension of lipid molecules in water is shown in Fig. 3.
It is the self-assembly nature of lipid bilayers that holds the key to both a fundamental understanding of lipid membrane structure, dynamics, and function as well as to many technological applications of lipids. However, lipid self-assembly and the complexity it imparts on lipid behavior is one of the main sources for the difficulties associated with a quantitative description of lipids in biology. A central dogma in molecular biology is molecular structure and the relationship between structure and function. This dogma has been a driving force for the grand achievements of molecular biology during the second part of the 20th century: the structure of the double DNA helix and the structural characterization of the gene products, the proteins. Speaking about structure in this context, it is high-resolution structure with atomic detail that is in focus. Although the importance of molecular dynamics and heterogeneity as well as the influence of solvent structure and dynamics on protein structure and function are acknowledged, it is clear that the unraveling of a well-defined atomic structure has been the Holy Grail in molecular and structural biology.
If one is looking for similar elements of molecular structure and order when it comes to lipids and membranes, one is going to be disappointed. The hallmark of lipids in functional membranes is just as much disorder as it is order. In fact the balance between order and disorder is likely to be at the core of regulation of biological function by lipids. However, disorder and the way order emerges out of disorder is not an easy concept to grasp, and it requires methods from physics and physical chemistry for dealing with in a quantitative manner. This situation has implied that lipids until recent years have been living in the shadow of the more fashionable study of genes and proteins. Lipids were at best described by such fuzzy terms as variability, diversity, plasticity, adaptability, fluidity, complexity, etc., cf. Table 1. These properties, which lipids share with other soft-matter materials, are all of collective and emergent nature and in principle basic consequences of the many-body nature of the lipid aggregates. None of these collective properties are easy to define and measure quantitatively and they are only related to the molecular and chemical structure of the individual lipid species in rather subtle ways. However, as we shall see later, it is exactly those fuzzy attributes to lipids that make lipids so useful for a wide range of technological applications.
|Soft-matter characteristics of lipid systems
|Length-scale tunable
One of the outstanding mysteries in lipid cell biology is lipid diversity, i.e., the fact that each type of membrane has a very large number of different types of lipid species. As information on the lipidome of various cells and subcellular structures is accumulated it is becoming clear, that this diversity is much larger than previously thought, and typically several thousands of different lipids are found to be present in each type of membrane. Considering the many ways all these different species can arrange among themselves, it is clear that the "language" or the "alphabet" of lipids is way beyond the four-letter alphabet of the nucleotides used to describe nuclei acids and the twenty-letter alphabet of the amino acids used to describe proteins. The omics-language of lipids is thus far richer than previously anticipated thereby exposing the full scope of the potential of what Rilfors and Lindblom in 2002 coined "functional lipidomics" 32.
The various lipid aggregates resulting from lipid self-assembly processes as shown in Fig. 2 are only a few of the many possible ones 33–37. Others are shown in Fig. 4. It is noteworthy that even topologically complex and highly curved structures like hexagonal and cubic phases, as well as a number of more disordered structures, are all found in living cellular systems 21. It should also be noted that even if a particular non-lamellar and curved structure is not found as an extended structure in a cell, it may well be so on a small and local scale, such as in the context of fusion and fission processes, cf. Fig. 1, as well as in the neighborhood of membrane inclusions/proteins or in the form of membrane defects such as pores. More importantly, a membrane may be subject to instabilities due to intrinsic curvature stress and propensity for forming curved structures.
It is possible qualitatively and in some cases semi-quantitatively to describe the lipid phase behavior via a simple geometric property of the lipid molecule, the so-called Israelachvili–Mitchell–Ninham packing parameter, P = v/al, where v is the molecular volume, a is the cross-sectional area of the head group, and l is the length of the molecule 37. Of course a lipid molecule in a dynamic lipid aggregate cannot be assigned a shape as such, and the geometric parameters v, a, and l should therefore be considered as average properties. Still, the value of P turns out to be surprisingly useful in predicting the structure of a lipid aggregate. Lipids with values of P not too close to unity are poor bilayer formers. However, often the lipids in the two lipid monolayer leaflets of a thermodynamically stable bilayer have, as illustrated in Fig. 5a and b, values of P different from unity and hence suffer from a built-in curvature stress. Such monolayers would curve if they were allowed to do so and not being confined to constitute a stable bilayer. In some cases, the effective value of P for a mixture of lipids with different values of P can be estimated by a superposition principle, provided that the lipid molecules are well mixed. As an example it is possible to form stable bilayers of equimolar mixtures of lysolipids and free fatty acids, that respectively have P<1 and P>1 38–40. Even in cases where the quantitative predictive power of the molecular packing parameter fails, it can be useful in estimating the influence of a particular molecular species on the stability of a given aggregate structure, e.g., the destabilizing effect of conical molecules added to a lamellar lipid bilayer. The packing parameter turns out to be linearly related to the old concept of hydrophilic-lipophilic balance (HLB) 41.
The self-assembled nature of lipid bilayers implies that they are normally in a tension-less state. The most conspicuous feature of a lipid bilayer is its transverse structure which is far from that of an isotropic fluid slab of hydrocarbons. It displays a distinct lateral stress- or pressure profile 42–45 as illustrated in Fig. 5c. The physics behind this profile is based on simple mechanics. In mechanical equilibrium in the tension-less state, the integral of the difference between the normal pressure and the lateral pressure, pN(z)–pL(z), has to become zero. However, the variation of the lateral pressure across the 5 nm thick membrane goes from positive, expansive pressures in the head group region, over regions of negative, tensile pressures in the interfacial regions, to expansive, positive pressures in the acyl-chain region, as illustrated in Fig. 5c. These variations can easily amount to the equivalent of hundreds of atmospheres pressure. It is this very stressful environment integral membrane proteins have to come to terms with.
In order to illustrate the potential of using molecular shape as a simple means of predicting the effect of various lipid species on the lateral pressure profile of membranes, we consider two types of molecules with different values of P: unsaturated lipids which tend to have disordered and curly chain configurations and hence P>1, and cholesterol which has a small head group and a bulky hydrophobic body and hence P<1. The unsaturated lipids are therefore expected to move the pressures toward the membrane–water interface, and this effect should increase with the degree of unsaturation. In contrast cholesterol is expected to shift the pressures toward the middle of the bilayer 46. The data shown in Fig. 6 indeed supports these expectations 47. These effects imply dramatic changes in the curvature stress of the bilayer and an increase in the flip-flop rate between the two monolayer sheets 48. Possibly even more important, introduction of an extra double bond in the acyl chain, specifically from five to six, has a significant effect on the lateral pressure profile whereas it appears only to have a marginal effect on other bulk bilayer properties 49. Furthermore, the actual position of the double bonds has a significant effect on form of the lateral pressure profile 50. All these findings are of importance for the functioning of neural membranes which are rich in superunsaturated ω-3 and ω-6 fatty acids.
Lipid bilayers and membranes exhibit substantial structure in the plane of the membrane. This has been known for a long time and has been described in terms like lipid domains and lateral heterogeneity 51–54. The lateral structure can be induced by thermodynamically driven phase separation in multi-component systems, lateral density and compositional fluctuations in equilibrium, non-equilibrium and steady-state driven lateral organization in the active state, as well as interactions between lipids and proteins. A particular important mechanism involves cholesterol which invariably is involved in domain organization in particular in plasma membranes 55. Cholesterol is known to be the source of the so-called liquid-ordered state of membranes 56, 57. The interest in the biological importance of lateral membrane heterogeneity and domains has been revived by the so-called raft hypothesis 16, 58–60 that assumes differentiated small-scale regions in biological membranes to be particular platforms for a variety of cell functions, such as signaling and different transport processes 14, 61.
The lateral structure may couple to curvature and enforce the membrane to make both dynamic and static excursions in the third dimension in the form of curved domains that may develop into caps and buds 62–65. An illustration of cap formation on a giant unilamellar liposome is shown in Fig. 7. The cap formation and the associated domain size are controlled by a balance between the bulk free energies of the different regions of the membrane and the line tension around the cap. The finding of finite-size domains in vesicles of lipid mixtures which otherwise would be expected to undergo macroscopic phase separation has also been described theoretically by a balance between the tendency to form macroscopic phases, the line tension of the domains, and a coupling to bilayer curvature 66.
As an example of the power of lipids with conical shape (P ≠ 1) to impact on lipid bilayer properties we show in Fig. 8 how a fatty acid (P>1) can lower the permeability barrier of lipid bilayers in the form of a closed liposome encapsulating an anti-cancer drug, doxorubicin 67. When integrating into the lipid bilayer, the fatty acid increases the curvature stress which leads to more leaky membranes. A similar behavior has been found for a wide range of saturated and unsaturated fatty acids as well as lysolipids which have the opposite sense of curvature (P<1) 39, 67–73. Lysolipids also promote drug release, although less dramatically, probably because they are more water soluble compared to a fatty acid with the same acyl chain. The details regarding how different fatty acids and lysolipids affect liposomal permeability and how it depends on the structure of the lipid bilayer (phase state, temperature, thickness, etc.) is complex and not fully understood at present. However, as we shall come back to later, these effects can be exploited to release the payload of drugs in liposome-based drug delivery.
Proteins associated with membranes, both integral and peripheral proteins, have to come to terms with the curvature stresses in the bilayer 42, 74, 75. In the case of integral membrane proteins, the concept of hydrophobic matching between the hydrophobic core of the lipid bilayer and the hydrophobic stretch of integral membrane proteins has been proposed 76–79 as a key determinant of lipid–protein interactions as illustrated in Fig. 9a. Mismatch carries an energy penalty which basically amounts to the elastic distortion of the lipid matrix around the protein. For a sufficient large value of this penalty, the protein may yield and undergo a conformational change, hence offering a mechanism for lipid-mediated effects on protein function, as illustrated in Fig. 9b. Hydrophobic matching provides in a membrane with several types of lipid species the possibility of sorting, selection, or enrichment of certain lipids near the protein 80, 81.
The hydrophobic matching and the induced membrane curvature around the protein constitutes a mechanism for lipid-mediated protein–protein interactions, typically attractive as illustrated in Fig. 9a, which will provide a driving force for protein aggregation and possibly crystallization in the plane of the membrane. The range of this protein–protein interaction will be controlled by the coherence length of the correlations between the lipids. This coherence length can be very large in special parts of the phase diagram, in particular close to critical points 82, 83, 84, and lead to capillary-condensation phenomena and wetting around proteins 85, 86.
The hydrophobic matching principle has been important in substantiating the concept of membrane rafts 14, which are domains enriched in cholesterol and high-melting lipids, in particular sphingolipids, and therefore generally thicker than the membrane matrix in which they reside. Matching then furnishes a possible mechanism for protein selection where those proteins, which match the raft thickness the better, e.g., via appropriate acylation or prenylation, are recruited to the raft. Conversely they can be released from the raft by appropriate enzymatic modification of the proteins. Hence, the concept of hydrophobic matching helps to establish a semi-quantitative physical framework for signaling cascades.
The propensity of some lipids for inducing curvature stress and possibly non-lamellar phases provides, via the lateral pressure profile, another mechanism for lipid–protein interactions 45, 87 as illustrated in Fig. 9b. This mechanism is not necessarily independent of the hydrophobic matching mechanism. An illustration of this curvature-driven mechanism is given in Fig. 9c and d respectively in the case of release of curvature stress by binding a peripheral membrane protein, such as cytochrome c 88, and a shift between two conformations of a membrane channel, such as the opening and closing of gramicidin A dimer channels 79. Certain proteins, e.g., the nicotinic acetylcholine receptor and the voltage-dependent potassium channel may also have conical shape 22 and they therefore tend to arrange themselves with lipids that match this shape in order to maintain the lamellar membrane structure. It is interesting to note that the total lipid extract of many plasma membranes do not form lamellar phases when suspended in water solution indicating that proteins and lipids exhibit some kind of shape compensation in intact biological membranes.
Most of the quantitative, fundamental insight into membrane structure, dynamics, and molecular organization has been obtained from various model studies, experimentally as well as theoretically, and they almost invariably refer to systems in or near thermodynamic equilibrium 31. However, functioning biological membranes are not in equilibrium but are constantly subject to exchange of energy and material with the environment or are being modulated by active proteins and enzymes that are associated with the membranes 89. This association often involves coupling between the protein and the membrane curvature or the stress fields of the lipid bilayer. It is well known from statistical physics that the properties of non-equilibrium systems are fundamentally different from their equilibrium counterparts, e.g., new levels of organization arise in driven-diffusive systems, and order may emerge out of disorder due to an external drive 90.
A quantitative study of the physical properties of model membranes out of equilibrium is extremely difficult. Hence the results of only few studies have been published 91–100. A typical example is a membrane with an ion pump that is driven by some kind of energy transduction mechanism 96, 101. Another example is the binding of ligands to receptors where the binding is influenced by a force, e.g., the binding of collectins in the innate immune system to sugar groups on invading pathogens 102. A third example is the set of responsive membranes in the dermal barrier that is subject to a gradient in water chemical potential 103. A fourth example is the morphogenesis of the endoplasmatic reticulum and the Golgi apparatus with membranes that owe their existence to non-equilibrium conditions of flow of energy and matter 25. It is interesting in this context to note that the plasma membrane can undergo phase separation when the cell dies and the activity comes to a stop 14.
A range of important biological functions mediated by membranes appear to be partly or fully controlled by local membrane curvature 23. Examples include membrane-curvature control of dynamin polymerization 104, phosphocholine cytidylyltransferase activity 105, and the binding of bar domains to membrane surfaces 22, 23, 106, 107 as illustrated in Fig. 10. This figure also indicates that the action of many enzymes and drugs, e.g., amphiphatic and antibiotic peptides 107, 108, is mediated by coupling to membrane curvature which in some cases induces morphological alterations at and in the membrane.
A particular class of enzymes acts on membranes by degradating phospholipids or sphingolipids, e.g., phospholipase A2 (PLA2), phospholipase C, and sphingomyelinase. These enzymes remodel the membranes by producing products that may have propensity for forming non-lamellar, curved lipid structures. Specifically PLA2 generates lysolipids and free fatty acids, and phospholipase C generates di-acyl glycerol, as illustrated schematically in Fig. 11. Sphingomyelinase produces ceramide which is known to lead to pronounced membrane curvature and blebbing, a phenomenon that has been associated with apoptosis 109.
Extensive studies have been carried out in order to unravel the mechanism of secretory phospholipase A2 (s-PLA2) action on lipid bilayers of different composition and under different physico-chemical conditions 110, 111, 112. s-PLA2 is only active at lipid interfaces and not on lipid monomers in solution. Moreover, it turns out that its enzymology is rather peculiar in the sense that the enzyme displays a so-called lag-burst behavior, as illustrated in Fig. 12. The lag-time turns out to be extremely sensitive to the physical state of the bilayer substrate, in particular its lateral heterogeneity and defect structure. The more defects and heterogeneity, the shorter the lag-time. The heterogeneities in turn can be controlled by a long list of factors, including temperature, composition, phase transitions, phase separations, compositional and density fluctuations, as well as edge effects. The structural heterogeneity can be seen as a kind of local defects with high curvature and associated with enhanced lipid protrusion modes 113, 114 that will trigger the enzyme activity. The heterogeneity is further enhanced by the hydrolysis products that lead to increased curvature stress and local defects in the bilayer. In this way the enzyme autocatalyzes its own activity which eventually leads to the burst in activity.
The important lesson from these studies is that s-PLA2 is extremely sensitive to the structure and physical properties of the lipid bilayer substrate, in particular local curvature and defects. The enzymatic action leads to a remodeling of the membrane 112. This observation can be exploited when constructing liposomal drug-delivery systems tailored to be sensitive to enzymatic breakdown and subsequent localized drug release in cancerous tissue which is characterized by elevated levels of s-PLA2. We shall address this in further detail below.
A particular way of activating s-PLA2 on liposomal surfaces was somewhat surprisingly discovered in studies of the activity on lipid bilayers incorporated with lipopolymers which are lipids to whose head group is covalently linked a water-soluble polymer, typically poly-ethylene-glycol (PEG). It turns out that s-PLA2 is more active on such surfaces compared to naked lipid bilayers. Furthermore, the activity is stronger, i.e., the lag-time is shorter, the larger the surface coverage of the polymers is and the longer the polymer chains are 115. The explanation of this phenomenon is an entropic pull on the lipopolymers which tends to enhance the protrusion modes of the neighboring lipid molecules rendering them more prone for attack of the lipase. The entropic pull is caused by the confinement of the water-soluble PEG chain which cannot penetrate the membrane leading to a decrease in the conformational entropy of the chain. To compensate for the corresponding loss in free energy, the lipopolymer tends to be displaced somewhat into the aqueous compartment 113. Hence, the physico-chemical properties of the PEGylated lipids offer themselves as another control parameter for regulation of the enzyme activity.
We will now show how it is possible to combine the insight in curvature stress and the physical chemistry of lipid bilayers with an understanding of the mechanism of activating s-PLA2 in order to construct a liposomal drug-delivery system that may remove a critical bottleneck in the use of liposomes for cancer therapy. The resulting delivery system is hence constructed on the basis of fundamental principles of physical chemistry and physical enzymology. This approach to drug research, which already has been subject to phase-I clinical trails, is unconventional in the sense that it is predominantly based on physical sciences and the concept of membrane curvature stress rather than medicinal chemistry and traditional drug-receptor considerations.
The proposed system takes advantage of the specific biophysical properties of the lipid bilayer 116, 117 of liposomes on the one side and the peculiar pathophysiological and biochemical properties of cancer cells on the other side. Thereby it becomes possible to passively target liposomes to diseased cells and with a particular mechanism, involving endogenously upregulated s-PLA2, to open the liposomal carriers and unload the drug precisely where the drug is supposed to act. It is furthermore possible to construct the liposomes of specific lipids that upon phospholipase-assisted hydrolysis are turned into products that may act as enhances, as permeabilizers, and even as drugs themselves 118–120.
Liposomes for drug delivery are usually protected from the human immune system by a polymer coat made up of PEG moieties that are covalently linked to the head group of charged lipids, such as DSPE or DSPS, cf. Fig. 13. This type of PEGylation, which is the basis of the so-called stealth liposomes 121, has two important consequences. Firstly, it helps to avoid release of the encapsulated drug upon intravenous administration in the blood stream, hence limiting the systemic side effects of the drug. Secondly, it leads to increased circulation lifetimes and hence enhances the likelihood for liposomes of appropriate size, typically 100 nm, to venture into the capillary network of, e.g., solid tumors. The tumor vasculature is often rather fenestered and since the lymphatic drainage of the tumors is suppressed in comparison with that in healthy tissue, liposomes tend to accumulate in the tumor. This effect is called the enhanced permeability and retention (EPR) effect.
It has been known for some time that liposomal drug-delivery systems can limit systemic side effects and one of the successful formulations is Doxil 122 which are stealth liposomes with doxorubicin approved for treating, e.g., ovarian cancer. A paradoxical limitation of the efficacy of the liposomes including Doxil is that their stability turns into a disadvantage at the target where the drug has to be unloaded and in many cases the unloading of the drug is very poor. Hence an effective trigger mechanism for discharging the payload is called for.
One such trigger mechanism is the use of heating the tumor in the case where the liposomes have been made thermosensitive, e.g., by having a phase transition that is a few degrees above physiological temperatures 123, 124. At the phase transition, the lipid bilayer of the liposomes becomes leaky 8 and the drug can escape into the tumor tissue. The thermal triggering mechanism requires that the tumor can be localized and heated by external heating devices. A system of this type is currently in phase-III clinical trials for treatment of liver cancer 124.
Another possible trigger mechanism is the use of endogenously upregulated s-PLA2 to destroy the liposomes at target. In turns out that many different kinds of tumors, e.g., breast, colon, gastric, pancreas, lung, liver, and prostate cancer, have such upregulated type IIA s-PLA2 in a local concentration in the tumor that is one or two orders of magnitude larger than serum levels and much higher than in the healthy tissue lining the tumor 125–127.
Stealth liposomes that have been made sensitive to hydrolysis by s-PLA2 have been coined LiPlasomes. These lipase-labile liposomes have been proposed as suitable carriers for drugs targeted to tumors with locally high levels of s-PLA2 activity 20, 117. The development and design of the LiPlasomes is based on years of extensive studies of lipid bilayers and model membranes and how the activity of s-PLA2 on these lipid systems can be controlled by the physical properties and qualities of the lipid bilayers 110.
LiPlasomes have been tested on a variety of in vitro cell cultures of cancer cell lines that secrete s-PLA220 with encapsulated anti-cancer drugs like doxorubicin, cisplatin, and 5-FU (fluorouracil), and in all cases it has been found that LiPlasomes poised to unload the drugs by s-PLA2 action limit the cell growth whereas conventional liposomes are much less effective. The crucial next step involves in vivo studies on mice, and Fig. 14 shows as an example that cisplatin-loaded LiPlasomes are very effective to limit the growth of human xenograft MT-3 breast cancer in mice. This encouraging in vivo proof-of-principle was the basis for bringing the first dose of LiPlasomes in man.
It is noteworthy from Fig. 14 that the mice treated with LiPlasome formulations with cisplatin are not only doing much better than the control group; in fact they do better than the group of mice treated with the free drug at similar toxic doses.
A plausible reason for this remarkable effect becomes clear when considering the action of s-PLA2 on the LiPlasomal carrier. The enzyme not only opens the capsule by hydrolyzing the lipids. It also releases the hydrolysis products, lysolipids and free fatty acids, as illustrated in Fig. 11a. As we described above and illustrated in Fig. 8 these products act as enhancers and permeabilizers because they induce curvature stress in the target membranes of the cancer cells, thereby lowering the permeability barrier and facilitating the transport of the active drugs into the cells. In this way the phospholipids of the liposomal carrier have acted not only as materials for the liposome; they have also performed as pro-enhancers and pro-permeabilizers that are turned into enhancers and permeabilizers exactly where they are needed.
Once it has been established that it is possible to construct LiPlasomes which are stable in the blood stream, which accumulates in the diseased tissue, and whose drug load can be released by endogenously upregulated s-PLA2; and once it has been established that the hydrolysis products can act as enhancers and permeabilizers; a scenario suggests itself by which the lipids in the liposomal carrier themselves are prodrugs which by s-PLA2 action are turned into active drugs precisely at the target. In principle, by this scenario the LiPlasomes could be empty and seen as a magic bullet, the LiPlasome acting at the same time both as a carrier and as a drug. Needless to say, such LiPlasomes could also be loaded with conventional drugs such as doxorubicin or cisplatin to be used in a special type of combination therapy.
The first type of prodrug lipids that come to mind are mono-ether-mono-ester glycerol-phospholipids, in which the sn-1 chain is linked to the glycerol backbone by an ether linkage and the sn-2 chain by an ester linkage 128. Upon s-PLA2 action, a lysoetherlipid and a free fatty acid are released. Certain types of lysoetherlipids are known to be strongly cytotoxic, but since the red blood cells lack enzymes to degradate these etherlipids, injection of such compounds in the blood stream leads to massive hemolysis. Cancer cells are also not able to break down the etherlipids and their membranes will be massively damaged by the compounds. Hence a unique possibility opens for using lysoetherlipids to treat cancer by tugging the hemolytic etherlipid away in a mono-ether-mono-ester phospholipid compound. As long as the etherlipid remains bound in this compound it turns out not to be hemolytic 128. However, once it is released by s-PLA2 action in the tumor tissue it can act. The feasibility of this mechanism has been demonstrated by in vitro studies on gastric cancer cell cultures that secrete s-PLA2.
We are now ready to make a further step and consider also making the entity linked to the phospholipid on the sn-2 position a potential drug, i.e., a prodrug that is turned into an active drug upon release by s-PLA2 action in the cancer tissue. This new type of phospholipid consisting of an lysoetherlipid and another active lipid drug substance can be considered a double lipid prodrug.
We have successfully synthesized a series of such double lipid prodrugs, with an etherlipid at the sn-1 position and potent drugs like chlorambucil 118 or derivatives of retinoic acid 119, 120 on the sn-2 position. An illustration of this double lipid prodrug principle in a liposomal formulation is provided in Fig. 15. The efficacy of these lipid prodrug systems has been evaluated in a number of different in vitro cell culture studies of various human cancer cell lines and it is found that the combination of the two lipid drugs enhances the cytotoxicity.
The further development of such double lipid prodrug systems requires optimization with respect to choice of both the actual active chemical components that are built into the lipids and the other lipid constituents of the liposome. Not all constructs will lead to stable liposomes. However, it is possible to secure liposome stability and optimize susceptibility to s-PLA2 action by premixing with other lipid species that do not act as drugs but facilitate the liposome formation and possibly even enhances the enzymatic breakdown of prodrugs 120. In this way a dilution of the prodrug may be amply outbalanced by a more effective turnover of the prodrugs into drugs. Finally, combination formulations including an encapsulated conventional drug should also be considered.
The concepts of lipid shape and packing, membrane curvature and curvature stress, as well as the lateral stress profile of lipid bilayers are not new concepts but their potential for use in developing novel types of nano-medicine should not be neglected. Even if these concepts in some cases are less well defined and possibly even difficult to measure and describe quantitatively they can serve as valuable guides for shaping the intuition that is necessary to mobilize for innovation in the treatment of serious diseases.
The present mini-review has illustrated how an insight into the basic physical chemistry of lipids, including their many seemingly fuzzy characteristics listed in Table 1, together with an understanding of the peculiar enzymology of interfacially activated phospholipases may provide a basis for a rational approach to liposome-based nano-medicine.
The author wishes to thank his many collaborators, in particular members of MEMPHYS-Center for Biomembrane Physics, for many years of stimulating and fruitful collaboration on a wide range of topics in membrane science and technology. MEMPHYS was supported as a center of excellence by the Danish National Research Foundation for the period 2001–2011. The research activities of the author within nano-medicine are supported by the Lundbeck Foundation's Nanomedicine Research Center for Cancer Stem Cell Targeting Therapeutics: NanoCAN.
The author has declared no conflict of interest.


text:
Simhasth Kumbh: Where traditions remain unchangedUjjain, May 20 (IANS) It was a tough journey for 84-year-old Kantabai Nagar, but she finally made it. Despite her stoop, an undeterred Kantabai came all the way from Tirupati Nagar, Indore, to be a part of the Simhasth Kumbh Mela and bathe in the ... Yahoo! India, 2 months ago
1 images for "kumbh nagar"
Govt to develop Rishikesh as 'Arogya Nagar': CM
Dehradun, June 22 -- The state government is planning to develop Rishikesh as 'Arogya Nagar', similarly Jageshwar, Lohaghat and Tungnath would be developed as Arogya Kendras, declared Uttarakhand Chief Minister Harish Rawat while speaking on the ...HT Syndication, 1 month ago
Notices issued in anti-dengue drive
Previous story: India Today TV screens film by Pradeep Sarakar at the first Transgender Akhara at Ujjain Kumbh Next story: Aruna Scan and Diagnostics Center inaugurated at AS Rao Nagar Hyderabad Over 4,800 notices have been issued including ...APN News, 2 months ago
Mini Kumbh scenario at Rang Mahal Dharmshala
12:12 am Ujjain : By rendering exceptional services in favour of the members of Rajasthan, Punjab, Hariyana, Ranchi, Bihar, etc, the Saaradhya Seva Samiti, Shri Ganga Nagar has created a Mini Kumbh like scenario at their base camp here at Rang Mahal ...The Freepress Journal, 2 months ago
For speedy justice, MP cabinet nod to 4,354 judges posts
To continue reading, we request you to support us by disabling your Ad Blocker In order to serve content on our website, we rely on advertising revenue which helps us to ensure that we continue to serve high quality unbiased journalism. To know ...Hindustan Times, 2 weeks ago
First few showers expose potholes
NASHIK: Shantanu Patil goes cycling every morning with his friends on different roads of the city. On Sunday, he and his friends missed the pleasure of cycling on city roads. On Monday, they tried a different route and faced the same problem.Times of India, 2 weeks ago
Indore is first MP city to have firefighters on bikes
INDORE: Indore has become the first city in Madhya Pradesh to have firefighting apparatus made available on motorcycles and backpacks, enabling firemen to move on narrow lanes and reach densely populated areas in case of emergencies. The fire ...Times of India, 1 month ago
Anandiben Patel refutes reports of her exit as Gujarat CM
"Nothing like that is on," Anandiben told reporters at Indore in Madhya Pradesh where she had gone to participate in the ongoing Simhastha Kumbh at Ujjain and meet spiritual guru Bhaiyu Maharaj. She blamed media for linking her ...Jagran Post, 2 months ago Anandiben denies she is on way out The Freepress Journal, 2 months ago Nothing like that is on: Anandiben refutes claims of her exit as Gujarat CM Rediff.com, 2 months ago Anandiben refutes reports of her exit as Gujarat CM Press Trust of India, 2 months ago
No. of child beggars down by 50%: NGO
NASHIK: The streets of Nashik have seen a welcome change — a considerable decline in the number of child beggars. Childline, a non-governmental organisation (NGO) working for children, has observed the decline in the number of the child beggars ...Times of India, 2 months ago
At rally, Jagmeet Brar terms Badals, Capt traitors; all praise for AAP
A month after his expulsion from the Congress , Jagmeet Brar on Saturday addressed a public rally as his show of strength, keeping his options open to join a party that would take the Shiromani Akali Dal (SAD) and the Congress head on in the run-up ...Hindustan Times, 2 months ago
Realtime News
on your WebpageAdd Widget >Get your members hooked!


text:
April 23, 2007
Houston -
What can't Pablo Solares do? The Rice senior middle-distance runner excels in so many things, it's hard to keep track of them all. Already one of the best milers in school history, Solares has his sights set on making it to Beijing for the 2008 Olympics for his native Mexico, but his long-term goals are even more lofty.
When Solares and his family first came to the United States, they sought the education that wasn't available in Mexico. "My parents always had a strong focus on school," Solares said. "My parents have been always very supportive of my brothers and I in whatever we want to do. I feel that support from my family is the best thing and most important attribute that I have."
One of Mexico's top tennis players as a teenager (his brother plays for SMU), Solares was initially excited about being in the NBA when he first came to the U.S. At 6-4, basketball was a natural activity for Solares in Mexico, where his father was also a talented player as a youngster. That hoops dream took a back seat to his tennis and running, though, and Solares eventually also gave up the racket during his senior year at Richardson High School to concentrate on his track career. Until his parents convinced him that the risk of injury was too high, Solares was also a budding mountain biker.
"Tennis was a big thing in my family, my brothers and I used to spend all of our time playing and competing at tournaments," Solares said. "I hope I can catch up once again when I stop running competitively."
Outside the world of sports, Solares has yet another talent. "I started painting my senior year in high school," he said "And I am not planning on stopping any time soon. I have completed over 100 oil paintings over the past five years, and if you ask me how successful I am as an artist, I would probably say that I don't really know, but I like what I am doing so that works for me."
With graduation on the horizon, and a Rice degree with majors in economics, managerial studies and visual arts soon to be in hand, Solares has long-term plans on an even grander scale. "I would like to start my own company since I don't see myself working 100 hours a week," Solares said. "After that, I would really like to get into politics in Mexico. I feel that there are many things that could be changed to improve the quality of life in my country, thus I feel the obligation to do my best to make it happen."
Given his Midas-like touch in all the activities he has tried so far, there is little doubt that Pablo Solares is poised to become one of Tomorrow's Leaders.
More Headlines
Filip Selected to Compete at 23rd Annual Thorpe...
07/25/2016 - M. Track - On the heels of a 10th place finish in the decathlon at the U.S. Olympic Team Trials in Eugene, Oregon, Rice junior All-American Scott Filip will...
Volleyball Earns AVCA Team Academic Award
07/25/2016 - W. Volleyball - The Rice University volleyball team received the American Volleyball Coaches Association (AVCA) Team Academic Award for an eighth consecutive...
Catching Up With 'Lo' The Pro
07/24/2016 - W. Soccer - Former Owl soccer standout Lauren Hughes (2016, Will Rice College) began playing professionally in Iceland after graduation. Here's a recent Q & A ...
Boys of Summer Ball; Weekly Update
07/24/2016 - Baseball - Rice baseball players are staying busy this summer playing in a host of collegiate leagues across the country. Here's a weekly look at the Owls'...
2016 Home Football Game Times Set
07/22/2016 - Football - Fans of Rice Football will have equal opportunities to watch the Owls during the day or at night in 2016 as the Owls have released their start...
Lee Named Cleveland Golf/Srixon All-America...
07/22/2016 - M. Golf - Former Rice men's golfer James Lee was named a Cleveland Golf/Srixon All-America Scholar, announced Thursday by the Golf Coaches Association ...
Rice Athletics Hosts 2nd Annual Owls Fall Fan Fest
07/21/2016 - Football - Rice Athletics will kick off an exciting fall season of football, soccer and volleyball on Saturday, August 13 when the Owls host their second...
Owls Picked Third in C-USA Media Poll
07/21/2016 - Football - The Rice Owls are predicted to finish third in Conference USA's West Division in a preseason vote conducted by a panel of media members that ...
- Top Videos /
- Online Store


text:
Battlefield Bad Company 2 PC walkthrough
An in-depth look at the specific PC features for BF:BC 2, including dedicated servers.
Comments (2)
Pokťmon Go guide, best tips and tricks Best ways to catch and level up Pokťmon out in the real world.
How to get XP fast in Pokťmon Go Earn a whopping 60,000 XP in 30 minutes.
Loading... hold tight!


text:
Radio Houstoned: Jennifer Egan and The Keep
Author Jennifer Egan isn't afraid of a little complication, like, oh, say, a plot that is a story within a story within a story. It's that circular, involved plotline that Egan gave readers with The Keep. "This is the story about a guy who comes to a castle and begins experiencing strange phenomena," she says. "And that story is being written by a man in a prison writing class. And it also turns out later that there's another layer around all of that that we're not aware of until the end of the book. So it's a tricky book. It has a lot of trap doors and false bottoms, and I found that to be a lot of fun."
Egan will be reading from The Keep for the Inprint Brown Reading Series on Monday, October 15. Novelist and MacArthur Foundation "Genius Grant" fellowship winner Richard Powers will also appear. 7:30 p.m. Alley Theatre, 615 Texas Avenue. For information, call 713-521-2026 or visit www.inprinthouston.org. $5. — Olivia Flores Alvarez
Get the This Week's Top Stories Newsletter
Every week we collect the latest news, music and arts stories — along with film and food reviews and the best things to do this week — so that you'll never miss Houston Press' biggest stories.
In Case You Missed It
Upcoming Events
WWE Presents NXT Live!
TicketsSat., Jul. 30, 7:30pm
Houston Texans
TicketsSun., Jul. 31, 8:55am
Houston Dynamo vs. San Jose Earthquakes
Sun., Jul. 31, 7:45pm
Houston Dynamo vs. Toronto FC
Sat., Aug. 13, 7:45pm
Popular Stories
Sponsor Content


text:
|Queen Adelaide
23 Ferry Road
East Sussex
|01797 224 276
|Visit Website
|Send E-Mail
Good news: the kitchen is re-open!
Rye Internet Cafe aims to provide you the best technical support for home and business. We will help you not only diagnose a computer problem, but also troubleshoot the concerns to provide a nifty solution. Further, for complex hardware and software issues, we will also provide you appropriate repair solutions for your computer. We identify the cause of crashes, lockups, slow speed or Internet problems and accordingly, provide necessary repairs for your computer.
Also listed in: Internet Cafes
Willow Tree House Luxury 5* Accommodation with FREE On-Site Parking
Jeake's House Award winning 17th century town house in medieval cobbled street
The Gallivant Hotel Beautiful boutique beach house hotel overlooking the dunes
Rye Audio Tour Download MP3 audio tour and Immerse yourself in Rye's medieval history!
Cadborough Cottages Walking distance from Rye. Ample parking. Peaceful location.
Sunday 31st July
@ 2:00pm
Location: Winchelsea
Winchelsea boasts over 50 medieval cellars, a number rivalled only in Bristol, Southampton and Norwich. They were all built between ... more
Sunday 31st July
@ 6:00pm
Location: Rye
Julie Edmonds playing at the King's Head, Rye Hill, Rye TN31 7NH ... more
Sunday 31st July
@ 7:30pm
Location: Rye
Sound Beach playing at Wipers. Please check website for updates as music listing may be subject to change. ... more
Tuesday 2nd August
@ 2:00pm
Location: Rye Harbour
Collect natural materials on the beach such as shells, pebbles, sea glass and other treasures washed up by the sea ... more
Wednesday 3rd August
@ 2:00pm
Location: Rye Harbour
Bring the family to find out about the weird and wonderful world of minibeasts. Suitable for accompanied children of all ... more
Thursday 4th August
@ 2:00pm
Location: Rye Harbour
A guided walk for children and their parents around Castle Farm finding out about the wildlife and the history. We ... more
Friday 5th August
Location: Rye
Summer Party for Rye Museum at the Ypres Tower. ... more
Friday 5th August
@ 10:00am
Location: Rye
Rye Country Market sells local produce which includes: Cakes, Preserves, Savouries, Free Range Eggs, Seasonal Vegetables and Fruit, Unusual Plants, ... more
Saturday 6th August
@ 10:30am
Location: Rye
Grand Jumble Sale in aid of ARRCC on the first Saturday of every month starting 7th May 2016. The Warehouse ... more
Sunday 7th August
@ 10:00am
Location: Rye Harbour
Another chance to find out about the huge variety of moths we find at the nature reserve when the warden ... more


text:
Developing Story
View All
View All
Content Type
View All
Research Activities
General Information
e.g. mm-dd-yyyy
51-75 of 310
February 8, 2015, Constanze Stelzenmüller
February 7, 2015, Constanze Stelzenmüller
February 4, 2015, Tim Boersma
February 2015, Steven Pifer, Strobe Talbott, Ambassador Ivo Daalder, Michele Flournoy, Ambassador John Herbst, Jan Lodal, et al.
January 28, 2015, Daniel V . Speckhard
January 26, 2015, Thomas Wright
January 21, 2015, Steven Pifer
January 2015, Kemal Kirişci
January 8, 2015, H.A. Hellyer
January 5, 2015, John McLaughlin
December 23, 2014, Diana Villiers Negroponte
December 17, 2014, Clifford G. Gaddy, Fiona Hill, Steven Pifer, Jeremy Shapiro and Lilia Shevtsova
November 29, 2014, Javier Solana
November 21, 2014, Steven Pifer, Angela Stent and Strobe Talbott
November 7, 2014, Steven Pifer
November 5, 2014, Constanze Stelzenmüller
October 30, 2014, Luay Al-Khatteeb
October 2014, Riccardo Alcaro and Ondrej Ditrych
October 28, 2014, Steven Pifer
October 27, 2014, Javier Solana
October 2014, Samuel Charap and Jeremy Shapiro
September 2014, John P. Banks, Charles K. Ebinger and Alisa Schackmann
Autumn 2014, Riccardo Alcaro and Aniseh Bassiri Tabrizi
September 5, 2014, Robert Kagan
September 2, 2014, Steven Pifer
The Brookings Institution is a nonprofit organization devoted to independent research and policy solutions. Its mission is to conduct high-quality, independent research and, based on that research, to provide innovative, practical recommendations for policymakers and the public. The conclusions and recommendations of any Brookings publication are solely those of its author(s), and do not reflect the views of the Institution, its management, or its other scholars.
More ›
1775 Massachusetts Ave, NW,
Washington, DC 20036
© 2016 The Brookings Institution


text:
FORTUNA - CHP continues to search for two people Friday, in connection with the fatal hit-and-run accident last week in Fortuna. Two young girls were killed, with no arrests still made.
However, the attorneys of the people being sought say they have contacted CHP numerous times to aid in the investigation.
"As a small community we mourn the tragic loss of two young teenagers that had such a bright future; so please assist us in seeking closure for this incident so we can all begin the healing process," said CHP Commander Brett Fabbri.
As the registered owner of the car involved in the crash, Marcia Kitchen, mother of one of the victims, and her boyfriend Joshua Pearlston, are being sought for questioning.
"Ms. Kitchen and Mr. Pearlston were contacted at the scene of the collision the night that it occurred. However the CHP has not had direct contact with them since the night of the collision," Fabbri said.
In their latest press release yesterday, CHP enlisted the public's help in finding Kitchen and Pearlston in order to determine whether they were involved or not
"We have made several requests to the attorney of our desire to interview her but she has not been made available to us to provide any type of a statement about her involvement," Fabbri said.
But the attorneys say, that's not true. In an email from CHP to Ms. Kitchen's attorneys Okin and Griego, the attorneys say that they quote "...have been in essentially daily contact with and available to CHP since July 13. We have consistently indicated that if you desired to arrest Ms. Kitchen prior to being able to complete our preliminary investigation that we would make her immediately available for arrest."
The attorneys said they will not be commenting further at this time.


text:
Apple acknowledges purple photo problem
Suggests a workaround
GADGET DESIGNER Apple has told users of its Iphone 5 how they can avoid having a purple hue on their photos.
Apple is reacting to reports that the Iphone 5 camera has an unusual feature, one that ruins photographs by giving them tinges of purple. The advice is not to use another camera or smartphone, but rather to change the way that you position yourself.
With typical Apple aplomb the firm says that a purple lens flare is a common feature in cameras and should not be seen as peculiar to the Iphone 5.
"Most small cameras, including those in every generation of Iphone, may exhibit some form of flare at the edge of the frame when capturing an image with out-of-scene light sources. This can happen when a light source is positioned at an angle (usually just outside the field of view) so that it causes a reflection off the surfaces inside the camera module and onto the camera sensor," it says.
"Moving the camera slightly to change the position at which the bright light is entering the lens, or shielding the lens with your hand, should minimize or eliminate the effect."
Apple has already taken something of a beating from users over the Maps app that it gave users along with the IOS 6 upgrade.
The firm's CEO Tim Cook publicly apologised to users and recommended that they use mapping software from an alternative provider. µ
INQ Latest
ISPs launch campaign to prise Openreach out of BT's hands
Unfortunately, it's led by TalkTalk
LastPass password manager gets a visit from insecurity hunter Tavis Ormandy
Google's bug hunter strikes again
Safe Harbour: EU data watchdog gives provisional nod to Privacy Shield
But Article 29 Working Party still has concerns
iPhone 7 release date, specs, price and rumours
Apple's next smartphone could, but probably won't, arrive as the iPhone 6SE


text:
|By Business Wire
Article Rating:
|August 21, 2014 03:06 PM EDT
Azimuth Systems, Inc. today announced the availability of its US Operator Performance Benchmarking Case Study. This case study leverages Azimuth's Analytics Solution to compare performance across four major US networks and highlights the impact of device-network interactions on key device and network KPIs. The case study also introduces "System Interaction KPIs" which are specifically designed to identify how devices impact the network.
Clear performance differences were observed, which led to insightful and in some cases counter-intuitive results:
- The fastest network is 20-50% faster than the other networks despite having more device-network interactions. This network is also the one most likely to offer the best battery life for the device.
- One network offered very good over-the-air data rate, but couldn't extend these gains to the subscriber resulting in low user perceived data rates.
- The device spent significantly longer (40-60%) time on 3G than on LTE for one operator, potentially due to the network settings among other factors. The relatively high time spent on 3G had a direct impact on user experience.
- The operator with the best application throughput also had the highest number of device-network interactions.
According to Vivek Vadakkuppattu, Director & Head of the Analytics Business unit at Azimuth, "Ever increasing network and device complexity has increased the impact of device-network interactions on the subscriber experience. Traditional testing has not yet caught up to this new reality and instead remains focused on device-specific or network-specific KPIs. The results from this case study highlight that an understanding of device-network interactions can provide new insights into device and network performance, ultimately impacting end user experience."
Conducting simple comparisons of throughput are no longer sufficient. Devices impact each network differently and a view into device-network interactions using metrics such as "System Interaction KPIs" can offer new insights into performance differences. Azimuth Analytics is a leading platform for automating benchmarking and regression testing of devices and network elements and is designed to provide operators, network equipment manufacturers and device OEMs the data they need to continually improve device and network performance.
The US operator comparison case study can be downloaded from Azimuth's Website at http://www.azimuthsystems.com/resource-library/case-studies/.
About Azimuth Systems
Azimuth Systems, Inc. is a leader in mobile performance test solutions for network operators, device OEMs, chipset vendors and infrastructure providers. The industry is in an unprecedented period of transition, with the introduction of major new network, device and service technologies, and aggressive competition for an increasingly saturated market. Azimuth delivers systems and software to enable measurement and correlation of user experience, device performance and network events, facilitating rapid identification and resolution of issues, maximizing quality and customer satisfaction, and minimizing time-to-market and network impact. The company is based in Acton, Massachusetts, USA with sales offices around the world. Contact Azimuth at +1 (978) 263-6610 or at www.azimuthsystems.com. Follow Azimuth on Twitter at: http://twitter.com/azimuthsystems.
Azimuth® is a registered trademark of Azimuth Systems. Azimuth Analytics and Diagnostics Network Analytics (DNA) are trademarks of Azimuth Systems.
What does it look like when you have access to cloud infrastructure and platform under the same roof? Let's talk about the different layers of Technology as a Service: who cares, what runs where, and how does it all fit together. In his session at 18th Cloud Expo, Phil Jackson, Lead Technology Evangelist at SoftLayer, an IBM company, spoke about the picture being painted by IBM Cloud and how the tools being crafted can help fill the gaps in your IT infrastructure.
Jul. 24, 2016 11:00 AM EDT Reads: 1,994
CenturyLink has announced that application server solutions from GENBAND are now available as part of CenturyLink's Networx contracts. The General Services Administration (GSA)'s Networx program includes the largest telecommunications contract vehicles ever awarded by the federal government. CenturyLink recently secured an extension through spring 2020 of its offerings available to federal government agencies via GSA's Networx Universal and Enterprise contracts. GENBAND's EXPERiUS™ Application...
Jul. 24, 2016 11:00 AM EDT Reads: 1,782
Much of IT terminology is often misused and misapplied. Modernization and transformation are two such terms. They are often used interchangeably even though they mean different things and have very different connotations. Indeed, it is somewhat safe to assume that in IT any transformative effort is likely to also have a modernizing effect, and thus, we can see these as levels of improvement efforts. However, many businesses are being led to believe if they don't transform now they risk becoming ...
Jul. 24, 2016 11:00 AM EDT Reads: 1,085
"We provide DevOps solutions. We also partner with some key players in the DevOps space and we use the technology that we partner with to engineer custom solutions for different organizations," stated Himanshu Chhetri, CTO of Addteq, in this SYS-CON.tv interview at DevOps at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 24, 2016 11:00 AM EDT Reads: 1,566
SYS-CON Events announced today the Enterprise IoT Bootcamp, being held November 1-2, 2016, in conjunction with 19th Cloud Expo | @ThingsExpo at the Santa Clara Convention Center in Santa Clara, CA. Combined with real-world scenarios and use cases, the Enterprise IoT Bootcamp is not just based on presentations but with hands-on demos and detailed walkthroughs. We will introduce you to a variety of real world use cases prototyped using Arduino, Raspberry Pi, BeagleBone, Spark, and Intel Edison. Y...
Jul. 24, 2016 11:00 AM EDT Reads: 1,287
Using new techniques of information modeling, indexing, and processing, new cloud-based systems can support cloud-based workloads previously not possible for high-throughput insurance, banking, and case-based applications. In his session at 18th Cloud Expo, John Newton, CTO, Founder and Chairman of Alfresco, described how to scale cloud-based content management repositories to store, manage, and retrieve billions of documents and related information with fast and linear scalability. He addres...
Jul. 24, 2016 10:45 AM EDT Reads: 863
DevOps at Cloud Expo – being held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA – announces that its Call for Papers is open. Born out of proven success in agile development, cloud computing, and process automation, DevOps is a macro trend you cannot afford to miss. From showcase success stories from early adopters and web-scale businesses, DevOps is expanding to organizations of all sizes, including the world's largest enterprises – and delivering real results. Am...
Jul. 24, 2016 10:45 AM EDT Reads: 2,121
Aspose.Total for .NET is the most complete package of all file format APIs for .NET as offered by Aspose. It empowers developers to create, edit, render, print and convert between a wide range of popular document formats within any .NET, C#, ASP.NET and VB.NET applications. Aspose compiles all .NET APIs on a daily basis to ensure that it contains the most up to date versions of each of Aspose .NET APIs. If a new .NET API or a new version of existing APIs is released during the subscription peri...
Jul. 24, 2016 10:00 AM EDT Reads: 551
SYS-CON Events announced today that LeaseWeb USA, a cloud Infrastructure-as-a-Service (IaaS) provider, will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. LeaseWeb is one of the world's largest hosting brands. The company helps customers define, develop and deploy IT infrastructure tailored to their exact business needs, by combining various kinds cloud solutions.
Jul. 24, 2016 09:30 AM EDT Reads: 1,055
Adding public cloud resources to an existing application can be a daunting process. The tools that you currently use to manage the software and hardware outside the cloud aren't always the best tools to efficiently grow into the cloud. All of the major configuration management tools have cloud orchestration plugins that can be leveraged, but there are also cloud-native tools that can dramatically improve the efficiency of managing your application lifecycle. In his session at 18th Cloud Expo, ...
Jul. 24, 2016 09:00 AM EDT Reads: 807
As companies gain momentum, the need to maintain high quality products can outstrip their development team's bandwidth for QA. Building out a large QA team (whether in-house or outsourced) can slow down development and significantly increases costs. This eBook takes QA profiles from 5 companies who successfully scaled up production without building a large QA team and includes: What to consider when choosing CI/CD tools How culture and communication can make or break implementation
Jul. 24, 2016 09:00 AM EDT Reads: 1,501
The best-practices for building IoT applications with Go Code that attendees can use to build their own IoT applications. In his session at @ThingsExpo, Indraneel Mitra, Senior Solutions Architect & Technology Evangelist at Cognizant, provided valuable information and resources for both novice and experienced developers on how to get started with IoT and Golang in a day. He also provided information on how to use Intel Arduino Kit, Go Robotics API and AWS IoT stack to build an application tha...
Jul. 24, 2016 08:45 AM EDT Reads: 882
It's 2016: buildings are smart, connected and the IoT is fundamentally altering how control and operating systems work and speak to each other. Platforms across the enterprise are networked via inexpensive sensors to collect massive amounts of data for analytics, information management, and insights that can be used to continuously improve operations. In his session at @ThingsExpo, Brian Chemel, Co-Founder and CTO of Digital Lumens, will explore: The benefits sensor-networked systems bring to ...
Jul. 24, 2016 08:30 AM EDT Reads: 1,459
Whether your IoT service is connecting cars, homes, appliances, wearable, cameras or other devices, one question hangs in the balance – how do you actually make money from this service? The ability to turn your IoT service into profit requires the ability to create a monetization strategy that is flexible, scalable and working for you in real-time. It must be a transparent, smoothly implemented strategy that all stakeholders – from customers to the board – will be able to understand and comprehe...
Jul. 24, 2016 08:30 AM EDT Reads: 2,053
"Tintri was started in 2008 with the express purpose of building a storage appliance that is ideal for virtualized environments. We support a lot of different hypervisor platforms from VMware to OpenStack to Hyper-V," explained Dan Florea, Director of Product Management at Tintri, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 24, 2016 08:15 AM EDT Reads: 1,812


text:
AmerisourceBergen News
News on AmerisourceBergen (Ticker: ABC) continually updated from thousands of sources around the net.
23 Celebrity Manhood Sizes You Definitely Couldn't Have...
Breastfeeding in public?
When Does Anti-Immigration Go Too Far?
AmerisourceBergen news is powered by NewsRank™
Trending Now
Updated: Mon Jul 25, 2016 05:17 am
Copyright © 2016 Topix LLC


text:
Previous poll Next poll
Do you consider yourself to be healthy?
hujiko 6 years, 9 months ago
I'm rarely inconvenienced by the state of my health, so yes.
riverdrifter 6 years, 9 months ago
Too much whisky, I suppose. 6', 165 lbs. I eat a lot of Sechuan, barbeque, smoked and other hi-spice foods. Fish also.
Whatever, "one day closer to death."
number3of5 6 years, 9 months ago
I don't consider myself to be healthy, because I have so many different health issues. My doctor on the other hand tells me I am healthy, just in a lot of pain.
Matt Warman 6 years, 9 months ago
Where is T_O_B? I need to know he is healthy, he is my favorite blogger! Good ton hear from Multidis and Ret_Irrev. Oh, and where is Autie. The only reason I read these things is because of you all!
coolmom 6 years, 9 months ago
i dont consider myself healthy yet but i have been running and walking for the last few month and i am getting there if you dont count the new pulled muscles each day and the limping.
Linda Aikins 6 years, 9 months ago
I was until Mother Nature struck.
Boosh 6 years, 9 months ago
To be. Or not.
denak 6 years, 9 months ago
guess it would depend on how one defines "healthy."
If one's weight is the determinating factor, then no, I'm not healthy but my cholestrol levels, blood sugar and everything else is very, very good. Thank God for good genetics!!!! :0)
Boosh 6 years, 9 months ago
Healthy for what? Don't the ads on the TV say consult your physician to find out if you are healthy enuff for *?
Matt Warman 6 years, 9 months ago
Whayever you are, RETICENT_IRR, I enjoy your wit
gsxr600 6 years, 9 months ago
400's the new 150. Nom nom nom.
Mel Briscoe 6 years, 9 months ago
eh... relatively. doing a little better everyday.
Ernest Barteldes 6 years, 9 months ago
Id say Im generally in good health. Just have to take better care of myself... but then the bed beckons for another 10 min... yawn
1029 6 years, 9 months ago
It's a wonder that anybody in this city is healthy when you got "gurus" coming to town for the purpose of encouraging people to go out in the cancer-causing sun of death, breathe toxic vehicle fumes, and dodge cars, busses, and homeless people, all while hoping to not break a leg or sprain an ankle.
mr_right_wing 6 years, 9 months ago
I'll be able to be a whole lot healthier once all of you start paying ALL my medical bills via BarryCare! I need a government prescription for facial tissues. $75/box..pay up!!
Reuben Turner 6 years, 9 months ago
besides this high blood pressure; yes yes yes.
jumpin_catfish 6 years, 9 months ago
Good health a relative term. What is good really or health for that matter or even relative. I try to be healthy but I'm not going to kill myself to stay healthy.
riverdrifter 6 years, 9 months ago
Autie: Thet decoy bag, er, it do have decoys in it, right?
Shrimp scampi tonight, with, ok, spinach pasta, which do offset the butter-based sauce. Spinach pasta, me? Whodathunkit.
riverdrifter 6 years, 9 months ago
"Spinach pasta is for impressing under-informed nookie hopefuls."
Damn. Wished I'd known this long ago...
Commenting has been disabled for this item.
The Law Office of David J. Brown, LC 785-842-0777
Find more businesses on Marketplace
Arts & Entertainment · Bars · Theatres · Restaurants · Coffeehouses · Libraries · Antiques · Services
- Letter to the editor: 'We like him' July 23, 2016 · 25 comments
- Basketball tournament brings 300 teams, thousands of people to Sports Pavilion Lawrence July 23, 2016 · 4 comments
- Journal-World staff changes announced with upcoming ownership change July 19, 2016 · 52 comments
- Kansas voters dissatisfied with presidential candidates, Gov. Brownback and Legislature July 24, 2016 · 6 comments
- Judge to monitor Kansas' actions on gay marriage for 3 years July 22, 2016 · 9 comments
- Scores of Jayhawk fans turn out to celebrate DeBruce Center's opening, rules of basketball July 23, 2016 · 1 comment
- Kansans split over questions about Melania Trump speech July 19, 2016 · 41 comments
- Opinion: Republicans set low bar on vision July 24, 2016 · 6 comments
- Letter to the editor: Hypocrisy showing? July 22, 2016 · 7 comments
- Brownback, chairman of Cruz campaign in Kansas knock refusal to back Trump July 21, 2016 · 18 comments
- What if Kansas paid its basketball players? It already does, sort of July 24, 2016
- Scores of Jayhawk fans turn out to celebrate DeBruce Center's opening, rules of basketball July 23, 2016
- Former Jayhawk Kaun reveals retirement July 23, 2016
- Kansas voters dissatisfied with presidential candidates, Gov. Brownback and Legislature July 24, 2016


text:
|Thread Tools
Toy Industry Analyst
Join Date: Dec 2007
Posts: 4,196
Location: Oklahoma
Collection Count: 1024
News Credits: 2
Superquad7 prompted this, [due to] time and complexity constraints, most of my fixes typically aren't too involved and are intended for beginners/intermediate modders. Because of the intended audience, I will repeatedly cover simple topics, like Pledge with Future floor polish, to ensure people are aware of them.
Transformers: Prime Powerizer [Voyager] Optimus Prime, in which I demonstrate how to improve his foot articulation. But beware, do not use a sharpie to color his arms, it smears off on fingers:
Last edited by Superquad7; 07-19-2012 at 03:13 AM..
|Thread Tools
|Latest News & Rumors Posts
|First Look at Prime 1 Beast Wars Optimus Primal
|Masterpiece Cheetor Color Images!
|Transformers The Last Knight banner in movie theaters
|New Stock Photos of TakaraTomy LG-31 Fortress Maximus
|Legends Hardhead, Skullcruncher, and Galvatron Pics
|Latest Toy Discussion Posts
|The hunt for TR Brainstorm
|Favorite Transformer of the day....................
|The Masterpiece Appreciation thread
|The UK Toy Discussion
|I want a 'new' Legends scale Jetfire.
|Latest 3rd Party Posts
|PerfectFusion Caesium (Masterpiece Slag)
|FansToys FT-16 Sovereign (Masterpiece Galvatron)
|CW/UW Devastator 3P megathread
|Toyworld Constructor (Devastator/Construc...
|Wei Jiang OS Hound 2.0
|Latest Radicons Posts
|Classics Black Zarak
|Titans Return Galvatron Mask Mod: A Few Words Of Advice!
|Make Hot Shot Great Again(WiP)
|G1 Apeface (TR Hardhead)
|Titan Returns faceplates


text:
Credit Union times deliver daily breaking news and information you need -- FREE.Sign Up Now!
October 9, 2013 | By Marc Rapport
CUNA Mutual Group said this week that it notched 2,185 registrants for its Online Discovery Conference, the most yet in the annual event's four years.
August 13, 2013 | By Marc Rapport
Day-long virtual conference set for Oct. 1.
From Virtual Hold Technology
From Datawatch Monarch
From ARCA
From Kaufman Hall
From Doxim
From Shoreline, a Gemalto Company
From D+H
Jul 19 | Peter Strozniak
Jul 17 | Marlene Y. Satter
Jul 18 | Peter Strozniak
Advertisement. Closing in 15 seconds.


text:
Narrow your search
Wireless carriers say they've got you covered with fast, reliable mobile service at this summer's big political events.
A handful of Snapchat celebrities are on hand for the RNC in Cleveland this week. We tracked them down to see how they're experiencing and sharing American democracy in action.
From Twitter's takeover of a tavern to Peter Thiel's prime-time speaking slot, tech titans have set up shop in Cleveland this week at the RNC.
CNET's Eric Mack runs into twin artists documenting the Republican National Convention in a most unusual way on the streets of Cleveland.
Political junkies can stay on top of next week's DNC with a new app that includes a 360-degree video stream and real-time access to speeches and photos.
From the networks to live streams online, there are many options to view the GOP's supposed coronation of Donald Trump.
ColorOfChange and Credo Action pressure 30 big companies to ditch or curtail their sponsorship of the Republican National Convention because of its divisive candidate. Half, including Apple and HP, listen.
Ohio law-enforcement agencies have at least 20 robots similar to the kind that was rigged with a bomb by Dallas police earlier this month.
The PayPal co-founder, venture capitalist and Donald Trump supporter is scheduled to speak on the last night of the GOP's convention, when Trump is expected to accept the nomination.
The social network will show CBSN's gavel-to-gavel coverage of the events that will officially pick the parties' presidential contenders.


text:
Categories > Comics > X-Men
Deleted story0 reviews
This story has been deleted, and will shortly vanish
Chapter 10 reviews
Sabretooth gets caught in the cross-fire of a drama he wanted no part of. Can he make it to the end, or will fate finally catch up with the Tooth-Monger? *this is old-skool Sabretooth, around the...0Unrated
Chapter 20 reviews
after his fun night at the club, Victor takes a breather. if only it would work out like he was hoping....0Unrated
Chapter 30 reviews
Waking up in strange places is nothing new. but will this be more of the same, or does Victor stand a chance against temptation when it walks his way?0Unrated
Chapter 40 reviews
Victor has a tech question. can he get the info and get out before all hell breaks loose yet again?0Unrated
Chapter 50 reviews
Victor does a little braking and entering. could he finally locate what he needs to solve this disaster?0Unrated
Chapter 6 - Final0 reviews
Sabretooth has some questions. Unfortunately, the people he's dealing with don't have answers.0Unrated


text:
slightly smudged yet clean, top bottom liner, bold, white highlights, extremely mod sassy cat eye
Keeping the retro theme going with a mod cut crease with a gorgeous @makeupbyjac
Awesome eye makeup <3
Pretty awesome mod eye makeup
Pretty sixties inspired makeup x
This is painfully awesome. The makeup is ALMOST too much. The hair is flawless. The collar on that dress/shirt/whatever is so mod. Her expression, the lighting...
An easy guide to 60s makeup - Sexy 60s makeup is a snowballing beauty trend. Tackle it with these tips
How to do comic-book inspired nails for Halloween: Batman
Incredible Italian tiles inspired by Any Warhol
Andy Warhol (as a dress) (and a woman?)
Google Image Result for http://www.creativeboysclub.com/wp-content/uploads/2011/08/0134.jpg
Candy Warhol By TOMAAS | Inspiration Grid | Design Inspiration
Masha by ~Ehinokokus.. ii was really drawn to this! fantastic make-up
Andy Warhol inspired banana nails
Brillo recently went back in time and featured Warhol-inspired #packaging to mark its 100th anniversary.
Recycled Warhol-Inspired Bracelet! Wood bangle+soup label+Glossy Mod Podge!
Andy Warhol inspired - Campbells Soup Leggings - I WANT!
And most people don't understand half the shit I do. Lmao Sweeet.
missing you so bad.
amazing andy warhol themed nails
I want an Andy Warhol themed entertainment room...
Spice girls themed nail art I created for District MTV. Check them out here: http://www.districtmtv.co.uk/article/topic/archive/yz30fb/nail-art-girl-pop-inspired/opwdoi
Comic Book Cartoon 50s Pinup 60s Pop Art Graphic Print Pant 17 mv Legging
Loving this Pop Art inspired trio.


text: Massive Lego model of Nvidia GeForce GTX 690 graphics cardTatiana Danger12/05/13 11:57amFiled to: Lego501EditInvite manuallyPromoteDismissUndismissHideShare to KinjaGo to permalink Xiosheng Li recreated his Nvidia GeForce GTX 690 graphics card as a massive Lego build. It's over six feet long and completely not functional, but pretty damn rad. Using 11,396 bricks and taking over three months, the cost of this build is around ¥10,000 (USD $1,640). "Xiaosheng used the Lego Digital Designer software to model the card, even managing to get the fan to function through the use of an electrical fan motor." Here's how he built the graphics card, with loads more photos. [TechSpot] You're reading Leg Godt, the blog with the latest Lego news and the most awesome Lego models in the web. Follow us on Twitter or Facebook.Reply50 repliesLeave a reply