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An up and down week
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Friday, September 23, 2011
It's been one of those weeks. I've not felt the best. My tummy has been all gurrilly(?), my bowels have been lose. I haven't felt like tracking. I've been hungry for somethng, but not quite sure for what.
Today we had some minor flooding or seeping water into our pantry. I was able to avoid more water by shoveling the neighbor's driveway stone back from the center of the road, we both live on the lower side of a mountain. The water was running down his driveway, washing his stones onto the road which runs between our places. He has a very long driveway. The water was being diverted across the road and running down our side of the road and across our parking area and driveway, both stone, which is now cratered out. My fear was that more stones would wash onto the road thus diverting the water towards our house.
Harrisburg, PA about 15 miles up the road beat it's all time yearly rain record today. Needless to say that the ground around here is quite saturated. The rain that entered our pantry area came in around our break in the cinderblock, underground wall and seeped down the wall. Damage was minimal. Nothing lost. Almost none existing compared to many who live along the river and creeked that flooded earlier this month.
Thanks for reading and prayers for the tummy and what ever I'm craving. Weight seems to be still going down, must be the loose bowels.
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Steak ' Shake is a classic American brand famous for the Original Steakburger™ and hand-dipped Milk Shakes. Stop in today for breakfast, lunch, dinner or late night. Dine in, drive thru or carryout.
Good food, but very slow service every time I've been here.
This one sucks. we have been waiting for 15 min and they just got our drinks and they have lousy help.... my second time here and I am just not happy at all both times long waits and crappy service
Terrible service, but good food. The waitresses don't care & neither does the manager. It's a shame.
Great service, food came really quickly. Food was very good, but Jamaican burger is way too spicy. Under $4 menu is really great and their breakfast menu starts at 12 midnight!
California Steakburger is no more.. :(
Had a horrible experience here. Waited 40 minutes for food that the server said she put in the system before she went on break, but she never did and we never got our food. We just left.
Ask for A-1 on your burger, it's wonderful. The new fresh banana shakes are great! Cheap and good.
$4.00 meals are all worth it on a budget.
Stood there waiting to be seated.....no one acknowledged us so we left.....won't go back
Get cheese for your fries, or for anything else. Love this cheese!
Frisco melt all day
Great service! Baby chair was dirty and sticky ! Manager came over and paid for our whole meal! They were over accommodating and really tried hard to make our stay and lunch there a great one!!
Shauna of the Dead is the BEST WAITRESS EVAAAAAR.
Frisco melt is serious
Popular place for college kids and hood rats to sober up at 2 am. Be aware.
Friday night + hungry people= slow drive thru... So hungry!
Surprisingly fast and friendly service at the drive-thru.
Night crew sucks.
Service at night blows. It looks like they just don't want to work. Terrible. It's a shame because the food is good
Looove the frisco melt
The Frisco Melt is awesome!!!
Fast service, great food, even better price
Number 7 combo is really good. Totally recomend it

subset: commoncrawl


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Prince's Sister Tyka Nelson Storms Out of Family Meeting. Why?
- 10:57 AM, Apr 29
Screening of FX's It's Always Sunny in Philadelphia and The League
Photo credit: Apega / WENN
To fit your screen, we scale this picture smaller than its actual size. The original picture size is 764x1000 pixels and this photo has been viewed 2071 times since September 13, 2011


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Talisman: Something or someone who produces apparently magical or miraculous effects. Often in soccer a player is deemed a talisman for the team. Think Ronadlinho when he played for Barcelona or Henry when he was with Arsenal. With that player the team can win, without that player they will often lose.
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Average Rating
User Reviews
1 out of 2 people found this review helpful:Looking back... why did I watch this?I watched all 220 episodes a while ago and I can't really tell what kept me watching. Naruto is a pretty lame ninja. At least his voice isn't as annoying as it is in English. All and all though, there are some good fights, a few good story arcs, and a few laughs. I could have done without the tons of filler at the end. Not that they aren't good episodes, there's just too much of it. Definitely ...Read more
2 out of 4 people found this review helpful:I love you Naruto BBG xox love <3fucking great show! quality filler! great if you love lasagna and balogna! Real ninjas are great in anime like theyre best friends and fight the bad guys its so emotional lol its like the best anime ever haha. Naruto x sakura 4 lyfe lol haha. xxx pce ty bye
Great if you skip fillerNaruto is by far my favorite series of all time, even over DBZ and SAO. If you skip the fillers (the second half of the first series) it is great. It just sucks that 50% of the episodes are a total waste of time.
Most intertaining shounen anime everI absolutely love this anime its one of the best of its kind also it is very famous from japan to the rest of the world. I can wait till i reach shippuden where it just gets even better it twists from a typical shounen too so much more with an amazing storyline and great battle sceans if our reading this now...watch.this.anime.
Naruto is good BUT!!One of my favorite animes. Pretty good storyline but there's just too many unimportant backtracks.. The first Season was great especially the forest of death fighting animation. You could tell, the animators put so much effort in the fighting scenes. Towards the very last episode though the animation wasn't the same as it used to be. BUT REALLY GOOD JOB THOUGH! I would give it 4.5/5 stars
love it love it <3 awesomeit has a great story line awesome characters great designs it gets better as u go it can be slow at first but the more you get in to it the better the anime is it self great twist and I hope you like the anime as much as I did ok straight of its AWESOME!!!!!!!!!!
Its mostly the fillersSometimes the filler episodes get on my nerves. a bunch of episodes in the middle of the series that seem tosidetrack from the main storyline. overall it is a very good anime one of my favorites. I recommend this to anime beginners.
1 out of 2 people found this review helpful:A DREAMER'S ADVENTURESThis anime series cover the stories of the struggles of three young ninjas, ninja graduates who are classified as Genins.Led by higher class Jounin Kakashi, Naruto Uzumaki,who constantly searches for recognition, Sasuke Uchiha, who is obsessed with killing a particular person and Sakura Haruno, who is obsessed with being noticed by Sauske and most of her likes and dreams involve him as well, ...Read more
It is thanks to this series that I became an anime fan!Naruto is the show that started all for me. Sure people hate on it but I found everything about it to be just right. Filler episodes in this series are a hit or miss but either way I enjoyed most of the fillers. (Unmasking Kakashi episode was my favorite) I praise this anime highly because well it got me into anime. (I am up to date with Shippuden) If you you are a fan of long running series then ...Read more


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Maritime Today
The Maritime Industry's original and most viewed E-News Service
Propulsion and steering systems manufacturer SCHOTTEL has unveiled its new EcoPeller (SRE), which it said offers improved efficiency and robustness. Playing a
Carnival Vista, the new flagship of the fleet of Carnival Cruise Line, brand of the Carnival Group, was delivered today at Fincantieri's shipyard in Monfalcone.
South Korea's shipbuilder Samsung Heavy Industries (SHI), the world's third-largest shipbuilder, has received a contract termination for three floating liquefied
The newly built tank barge, the Fight A.L.S., was delivered to Harley Marine Services on February 19, 2016.
Designed by Elliott Bay Design Group (EBDG) and constructed at Vigor Fab in Portland,
Oregon State University to issue RFI on ship project after design completion
The design phase for a project to construct a new regional class research vessel
Incat Crowther has been awarded a contract with shipbuilder Astinave EP of Guayaquil, Ecuador for the supply of vessel design services and aluminum component kits for a pair of 22.


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Fox's Midseason Schedule: New Girl Returns, Brooklyn Nine-Nine on the Move, Bones, Last Man MIA and More
Brooklyn Nine-Nine is being reassigned.
Fox unveiled its midseason schedule on Tuesday, and the big news is that Nine-Nine — which currently airs on Sunday night — is moving back to its old Tuesday stomping ground. READ MORE & VIEW SCHEDULE


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Seymour Johnson Airman Charged In Child's Death
Updated: 03/13/2013 - Authorities at Seymour Johnson Air Force Base are investigating the death of a baby and have charged its father with murder.
Updated: 03/13/2013 - Authorities at Seymour Johnson Air Force Base are investigating the death of a baby and have charged its father with murder.
Updated: 03/14/2013 - Police in upstate New York are searching for a suspect after shootings at a car wash and a barbershop a mile away left four people dead and at least two wounded.
Updated: 03/13/2013 - A superior court judge here in Eastern Carolina has been given an official public reprimand after complaints of judicial misconduct.
Posted: 03/13/2013 - Police say they need your help in identifying two women who they say walked out of a store with thousands of dollars worth of computers.
Updated: 03/13/2013 - Police say they are searching for a Chester County, Pennsylvania man who allegedly kidnapped his estranged wife and three young children and drove them to Eastern Carolina.
Updated: 03/15/2013 - Police said they put a face caught on surveillance cameras to a name, and now need help to find the man.
Posted: 03/13/2013 - Police want your help in finding a woman who reportedly ripped off a customer in a local department store.
Updated: 03/13/2013 - North Carolina regulators are holding their latest hearing into a request by Duke Energy to raise electricity bills by almost 10 percent for nearly 2 million customers of Progress Energy Carolinas.
Updated: 03/13/2013 - Trooper C.J, Matos with the Onslow County Highway Patrol said a woman turned in front of a deputy before he could hit the brakes.
Updated: 03/12/2013 - For those of you with allergies, it's a sad day when pollen season rolls around. But ready or not-here it comes.
Updated: 03/12/2013 - A woman who says she allowed a man to come into her home to use her phone, ended up the victim of a home invasion and was robbed at gunpoint.
Updated: 03/13/2013 - One of the few old-time hardware stores still around will close up shop next month.
Posted: 03/12/2013 - Drier and cooler conditions can be expected across eastern Carolina on Wednesday
Posted: 03/12/2013 - Hostess is moving ahead with plans to sell its Twinkies, and one of the new owners says the spongy cream-filled snacks could be back on shelves by summer.
Updated: 03/12/2013 - About a thousand homes and business remain without power after a substation lost power in Hyde County.
Updated: 03/13/2013 - State Troopers say 21-year-old Lashunqua Cooper, and her son, Jiquel Copeland died after their Honda was struck by a pickup truck.
Posted: 03/12/2013 - The U.S. Army, U.S. Marine Corps and U.S. Coast Guard suspended their assistance programs last week. A decision by the U.S. Navy is pending.
Posted: 03/12/2013 - Cornelia Cox from Creekside Elementary School has been named Assistant Principal of the Year by the North Carolina Association of Educators.
Updated: 03/18/2013 - A man in jail for a nearly six weeks on a murder charge is now out on bond.
Updated: 03/12/2013 - Southwest High School dismissed students at 10:45 a.m.
Updated: 03/12/2013 - Thick black smoke emerged from the Sistine Chapel chimney, indicating cardinals had failed to select a new pope after their initial vote.
Updated: 03/12/2013 - On Tuesday, the City of New Bern announced it was awarded for it's forestry efforts for the 15th year in a row by a national organization.
Posted: 03/12/2013 - Dozens of citizens and interest groups are prepared to try to persuade North Carolina House members to their way of thinking on requiring citizens to show photo identification before voting.
Posted: 03/12/2013 - No stone unturned, Camp Lejeune said a standard health and comfort inspection landed some Marines in handcuffs.
Updated: 03/11/2013 - Nearly 2,000 illegal immigrants have been released from Immigration and Customs Enforcement detention centers in what the Department of Homeland Security says is a result of sequestration, and now Congressman Walter Jones and others want some answers.


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529 Views 2 Replies Latest reply: Jan 23, 2013 10:46 AM by lodema
Winston Churchill Jan 23, 2013 9:47 AM
in response to lodema Solved
Connect it to iTunes, select it from the device list, navigate to the tones tab, check the ringtones you want to sync, click apply/sync.
lodema Jan 23, 2013 10:46 AM
in response to Winston Churchill
Thank you, thank you! It was pretty easy, once you explained it to me.
Now, do you have any idea why my iPhone looks like it's connected to my Airport Extreme, but will not open pages? My iMac, desktop and my iPad connect, no problem, but my phone won't. Verizon even replaced my phone, but it still won't connect. ?????


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Bernd Osterloh
Why the Porsche-Piech family is not rushing in to fix VWWed, 27, Apr 2016
The Porsche-Piech clan, led by Wolfgang Porsche, that controls scandal-hit VW Group has the voting power to muscle through change at the automaker, but family members are not acting on it. That has left a power vacuum even as VW faces costs that could top $30 billion.
VW said to hire McKinsey to address diesel scandalWed, 27, Apr 2016
VW Group has hired external advisers McKinsey & Co. to better react to the turmoil caused by its emissions cheating and help draft a strategy to move beyond the scandal, people familiar with the matter told Bloomberg.
VW labor chief calls for managers to waive bonusesTue, 19, Apr 2016
Bernd Osterloh, Volkswagen Group's top labor boss, believes the automaker's management board should volunteer to waive their bonus payments ahead of an April 22 decision on the subject, a German paper reported.


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BBB Accredited Business since 01/07/2009
Laz-Trans, Inc.Find a Location
(661) 833-37875200 District Blvd, Bakersfield, CA 93313-2330www.laztrans.com
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This company is in an industry that may require licensing, bonding or registration in order to lawfully do business. BBB encourages you to check with the appropriate agency to be certain any requirements are currently being met.
These agencies may include:DMV - Motor Carrier Services
2415 1st Ave
Sacramento, CA 95818-2606
(800) 777-0133
U.S. Department of Transportation
400 7th St SW
Washington, DC 20590
(855) 368-4200
BBB records show a license number of CA0026149 for this company, issued by DMV - Motor Carrier Services. Their web address is http://www.dmv.ca.gov.Type: Department of Motor Vehicle
BBB records show a license number of 539251 for this company, issued by U.S. Department of Transportation. Their web address is http://www.dot.gov.Type: Transportation
Type of Entity
Incorporated: July 1982, CA
Contact InformationPrincipal: Mr. William Lazzerini Jr. (President)
Business Category
Trucking - Heavy Hauling


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|Prion Diseases (TSEs)
A prion is an infectious agent, composed entirely of protein, presumed to be the cause of the transmissible spongiform encephalopathies (TSEs). The protein it is composed of, called PrP (short for prion protein) can fold in multiple, structurally distinct ways, at least one of which is transmissible to other prion proteins. It is this form of replication that leads to disease that is similar to viral infection. The word prion, coined in 1982 by Stanley B. Prusiner, is short for "proteinaceous infectious particle"[1] derived from the words protein and infection, hence prion, in reference to a prion's ability to self-propagate and transmit its conformation to other prions.[2] While several yeast proteins have been identified as having prionogenic properties, the first prion protein was discovered in mammals and is referred to as the major prion protein (PrP). This infectious agent causes mammalian transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") and scrapie in sheep. In humans, PrP causes Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann–Sträussler–Scheinker syndrome, Fatal Familial Insomnia and kuru.[3]
A protein as an infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, or parasites, all of which must contain nucleic acids (either DNA, RNA, or both). For this reason, a minority of researchers still debate whether prions are the cause of the TSEs.[4] All known prion diseases in mammals affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.[5]
Prions are not considered living organisms because they are misfolded protein molecules which may propagate by transmitting a misfolded protein state. If a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the misfolded prion form. In this way, the prion acts as a template to guide the misfolding of more proteins into prion form. In yeast, this refolding is assisted by chaperone proteins such as Hsp104p. These refolded prions can then go on to convert more proteins themselves, leading to a chain reaction resulting in large amounts of the prion form.[6] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicate when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.[7] (Note that the propagation of the prion depends on the presence of normally folded protein in which the prion can induce misfolding; animals that do not express the normal form of the prion protein can neither develop nor transmit the disease.)
Prion aggregates are extremely stable and accumulate in infected tissue, causing tissue damage and cell death.[8] This structural stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult. Prion structure varies slightly between species, but nonetheless prion replication is subject to occasional epimutation and natural selection just like other forms of replication.[9]
See also: Major Prion Protein (PRNP).
During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and mathematician John Stanley Griffith, developed the hypothesis that some transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins.[10] [11] Earlier investigations by E. J. Field into scrapie and kuru had identified the transfer of pathologically inert polysaccharides that only become infectious in the host.[12] [13] Alper and Griffith wanted to account for the discovery that the mysterious infectious agent causing the diseases scrapie and Creutzfeldt–Jakob disease resisted ionizing radiation.[14] (A single ionizing "hit" normally destroys an entire infectious particle, and the dose needed to hit half the particles depends on the size of the particles. The data suggested that the infectious agent was too small to be a virus.)
Francis Crick recognized the potential importance of the Griffith protein-only hypothesis for scrapie propagation in the second edition of his "Central dogma of molecular biology" (1970): While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was "precluded", he noted that Griffith's hypothesis was a potential contradiction (although it was not so promoted by Griffith).[15] The revised hypothesis was later formulated, in part, to accommodate reverse transcription (which both Howard Temin and David Baltimore discovered in 1970).
In 1982, Stanley B. Prusiner of the University of California, San Francisco announced that his team had purified the hypothetical infectious prion, and that the infectious agent consisted mainly of a specific protein – though they did not manage to isolate the protein until two years after Prusiner's announcement.[16] While the infectious agent was named a prion, the specific protein that the prion was composed of is also known as the Prion Protein (PrP), though this protein may occur both in infectious and non-infectious forms. Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for his research into prions.[17]
See also: PrP structure.
The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc — the C refers to 'cellular' PrP, while the Sc refers to 'scrapie', the prototypic prion disease, occurring in sheep.[18] While PrPC is structurally well-defined, PrPSc is certainly polydisperse and defined at a relatively poor level. PrP can be induced to fold into other more-or-less well-defined isoforms in vitro, and their relationship to the form(s) that are pathogenic in vivo is not yet clear.
PrPC is a normal protein found on the membranes of cells. It has 209 amino acids (in humans), one disulfide bond, a molecular mass of 35–36 kDa and a mainly alpha-helical structure. Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms.[19] The normal protein is not sedimentable; meaning that it cannot be separated by centrifuging techniques.[20] Its function is a complex issue that continues to be investigated. PrPC binds copper (II) ions with high affinity.[21] The significance of this finding is not clear, but it is presumed to relate to PrP structure or function. PrPC is readily digested by proteinase K and can be liberated from the cell surface in vitro by the enzyme phosphoinositide phospholipase C (PI-PLC), which cleaves the glycophosphatidylinositol (GPI) glycolipid anchor.[22] PrP has been reported to play important roles in cell-cell adhesion and intracellular signaling in vivo, and may therefore be involved in cell-cell communication in the brain.[23]
Protease-resistant PrPSc-like protein (PrPres) is an isoform of PrPc from which is structurally altered and converted into a misfolded proteinase K-resistant form in vitro. To mimic conversion of PrPC to PrPSc in vitro, Saborlo et al. rapidly converted PrP.C into a PrPres by a procedure involving cyclic amplification of protein misfolding.[24] The term "PrPres" has been made to distinguish between PrPSc, which is isolated from infectious tissue and associated with the transmissible spongiform encephalopathy agent.[25] For example, unlike PrPsc, PrPres may not necessarily be infectious.
The infectious isoform of PrP, known as PrPSc, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation, or shape; this, in turn, alters the way the proteins interconnect. PrPSc always causes prion disease. Although the exact 3D structure of PrPSc is not known, it has a higher proportion of β-sheet structure in place of the normal α-helix structure.[26] Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques. It is unclear as to whether these aggregates are the cause of cell damage or are simply a side-effect of the underlying disease process. The end of each fiber acts as a template onto which free protein molecules may attach, allowing the fiber to grow. Under most circumstances, only PrP molecules with an identical amino acid sequence to the infectious PrPSc are incorporated into the growing fiber.[20] However, rare cross-species transmission is also possible.
The physiological function of the prion protein remains a controversial matter. While data from in vitro experiments suggest many dissimilar roles, studies on PrP knockout mice have provided only limited information because these animals exhibit only minor abnormalities. In recent research done in mice, it was found that the cleavage of PrP proteins in peripheral nerves causes the activation of myelin repair in Schwann Cells and that the lack of PrP proteins caused demyelination in those cells.[27]
A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory.[28] As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation.[29] [30]
A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organism's self-renewal of bone marrow. The study showed that all long-term hematopoietic stem cells express PrP on their cell membrane and that hematopoietic tissues with PrP-null stem cells exhibit increased sensitivity to cell depletion.[31]
The first hypothesis that tried to explain how prions replicate in a protein-only manner was the heterodimer model.[32] This model assumed that a single PrPSc molecule binds to a single PrPC molecule and catalyzes its conversion into PrPSc. The two PrPSc molecules then come apart and can go on to convert more PrPC. However, a model of prion replication must explain both how prions propagate, and why their spontaneous appearance is so rare. Manfred Eigen showed that the heterodimer model requires PrPSc to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 1015.[33] This problem does not arise if PrPSc exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion. What is more, despite considerable effort, infectious monomeric PrPSc has never been isolated.
An alternative model assumes that PrPSc exists only as fibrils, and that fibril ends bind PrPC and convert it into PrPSc. If this were all, then the quantity of prions would increase linearly, forming ever longer fibrils. But exponential growth of both PrPSc and of the quantity of infectious particles is observed during prion disease.[34] [35] [36] This can be explained by taking into account fibril breakage.[37] A mathematical solution for the exponential growth rate resulting from the combination of fibril growth and fibril breakage has been found.[7] The exponential growth rate depends largely on the square root of the PrPC concentration.[7] The incubation period is determined by the exponential growth rate, and in vivo data on prion diseases in transgenic mice match this prediction.[7] The same square root dependence is also seen in vitro in experiments with a variety of different amyloid proteins.[38]
The mechanism of prion replication has implications for designing drugs. Since the incubation period of prion diseases is so long, an effective drug does not need to eliminate all prions, but simply needs to slow down the rate of exponential growth. Models predict that the most effective way to achieve this, using a drug with the lowest possible dose, is to find a drug that binds to fibril ends and blocks them from growing any further.[39]
See main article: Transmissible spongiform encephalopathy.
|Affected animal(s)
|sheep, goat
|Bovine spongiform encephalopathy (BSE), mad cow disease
|Transmissible mink encephalopathy (TME)
|white-tailed deer, elk, mule deer, moose
|Chronic wasting disease (CWD)
|Feline spongiform encephalopathy (FSE)
|nyala, oryx, greater kudu
|Exotic ungulate encephalopathy (EUE)
|Spongiform encephalopathy
(Has not been shown to be transmissible.)
|Creutzfeldt–Jakob disease (CJD)
|Iatrogenic Creutzfeldt–Jakob disease (iCJD)
|Variant Creutzfeldt–Jakob disease (vCJD)
|Familial Creutzfeldt–Jakob disease (fCJD)
|Sporadic Creutzfeldt–Jakob disease (sCJD)
|Gerstmann–Sträussler–Scheinker syndrome (GSS)
|Fatal familial insomnia (FFI)[42]
All known mammalian prion diseases are caused by the so-called prion protein, PrP. The endogenous, properly folded form is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie, after one of the diseases first linked to prions and neurodegeneration.)[20] [43] The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids in a Protein Misfolding Cyclic Amplification (PMCA) reaction. Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts.[44]
Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.[45] Other histological changes include astrogliosis and the absence of an inflammatory reaction.[46] While the incubation period for prion diseases is relatively long (5 to 20 years), once symptoms appear the disease progresses rapidly, leading to brain damage and death.[47] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.
All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal.[48] However, a vaccine developed in mice may provide insight into providing a vaccine to resist prion infections in humans.[49] Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE,[50] building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein.[51] In 2013, a study revealed that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes vCJD.[52]
Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.[53] Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another. The human prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a prion that typically infects cattle, causing Bovine spongiform encephalopathy and is transmitted through infected meat.[54]
It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic.[55] It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.[56]
Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.[57]
A University of California research team, led by Nobel Prize winner Stanley Prusiner, has provided evidence for the theory that infection can occur from prions in manure.[58] And, since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. It was reported in January 2011 that researchers had discovered prions spreading through airborne transmission on aerosol particles, in an animal testing experiment focusing on scrapie infection in laboratory mice.[59] Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011.[60]
Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the denaturation of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to proteases, heat, ionizing radiation, and formaldehyde treatments,[61] although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure. Examples include sodium hypochlorite, sodium hydroxide, and strongly acidic detergents such as LpH.[62] 134 °C (274 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease.[63] [64] Ozone sterilization is currently being studied as a potential method for prion denaturation and deactivation.[65] Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.[66]
The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:
Advancements in computer modeling have allowed scientists to identify compounds that can treat prion-caused diseases, such as one compound found to bind a cavity in the PrPC and stabilize the conformation, reducing the amount of harmful PrPSc.[68]
Recently, antiprion antibodies capable of crossing the blood-brain-barrier and targeting cytosolic prion protein (an otherwise major obstacle in prion therapeutics) have been described.[69]
In the last decade, some progress dealing with ultra-high-pressure inactivation of prion infectivity in processed meat has been reported.[70]
In 2011 it was discovered that prions could be degraded by lichens.[71] [72]
There continues to be a very practical problem with diagnosis of prion diseases, including BSE and CJD. They have an incubation period of months to decades, during which there are no symptoms, even though the pathway of converting the normal brain PrP protein into the toxic, disease-related PrPSc form has started. At present, there is virtually no way to detect PrPSc reliably except by examining the brain using neuropathological and immunohistochemical methods after death. Accumulation of the abnormally folded PrPSc form of the PrP protein is a characteristic of the disease, but it is present at very low levels in easily accessible body fluids like blood or urine. Researchers have tried to develop methods to measure PrPSc, but there are still no fully accepted methods for use in materials such as blood.
In 2010, a team from New York described detection of PrPSc even when initially present at only one part in a hundred billion (10−11) in brain tissue. The method combines amplification with a novel technology called Surround Optical Fiber Immunoassay (SOFIA) and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a micro-capillary tube. This tube is placed in a specially constructed apparatus so that it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals' brains were analysed once any symptoms became apparent. The researchers could, therefore, compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals' lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared.[73] [74]
In 2014 collaboration between Rocky Mountain Laboratories, Hamilton, Montana USA and the University of Verona, Italy developed for the first time a protocol for the detection of CJD in living patients. The RT-QuIC assay, a microplate reader-based prion detection method, was applied to nasal brushings obtained from the olfactory epithelium of living patients affected with CJD. The assay had a sensitivity of 97% and specificity of 100% for the detection of CJD. Though a preliminary study, researchers were for the first time able to diagnose Creutzfeldt-Jakob disease in living patients.[75]
Astemizole has been found to have anti-prion activity.[76]
Whether prions cause disease or are merely a symptom caused by a different agent is still debated by a minority of researchers. The following sections describe several hypotheses: Some pertain to the composition of the infectious agent (protein-only, protein with other components, virus, or other), while others pertain to its mechanism of reproduction.
Prior to the discovery of prions, it was thought that all pathogens used nucleic acids to direct their replication. The "protein-only hypothesis" states that a protein structure can replicate without the use of nucleic acid. This was initially controversial as it contradicts the central dogma of molecular biology, which describes nucleic acid as the central form of replicative information.
Evidence in favor of a protein-only hypothesis includes:
A gene for the normal protein has been identified: the PRNP gene.[80] In all inherited cases of prion disease, there is a mutation in the PRNP gene. Many different PRNP mutations have been identified and these proteins are more likely to fold into abnormal prion.[81] Although this discovery puts a hole in the general prion hypothesis, that prions can aggregate only proteins of identical amino acid make-up. These mutations can occur throughout the gene. Some mutations involve expansion of the octapeptide repeat region at the N-terminal of PrP. Other mutations that have been identified as a cause of inherited prion disease occur at positions 102, 117 & 198 (GSS), 178, 200, 210 & 232 (CJD) and 178 (Fatal Familial Insomnia, FFI). The cause of prion disease can be sporadic, genetic, and infectious, or a combination of these factors.[82] For example, to have scrapie, both an infectious agent and a susceptible genotype must be present.[81]
Despite much effort, significant titers of prion infectivity have never been produced by refolding pure PrP molecules, raising doubt about the validity of the "protein only" hypothesis. In addition the "protein only" hypothesis fails to provide a molecular explanation for the ability of prion strains to target specific areas of the brain in distinct patterns. These shortcomings, along with additional experimental data, have given rise to the "multi-component" or "cofactor variation" hypothesis.[83]
In 2007, biochemist Surachai Supattapone and his colleagues at Dartmouth College produced purified infectious prions de novo from defined components (PrPC, co-purified lipids, and a synthetic polyanionic molecule).[84] These researchers also showed that the polyanionic molecule required for prion formation was selectively incorporated into high-affinity complexes with PrP molecules, leading them to hypothesize that infectious prions may be composed of multiple host components, including PrP, lipid, and polyanionic molecules, rather than PrPSc alone.[85]
In 2010, Jiyan Ma and colleagues at The Ohio State University produced infectious prions from a recipe of bacterially expressed recombinant PrP, POPG phospholipid, and RNA, further supporting the multi-component hypothesis.[86] This finding is in contrast to studies that found minimally infectious prions produced from recombinant PrP alone.[87] [88]
In 2012, Supattapone and colleagues purified the membrane lipid phosphatidylethanolamine as a solitary endogenous cofactor capable of facilitating the formation of high-titer recombinant prions derived from multiple prion strains.[89] They also reported that the cofactor is essential for maintaining the infectious conformation of PrPSc, and that cofactor molecules dictate the strain properties of infectious prions.[90]
Recent reports suggest that imbalance of brain metal homeostasis is a significant cause of PrPSc-associated neurotoxicity, though the underlying mechanisms are difficult to explain based on existing information. Proposed hypotheses include a functional role for PrPC in metal metabolism, and loss of this function due to aggregation to the disease-associated PrPSc form as the cause of brain metal imbalance. Other views suggest gain of toxic function by PrPSc due to sequestration of PrPC-associated metals within the aggregates, resulting in the generation of redox-active PrPSc complexes. The physiological implications of some PrPC-metal interactions are known, while others are still unclear. The pathological implications of PrPC-metal interaction include metal-induced oxidative damage, and in some instances conversion of PrPC to a PrPSc-like form.[91]
The protein-only hypothesis has been criticised by those maintaining that the simplest explanation of the evidence to date is viral.[92] For more than a decade, Yale University neuropathologist Laura Manuelidis has been proposing that prion diseases are caused instead by an unidentified slow virus. In January 2007, she and her colleagues published an article reporting to have found a virus in 10%, or less, of their scrapie-infected cells in culture.[93] [94]
Evidence in favor of a viral hypothesis includes:[95]
Recent studies propagating TSE infectivity in cell-free reactions[101] and in purified component chemical reactions[84] is thought to strongly suggest against TSE viral nature. However, some viruses, such as Poliovirus, have the ability to replicate in cell-free reactions.[96] [102] [103]
More recently, using a similar defined recipe of multiple components (PrP, POPG lipid, RNA), Jiyan Ma and colleagues generated infectious prions from recombinant PrP expressed from E. coli,[86] casting further doubt on the viral hypothesis. However, the infectivity reported in Ma et al. experiments could be explained by contamination,[104] as infectious material from scrapie infected mice was used to seed the reaction.[97]
The 'virino hypothesis' states that the TSE agent is a foreign, self replicating nucleic acid or nucleic acid fragment bound to PrP.[105] Many TSEs, including scrapie and BSE, show strains with specific and distinct biological properties, a feature that supporters of the virino hypothesis think prions do not explain. It tries to explain the resistance of the agent to radiation by suggesting that the agent's genome likely contains 50 nucleotides or less, thus making the agent's genome too small to be destroyed easily by ionizing radiation. It also tries to explain the lack of an immune response by proposing a host protein, PrP binds to and wraps around the nucleic acid, protecting it from digestion by nucleases and prevents the host from raising an immune response, since the protein/nucleic acid complex is seen as a legitimate part of the host. It may even explain the conversion of PrPC to PrPSc. However, the presumed scrapie-associated nucleic acid has not been identified, and physical or chemical evidence for its presence is lacking. A 2015 publication provides evidence for nucleic acid involvement in infectious agents structure.[106]
Spiroplasma is a cell wall deficent bacteria related to Mycoplasma, which some think may be the cause of the TSEs. The lack of a cell wall means they are not susceptible to conventional antibiotics such as penicilin, which target cell wall synthesis. Supporters of the Spiroplasma hypothesis think that there are holes in the Protein Only Hypothesis, and that the best way to explain the TSEs is the Spiroplasma. Frank O. Bastian, of Louisiana State University first discovered Spiroplasma-like inclusions in the brain of a CJD paitent during an autopsy in 1979.[79] He hypothesized that this bacterium could possibly be the cause of the TSEs. Since then, he has come out with several lines of evidence to support his hypothesis.Evidence in favor of the Spiroplasma hypothesis includes:[107]
Acinetobacter is a bacterium which some think is the cause of the TSEs. Evidence in favor of the Acinetobacter-autoimmunity hypothesis include:
While PrP is considered the only mammalian prion, prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer's disease, and Huntington's disease.[111] as well as some forms of Systemic Amyloidosis including AA (Secondary) Amyloidosis that develops in humans and animals with inflammatory and infectious diseases such as Tuberculosis, Crohn's disease, Rheumatoid arthritis, and HIV AIDS. AA amyloidosis, like prion disease, may be transmissible.[112] This has given rise to the 'prion paradigm', where otherwise harmless proteins can be converted to a pathogenic form by a small number of misfolded, nucleating proteins.[113]
The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP.[111] These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content. Recently, however, this has been shown to be false, with the spacing of prolines and charged residues having been shown to be critical in amyloid formation.
Recent bioinformatic screens have predicted that over 250 human proteins contain prion-like domains (PrLD). These domains are hypothesized to have the same transmissible, amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding seem to be particularly enriched in PrLD's, compared to other classes of protein. In particular, 29 of the known 210 proteins with an RNA recognition motif also have a putative prion domain. Meanwhile, several of these RNA-binding proteins have been independently identified as pathogenic in cases of ALS, FTLD-U, Alzheimer's disease, and Huntington's disease.
The pathogenicity of prions and proteins with prion-like domains arises from their self-templating ability and the resulting exponential growth of amyloid fibrils. The presence of amyloid fibrils in patients with degenerative diseases has been well documented. These amyloid fibrils are seen as the result of pathogenic proteins that self-propagate and form highly stable, non-functional aggregates.[114] While this does not necessarily imply a causal relationship between amyloid and degenerative diseases, the toxicity of certain amyloid forms and the overproduction of amyloid in familial cases of degenerative disorders supports the idea that amyloid formation is generally toxic.
Specifically, aggregation of TDP-43, an RNA-binding protein, has been found in ALS patients, and mutations in the genes coding for these proteins have been identified in familial cases of ALS. These mutations promote the misfolding of the proteins into a prion-like conformation. The misfolded form of TDP-43 forms cytoplasmic inclusions in afflicted neurons, and is found depleted in the nucleus. In addition to ALS and FTLD-U, TDP-43 pathology is a feature of many cases of Alzheimer's disease,Parkinson's disease and Huntington's disease. The misfolding of TDP-43 is largely directed by its prion-like domain. This domain is inherently prone to misfolding, while pathological mutations in TDP-43 have been found to increase this propensity to misfold, explaining the presence of these mutations in familial cases of ALS. As in yeast, the prion-like domain of TDP-43 has been shown to be both necessary and sufficient for protein misfolding and aggregation.[111]
Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation.[115]
See main article: Fungal prion. Fungal proteins exhibiting templated conformational change were discovered in the yeast Saccharomyces cerevisiae by Reed Wickner in the early 1990s. For their mechanistic similarity to mammalian prions, they were termed yeast prions. Subsequent to this, a prion has also been found in the fungus Podospora anserina. These prions behave similarly to PrP, but, in general, are nontoxic to their hosts. Susan Lindquist's group at the Whitehead Institute has argued some of the fungal prions are not associated with any disease state, but may have a useful role; however, researchers at the NIH have also provided arguments suggesting that fungal prions could be considered a diseased state.[116] Thus, the issue of whether fungal proteins are diseases, or have evolved for some specific functions, still remains unresolved.[117]
As of 2012, there are eight known prion proteins in fungi, seven in Saccharomyces cerevisiae (Sup35, Rnq1, Ure2, Swi1, Mot3, Cyc8, and Mod5) and one in Podospora anserina (HET-s). The article that reported the discovery of a prion form the Mca1 protein has recently been retracted due to the fact that the data could not be reproduced.[118] Notably, most of the fungal prions are based on glutamine/asparagine-rich sequences, with the exception of HET-s and Mod5.
Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion into a prion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions, though fungal prions appear distinct from infectious mammalian prions in the lack of cofactor required for propagation. The characteristic prion domains may vary between species—e.g., characteristic fungal prion domains are not found in mammalian prions.
|Fungal prions
|Natural host
|Normal function
|Prion state
|Prion phenotype
|Year identified
|Saccharomyces cerevisiae
|Nitrogen catabolite repressor
|Growth on poor nitrogen sources
|S. cerevisiae
|Translation termination factor
|Increased levels of nonsense suppression
|Podospora anserina
|Regulates heterokaryon incompatibility
|Heterokaryon formation between incompatible strains
|S. cerevisiae
|Protein template factor
|Promotes aggregation of other prions
|S. cerevisiae
|Putative yeast caspase
|S. cerevisiae
|Chromatin remodeling
|Poor growth on some carbon sources
|S. cerevisiae
|Transcriptional repressor
|Transcriptional derepression of multiple genes
|S. cerevisiae
|Nuclear transcription factor
|Transcriptional derepression of anaerobic genes
|S. cerevisiae
|Putative transcription factor


text:
Why Masdar is about more than realty
Plans for the construction of Abu Dhabi's ambitious eco city have been scaled back. But that doesn't diminish the wider purpose of the initiative: To preserve the UAE's energy-producer status after the oil runs out.
March 25, 2010 6:20 by Emily Meredith
When the price of sweet crude jumped in mid-February following tensions between the West and Iran over the country's nuclear program, many of today's nuclear producing countries had a glimpse of the future they are trying to avoid.
In the UAE, the government is aggressively pushing alternative energy through its state-backed companies. And although concerns over sustainability and the environment are frequently cited as the drivers for this diversification, the country's desire to maintain its energy-producer status even after hydrocarbons no longer dominate the energy field look increasingly important.
According to projections from the research organization Chatham House in London, most oil-producing countries will run out of oil by 2040. Iran and Kuwait are the exceptions, sitting atop their reserves for 20 years beyond that.
"I think that a lot of analysts see this coming and part of thinking about this now is preparing for the future in 20 to 50 years," said Theodore Karasik, Ph.D., the director for research and development at UAE based think-tank Inegma. "The energy dynamics of the situation will influence or create drivers to influence political agendas in the region. This is going to affect how businesses and politics are conducted between all the states around the Gulf."
Early this year, thousands of people gathered in Abu Dhabi for the third installment of the World Future Energy Summit's trade fair and energy-related panel discussions. In a futuristic booth complete with identically dressed models and individually wrapped dates, the government-backed Abu Dhabi Future Energy Company, known widely as Masdar, showcased the many tentacles of its sprawling projects, initiatives, educational programs, and investments.
Since then, plans for Masdar City, Abu Dhabi's clean energy community, have been scaled back under a review of the ambitious 'green' development. There will now be fewer buildings, and the structures will be built taller over a longer period of time, with technical features like the futuristic 'car pod' system scrapped.
But there is more to Masdar than a real estate development: It is not just another Emaar or Aldar. The company certainly has diverse investments, ranging from a company producing wind turbines in India, to funding Japanese venture capital firms investing in clean technology startups.
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text:
The whistleblower performs a valuable service in a world where large corporate entities have a lot of power, but not always a lot of moral restraint in protecting and furthering their interests.
But things don't always go well for the whistleblower – names like Julian Assange and Edward Snowden immediately spring to mind - and there's a sense in which the whistleblower is working in a tradition that goes all the way back to the ancient Hebrew prophets.
- Producer
- Wendy Barnaby
Comments (13)
David Miller, Atheist Society :
15 Feb 2014 7:13:13pm
We atheists take delight in pointing out the inconsistencies and contradictions within Christianity.
But we must acknowledge that it is these very disparities which have given Christianity the ability to adapt to changing circumstances over the millennia.
Variant impulses within Christianity have often been the voices of both the repressive as well as the libertarian elements within society.
Paul :
15 Feb 2014 11:30:37pm
This was an enlightening program about a difficult subject. A lot of people working in large organisations (whether public of private) have little real appreciation of the fact that all organisations are actually highly political entities that consist of complex matrices of power and authority – both official and unofficial, visible and invisible. (I don't mean party political).
Overlaid on this are the myriad personality types of the people and managers who work in the organisation. Many employees and managers will be genuine individuals trying to do their best, but some will be snakes in suits (or overalls), and others will be just plain incompetent. Survival in this corporate jungle depends on how well one can identify friends and foes and decide what defensive action should be taken. If you fail to do this then working life can be brutally dangerous, as it turned out for the two unfortunate individuals who feature in the program.
I spent much of my working life in the airline industry and over several generations this industry has been forced by the reality of the risks involved in air operations to develop formal safety management systems which require mandatory reporting of safety incidents by all operational staff. These reports can be de-identified if the staff member requests it. The data stream thus obtained is large – I can assure you – but this is carefully quantified, analysed, and tracked, so that organisational and operational weaknesses are quickly identified and remediated. That is why in a country like Australia where you have over 30,000 airline flights a month we don't have regular air disasters as they do in some countries. A formal safety management system such as the one described is mandated by regulation in most Western countries, although actual implementation may be variable.
The difficulty in the two cases cited in the program seems to have been that the management of both the organisations involved had no idea that they needed to do something similar in order to encourage staff to provide genuine feedback on organisational failures, or if they did have such a program, they were just shams for window-dressing. The authority for these sorts of programs has to come from the very top of the management pyramid – that is, it needs to be mandated (and periodically scrutinised) by the board of directors. To actually make such a system work however, is another question, because a culture must be diligently promoted to ensure that all employees take it seriously. That is no easy task.
The consequences of management failure to genuinely implement such a "safety/quality management system" will inevitably result in a major organisational disaster of some description. It happens often in industry and public service organisations – just keep reading the newspapers and when you see it reported next, remember the two unfortunate whistleblowers in the Encounter program.
Ann Schofield :
16 Feb 2014 4:14:01pm
I realised that I am whistleblower type and that it has been difficult for me to cope with work situations which I know to be wrong and not speak the truth about them. Thanks for the programme. I understand my life and work more now.
elizabeth Re :
16 Feb 2014 7:24:47pm
Whistleblowers are encouraged by the media and the system particularly in the public service to raise concerns / inappropriate activties / bullying / harrassement / exclusion etc.
However, when you raise these concerns you are then targeted and through the system of lies and corruption they turn on the person who was honest with concerns and frame them.
The PID has their hands tied so you are then persecuted and with the personal strength and the finding of an honest and like minded person at the PSC then we can only hope that the truth will be revealed.
However at what cost? and the bullies and their faceless men flourish.
Peak Warming Man :
17 Feb 2014 10:47:58am
In the Union movement people who break the code and rat on their colleges are known as scabs not whistleblowers.
Kaz from the North :
17 Feb 2014 1:29:53pm
While whistleblowers can and often do perform a valuable function, not all those who claim whistleblower status have honourable intentions. "Whistleblowing", so called, can also be used for malicious attacks on innocent people for reasons that have nothing whatsoever to do with protecting companies or doing good. Sadly it seems that the status of whistleblower can be invoked to deny the subject of allegations the presumption of innocence; a right that should be inalienable. There is a delicate balance to be called for here - the right to speak out, but also the need to be held accountable for what is said by those who would claim (sometimes rightly and sometimes not) the status of whistleblower.
Ron Tolkien :
19 Feb 2014 1:47:52pm
Unfortunately your thinking is another excuse used by the powers that be to destroy the credibility of anyone 'whistling'. What you ignore is that whistleblowers have evidence. Evidence in the form of facts; not hearsay, tittle tattle or spite.
Stephen :
17 Feb 2014 1:35:22pm
Despite being at all times hugely resistant to linking any darned thing back to the Hebrew prophets, I thought this was a terrific program that delivered unexpected insights.
Adam :
17 Feb 2014 5:55:41pm
Whistle-blowers are a necessary part of a democracy, unfortunately the government at all levels job is to shut them down.
The government is completely corrupt and hates it when its crimes are publicly disclosed.
Look at Julian, he is being hunted off the face the earth, not a mention of the murderers he exposed. These murderous invaders are kicking back protected by government.
The government will protect corrupt public servants as long as they can, it is not until the story makes continuous headlines in the media cycle that they do anything.
The Ombudsmans and Public Service Crime fighting (CMC) bodies job is to bury whistleblowers, literally.
Look at the Qld CMC. 13,000 complaints against corrupt public servants last year, 100 investigations. The Premier can cover up 99.9% of cases. The only ones he prosecutes are for political purposes.
It's a complete joke. Look at GLORICIDE and the trail of blood that goes right to the top of government, who cares? Not the burecrats or politicians or the ABC.
val u :
19 Feb 2014 1:54:26pm
Amazing validation, it is true that telling power in the workplace the truth is because I assumed they didn't know. I thought I had a moral imperative to help them and society. It is only after having my career destroyed, my reputation shot, suffering major depression that I learnt: once you lose your health they don't need to anything else to you, you they can watch you do it all to yourself.
I was told I was political but I don't belong to any party, or even remember politicians' names. I was called naive, but brushed that off because I have a certificate stating I have an IQ of 130.
Now when other people tell me about some workplace misrepresentation, fraud, bullying, mismanagement, plagiarism etc, I tell them everyone already knows - perhaps you need to learn to manage your honest personality?
Regarding religious people, they need to be aware that God is whatever binds their conscience, and anyone who abdicates their conscience to keep a job is suffering from idolatry - their boss is their God.
Thanks for a great radio program, no doubt you will have helped many people understand about cultures of secrecy.
Julian Asaint :
19 Feb 2014 5:12:12pm
Whistleblowers working within the political system have the toughest time of all. Apart from the usual corporate distaste for boat-rockers, this antagonism is hugely magnified in the political sphere, since politics itself is, fundamentally, about the management of deceit. So, any insider exposing this deceit is automatically viewed as a traitor, and treated accordingly.
Australia's MSM is so cosily embedded in the political system that this often outrageous punishment is never judged – reported maybe, but not judged. To give a classic example from recent times: when Andrew Wilkie blew the whistle on the blatant lies peddled by the Coalition in "selling" the need for the Iraq invasion, the slime-balls immediately slithered into action – leaking rumours to their favourite sycophantic lackey-hacks, smearing Wilkie - that he was mentally unstable, his marriage was on the rocks, etc.
For those holding the levers of power, there are never any repercussions for this type of outrage, and with a complicit MSM they will always have this blank cheque in their dirty tricks bag.
Pilot :
19 Feb 2014 6:07:08pm
There was only ever one real Christian and they crucified him!
Lizard Liz :
20 Feb 2014 4:14:15pm
Every single one of those bully nurses at Stafford Hospital should have been sacked and thrown out of the nursing profession. A high and genuine level of compassion is not just a nice thing to have in a nurse, it is an essential requisite for anyone to be employed as a nurse.
I've noticed that there is a Wikipedia page for the "Stafford Hospital Scandal" and there has been over a million pages written about the problems of poor care there in that period, and recommendations made and criticised, but I've got to wonder whether these scandalous situatios that lead to the need for whistleblowers to speak out could simply be the result of the wrong types of people being hired and promoted. Instead of focusing on regualtions and management, do we need to take on the concept of an immune system for organizations? How can we keep the wrong kinds of people outside of the organization, and how can we identify them and control them if they get in? What can good people do when an organization is irretrievably infected and infiltrated by the wrong kinds of people? How many businesses and public institutions have the equiavalent of AIDS?


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janelle warden
member for 6 years, 1 month, 4 days
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I have been doing genealogy since 1983 and full time since 2004. I do enjoy taking trips for genealogy and walking around cemeteries looking for family even as far away as Auckland, New Zealand. So much can be learned just from grave photos.
Find A Grave has really been helpful in locating some of the graves. You may copy photos and genealogy information for your family research ...all I ask is that you remember where you got them in case someone needs a source.
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Messages left for janelle warden (115)
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RE: Sarah Steele Farrar
Hello Janelle - sorry but I am not related. Do you know where she died? I don't see her death record in NYC databases. Best, Cara
Added by
on Mar 28, 2016 7:36 AM
Wallace G Lane Jr
RE: Robertson surname
Robert A. Robertson was interred it the Robertson/Morrell family lot; there is a single central monument on the lot and his name does not appear on it. Walter & Mary Robertson.
Please submit photo request for the other Robertsons you are looking for.
Thank you.
Added by
Wallace G Lane Jr
on Feb 24, 2016 2:52 AM
sherri schaefer bagby
Thank you for creating and processing updates for Ryland family memorials !
Added by
sherri schaefer bagby
on Jan 14, 2016 7:45 AM
Ann Gardner
Hi, --- I received your message about the parents of Isaac Bacon, b. 1818. If you have viewed the Ancestry.com family trees, you will know that there are at least 3 different fathers listed for him. The Walker Family Tree has quite a few sources and lists his parents as Jesse Bacon, 1790 PA - 1819 TN, and Elizabeth Pritchard / Prichett, 1790 - 1851 AR. Several other trees list his parents as Jonathan Bacon & Mollie Adams. Another tree has Aaron Bacon as Isaac's father.
--------- I'm not related and mainly researched George Bacon because he served during the Civil War. George's parents were together in Barton County, Kansas from 1875 - 1895. I added a little more information to the memorial for George Bacon, but I don't think I can help you determine who the parents of Isaac were ! It looks like an on-going discussion and perhaps something definitive will turn up.
Added by
Ann Gardner
on Oct 30, 2015 7:03 AM
RE: Earl Murray
Thanks for sharing with me how you have connected family members. It must be very satisfying to know where your kin went. I always wonder why people would move to Walla Walla, Washington, "back then", but I guess I will never really know! I hope they had a good life while here!
Added by
on Oct 28, 2015 10:21 AM
Kathy Holland, Gates to the Past Genealogy
RE: Shipley grave
There are nearly 300,000 people buried at this cemetery. So, it's huge!
For the other Shipley's that you are looking for, perhaps you can make a photo request for them. The Forest Lawn website does have a search engine to look people buried at their Los Angeles-area cemeteries.
Added by
Kathy Holland, Gates to t...
on Oct 07, 2015 9:38 AM
Kathy Holland, Gates to the Past Genealogy
RE: Shipley grave
Just the two that I saw. This is a really huge cemetery, so the others could be spread out over the entire cemetery.
Added by
Kathy Holland, Gates to t...
on Oct 06, 2015 8:46 PM
RE: cora deakins
Rowe Cemetery is on the Elizabethton side of Johnson City, TN. Go out Watauga St. toward Elizabethton. "Roweland" Drive will be on the right off Watauga. Kennametal plant is on Roweland Drive. Go to the end of the street. Alemite is on the right. The cemetery is at the extreme back right corner of the property across from Alemite, at the back of the property of a distribution place called Jammin Butter. Cemetery is about 300-400 feet back off Roweland.
Google Map. 36.352510, -82.315179
Added by
on Oct 02, 2015 3:53 PM
Bob Copeland
Hi Janelle,
Just received your (EDIT notice from Find A Grave) I need a little help I guess. I am going to send you an email & just thought I would give you a heads up.
Thanks for contacting me
Added by
Bob Copeland
on May 31, 2015 9:42 AM
Marjorie and Alexander Godfrey
Janelle, Unfortunately, the headstone for Marjorie and Alexander is broken and there are apparently no names on it. There are two small markers for Andrew d 1895 and Annie d 1917 Godfrey. I placed photos on their respective memorials.
Pat Shearer
Added by
on May 29, 2015 8:58 AM
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text:
|Comment posted by steve and carol vardy at 15:16 on 7th Jun 2009
Post Yours Here
|steve and carol vardy says:
|we arrived at the hotel around 2.30 on fri afternoon for a 2 night stay,..at reception we were met by dougie.who immediately offered us a drink of tea or coffee..one of the staff took our case up2 our room while we had our drink, both mornings there was free papers for the guests and tea and coffee to drink all day for free..the breakfast were really nice as was all the staff...the rooms were nice and clean..we have stopped in many hotels in blackpool over the years but we must say that this is the friendlyist and best run..nothing is too much trouble for any of the staff.....well done to all at the canasta...we will be back...
|Our Reply:
|well thanks VERY much for that Steve and Carol. It's nice to be appreciated!!! I'll let the team know they're doing a good job!!
|Comment number 836 of 1166
|Comment posted by Becky at 22:38 on 3rd Jun 2009
Post Yours Here
|Becky says:
|Hi Doug and Swampy, sorry our comment is late but we would like to once again thank the Canasta team for the great holiday we had in May. Also the new year break was the best ever party we've been to. The buffets were out of this world, there was food for everyones taste and it was beautifully presented, excelling anything we've seen prepared before. A bit of advice for all you holiday makers, if you are looking for an enjoyable holiday Canasta is the place to stay, with tasty food, great company, comfortable and spotless rooms, brilliant entertainment and reasonable bar prices. It has become like home from home and we won't be staying anywhere else. Thanks Doug & Swampy, hope to see you for the illuminations. Becky, Lynn, Paddy (Taffy tom tom) & Cath xxx (sorry about the essay)
|Our Reply:
|Hahaha - thanks very much for that kiddo!!!
|Comment number 835 of 1166
|Comment posted by mr. bussey at 17:07 on 26th May 2009
Post Yours Here
|mr. bussey says:
|we stayed at the hotel over the may break, we could not fault the service or the staff, very friendly and eager to please. we will visit again. thanks
|Our Reply:
|Thanks very much!!
|Comment number 834 of 1166
|Comment posted by Julie at 12:35 on 11th May 2009
Post Yours Here
|Julie says:
|Yet again we had a wonderful time at the Canasta! What can I say but the best time to be had by all when you stay here! Thanks Doug, Mandy and staff for a brilliant time and special thanks to Mandy for getting the karaoke out when it was very quiet! Had a real good belly laugh on Saturday and met some real nice people.... See you in October.Julie & Steve
|Our Reply:
|Cheers Julie and Steve....looking forward to seeing you again!!!
Doug & Mandy
|Comment number 833 of 1166
|Comment posted by shirley morley at 21:04 on 26th Apr 2009
Post Yours Here
|shirley morley says:
|Just wanted to say thanks to Doug, Mandy and staff for making us feel so welcome when we stayed on Friday. Just wished we could have stayed longer. The karaoke was really entertaining lol. There wasn't many of us, but the atmosphere was better than most full. Was nice making new friends, and hope we can get back to see you all again soon, Steve & Shirley
|Our Reply:
|Cheers Shirley and Steve - thanks for your business and campany - see you again
|Comment number 832 of 1166
|Comment posted by Julie at 19:16 on 25th Apr 2009
Post Yours Here
|Julie says:
|Hi Doug and Swampy, just looked at your pics from Paris, they are great! Glad you had a good time there. See you soon! Julie & Steve
|Our Reply:
|Hi Julie. Yes...Mandy calls me David Bailey now!! Thanks...see you on the 6th May
|Comment number 831 of 1166
|Comment posted by val and phil malbon at 17:32 on 17th Apr 2009
Post Yours Here
|val and phil malbon says:
|We have just had a lovely two night stay. Everything was excellent. Breakfast was fantastic and we were made to feel very welcome. Never stayed in Blackpool before but will definitely return.Thanks to all the staff. Will see you again.
|Our Reply:
|Thanks for that Val & Phil..I'll give the staff a thumbs up!
|Comment number 830 of 1166
|Comment posted by becky at 21:16 on 15th Apr 2009
Post Yours Here
|becky says:
|Hiya Doug, jus booked up for 1st of may, cant wait come back, taffy erm i mean paddy has had his tomtom updated so hopefully wont get lost this time lol xx
|Our Reply:
|LOLOLOL!!!! There's only one Taffy Tom Tom! Cheers, The Bexter....see you in May!!
|Comment number 829 of 1166
|Comment posted by Jonathan and Claire at 20:08 on 13th Apr 2009
Post Yours Here
|Jonathan and Claire says:
|Hi thereAnother great stay in February - food was excellent, staff as friendly as ever, room was perfect.THANK YOU!!!! Cant wait for our next stay later in the year!!!
|Our Reply:
|Thanks Jonathan and Claire
Look forward to seeing you later in the year
|Comment number 828 of 1166
|Comment posted by Chris Davey at 15:24 on 8th Apr 2009
Post Yours Here
|Chris Davey says:
|Hi, I have enjoyed watching trams on the webcams, but have had problems connecting in the last few days. I was just wondering if there is a problem with them?This comment doesn't need to be published on the site, feel free to email me.
|Our Reply:
|Hi Chris....I'll answer this here just so everybody knows because I may not get chance to update the webcam page until next week. The webcams are offline. The computer which works them has decided its had enough (not surprising because its been on 24/7 for 5 years now...and probably only a dozen reboots...)
Tramspotters will be pleased to know that we are upgrading the system to include another webcam and MAYBE one that you can rotate yourself....it will be a week or two yet though.
|Comment number 827 of 1166
|Comment posted by Tracey Lord at 10:17 on 4th Apr 2009
Post Yours Here
|Tracey Lord says:
|Had a two night stay 27,28th March great hotel friendly and welcomming,excellent breakfast,bar very reasonable cant wait to go again definately reccommended.
|Our Reply:
|Thanks for that Tracey!!!
|Comment number 826 of 1166
|Comment posted by suranne & ali at 18:28 on 5th Apr 2009
Post Yours Here
|suranne & ali says:
|Wot can i say yet another great weekend to celebrate doug's 50th and his brother david,it was nice meeting them again. Thanks for a great stay and enjoyed the meal.See you and Mandy in about 4 weeks would be sooner if i got my way. Thanks again
|Our Reply:
|Cheers Suranne and Ali and THANKS for my pressies - lovely!! See you soon then!
|Comment number 825 of 1166
|Comment posted by DONNA MORRISON at 01:10 on 29th Mar 2009
Post Yours Here
|DONNA MORRISON says:
|Our Reply:
|Hello Donna!!!
See you in July!!
|Comment number 824 of 1166
|Comment posted by Ann Winstanley at 19:21 on 14th Mar 2009
Post Yours Here
|Ann Winstanley says:
|Clean and comfortable, just like home from home with all the tea I could drink. We REALLY enjoyed it and next time we want to go away for a short break my vote will be Blackpool and the Canasta!
|Our Reply:
|Cheers Ann - hope to see you later in the year!!
|Comment number 823 of 1166
|Comment posted by C Foster at 10:19 on 13th Mar 2009
Post Yours Here
|C Foster says:
|Great weekend, great hotel, great breakfast. Loved the free tea and coffee all day (sorry if we abused that!)Lovely clean friendly hotel and great value too! We'll definitely be back!
|Our Reply:
|Thanks for that - we'll look forward to seeing you again
|Comment number 822 of 1166
"Blackpool is bright busy and noisy, yet step into the confine of the Canasta H4otel, it's very relaxing, drinking at the table watching the sun go down. "


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We offer a rundown of media coverage related to the new multimillion dollar Asia Society buildings opening soon in Asia and the United States.
In today's New York Times, former Harvard academic Paul V. Kane writes that the United States should terminate its defense arrangement with Taiwan in exchange for China forgiving the $1.14 trillion of U.S. debt that it holds. Kane argues that this move would be:
Before he was featured on the front page of the New York Times, the 37-year-old novelist spoke at Asia Society in New York. Click the headline to read and watch.
Deng Xiaoping biographer Ezra Vogel discusses to what extent the Tiananmen Square incident tarnished Deng's record of reform.
The New York Times devotes major coverage to Asia Society Museum's upcoming exhibition The Buddhist Heritage of Pakistan: Art of Gandhara today, in a piece with enough international intrigue and behind-the-scenes maneuvering to fill a thriller novel.
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Reviews - BEST WESTERN Heath Court Hotel3
Moulton Road, Newmarket, CB8 8DY
Price FromView Rooms
Customer Reviews
Our reviews are from genuine LateRooms.com customers. We verify that the customer has stayed before leaving a review.
Very Good
58% would recommend it to a friend
Customer service
Food quality
Room quality
Central location, beautifully set away from noisey traffic
You would not think that you were so close to the high street, which comes alive so early in Newmarket.
We came out of the hotel and walked a 100yds to the bottom of the long mile gallops where there were strings of racehorses out for their early morning gallops. What a sight, must be even more amazing on a spring morning. Polite service with very good parking facilities. Couldn't,t fault the breakfast Clean bright hotel, although the room was very homely. Large comfortable room with no noise - great. We would definitely use this hotel next trip to Newmarket
Read More Less
Was few times before.
Still everything excellent.
Read More Less
Room very nice but bathroom poor
The room was very nice but the bathroom really let it down, it smelt of mould and the shower was very poor.
I was happy with the value for money of the room but the bathroom/shower really pulled it down
Read More Less
Get the basics right
Bed - mattress shot
Room too hot - no way to open window
Doors slamming no soft closures - woken up at 5am by next door's door slamming
TV not working
Slightly dated and expensive for the quality of the room.
Great customer service and excellent location though.
Read More Less
great hotel
This is a lovely little hotel, ideally placed near the High Street, very good staff, fantastic bedrooms, cannot find a single fault.
If only all hotels could be as good as this it it would be a very easy way to travel around the country knowing that when you arrived there would be no problems waiting for you!. 10/10 is the only score I can award. Thank you.
Read More Less
Very good
Good location in the centre of Newmarket, breakfast very good value and room had everything you would need.
Read More Less
National Stud Visit
Fantastic location for us personally and having asked for a room overlooking the gallops - we could not have wished for better.
The staff were friendly and informative, and the food was very good. The only slight criticism we had was the room was so hot - but then again - all hotel rooms are aren't they. So based on that it is equal to other hotel rooms we have stayed in. At least in this one we could open the windows wide to let some air in.
Read More Less
newmarket for racing
good location just off the high street friendly staff must have the newmarket sausage for breakfast gallops just up the road and horse racing museum five minute walk would stay here again
Dated and expensive
Drunks slamming doors at 1am also women fighting and assailing partner in car park
If you want a quiet nights sleep avoid this place
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