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Home | Wire | New Resolutions for a New Presidential Term
New Resolutions for a New Presidential Term
12/03/2020Gary Galles
Most Americans probably thought they would know who the President will be shortly after the ballot boxes closed. But after three weeks, the results are still somewhat in doubt. That has thrown a wrinkle into the usual pundit calendar, focused on what the loser should have done, what the winner did well and now should do, and other lessons to be learned. And I have noticed that our unusual circumstances have led to very little consideration of what would be wise, regardless of the ultimate winner.
In particular, I have seen very little commentary that begins from what the defensible, moral role for government is. Consequently, it seems to be worth considering what valuable new term resolutions (rather than new year's resolutions) might move America closer to, rather than farther from, the ideals that gave it birth, no matter who is in office.
Such resolutions require that we realize the centrality of "liberty and justice for all" to any good and moral life. And F.A. Harper provides us a good place to turn, because, he recognized that "The great social problem of our age is that of designing the preventive medicine that will stop the eroding liberty in the body politic." And in his Liberty: A Path to its Recovery, Harper offers us useful insights into resolutions that would advance liberty, and with it, justice. His chapters on "Special Privilege" and "Recovering Liberty" offer the key.
This should be the guiding rule: Grants of special privilege to any person or group of persons should be denied, because these grants can be made only by infringement on the rights of others--on liberty. "Benefits" for this and "benefits" for that should be denied. The granting of any of the so-called benefits by government violates the foundation of liberty--that a person should have the right to the product of his own labor, and the right to dispose of it or to keep any part of it as he desires.
Special privilege is any item of income or of position in the market…where the amount paid and received fails to reflect the judgment of "the judges of the market place" as to its worth…where the judgment of the voters in the economic market place is overruled by their political servants.
The government, having no independent source of income except what it takes from the incomes of the citizens, cannot give a "benefit" to any one person…without correspondingly denying another the right to the product of his labor.
"The power to tax is the power to destroy." Special privilege is of necessity the process of destruction in operation, always and everywhere.
The basis of a free society is the absence of parasitism. ..[Therefore, we should] encourage a complete about-face in policy…oppose special privilege for each and every person and group, rather than try to acquire compensatory parasitism for one's self?
If the principle of "no special privilege" is to prevail, it will be necessary to support that principle in its every application as a principle. It should be adopted as a uniform rule, across the board.
Recovering Liberty
It is important to be ever mindful that the foundations of liberty embrace the foundations of justice and morals, and of a moral civilization.
If lost liberty is to be regained, the general course to be followed is simple. Liberties that have been taken away from individuals must be restored; there can be no other answer.
Weeds the size of sequoia trees have grown up in our vineyard of liberty, and one cannot eliminate a forest of sequoia trees by using a jackknife at the tips of the branches.
The hope of citizens' supervision of governmental expenditures…by the "democratic process" is a futile hope…It is foolish to expect to recover liberty in that manner…The hope that [Americans] can maintain control over such a stupendous expenditure, merely by the device of a few of them going to the polls once in a while, is pure fantasy. Until it is realized to be a fantasy, we are destined to pursue futility, buoyed only by a little fleeting hope every two or four years at election time.
When once the power of free choice in the spending of their incomes has been abandoned by the citizens, and these economic rights surrendered to government, their liberty will have gone with it…Either you spend your own income as you deem best or someone spends it for you in some way that he deems best.
After liberty has been lost beyond a certain point, its recovery is difficult…The peaceful solution is to unwind the accumulated powers of government over the lives and incomes of the citizens. Eternal vigilance is not now enough; it is too late for that to be adequate, for the same reason that eternal vigilance of the barn door is no help after the horse has been stolen. Nor is the changing of top personnel in the government…any answer to the basic problem. The gaining of better administration of an evil in the form of unwarranted power is a victory without virtue. The most efficient and best possible administration of slavery will not transform it into liberty.
Unwinding an illiberal government…the principle that should guide the process is: No special privilege, no trading of special privileges.
When the advocate of liberty speaks with disfavor about some program that would violate liberty, he is likely to be met with…"but how do you propose that the program be set up?" The answer is that, consistent with liberty, you would have no "program"…To one who believes in liberty, liberty is a positive program of the highest order. To one who believes otherwise, the only "positive" program is that which is destructive of liberty.
To one who has acquired a mastery of the subject of liberty…action consistent with liberty will become a positive program, supported by considered reasons. He will know why the so-called "positive" programs, currently so popular, are programs that destroy liberty. Then…he will take a clear and firm position against each and every means of destroying or diluting liberty.
This method is…slow. But there are no shortcuts to liberty. Shortcuts taken in a haste for action usually violate the basic tenets of liberty in the process, and for that reason they lead one further from his intended goal.
Understanding [is] the only route to correct action. Nothing else will serve. If this process seems hopelessly slow, there should be the sustaining faith that liberty is in harmony with truth, and with the intended design of the human social order.
Truth has a power that cannot be touched by physical force. It is impossible to shoot a truth.
In Liberty: A path to its recovery, F.A. Harper claimed that the "The lover of liberty will find ways to be free." That love of liberty is the sine qua non ("without with not") of slowing or overcoming the government juggernaut that continues to erode our freedoms. Knowing that, Harper offered us the core of what could actually succeed in expanding liberty--eliminating special privilege. As he noted, we may hate that such progress would be slower than we wish, but slow progress toward liberty is far better than either no progress or efforts that are at variance with the liberty we want to restore. And those words are worth thinking about if we want the coming administration to represent progress rather than regress.
Gary Galles
Gary M. Galles is a Professor of Economics at Pepperdine University and an adjunct scholar at the Ludwig von Mises Institute. His research focuses on public finance, public choice, economic education, organization of firms, antitrust, urban economics, liberty, and the problems that undermine effective public policy. In addition to his most recent book, Pathways to Policy Failures (2020), his books include Lines of Liberty (2016), Faulty Premises, Faulty Policies (2014), and Apostle of Peace (2013).
Note: The views expressed on Mises.org are not necessarily those of the Mises Institute.
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Q: What exactly does this Batch Scripting syntax do? SET jobnumber=%CD:~6,6%

While I am familiar with the CD command, I have never seen this particular syntax before and I can't manage to hunt down the exact purpose. The closest thing that I have found is:
CD /d "%~dp0"

-which merely performs a CD to the location of the batch script file. I can't find anything on the exact syntax that is shown in the first example, however. In the batch file, the variable is later called like so:
SET filepath=C:\info\jobs\%jobnumber%

The job folder contains several dozen subfolders, all of which have a six-digit name. The script was never completed so there is nothing left to go on, leaving me in a state of extreme curiosity. Ideas?

A: The %CD% variable contains the current directory.
The other syntax specifies substrings for an expansion.
(from set /?)
%PATH:~10,5%

would expand the PATH environment variable, and then use only the 5
characters that begin at the 11th (offset 10) character of the expanded
result.  If the length is not specified, then it defaults to the
remainder of the variable value.  If either number (offset or length) is
negative, then the number used is the length of the environment variable
value added to the offset or length specified.
%PATH:~-10%

would extract the last 10 characters of the PATH variable.
%PATH:~0,-2%

would extract all but the last 2 characters of the PATH variable.

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Business analyst Ben Stein on Wednesday said prohibiting the AR-15 would be "a damn smart thought," and called the weapon utilized by the mass shooter a week ago in Florida to kill 17 individuals, an "amazingly enchanting weapon" that makes "a man who's a major geek have the capacity to go into a firearm shop, get it, turn out feeling like he's a Rambo," as indicated by a report in Mediaite.
The AR-15 is a self-loading rifle that has been utilized by various shooters to butcher individuals in Newtown, San Bernardino, and Las Vegas. Nikolas Cruz, 19, bought his lawfully yet then utilized it to weapon down understudies at Marjory Stoneman Douglas High School in Parkland, Florida.
"There's no motivation to have it," Stein said amid a meeting with Fox News' Neil Cavuto.
On Wednesday, he composed an article in the American Spectator saying the ideal opportunity for regular people to claim AR-15's is finished.


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City breaks in Spain are good value for money. It does not matter if you are coming to party in Madrid, or go rambling in Barcelona, self-catering villas in Spain represent excellent value for money. This is a great country to visit at any time of the year, and you will soon realise how much there is to do and see in Spain. Are you not quite sure what to decide or where to go for your holidays? You can take a look at Interhome's cheap last minute deals to Spain for inspiration.
The climbers and hikers amongst you will plan their holiday villa in Spain not too far away from the Sierra Nevada, the mountains in the south and east of Andalucia with its many peaks above three kilometres. Wherever you go in Andalucia, the landscape will not bore you.
Near Valencia, and then about 200 kilometres from the Mediterranean coast you will find the beautiful holiday islands of the Balearics. Of course everyone knows the famous Mallorca, but also the smaller Menorca is very special and should be considered if you are looking for a holiday villa in Spain.
These peaks are Gran Canaria, Tenerife, Lanzarote and Fuerteventura, volcanic islands that form the Canary Islands together with lesser known islands such as La Palma and La Gomera. Thanks to their wonderful climate, beautiful beaches and nature and the almost alien appearance of the volcanic landscape, the Canary Islands are a wonderful choice if you are looking for a holiday rental or villa in Spain.


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CRONICA DE UNA MUERTE ANUNCIADA ANALISIS PDF
Main Ideas. Here's where you'll find analysis about the book as a whole, from the major themes and ideas to analysis of style, tone, point of view, and more. ANALISIS DE LA OBRA CRONICAS DE UNA MUERTE ANUNCIADAENSAYO MUERTE ANUNCIADA DE SANTIAGO NASAR Esta novela está basada princip.. . Chronicle of a Death Foretold is a novella by Gabriel García Márquez, published in It tells . Gabriel García Márquez: Crónica de una muerte anunciada. Analysis and quizzes for Chronicle of a Death Foretold by GradeSaver.
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In real life, they were simply brothers. No one believes the threat because the brothers are such "good people", or they interpret the threat as "drunkards' baloney". The bishop's boat passes by the town without stopping even though people have been waiting for him with various gifts. The murder is brutal as Santiago carries his own mudrte and enters the back door of his home.
Since the brothers had announced their plans to kill Santiago at the meat market and the milk store, the news spreads through town, but no one directly warns Santiago. He collapses in his kitchen and dies. InGraciela Daniele adapted it into the Tony Award -nominated Broadway musical of the same namewhich she also directed and choreographed.
It tells, in the form of a pseudo- journalistic reconstruction, the story of the murder of Santiago Nasar by the two Vicario brothers. The murder of Santiago Nasar is described. His mother, who is finally told, believes he is inside the house and, therefore, bars the front door to which Santiago is running while being chased by the Vicario brothers.
This page was last edited on 24 December ua, at This doesn't mean that anyone who uses your computer can access your account information as we separate association what the cookie provides from authentication.
The bride was determined to have had relations with her former boyfriend, who was consequently pursued and murdered by the bride's two brothers in order to avenge the family's xnunciada. The non-linear story, told by an anonymous narrator, begins with the morning of Santiago Nasar's death.
In a somewhat spurious manner, she reveals the man to be Santiago. TV series Capadocia He is repeatedly stabbed as he attempts to enter his home, over twenty times total with seven fatal wounds, as they discovered in an ill-performed autopsy performed by the priest.
LATIHAN FARTLEK PDF
Transient cookies are kept in RAM and are deleted either when you close all your browser windows, or when you reboot your computer. Bayardo San Roman leaves mherte as well; his family comes by boat and picks him up. Santiago becomes disoriented from the news and starts to run home.
Retrieved from " https: There are a few key differences in the action of the story and what took place in reality.
Analisis de Cronica de una Muerte Anunciada : Eframn Bahamsn :
Croncia proceed to the meat market in the pre-dawn hours to sharpen their knives, and announce to the owner and other butchers that they plan to kill Santiago. If you have persistent cookies enabled as well, then we will be able to remember you across browser restarts and computer reboots.
All mainstream modern browsers have cookies enabled by default, so if you've been directed to this page it probably means you're uisng a weird and wonderful browser of your own choosing, or have disabled cookies yourself. When the expiry date is reached your computer deletes the cookie. For other uses, see Chronicle of a Death Foretold disambiguation.
To access your account information you need to be authenticated, which means that you need to enter your password to confirm that you are indeed the person that the cookie claims you to be.
Let's connect Contact Un Facebook Twitter. The book delves into issues of gender and chastity as well.
I hope they kill you! He misses the note on anuncaida floor that someone has left with a warning and details anjnciada the Vicario plan. By using this site, you agree to the Terms of Use and Privacy Policy. Nevertheless, they yell their plans to kill Santiago. Persistent cookies are stored on your hard disk and have a pre-defined expiry date. Even the priest later confesses, "I didn't know what to do Two hours after the wedding, Angela was dragged back to her mother's home by Bayardo because she was not a virgin.
After a beating from her mother, Angela is forced to reveal the name of the man who has defiled her purity and honor.
04 101V5 PDF
Analisis de Cronica de una Muerte Anunciada
He does nothing more. At the end of seventeen years, Bayardo returns to her, carrying all of her letters in bundles, all unopened. The narrator explores the circumstances surrounding his death by meticulously collecting the testimonials of the villagers who were present during his murder and exploring the seeming contradiction of a murder that was predicted in advance. Santiago Nasar, for example, exhibited sexism at several points during the novella, even threatening to rape the daughter of his servant in order to "tame" her.
The central question at the core of the novella is how the death of Santiago Nasar was foreseen, yet no one tried to stop it. Clotilde asks everyone she sees to warn Santiago, but people do not warn him for analosis reasons: Santiago took over the successful family ranch after the death of his father Ibrahim, who was of Arab origin.
Análisis de Crónica de una muerte anunciada : Gabriel García Márquez (Colombia)
Meanwhile, Officer Leandro talks with Colonel Aponte who, after leisurely dressing and enjoying his breakfast, proceeds to the milk shop and takes away their knives and sends them off to sleep though he considers them "a pair of big bluffers". A activation email has been sent to you. From Wikipedia, the free encyclopedia. In real life, there was no such reconciliation. After the murder, the Vicario family leaves town due to the scandal and disgrace surrounding the events of Angela's wedding and Santiago's murder.
Crónica de una Muerte Anunciada by Philippe Olmos on Prezi
Cookies come in two flavours – persistent and transient. When Flora Miguel's father finds out, he warns Santiago minutes before the twins reach Santiago.
The weather, dreams, and nature all provide evidence of what is to come cronca the novella. This further complicates the central theme of the book for modern readers as Santiago Nasar may therefore be viewed as a morally dubious character, despite the narrator's claims that he was a stand-up youth.
BIOGRAFIA DE ESTANISLAO ZULETA PDF
LIBRO COMO PROGRAMAR EN C C DEITEL Y DEITEL PDF
ERASE UNA VEZ EL ZORRO Y EL ERIZO PDF
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GESTA HUNGARORUM ROMANA PDF
ALLAN MASSIE CALIGULA PDF
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Justice Dec 11, 2022 – 10:47 pm EST
Elisabeth Salm's family feels 'relief,' 'compassion' after Hikoalok verdict
Tyler Hikoalok found guilty of first-degree murder in 2018 killing of Salm, 59, in Ottawa
Mundie Salm, centre, the sister of Elisabeth Salm speaks to reporters outside the Ottawa courthouse on Sunday, following the conviction of Nunavut man Tyler Hikoalok on a first-degree murder charge in Elisabeth's 2018 death. Her brothers Floris Salm, left, and Roland Salm, stand behind her. Family members brought yellow carnations to the courthouse as a tribute to their sister's happy, sunny disposition. (Photo by Corey Larocque)
There were tears and audible sighs of relief in Room 34 at the Ottawa courthouse Sunday as the family of Elisabeth Salm learned the man accused of killing her had been found guilty of first-degree murder.
Tyler Hikoalok, 22, of Cambridge Bay received an automatic sentence of life in prison with no chance of parole for 25 years for the violent sexual assault and murder of Salm, a 59-year-old volunteer librarian.
The family of Elisabeth Salm said they are relieved after Tyler Hikoalok, 22, was convicted of first-degree murder on Sunday in the 2018 death of Salm, 59. Salm's family remembered her as "courageous" and "the kindest" human being in their emotional victim impact statements. (Photo courtesy of Lyle Young)
Salm was attacked May 24, 2018, in Ottawa as she worked alone in the library of the Christian Science Reading Room, just metres from the Ottawa courthouse where the six-week trial took place.
The verdict came in at 3 p.m. Sunday. The 12-member jury had deliberated for two days.
Hikoalok, his hair pulled back and wearing his red sweatshirt he usually wore during the trial, stood still and hung his head while the verdict was read.
Moments later, a dozen of Salm's family members and friends stood, hugging each other in the courtroom, wiping away tears of relief. Many had attended the courthouse every day of the trial, and the ones who couldn't be there followed on Zoom.
Each of Salm's four siblings and her husband, Lyle Young, read emotional victim impact statements.
"My empathetic, courageous sister deserved better," said Salm's brother, Roland Salm.
"It bolts me awake at night that she didn't have a peaceful transition to the beyond," he said, remembering his sister as the "reliable rock with an inner resolve" who helped keep their family together after their father died in a car accident in 1975.
Brother Floris Salm remembered his sister as the "kindest, most caring human being."
He and the rest of his family wore yellow ribbons and carried yellow carnations in remembrance of her.
"These flowers represent the sunshine that she brought," he said.
Salm's younger sister, Mundie Salm, travelled from her home in the Netherlands to be in the courtroom for the verdict.
She shared that she was born on Elisabeth Salm's eighth birthday, and the sisters shared a close bond.
"She found beauty all around her," she said, remembering her sister's gentleness and keen interest in nature and the environment.
"You removed a bright light from our constellation," Mundie said directly to Hikoalok.
Mundie Salm said she was in the Netherlands on May 24, 2018, when she saw a news article online that a woman had been attacked at the Christian Science Reading Room. Immediately alarmed, she called Salm but got no answer.
Soon, she learned her sister was, in fact, the woman who had been attacked, and that she was in the hospital.
Mundie Salm described the overwhelming emotion she felt when she landed in Ottawa on May 25 after booking a last-minute flight, only to find out her sister had already died.
Once the trial got underway in September, after years of delays, Mundie Salm watched it on Zoom from overseas every day after work.
She would often go to bed having just heard the excruciating details of what happened to her sister the day she was attacked.
"I felt a deep anguish at not being there for her," said Salm's other sister, Luc-Anne Salm, who had been with Elisabeth only two days before the attack at a local environmental event.
"We were very different individuals," she smiled as she read, "but Elisabeth had my back completely."
Then Young, Salm's husband of 28 years and the first witness to testify at the trial, spoke of his wife's enduring impact on him and their family.
Though the sexual attack on her affected him in profound ways, he said, he was steadfast in honouring the kind woman she was in life.
"I think of her selflessness, generosity, love, intelligence and goodness," he said.
Lyle Young, the husband of murder victim Elisabeth Salm, listens to a reporter's question outside the Ottawa courthouse following the conviction of Tyler Hikoalok of first-degree murder on Dec. 11, 2022. (Photo by Corey Larocque)
Salm and Young were Christian Scientists, devoted to their faith and community.
Earlier in the trial, Young shared that his wife sang in the church choir, taught Sunday school and volunteered much of her time to local causes like environmental activism and municipal elections.
Young spoke about the strength he finds through religion and how it helped carry him through his wife's death.
"I've never felt anything but compassion" throughout the trial, he said. "I seem to be incapable of feeling bitterness or hate."
"Elisabeth would have never expected me to be impacted by evil," he said.
"I'm trying to stay true to what she would have expected of me."
Throughout, Hikoalok sat in the prisoner's box wiping away tears and shaking his head at times.
Then Judge Anne London-Weinstein gave Hikoalok a chance to speak.
"I'm sorry," he said, through tears. "I truly didn't know I had killed her."
"You did something so evil to someone so good," London-Weinstein told Hikoalok, "but given how young you are, I hope [this sentence] gives you time to heal."
Later outside the courtroom, Mundie Salm reflected on what she heard.
"I'm glad that he said sorry. He hasn't said that before," she said.
Despite feeling relieved the trial is over and that the man responsible for Salm's murder was convicted, the verdict brought up complicated emotions for her family.
Hikoalok is an Inuk from Cambridge Bay. He was 18 years old and homeless when he killed Salm in 2018.
Mundie Salm said her sister believed in reconciliation and justice for Indigenous Peoples and had worked to support people living with poverty and homelessness.
"We don't like the fact that we're sending an Indigenous man to prison for life," Mundie Salm said outside the courthouse, with Young echoing the same sentiment.
Posted by Time on Dec 12, 2022
I hope life in prison really ends up being life in prison for this man. He is so dangerous. Women need to be kept safe from him. I don't wish for anything bad to happen to him in prison, I hope the routine of life there gives him some stability and peace, but he should not be allowed out to live independently, ever.
Posted by Nunavut needs a better court on Dec 12, 2022
Too bad the families of people murdered in Nunavut never feel relief like this from our courts
Posted by JT on Dec 12, 2022
Imagine if a white kid had done this to an indigenous woman. It would be front page news every day on the CBC. Instead, pretty much the only place to consistently read about this case has been nunatsiaq.com. Thank you for the coverage and may this loser rot in jail for the rest of his miserable life.
Posted by Nunavut on Dec 12, 2022
Atleast he's not going to walk around free, Seen people charged with hit and run and dui walking free while the victims parents are suffering after losing a child to an accident
They still have to apply the Gladue doctrine. Appears he has a lot of past dysfunction. See how that pans out in the end.
Posted by Jay Arnakak on Dec 13, 2022
The Gladue provision needs to be sunsetted. and, fast.
It is a very passive, half-hearted way of dealing with social dysfunction given that it hasn't provided any effectual and sustainable funding for treatment programs at the territorial and provincial levels where people like Hikoalok fall easily through the cracks in the system.
Sad all ways 'round. Perhaps this type of funding should be part of the T&R efforts by FPT governments.
Posted by Scrubs on Dec 14, 2022
Gladue was well intentioned, but has turned into the biggest drivers and perpetuators of cycles of abuse in Nunavut. Violent crime, gladue, hardly any time in prison. Release, violence, gladue…
Posted by 180 on Dec 13, 2022
So sad he did this to this woman who seemed to be a bright light in her families life, so sad this young man has no life to look forward to. Just a sad situation all way around.


Malaria is caused by protozoan parasites of the genus Plasmodium. Five species of Plasmodium cause infection in humans, with the majority of lethal cases caused by Plasmodium falciparum. This species is responsible for more than 500 million clinical cases of malaria each year (59). In the past 2 decades, efforts to combat this disease have been met with the emergence of widespread resistance to most of the commonly used antimalarial drugs (68). The poor efficacy of current drugs and the lack of a promising vaccine have resulted in alarming increases in the rates of malaria morbidity and mortality worldwide, with the major toll felt in the developing world.
P. falciparum is transmitted to humans via the bite of an infected female anopheline mosquito. In humans, the parasite undergoes one cycle of asexual multiplication in hepatocytes, followed by several cycles of infection and multiplication in red blood cells. Whereas the hepatocytic stage is asymptomatic, the erythrocytic stage is accompanied by the destruction of the host erythrocytes, resulting in anemia and, in the absence of treatment, death. Extensive efforts are presently under way to develop a vaccine, and advances in our understanding of the biology of the parasite and its metabolic and nutritional needs offer new routes for chemotherapy. In this regard, purine metabolism holds significant promise as a target for drug development.
It has long been recognized that protozoan parasites, including Plasmodium spp., are unable to synthesize purine rings de novo (4). Consistent with this observation, the sequencing of protozoan genomes has failed to uncover any genes encoding enzymes involved in the biosynthesis of purine nucleosides or nucleobases (12). Protozoan parasites rely instead on salvage of purines from the host. The strategies used in acquiring purines vary significantly among parasite genera. This review will focus primarily on the purine salvage pathways present in the Plasmodium parasite. Recent reviews have examined the metabolic pathways for purine salvage in other protozoa (11, 17, 29).
Initial studies on purine and pyrimidine synthesis in Plasmodium parasites were performed on erythrocytic stages of the rodent malaria species P. berghei (7, 8, 65), the macaque monkey malaria species P. knowlesi (46), and the avian malaria parasite P. lophurae (61, 66). Work by Sherman and colleagues indicated a functional purine salvage pathway in P. lophurae (61, 66). Bungener and Neilsen demonstrated that P. berghei can incorporate the purines [3H]adenosine and [3H]hypoxanthine, but not the pyrimidines [3H]uridine and [3H]thymidine, into nucleic acids (7, 8). Van Dyke and colleagues showed that uptake and incorporation (into nucleic acid) occur for the purine adenosine but not for the pyrimidines uridine and cytidine and that adenosine is incorporated far more efficiently than adenine, guanosine, and deoxyadenosine (65). Polet and Barr demonstrated that monkey erythrocytes infected with P. knowlesi were unable to incorporate [14C]thymine, [14C]thymidine, [14C]uracil, or [14C]uridine but could incorporate [14C]- and [3H]orotate (a pyrimidine precursor) and [14C]adenine into nucleic acids (46). Following on from these findings, Gutteridge and Trigg found that, in P. knowlesi, all radiolabeled purines were significantly incorporated into nucleic acids while none of the pyrimidines tested were (28). These early biochemical studies demonstrated that Plasmodium parasites lack the ability to metabolize exogenous pyrimidines and instead are entirely dependent on de novo synthesis. Conversely, Plasmodium parasites are entirely reliant upon the salvage of extracellular purines (4) and are capable of metabolizing a wide variety of exogenous purine nucleobases and nucleosides.
The continuous culture of P. falciparum in serum-free media is dependent upon the supply of exogenous purines (1, 43), suggesting that the erythrocyte adenylate nucleotide pool is not a sufficient purine source and that the parasite is dependent upon extraerythrocytic purine salvage for survival. The first step in purine salvage is, therefore, the transport of purines into the infected cell and, from there, into the intracellular parasite. We provide a short description of this process below; more-thorough reviews of purine transport in Plasmodium spp. have been provided elsewhere (2, 29).
Within the erythrocyte, the Plasmodium parasite resides within a parasitophorous vacuole created upon parasite invasion by the invagination of the host cell membrane. The parasite cytosol is therefore separated from the nutrient-rich extracellular medium by a series of three membranes: the host cell membrane, the parasitophorous vacuole membrane, and the parasite plasma membrane.
Nucleosides and nucleobases cross the host cell membrane via a combination of a high-affinity transport process and, in mature trophozoite-stage parasites, nonsaturable, broad-specificity new permeability pathways induced by the parasite in the erythrocyte membrane (25, 26, 36, 37, 64). The high-affinity transport process is sensitive to inhibition by nitrobenzylthioinosine and probably represents transporters native to the erythrocyte (25), such as human ENT1. The infected erythrocyte also displays the ability to transport l-enantiomers of nucleosides, and this uptake is inhibited by classical new permeability pathway blockers, such as furosemide and 5-nitro-2-(3-phenylpropylamino)benzoic acid (25, 27, 64). Once inside the infected erythrocyte, the nucleosides are presumed to cross the parasitophorous vacuole membrane via the large-diameter, nonselective pores present on this membrane (18).
From early work by Gero and colleagues, it was clear that the uptake of at least one nucleoside, the purine adenosine, across the parasite plasma membrane is extremely rapid (27, 64). In the first study of the functional expression of P. falciparum-encoded transporters in Xenopus laevis oocytes, cells injected with total mRNA from blood-stage parasites showed elevated transport of adenosine and hypoxanthine, consistent with the expression of one or more parasite-encoded nucleoside transporters (45); however, the proteins responsible were not identified. Subsequently, two independent studies reported the cloning of a P. falciparum nucleoside transporter, designated either P. falciparum NT1 (PfNT1) (10) or PfENT1 (44). In both cases, the protein was identified by searching for homologues of known nucleoside transporters in the P. falciparum genome sequence. The gene was cloned and expressed in Xenopus oocytes and shown to transport a range of nucleosides and nucleobases (10, 44). There were significant differences between the results of the two studies with regard to the reported characteristics of the transporter. Carter et al. (10) described the transporter (referred to hereafter as PfNT1) as having a high affinity for adenosine (Km = 13 μM) and being sensitive to inhibition by 10 μM dipyridamole, whereas Parker et al. (44) described it as having a much lower affinity for adenosine (Km = 320 μM) and being insensitive to 10 μM dipyridamole. These differences notwithstanding, it is clear that PfNT1 is a nucleoside transporter. In a subsequent study, Rager et al. used immunoelectron microscopy to obtain strong evidence that the protein is localized predominantly, if not exclusively, to the parasite plasma membrane (and not to the parasitophorous vacuole or host erythrocyte membrane) (51). Transport experiments on parasites isolated from their host cells by saponin treatment (which renders the host cell membrane freely permeable to macromolecules while leaving the parasite plasma membrane intact) revealed that nucleosides (20) and nucleobases (19) are transported across the parasite plasma membrane by a fast, low-affinity process, similar to that seen for the transport of these substrates by PfNT1 in Xenopus oocytes (19, 20). The absolute dependence of the parasite on PfNT1 expression was demonstrated in experiments by El Bissati and colleagues, in which it was shown that parasites harboring a genomic deletion of the PfNT1 gene (pfnt1Δ) were viable only when the purines adenosine, inosine or hypoxanthine were present at super-physiological concentrations (21). While initial transport studies in pfnt1Δ parasites (21) suggested that pfnt1Δ parasites exhibited residual (PfNT1-independent) adenosine and inosine transport, further studies (taking into account the metabolic properties of the parasite) have shown that pfnt1Δ parasites were unable to transport adenosine, inosine and hypoxanthine (21a). Further studies with this parasite strain have indicated that pfnt1Δ parasites were unable to grow when guanine, guanosine, xanthine, or adenine were present at physiological concentrations (21a) and that pfnt1Δ parasites were unable to transport guanine, guanosine, or xanthine but were able to transport adenine, albeit at a lower rate (21a).
Recently, Quashie and colleagues have proposed the presence at the parasite plasma membrane of a high-affinity adenosine transport mechanism, which they have equated with PfNT1 (48). Their experimental design and subsequent interpretation of the data, however, do not take into consideration the rapid metabolism of purines, which is a high-affinity process. Taking into account the difficulties of distinguishing between transport and metabolism, a comprehensive analysis of all the available PfNT1 transport data (10, 19-21a, 44, 48) would suggest that PfNT1 is a low-affinity transporter that mediates the rapid uptake of adenosine, inosine, hypoxanthine, adenine, guanine, guanosine, and xanthine. There is some evidence that for adenine there is, in addition to PfNT1, a PfNT1-independent mechanism (21a, 48), yet to be characterized.
While available studies demonstrate an essential function for PfNT1, the completion of the P. falciparum genome sequencing project revealed three additional nucleoside transporters (PfNT2, PfNT3, and PfNT4) (24, 40). Like PfNT1, these proteins are expressed during the intraerythrocytic stage of the parasite life cycle as well as in gametocytes (5, 40, 70). Their cellular localization, as well as their role in parasite physiology, is yet to be elucidated.
Studies of P. falciparum parasites isolated from host erythrocyte membranes by mechanical rupture showed the presence of the purine salvage enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and phosphoribosyl transferase (PRT) (52). Only minimal adenosine kinase activity was observed in this study (52). Subsequent studies have indicated that the parasite lacks adenosine kinase activity (55), and no adenosine kinase gene has been found in the genome (24). This is consistent with the idea that the majority of purine salvage occurs via the sequential conversion of adenosine and inosine to hypoxanthine, which is then phosphoribosylated to form IMP (52).
The enzyme ADA catalyzes the irreversible hydrolytic cleavage of adenosine to produce inosine and ammonia. As native human ADA (hADA) activity is high in uninfected erythrocytes (15, 69), parasite-encoded ADA (PfADA) was initially characterized by infecting erythrocytes taken from a human donor genetically deficient in ADA with P. falciparum (15). Parasite growth levels were comparable in normal and deficient host cells, and infected deficient host cells exhibited a level of ADA activity twice that seen in normal, uninfected erythrocytes. The ADA activity in parasite protein preparations exhibited essentially the same Km for adenosine as the ADA activity in protein preparations from uninfected, normal erythrocytes (15). Both erythrocyte and parasite ADA enzymes are inhibited by nanomolar concentrations of deoxycoformycin (15). PfADA, however, has a much lower sensitivity than hADA to the inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (15). Recombinant PfADA (expressed in Escherichia coli) has a Km of 11 ± 2 μM for adenosine (22), a figure similar to that reported for free P. falciparum parasite lysates (7 μM) (6) and to that seen for lysates from the duck parasite P. lophurae (23 μM) (69). The P. falciparum enzyme is also reportedly sensitive to two l-nucleoside structural analogues of deoxy-d-coformycin that have no effect on hADA (6) as well as to 5′-methylthio coformycins (as detailed below) (63).
PNP enzymes are responsible for the phosphorolysis of nucleosides into the corresponding nucleobases and ribose groups. This reaction is reversible and is carried out in the presence of inorganic phosphate (9). There are two major families of nucleoside phosphorylases: the low-molecular-mass homotrimers, which include all mammalian PNPs and some bacterial PNPs, and the high-molecular-mass homohexamers, which include most bacterial PNPs, along with mammalian and bacterial uridine phosphorylases (9). Most PNPs contain consensus sequences specific to the relevant family (33). Initial studies of P. falciparum PNP (PfPNP; utilizing red blood cells taken from a child deficient in PNP) (16) showed that PfPNP is capable of utilizing inosine, guanosine, and deoxyguanosine but not adenosine or xanthosine. Expression of the gene encoding PfPNP in E. coli revealed that PfPNP is not a typical member of either of the two major classes of PNPs, having low sequence homology and a distinct substrate specificity to PNPs from other species (33). The purified enzyme has a Km for inosine of 5.0 ± 0.9 μM and can be inhibited by immucillins with dissociation constants as low as 0.6 nM (33). Immucillins are PNP transition state analogues, some of which have Kd values as low as 7 pM (54). Immucillin-H is currently in clinical trials for treating human T-cell malignancies (23, 54) and has been shown to inhibit PfPNP, as well as inhibiting P. falciparum growth, in vitro (33, 34). This in vitro inhibition of parasite growth can be reversed by the addition of hypoxanthine, but not inosine, to the culture medium, indicating that PNP is the target for this drug (34).
The crystal structure of PfPNP in complex with immucillin-H revealed a homo-hexamer, organized as a trimer of dimers, with an immucillin-H molecule bound at each of the catalytic sites (58). The structure also revealed that the catalytic site has a capacity for binding 5′-substituted nucleosides, and kinetic studies have confirmed that 5′-methylthioinosine (MTI) is a good substrate for PfPNP, being converted to hypoxanthine, indicating that this protein has dual catalytic functions in the parasite (58). Methylthioadenosine (MTA) is a common by-product of polyamine metabolism, and like PfPNP, PfADA is able to utilize this 5′-substituted compound, converting it to MTI (58, 60). The abilities of PfADA and PfPNP to utilize methylthiopurines allow the salvage of purines from both the traditional purine nucleoside pathways and the polyamine synthesis pathway (Fig. 1).
Purine metabolism within the infected erythrocyte. Inosine is produced from adenosine by ADA. Inosine is then converted to hypoxanthine by PNP). hADA and hPNP are present in the red blood cell cytoplasm, while the parasite ADA (PfADA) and PNP (PfPNP) are active in the parasite cytosol. Both PfADA and PfPNP are capable of acting on 5′-substituted compounds, and so the parasite is able to salvage purines from the polyamine biosynthesis pathway (58, 60). Ado, Ino, Hxt, Guo, Gua, Xan, and Ade are transported across the parasite plasma membrane by PfNT1. Adenine also enters the cell via a second, PfNT1-independent mechanism. Adenine may be metabolized to other nucleosides/nucleobases (Ns/Nb) in the erythrocyte cytoplasm. PRT activity converts hypoxanthine to IMP, guanine to GMP, and xanthine to XMP. IMP, GMP, and XMP are then converted to guanylate and adenylate nucleotides by the action of several more enzymes, outlined in the text and in Fig. 2. There is some evidence to suggest that the parasite can also convert adenine to AMP by using a parasite-encoded APRT (PfAPRT). Abbreviations: Ado, adenosine; Ino, inosine; Hxt, hypoxanthine; Guo, guanosine; Gua, guanine; Xan, xanthine; Ade, adenine; PRPP, phosphoribosylpyrophosphate; RBC, red blood cell; PV, parasitophorous vacuole; MTA, methylthioadenosine; MTI, methylthioinosine.
When supplied in vitro, [14C]MTI is metabolized by P. falciparum and incorporated into nucleic acids (60). A reaction mixture of purified PfADA and PfPNP efficiently converted MTA to hypoxanthine, but replacement of either enzyme with its mammalian counterpart stopped the reaction (60). Likewise, purified E. coli PNP had no detectable activity against MTI or MTA, despite phosphorolysing both adenosine and inosine (60).
The abilities of PfADA and PfPNP to recognize methylthio-substituted purines led to the development of 5′-methylthio coformycins (63) and methylthio-immucillin-H (MT-immucillin-H) (60). The 5′-methylthio coformycins inhibit PfADA at very low concentrations but do not inhibit hADA (63). The abilities of these compounds to inhibit parasite growth in the presence of physiologically relevant concentrations of inosine and hypoxanthine remain to be established. The validity of ADA as an antiplasmodial target is questionable, however. While early studies showed that 2′-deoxycoformycin can clear an in vivo P. knowlesi infection (67), the in vitro growth of P. falciparum was not inhibited by 10 μM 2′-deoxycoformycin, despite complete inhibition of (both host and parasite) ADA enzyme activity at this concentration (15, 53). Whether this discrepancy is due to species-specific differences or due to in vitro culture conditions is unknown.
The addition of a 5′-methylthio group to immucillin-H allows the preferential binding of MT-immucillin-H to PfPNP over human PNP (hPNP) by a factor of 112 (58). MT-immucillin-H kills P. falciparum in vitro with a 50% inhibitory concentration of 50 nM, compared to a 50% inhibitory concentration of 63 nM for immucillin-H (60). It should be noted, however, that these values were derived from inhibition curves carried out with culture media containing no hypoxanthine, under which conditions parasite growth would be completely reliant upon PNP activity (60).
The potential of PfADA and PfPNP as therapeutic targets is yet to be validated by genetic means. While the extent to which purine concentrations fluctuate in mammalian blood is unknown and the amounts of adenosine, inosine, and hypoxanthine available in human plasma are a source of contention, several groups report that hypoxanthine is the major purine available in human serum in vivo (42, 62). Therefore, it seems likely that a block in the purine salvage pathway at the ADA or PNP step could be circumvented by the downstream salvage of hypoxanthine, guanine, or xanthine from the host, all of which are transported into the parasite by PfNT1 and phosphoribosylated by P. falciparum hypoxanthine-guanine-xanthine PRT (PfHGXPRT). There is a clear need for in vitro studies in which the serum concentrations of all purines are replicated or, ideally, in vivo animal studies on the effects of these compounds on Plasmodium growth. Despite the fact that recombinant Toxoplasma gondii PNP is sensitive to immucillin-H, the in vitro growth of the parasite is unaffected due to the presence of a redundant purine salvage pathway (the direct phosphorylation of adenosine by adenosine kinase). While T. gondii parasites deficient in adenosine kinase are sensitive to immucillin-H, this sensitivity can be rescued by addition of hypoxanthine to the medium (13).
Nucleobases can be converted directly to nucleoside monophosphates by the action of PRT enzymes. PRT enzymes catalyze the reversible transfer of a phosphoribosyl group from phosphoribosylpyrophosphate to a nucleobase, resulting in the production of a nucleotide and pyrophosphate (14). In P. falciparum, PRT activity is catalyzed by a single enzyme, HGXPRT (49), while a second enzyme was shown to account for adenine PRT (APRT) activity (Fig. 1) (50), as is the case for mammalian cells. The ability of the enzyme to utilize xanthine as a substrate distinguishes PfHGXPRT from its counterpart enzyme in the human red blood cell.
Although P. falciparum has only low levels of APRT activity (high-performance liquid chromatography data indicated that the amount of HGXPRT activity is about 1,500 times greater than that present for APRT) (50), this activity does exhibit properties that differ from those of the APRT present in human erythrocytes. These include a lower apparent molecular weight and a differing inhibition profile (50). Studies on duck erythrocytes infected with P. lophurae indicated that the avian parasite also has APRT activity with kinetic properties different from those of the host cell APRT enzyme (Plasmodium Km = 3.4 μM, and host Km = 69 μM) (69). Pollack and colleagues (47) reported the cloning of P. falciparum APRT, although the gene sequence was not determined. Mouse cell lines transfected with this gene exhibited APRT activity with a Km value similar to that seen for lysates from isolated P. falciparum (47). However, the presence of APRT activity in Plasmodium parasites remains an area of contention. A recent study suggested (based on genetic, biochemical, and genomic data) that APRT enzymes are not present in Plasmodium, Eimeria, or Cryptosporidium spp. (12). Although wild-type parasites are able to grow on adenine as a sole purine source, pfnt1Δ parasites are unable to complete the intraerythrocytic life cycle on physiological concentrations of adenine, despite measurable uptake of adenine by saponin-isolated pfnt1Δ parasites (21a). This suggests either that all adenine is converted in the red blood cell such that the parasite cytosol never sees adenine or that adenine cannot be metabolized by the parasite, a hypothesis consistent with the suggestion that the parasite lacks an APRT enzyme.
The PfHGXPRT enzyme displays high activity for all three purine substrates, with some variation in affinity for them (Km of hypoxanthine = 0.46 μM, Km of guanine = 0.30 μM, and Km of xanthine = 29 μM) (49). King and Melton reported the first cloning and sequencing of PfHGXPRT (35). When expressed in E. coli (31), the recombinant enzyme was shown to differ from the human enzyme in several respects, including an increased ability to utilize allopurinol as a substrate. There are many good inhibitors of PRT enzymes, including phosphorylated versions of the previously described immucillins (e.g., immucillin-HP and immucillin-GP). The cell permeability of phosphorylated inhibitors is, however, an obvious concern. The available crystal structures of PfHGXPRT (56) and human HGPRT (57), each in complex with these compounds, should aid in the design of species-specific inhibitors (38). Recently, several purine nucleobase analogues were identified that, while being good substrates for PfHGXPRT, were comparatively weak substrates for the human enzyme (32). The discovery of compounds that can interact preferentially with the parasite enzyme, together with the reported lack of nucleobase phosphoribosylation redundancy in P. falciparum, makes PfHGXPRT a promising target for the development of antimalarial therapies.
As detailed above, the great majority of purines salvaged by P. falciparum are funneled through hypoxanthine to IMP. To generate adenylate nucleotides within the parasite, IMP is first converted to adenylosuccinate (by adenylosuccinate synthetase), which is then converted by adenylosuccinate lyase to AMP (Fig. 2) (30, 39). In order to obtain guanylate nucleotides, IMP dehydrogenase converts IMP to XMP, which is then converted to GMP by GMP synthetase (41). A recent biochemical characterization of this enzyme suggests that it differs from its mammalian counterpart on several levels, including differences in ligand specificity (3). HGXPRT can also convert xanthine base directly to XMP and guanine base to GMP. AMP and GMP are then converted to the final nucleotides used in nucleic acid synthesis (Fig. 2).
Nucleotide production in P. falciparum. Hypoxanthine, which is both transported into the cytoplasm from plasma and produced from adenosine and inosine metabolism (indicated by multiple arrows; see Fig. 1 for more detail), is converted to IMP by PfHGXPRT. IMP can then be converted to adenylate or guanylate nucleotides. To make adenylate nucleotides, IMP is converted to adenylosuccinate by adenylosuccinate synthetase. Adenylosuccinate lyase then converts adenylosuccinate to AMP. AMP is phosphorylated to ADP (by adenylate kinase). Alternatively, IMP can be converted to XMP by IMP dehydrogenase. XMP (which can also be produced directly from xanthine by PfHGXPRT) is converted to GMP by GMP synthetase. GMP can also be produced from guanine by PfHGXPRT. Guanylate kinase phosphorylates GMP to form GDP. Both GDP and ADP are then converted to the NTP or deoxynucleoside triphosphates used in nucleic acid synthesis. PRPP, phosphoribosylpyrophosphate; RBC, red blood cell; PV, parasitophorous vacuole.
Purines enter the intraerythrocytic malaria parasite via a fast, low-affinity, broad-capacity process that can be attributed primarily to the parasite plasma membrane transporter PfNT1. The reliance of the parasite on PfNT1 makes this protein a worthy target for further investigation, while the determination of the roles played by PfNT2, PfNT3, and PfNT4 in parasite physiology should also prove interesting. Within the parasite, the metabolism of purines appears to be funneled through hypoxanthine by the sequential actions of ADA and PNP, prior to phosphoribosylation of hypoxanthine by PRT. The fact that hypoxanthine is the main purine source found in human serum suggests that PfADA and PfPNP are unlikely to play an essential function under physiological conditions or be considered good drug targets. However, the apparent dependence of the parasite on PfHGXPRT for nucleotide synthesis makes this protein a promising drug target. Efforts to develop compounds that can distinguish between this enzyme and the human counterpart are well justified and may well form the basis for future antimalarial drug strategies.
This research was supported by National Institute of Health and Department of Defense grants AI51507 and PR033005 as well as by Burroughs Wellcome Award 1006267 to C.B.M. and by grants from the Australian Research Council and the Australian National Health and Medical Research Council to K.K. C.B.M. is a recipient of the Burroughs Wellcome Award, Investigators of Pathogenesis of Infectious Diseases.
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Li, C. M., P. C. Tyler, R. H. Furneaux, G. Kicska, Y. Xu, C. Grubmeyer, M. E. Girvin, and V. L. Schramm. 1999. Transition-state analogs as inhibitors of human and malarial hypoxanthine-guanine phosphoribosyltransferases. Nat. Struct. Biol. 6:582-587.
Marshall, V. M., and R. L. Coppel. 1997. Characterisation of the gene encoding adenylosuccinate lyase of Plasmodium falciparum. Mol. Biochem. Parasitol. 88:237-241.
Martin, R. E., R. I. Henry, J. L. Abbey, J. D. Clements, and K. Kirk. 2005. The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 6:R26.
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Parker, M. D., R. J. Hyde, S. Y. Yao, L. McRobert, C. E. Cass, J. D. Young, G. A. McConkey, and S. A. Baldwin. 2000. Identification of a nucleoside/nucleobase transporter from Plasmodium falciparum, a novel target for anti-malarial chemotherapy. Biochem. J. 349:67-75.
Penny, J. I., S. T. Hall, C. J. Woodrow, G. M. Cowan, A. M. Gero, and S. Krishna. 1998. Expression of substrate-specific transporters encoded by Plasmodium falciparum in Xenopus laevis oocytes. Mol. Biochem. Parasitol. 93:81-89.
Polet, H., and C. F. Barr. 1968. DNA, RNA, and protein synthesis in erythrocytic forms of Plasmodium knowlesi. Am. J. Trop. Med. Hyg. 17:672-679.
Pollack, Y., R. Shemer, S. Metzger, D. T. Spira, and J. Golenser. 1985. Plasmodium falciparum: expression of the adenine phosphoribosyltransferase gene in mouse L cells. Exp. Parasitol. 60:270-275.
Quashie, N. B., D. Dorin-Semblat, P. G. Bray, G. A. Biagini, C. Doerig, L. C. Ranford-Cartwright, and H. P. De Koning. 2008. A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites. Biochem. J. 411:287-295.
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ORANGE UNITED SPORTS CLUB INC.
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Examples of NEW PARADIGM Splitting and Pairing Accelerated MASSLESS (Micro) Black Holes.: Charge differences of D and U quarks according to Quantum FFF Theory.
Charge differences of D and U quarks according to Quantum FFF Theory.


Diana Pavon is a student at the University of Wisconsin Madison majoring in political science and Latin American Caribbean and Iberian Studies with a minor Chican and Latin studies. Diana's campus involvement includes serving as the co-chair for La Mujer Latina, a student organization that creates an annual conference with resources for all the Madison community. She has gotten political involved as an undergraduate interning for both Senator Tammy Baldwin and State Representative Jocasta Zamarripa which allowed her access to the inner-working of the political sphere. Diana has previously conducted research for the Labor Historical Society in Madison that is developing an educational map website. She is also an open advocate against social injustice which she hopes to address these issues in her community. Diana has won the Jesus Salas Activist Scholarship for serving as an advocate in her Latino community as well. Last summer, Diana was awarded the UW Global Getaway due to high academic achievement and accomplishments. As a result, she was able to travel to Rio de Janeiro where she became educated about Brazil's government and international law. In the future, she hopes to educate marginalized students about social inequalities and become involved in political campaigns.


The Ritual Fire Offering, which is derived from Indian tradition, plays an important part in buddhist Tantric Practice. The Ritual Fire Offering for Peace is commonly performed at the conclusion of the prescribed meditation retreat associated with specific meditational deities, in order to compensate for any errors that may have occurred during the practice. The Ritual Fire Offering for Increase may be Performed to increase merit, wealth, life span and so forth.
This manual contains translations of texts required to perform the Ritual Fire Offering for Peace associated with six meditational deities: Thirteen Deity Vajrabhairava, Solitary Hero Vajrabhairava, Guhyasamaja, Heruka, Vajra Yogini, and Cittamani Tara, according to the Gelugpa traditon of Tibetan Buddhism. It further includes a description of the changes required to convert the ritual for peace to the ritual for increase in association with Guhyasamaja.
The texts have been clearly presented in English to enable people who are qualified by initiation, but who do not know Tibetan, to understand the stages and Procedures of Ritual Fire Offerings so that they may perform them effectively.


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Hi Mike, I know this is a really old thread, but i'm just wondering if you still have that tutorial? I'm still hesitating whether i want to scratch build my backpack or buy the kit. If its doable, i would prefer to make my own and hope i can save lots of cash during the process! Thanks a lot man!
Hi Guys! Kindly requesting 501st access http://www.501st.com/members/displaymember.php?userID=18114&costumeID=136 TB/TX 70385 here!


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Bronx apartment fire kills 19, including 9…
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Bronx apartment fire kills 19, including 9 children
Ladders are seen erected beside the apartment building where a fire occurred in the Bronx on Sunday, Jan. 9, 2022, in New York. (AP Photo/Yuki Iwamura)
PUBLISHED: January 10, 2022 at 1:02 a.m. | UPDATED: January 10, 2022 at 4:54 a.m.
By DAVID PORTER, BOBBY CAINA CALVAN and MICHELLE L. PRICE
NEW YORK (AP) — A malfunctioning space heater sparked a fire that filled a high-rise Bronx apartment building with thick smoke Sunday morning, killing 19 people including nine children in New York City's deadliest blaze in three decades.
Trapped residents broke windows for air and stuffed wet towels under doors as smoke rose from a lower-floor apartment where the fire started. Survivors told of fleeing in panic down darkened hallways and stairs, barely able to breathe.
Multiple limp children were seen being given oxygen after they were carried out. Evacuees had faces covered in soot.
Firefighters found victims on every floor, many in cardiac and respiratory arrest, said Fire Commissioner Daniel Nigro. Some could not escape because of the volume of smoke, he said.
Some residents said they initially ignored wailing smoke alarms because false alarms were so common in the 120-unit building, built in the early 1970s as affordable housing.
More than five dozen people were hurt and 13 were hospitalized in critical condition. Nigro said most of the victims had severe smoke inhalation.
Firefighters continued making rescues even after their air supplies ran out, Mayor Eric Adams said.
"Their oxygen tanks were empty and they still pushed through the smoke," Adams said.
Investigators said the fire, triggered by the electric heater, started in a duplex apartment on the second and third floors of the 19-story building.
The flames didn't spread far — only charring the one unit and an adjacent hallway. But the door to the apartment and a door to a stairwell had been left open, letting smoke quickly spread throughout the building, Nigro said.
New York City fire codes generally require apartment doors to be spring-loaded and slam shut automatically, but it was not immediately clear whether this building was covered by those rules.
Building resident Sandra Clayton grabbed her dog Mocha and ran for her life when she saw the hallway fill with smoke and heard people screaming, "Get out! Get out!"
Clayton, 61, said she groped her way down a darkened stairway, clutching Mocha. The smoke was so black she couldn't see, but she could hear neighbors wailing and crying nearby.
"I just ran down the steps as much as I could but people was falling all over me, screaming," Clayton recounted from a hospital where she was treated for smoke inhalation.
In the commotion, her dog slipped from her grasp and was later found dead in the stairwell.
About 200 firefighters responded to the building on East 181st Street around 11 a.m.
Jose Henriquez, an immigrant from the Dominican Republic who lives on the 10th floor, said the building's fire alarms would frequently go off, but would turn out to be false.
"It seems like today, they went off but the people didn't pay attention," Henriquez said in Spanish.
He and his family stayed, wedging a wet towel beneath the door once they realized the smoke in the halls would overpower them if they tried to flee.
Luis Rosa said he also initially thought it was a false alarm. By the time he opened the door of his 13th-floor apartment, the smoke was so thick he couldn't see down the hallway. "So I said, OK, we can't run down the stairs because if we run down the stairs, we're going to end up suffocating."
"All we could do was wait," he said.
The children who died were 16 years old or younger, said Stefan Ringel, a senior adviser to the mayor. Adams said at a news conference that many residents were originally from the West African nation of Gambia. Many survivors were brought to temporary shelter in a nearby school.
The drab, brown apartment building looms over an intersection of smaller, aging brick buildings on Webster Avenue, one of the Bronx's main thoroughfares.
By Sunday afternoon, all that remained visible of the unit where the fire started was a gaping black hole where the windows had been smashed.
"There's no guarantee that there's a working fire alarm in every apartment, or in every common area," U.S. Rep. Ritchie Torres, a Democrat who represents the area, told the AP. "Most of these buildings have no sprinkler system. And so the housing stock of the Bronx is much more susceptible to devastating fires than most of the housing stock in the city."
Nigro and Torres both compared the fire's severity to a 1990 blaze at the Happy Land social club where 87 people were killed when a man set fire to the building after getting into an argument with his former girlfriend and being thrown out of the Bronx club.
Sunday's death toll was the highest for a fire in the city since the Happy Land fire, other than the Sept. 11 terror attacks.
It was also the deadliest fire at a U.S. residential apartment building in years. In 2017, 13 people died in an apartment building, also in the Bronx, according to data from the National Fire Protection Association.
That fire started with a 3-year-old boy playing with stove burners and also spread because the door to an apartment that lacked a closing mechanism had been left open. The fire led to several changes in New York City, including having the fire department create fire safety education plans for children and parents.
Sunday's fire happened just days after 12 people, including eight children, were killed in a house fire in Philadelphia. In 1989, a Tennessee apartment building fire claimed the lives of 16 people.
Associated Press reporters Michael R. Sisak and Jennifer Peltz in New York and Andrew Selsky in Salem, Oregon, contributed to this report.
Morning Briefing: Pilot faces surgery as downed helicopter removed; Voice opinion about new legislative districts; Eagles set for Bucs
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Rebecca Clark / 10th July 2018
An Intimate Evening with Sophia Loren comes to London
Silver-screen star Sophia Loren debuts at the West End's Aldwych Theatre for one night only.
Spend an intimate evening with silver-screen goddess, Sophia Loren this Autumn.
Celebrating one of Italy's biggest cinema icons, the special event marks Loren's West End debut, taking place at the Aldwych Theatre on 28 October 2018.
Hosted by Jonathon Ross, the unmissable evening will span her glorious career, followed by a Q&A where fans will have the once in a lifetime opportunity to ask Sophia questions.
Loren began her film career in 1951, before starring in her first Hollywood film, The Pride and the Passion, in 1957 alongside the legendary Cary Grant and Frank Sinatra.
In 1960, she starred in her most acclaimed role to date, as the lead in Two Women – which won her the 1961 Academy Award for Best Actress, as well as being the first to win it for a non-English-language film.
As one of the biggest actresses of the '60s, she also starred opposite Marlon Brando in 1967's A Countess from Hong Kong, as well as roles in Yesterday, Today, and Tomorrow (1963), which won the Oscar for Best Foreign Film and Marriage, Italian Style (1964), which earned Loren another Oscar nomination.
During her extensive almost-seven-decade career, she has also won a Bafta, a Grammy, and five special Golden Globe Awards, and continues to appear in films including 1995's Grumpier Old Men and 2009's Nine.
Check out The Evolution Of Sophia Loren courtesy of Elle below:
The Evolution of Sophia Loren | ELLE
Known for her reluctance to give interviews, this very special occasion promises a unique not-to-be-missed opportunity to see the iconic actress, singer and beauty queen in an intimate setting.
Tickets will be available via presale at 09:00 on Thursday 12 July, and via general on sale at 09:00 on Friday 13 July 2018 through Ticketmaster.co.uk
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