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Brandeis University Professor John Burt wrote one of the most-praised books about Abraham Lincoln in recent years. In this essay for Constitution Daily, Burt talks about the three verbs that define the first sentence of the Gettysburg Address.
The verbs of the first sentence of the Gettysburg Address are drawn from organic life, and they imagine the United States as a developing child. The new nation is "conceived" (by the Fathers), "brought forth" (upon this continent), and "dedicated" to the proposition that all men are created equal. And the speech ends by projecting a "new birth" of freedom, transmuting, by means of a life-giving idea, the deaths of the men who struggled in that place into a new form of life, held in common by the entire nation, North and South, Black and White. Even the date of the Declaration of Independence ("Fourscore and seven years ago") is given in terms that call to mind the biblical phrase from Psalm 90 for the length of a human life.
This organic metaphor was noticed at the time by several hostile critics. The New York World, for instance, ridiculed the speech for representing "the 'fathers' in the stages of conception and parturition," and the Boston Daily Courier sneered at the "obstetric allusion.' But the organic metaphor plays several important purposes in the rhetoric of the speech.
First, as John Channing Briggs has pointed out, if the nation grows like a child, then the founders can beget it and nurture it, and they can dedicate it, but they can't assemble it or design it. The nation is not to be seen as the product of a contract, something subject to strict construction, and completely subordinated to the plan of the founders, but rather is to be seen as something that grows from within, in its own way, towards ends which it gropingly, and only gradually, realizes. A child like this one, a "dedicated" child, is born with a calling, but it must find its own way to realizing that calling, and even its parents cannot fully understand where that calling will take it, although they know where it began, and how it began to take shape. The "dedication" of the young nation is not merely a covenant, but a baptism, the giving of its true name, the sign that its identity includes a destiny which, at that moment, could only be seen as in a glass darkly.
Defining the war in an unexpected way
A second effect of the organic metaphor of the first sentence is that it enabled Lincoln to define the meaning of the Civil War in an unexpected way. If the nation is a growing child, the Civil War is an almost inevitable, life-threatening childhood trauma which either kills or transforms the child. By phrasing the legacy of the Declaration as a "proposition" rather than as a self-evident truth, Lincoln implied that that legacy has to be tested, has to undergo a trial by fire before its truth can be recognized. What is at stake is not the mere survival of the United States, but whether any society dedicated to equality can survive. Moreover, any society dedicated to equality must risk a similar test, and cannot authentically affirm equality until it has undergone such a test. The republic had to survive the almost mortal test of Civil War as children had to survive the almost mortal test of disease.
The citizens' watch over their imperiled republic was analogous to the parents' watch over their dangerously ill children, a touchstone of nineteenth century fiction from Little Nell to Little Eva to Beth March. Lincoln himself, during the ceremony at the Gettysburg National Cemetery, still wore the black band on his hat he put on after the death of his son Willie the previous year.
In all of these novels of the death of children from Uncle Tom's Cabin to Little Women the dying children became a source of transformative wisdom to their grieving families. Eva St. Clair in Uncle Tom's Cabin, for instance, saw the wrong of slavery clearly, and, in dying, brought her father to recognize that wrong, something he had perhaps dimly known from the beginning, but had never fully acknowledged to himself, blinded as he was by the ironies and double-binds of adulthood. The care and grief of the worried parent is transformed into the wisdom given that parent by the dying child, and the direction of the action reverses itself, so that the parents, who dedicated the child, are rededicated by their dying children to a cause the children saw more clearly than their parents did. Indeed, in the final movement of the Gettysburg Address, in which the living are rededicated by the dead, only the experience of mourning their children frees the adults, as Mr. St. Clair is freed, from illusions, in the citizens' case the illusion that the aim of the war is restoration of the old Union rather than the development of equality, an illusion in which they would otherwise have been imprisoned forever.
The fiery trial of the Union differs in one crucial respect from the deaths of children in 19th century fiction, and that is that a childhood disease is a random event, whereas the trial of democracy is built into the design of democracy itself. Democracy could not develop without this trial, and what democracy becomes under pressure of this trial is more truly what democracy is than what it was beforehand: only the mortal pressure of civil war forces an honest reckoning with the problem of democracy, and without what Melville called the power of a bullet to undeceive, democracy would have settled for an illusory life, a once-born life without a "new birth of freedom." Without the violence of the war, Union-loyal Americans, Lincoln included, would have settled for that oxymoron, a slaveholder democracy. Further, without the proper reflection on the meaning of the war, Lincoln implies, America might settle for another oxymoron, racist democracy. The war, this is to say, is a necessary episode in the becoming of democracy, without which democracy cannot come to fulfillment.
When we wonder whether a nation will "endure" we wonder rather more than merely whether it will be able to continue. "Enduring" is something you do, something that requires stern strength of will; "surviving" is just something that happens to you. To endure is to face down suffering; indeed, it is to continue bear the mark of that suffering past the end of suffering. Even more than "survive," the word "endure" registers a continuing struggle for life, and registers also that the struggle itself is somehow transformative. Those who "survive" may be exhausted and emptied by the experience, but those who "endure" have proven something about themselves that otherwise might not have been expected.
Because the war is a necessary if almost fatal trauma in the growth of democracy neither side stands in a position of moral privilege relative to the other: the nation must be tested, and North and South both have roles to play in that test. The war is not the outcome of a malign conspiracy of slaveholders seeking to confirm themselves in power. Nor is it a crusade by opponents of slavery against a signal evil. The war is a trial given to North and South on account of slavery, an unavoidable although dangerous episode in the coming to be of democracy, necessary because of their mutual complicity in slavery.
Conceiving of the war as an necessary trial of democracy also enabled Lincoln to account not only for the meaning of the war, but also for why it was so violent, so long, and so inconclusive, for the Republic was given to suffer until it learned to repudiate certain corrupt values — slavery and inequality — which it not only held deeply but felt to be constitutive of its politics; the extended slaughter of the war was necessary to disabuse both North and South of crippling illusions about democracy.
Defining American life
A third effect of Lincoln's organic metaphor was to enable us to see America as an organic collective form of life, as a nation rather than as merely a state, as something that has a biography, not just a history. A state is a body of concrete institutions, laws, deliberative bodies, agencies of enforcement, regulation, and registration — an organization having a monopoly over the means of violence, to cite Max Weber's pungent definition of the state from "Politics as a Vocation." A nation is something muddier but deeper. To a first approximation, a nation is a people, but what makes a mass of human beings a people is hard to say.
In the 19th century, the role of making a mass of people into a nation was sometimes attributed to blood, and more often to blood's metaphorical cousins, culture and language. Under that definition of "nation," it is hard to see that the term applies to the United States, whether in the 19th or in the 21st century. The United States has typically imagined itself, except in eras of xenophobic frenzy such as the 1920s, or the 1850s (or the present), as a nation of newcomers. The reason immigration can make one American is, as Lincoln argued in his 1858 Chicago speech, that political traditions in America stand in the place cultural history and language and blood do in other nations. To be American is not a matter of blood but a matter of an idea.
When Matthew Arnold encountered the word "proposition" in the Gettysburg Address, he is said to have reacted with disgust at the clash between the high biblical rhetoric of the opening phrase and the descent to the language of legal pettifogging at its conclusion. But "proposition" is a word that has majesty for Lincoln, because it suggests to him the principled drawing of a line, the definition of an identity-giving and life-risking moral stake. A proposition is something one might nail to a cathedral door, or put one's name to, hazarding one's life and one's sacred honor. A proposition is something one might be dedicated to.
A proposition about equality
Whatever the provenance of the word, the contrast between the organic "bringing forth" of the new nation, and the metaphysical "proposition" to which it is dedicated, captures something of the central crux of the idea that something like the United States can be a nation: it is made a nation not by blood or history but by an identity-founding commitment to a value, available to everyone, but given special local salience by being tested there and then. This is why that proposition is about human equality, rather than about self-rule or limited government, because equality is a value intended to transcend concrete political traditions and to resist being seen merely as the upshot of a particular history and particular traditions, as, say the "rights of Englishmen" are. America is the nation whose identity is created by its being in a position to test values it hopes will be found good for all nations; its uniqueness is given to it by its calling of testing a set of values which, if they stand the test, are not then to be seen as unique to it but as universal.
The word "proposition" captures the common awareness that American identity both is and is not organic. For the immigrant, it is something chosen, but chosen in a way that has the identity-making power of something given. For the native-born, it is something given, but is taken as if it were chosen, the fruit of agency rather than agency's precondition. That is why the sentence uses the metaphor of baptism: the nation is "dedicated" to a proposition, given its identity in that proposition, called into being as a test of that proposition, discovering its meaning in piecing together the significance and the consequences of that proposition.
The aim of this dedication, the value Lincoln saw as at the heart of the prospective American character, is equality, a value in fact not achieved by the United States then or now. Lincoln's choice, like his choice of the founding moment in 1776 rather than in 1787, the sweeping promises of the Declaration rather than the painful and exacting compromises of the Constitution, was a polemical one. One could easily imagine another figure choosing self-rule, the consent of the governed, before choosing equality. Or Lincoln could have chosen the three inalienable rights, life, liberty, and the pursuit of happiness. Lincoln chose equality because it seemed to him to be somehow logically prior to all of the others, because only moral equality enables one to distinguish between self-rule as the political project of moral autonomy and self-rule as merely the habit of honor among thieves. Only equality founds self-rule in respect for the human person; without equality self-rule is little more than the privilege of exemption from servitude.
What the Civil War tests, Lincoln argued, is not only, as he might have said earlier, whether a government of the people would be able to preserve its stability in the face of disagreements, or whether it must ever fracture into ever smaller Confederacies whenever it faces a conflict. The issue was not even, as Lincoln had also said elsewhere, only whether a minority can contest by force the majority's fairly won power to rule, whether the minority can claim by the bullet what it had lost by the ballot. The central issue, from which all of the other issues depended, was whether any government was capable of making and keeping the promise of equality. As the issue of slavery somehow underlay the issue of the tariff, of internal improvements, and of strict or loose construction of the Constitution, so under all of the other things at stake in the war, under Union, under political stability, under majority rule, lay the issue of racial equality.
Lincoln did not say that the equality he had in mind was racial equality. But he did not have to, since class equality or gender equality or ethnic equality were not at the center of a great war. Freedom and equality are not contrary values for Lincoln, for freedom as a political value depends upon the mutual acknowledgment of free persons as free persons; freedom is agency, and agency happens only among moral equals. That is why, towards the end of the speech, Lincoln imagined that the fruit of a victory in a war over moral equality will be a "new birth of freedom," the transformation of freedom into a deeper thing than the ability of the strong to exploit the weak without interference by any third party. The new birth of freedom can only be a new depth of acknowledgment, such as that later embodied in the three Reconstruction amendments to the constitution, whose actual contents Lincoln had not yet imagined, and which the Republic had no sooner articulated than it thoroughly betrayed.
Lincoln did not specify the particulars of the new birth of freedom, although certainly it has something to do with the proposition that all men are created equal. The realization of a new commitment to equality, not mere military victory, is the test of Union success in the war. We will not know who really won the war, Lincoln argued, until we know what kind of Union emerges out of it. Lincoln did not in so many words press the issues that were later embodied in the three Reconstruction Amendments, only the first of which could have been in his focal attention anyway. But the test of a new birth of freedom is a stern one, and it is not certain even to this day how close our Republic is to passing that test.
John Burt is a Professor of English at Brandeis University and the author of "Lincoln's Tragic Pragmatism."
More Constitution Daily Stories About Lincoln
Myths and mysteries about the Gettysburg Address
href="http://blog.constitutioncenter.org/2013/10/lincolns-comments-from-1861-relevant-to-todays-government-shutdown/" target="_blank">Lincoln's comments from 1861 relevant to today's government shutdown
Did Abraham Lincoln omit God from the Gettysburg Address?


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THIS was far from an Oval classic, but come September Hampshire's draw against Surrey may be recalled as one of their most important results of the season.
At the end of a turgid final day, Hampshire had restricted third-placed Surrey to a three-point gain on the LV County Championship's top two.
Hampshire may lose top spot to Worcestershire in the next 24 hours.
But, crucially, they have denied Surrey the win that would have thrown the Championship's promotion race wide open.
A disciplined batting performance means Hampshire still have a 16-point advantage and a game in hand on the pre-season favourites.
Hampshire began the final day on 167-3 and, despite twice losing three wickets in five overs, they managed to get the 325 needed to avoid the follow on, which effectively ended any remaining Surrey hopes of a third successive Championship win.
Surrey needed an unlikely 17 wickets and their chances improved when Hampshire collapsed from 226-3 to 237-6 and then from 286-6 to 295-9.
But Will Smith took up more vital time after resuming on 61.
Sean Ervine's excellent 80 (149 balls, ten fours) added to Surrey's frustration before a tenth-wicket partnership of 59 between James Tomlinson and Danny Briggs took Hampshire to 354.
Playing on what was effectively a seven-day old wicket (the same track was used for a recent Championship match), Hampshire were relieved not to have to contend with any significant deterioration.
There was surprisingly little in the wicket for the bowlers, which added to the frustration of the home side, particularly off-spinner Gareth Batty, who took 3-74 in 41 overs. "I was very surprised at how flat it was and they were as well, they weren't too happy with how little it turned," said Ervine.
But Surrey were given glimmers of hope.
Having batted for more than an hour with no real alarms, Hampshire lost Smith, Adam Wheater and Matt Coles against the second new ball.
Smith was lbw attempting to sweep the slow left-arm of Zafar Ansari after batting for nearly five hours for his 82 (257 balls, nine fours).
And in the next over, the eighth with the second cherry, Adam Wheater was out for a golden duck when a Tim Linley off-cutter dismantled his middle and off stumps.
Four overs later, Coles was caught and bowled attempting to drive Gareth Batty off the back foot.
But Ervine stood firm. The Zimbabwean faced 83 balls for his second Championship half-century of the season.
He put on 66 with Smith, whose nine fours included two clipped through mid-wicket from successive Matthew Dunn deliveries at the beginning of the final day.
Ervine was decisive off front foot and back in hitting his ten boundaries and added a further 49 with Kyle Abbott either side of lunch, when Hampshire still needed 71 to avoid the follow on. But then came another mini collapse.
Abbott became Vikram Solanki's first victim of the season when he hit a flighted off-break straight to mid-on.
And Ervine, with his first Championship century for more than two years in his sights, sliced Tillakaratne Dilshan's off-spin to backward point when he attempted to hit the Sri Lankan back over the top.
Hampshire still needed 31 to avoid the follow-on when 17 year-old Brad Taylor was lbw to Dilshan's arm ball, having seen off 17 balls in only his second first-class match.
No matter. Briggs (38*) and Tomlinson (27) ensured Hampshire got there to dissipate any remaining tension, before a flurry of boundaries against Kevin O'Brien's medium pace.
After they had added 60 in 15 overs, Tomlinson holed out before striving for striving for a wicket as frustrated Surrey went through the motions following a delayed tea.
"It was a massive effort considering the situation," said Ervine. "We would have liked to get a few more batting points but our major concern was to bat out the game. And the good thing is we're still unbeaten."

subset: commoncrawl


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20% off apparel. New stuff for all. Use code GIFTON20
flower purple green purple denver botanical garden jen wahl floral pattern nature outdoors
so beautiful Jen….love the light and softness xxx big hug xxx
Thanks so much Ingrid :) that means so much coming from you! Big hug back xoxox
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Thank you!
Oh wow! Thanks Barry!! I totally missed this! :) That totally makes my day! :)
Thanks so much Carol :) x
Beautiful work !
Thanks so much, withsun!
Great talent to created beautiful artwork, I like it so much:)…………..Thoughtfully;Nature Quote of the DayMy boy, one small breeze doesn't make a wind storm.John McGraw mentioned.………..Take care yourself, you're precious…Sunny
Thank you so much Kornrawiee… you're so sweet :)
Thank you very much Lozzar!
I love your macro photography.
Thank you, Margaret! :) So sweet of you to say.
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United States. Congress. Office of the Attending Physician7 works / 0 ebooks Search for books with subject United States. Congress. Office of the Attending Physician.
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Irish novelist Colum McCann on attack: 'I was cold-clocked without warning and I had severe concussion, broken cheekbone and broken teeth'
Dublin-born author Colum McCann has spoken of the shocking ordeal he suffered when he attempted to come to a woman's aid in a dispute.
The novelist said he was "cold-clocked" in a shocking daylight attack at the weekend, and suffered concussion, a broken bone, broken teeth, and a broken spirit.
Luckily, an off-duty paramedic came straight to the his aid on Saturday night, he said.
The attack reportedly happened when McCann tried to help a woman in a dispute.
In a statement the novelist said: "It was a shocking, cowardly attack in broad daylight on a busy street. I was trying to help someone out. I was cold-clocked without warning. I had a severe concussion, a broken cheekbone, some broken teeth and a spirit that has been temporarily bruised."
"But I am recovering quickly and I've been overwhelmed by the generous response from friends and strangers alike."
"Luckily, there was an off-duty paramedic on the street and he came straight to my aid. The irony of it all is that I was at a conference on "Empathy" at Yale University with a non-profit I'm involved in, Narrative 4," he added.
The New York-based novelist said police are close to finding the attacker and pressing charges.
"The police have not yet arrested the attacker but I believe they are very close to pressing charges, using video and witness evidence," McCann said.
"I suffered a few injuries but nothing that can't be quickly healed. If anything, I was shaken out of the ruts of my ordinary perception, and I have been struck [by] the genuine caring nature of people asking about how they can help out."
"What I think is most important about this is that there are others who suffer far worse violence, and I think it's important that we try to understand that the deep roots of silence are not helpful. We need to speak out against this sort of thing."
He added: "It could have happened anywhere in the world. The fact that it happened on the edge of one of the world's foremost colleges campuses simply highlights how prevalent this sort of situation is."
The novelist said the medical personnel who helped him were "outstanding".
"I am deeply thankful to all who have given me support," he said.
McCann has just released his first short story in a decade, "Gone", through the online publisher and subscription service Byliner.
Online Editors


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It's often believed that to make it in the financial world you need to always be some form of guru or perhaps currently have a good investment broker. Neither of the 2 is necessarily correct. It is quite possible to become your own best ally in relation to investment. It isn't usual that you are going to put your money and walk away with tons of money. Nevertheless there is dollars to recieve and more to have should you get rid of the actual agent. Similar to most things in life, however, one shouldn't enter into trading blindly. In this time period of information staying readily available, there's not a lot of defense for not reading the way to invest before you decide to jump in with your wallet.
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Hard to believe my baby is 2 years old on April 1st. Here is one of two pics. Sorry these are so big. Photobucket has updated its sight and I can not find how to do anything on it any more. sheesh
Dog of the Day
Cat of the Day
Pet of the Day
Hard to believe my baby is 2 years old on April 1st. Here is one of two pics. Sorry these are so big. Photobucket has updated its sight and I can not find how to do anything on it any more. sheesh
Last edited by momoffuzzyfaces; 04-01-2013 at 11:24 AM.
No matter what anyone does, someone some where will be offended some how!!!!
Grandma (RB), Chester, Angel, Chip
Leonardo (RB), Luke (RB), Winnie, Chuck,
Frankie sure is a handsome boy. My Reece will turn 1 on April 1st too and Rory will turn 1 on April 4th.
HAPPY 2nd BIRTHDAY FRANKIE!!! I hope you have many many more happy and healthy years ahead of you.
Owned by Sky, Pearl, Ziggy Stardust, Alani, Blaze, Colby, Finnegan, and Summer.
My Rainbow Bridge Babies:
RB Pepper 3/17/97- 2/3/03 RIP Sweet Pepper
RB Starr 3/22/05- 7/1/09 RIP Sweet Starr
RB Sunny 8/25/00- 2/28/10 RIP Sweet Sunny
RB Storm 1/11/96- 8/2/12 RIP Sweet Storm
Happy Birthday Frankie! You are a beauty... loves those eyes.
What??? He's two already??? Well, this calls for a celebration.
Happy happy purrffday dear boy. I do hope you are keeping out of trouble on this special day. Merlin and I send good wishes for a wonderful day.
Love Slick and Merlin
Life should NOT be a journey to the grave with the intention of arriving safely in an attractive and well preserved body, but rather to skid in sideways, champagne in one hand and strawberries in the other, body thoroughly used up, totally worn out, and screaming WOO HOO - What a Ride!
Sometimes the most real things in the world are the things we can't see
--Polar Express
Until one has loved an animal, part of their soul remains unawakened.
Two, already! Sheesh how time flies. Happy Birthday Frankie!! Hope you get lots of lovies and treats!!!
Gayle - self proclaimed Queen of Poop
Mommy to: Cali and Diego (nine year old kittens)
(RB furbabies: Rascal RB 10/11/03 (ferret), Sami RB 24/02/04 (dog), Trouble RB 10/08/05 (ferret), Miko RB 20/01/06 (ferret) and Sebastian RB 12/12/06(ferret), Sasha RB 17/10/09 (border collie cross)
Hi, Frankie, sweet boy! Happy 2nd PURR-thday! *kisses* *kisses* and *extra kisses for Grandma, Angel and Winnie, Chester, Chip and Chuck*
I've been Boo'd ... right off the stage!
Aaahh, I have been defrosted! Thank you, Bonny and Asiel!
Brrrr, I've been Frosted! Thank you, Asiel and Pomtzu!
"That's the power of kittens (and puppies too, of course): They can reduce us to quivering masses of Jell-O in about two seconds flat and make us like it. Good thing they don't have opposable thumbs or they'd surely have taken over the world by now." -- Paul Lukas
"We consume our tomorrows fretting about our yesterdays." -- Persius, first century Roman poet
Cassie's Catster page: http://www.catster.com/cats/448678
Copyright © 2001-2013 Pet of the Day.com


text:
Issue No. 04 - July/August (2007 vol. 24)
pp: 408
DOI Bookmark: http://doi.ieeecomputersociety.org/10.1109/MDT.2007.134
Tomorrow's engineers will need to be familiar with a wide range of fields, necessitated by rapid advances in technology that span several areas of expertise. This will be even more true for CAD engineers. Just as CAD tool suites of the future will have to integrate physics, optics, mechanical engineering, statistics, and perhaps biology, the design team of the future must include people who understand all those things. The universities of today should start training engineers to work on the design teams of tomorrow.
engineers, training, university education, CAD, DNA devices, nanomachine cores
Scott Davidson, "How do we train today's students to become tomorrow's engineers?", IEEE Design & Test of Computers, vol. 24, no. , pp. 408, July/August 2007, doi:10.1109/MDT.2007.134


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WHO commends China on lifting entry and travel restrictions for HIV-positive people
"China's decision to categorically remove HIV/AIDS from the list of conditions subject to entry restrictions is a significant step in the right direction," said Dr Margaret Chan, WHO Director-General. "This decision should inspire other nations to change laws and policies that continue to discriminate against people living with HIV."
More than 50 countries still have laws and restrictions that exacerbate the marginalization of people living with HIV, particularly vulnerable populations such as sex workers, young people, and men who have sex with men, limiting their opportunities to access HIV/AIDS prevention, treatment, care and support services.
"Many policies that discriminate against people living with HIV were enacted at a time when AIDS was surrounded by widespread fear and hopelessness. With HIV prevention and treatment now saving millions of lives, this is no longer the case. Policies that help curb discrimination can help prevent further transmission," said Dr Chan.
China's announcement is made in the lead up to the opening of the Shanghai Expo on 1 May.


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Lord McIntosh of Haringey: I shall try.
Lord Higgins: I thank the noble Lord. We hope he will be successful. As far as concerns the other point which the noble Lord made of a more general nature in reply to the points that I raised as regards the timing, we have asked whether the matter should be delayed in order to incorporate into the Bill the recommendations of the Sharman committee.
We have taken note of what the noble Lord said about that, but what we are not really clear aboutand perhaps the noble Lord could now enlighten usis whether the programme is on schedule. That is to say, the reports of the Public Accounts Committee suggested that the arrangements for introducing resource accounting had been introduced more easily, or preparation for the matter had been carried out more successfully, in some departments than others.
Is the noble Lord now confident that the programme which the Government originally envisaged, despite the setbacks which they appear to have experienced, will actually be completed on time? Obviously his argument about timing turns crucially on whether the Government believe that they can go ahead with their programme on the original schedule.
Lord McIntosh of Haringey: Before the noble Lord, Lord Higgins, leaves that point, he will recall from the
We have reached and achieved on time every figure that has been set down so far, and in that sense we are confident that we are not falling behind. I understand that the Public Accounts Committee met last Wednesday. It has taken evidence and will be reporting, although it has not yet done so. Clearly we will take very seriously what the Public Accounts Committee says about the readiness of departments. As matters stand, we have no reason to suppose that, for the first time in the whole process, we are falling behind our targets.
Lord Higgins: I am sure the Committee will be grateful for that. The two points are, of course, inter-related. If, indeed, the programme falls behind time, the case for incorporating whatever the noble Lord, Lord Sharman, may sayif indeed he does say something quite specificfalls into a different time framework.
I turn to the points made by the noble Lord in regard to the specific amendments. I must say I was puzzled by what he said. He seemed to be saying that if we accepted Amendment No. 4, rather than the wishy-washy contents on page 3, it might set things too much in concrete and would then be inconsistent with subsequent changes which one wished to make to the concept involved. Our amendment simply says that there should be a,
As to defence, in general it is the not the intention of my noble friend Lord Bridgeman and myself to speak to every amendment, which the Committee will be pleased to hear. However, in this case I believe that it is appropriate for my noble friend to deal with this matter which arises out of the amendments that we are considering. Other than that, our Front Bench will divide up the Bill between the two of us. My noble friend was also unhappy about the reply received. As far as I understand it, we are unable to deal with the matter now. We must take into account some of the points raised by the Minister which appear to be plausible. We shall return to this matter when we come to Report stage. I beg leave to withdraw the amendment.
Amendment, by leave, withdrawn.
Lord Higgins moved Amendment No. 6:
The noble Lord said: We come to an important series of amendments. Our concern is that the Bill as now drafted gives far more power to the Treasury than it should have. In financial matters such as these Parliament should be supreme in determining the definitions at a simple level. If we are moving towards a more commercial basis, clearly it is not the case that individual private or public companies can decide what the accounting rules should be. They should be decided by an independent body. It appears that if we go along with what the Government now propose there is a danger that the Treasury will produce rules with which Parliament is not entirely happy. However, the Treasury will be given power to do that if we accept the Bill without amendment.
We suggest, therefore, that a separate bodythe so-called national accounts commissionshould be set up in order to reach an impartial view as to what definitions the Government should use. We propose that the Comptroller and Auditor General should determine the duties of the commission, which will include the definition of standards of national accounting practice to be applied to all departmental accounts and also in the context of the Bill as a whole.
One of the reasons for our concern is the extent to which under the present arrangements it is possible for the GovernmentI hesitate to use the expression but it is the simplest one to useto fiddle the figures. That was certainly the case as far as concerned the working families' tax credit which was suddenly redefined by the Government in such a way as to present something as a tax reduction rather than an increase in public expenditure, even though general bodies outsidefor example, the OECD had expressed the clear view that it should be defined in the opposite sense.
We argue that the Government should be subject to an independent body, and Parliament should be able to ensure, through the workings of the Comptroller
It is the case, of course, that the Government could say that the Financial Reporting Advisory Board is sufficiently independent for this purpose and we on this side of the Committee would accept that. However, it would not achieve the objectives that these amendments seek to achieve because it is simply a consultative body. It is not empowered to set down definitions in statute or under a statutory regime, which would ensure that Parliament rather than government should have the power to decide the accounting framework within which the national accounts and the department accounts are produced. I beg to move.
Baroness Sharp of Guildford: I rise to support the series of amendments put forward by the noble Lord, Lord Higgins. The key issue here is parliamentary control of the Executive. The Treasury could be seen as the guardian of the budget which Parliament votes, whereas in many senses it should be the guardian of parliamentary control. Its power over other departments in the Executive derives from its being answerable to Parliament for what is spent. It is, therefore, able in many ways to discipline the other departments because of its powers.
We in the Liberal Democrats would argue that over the course of time it has perhaps abused this power and gone beyond it, to create a grossly over-centralised regime which extends well beyond the moneys voted by Parliament itself. However, that is not directly at issue here.
What is at issue here is the fact that the Treasury may be a guardian, but quis custodiet ipsos custodes?who guards the guardians? One answer is that it is the Comptroller and Auditor Generalthe parliamentary watchdogbut what good is a watchdog if the Treasury is setting its own rules? That is precisely the proposal in the Bill. Under Clause 5(2):
In the private sector we expect to have independent authority; we have the Accounting Standards Board, which lays down standards for the private sector. The Public Accounts Committee called in 1994-95, 1996-97 and 1998-99 for a national accounting commission to be set up. The Government cannot argue that they have not had time to think about it. The Comptroller and Auditor General has drawn attention to the need for an independent commission, not for him to set the guidelines himself. CIPFA has also called for a national accounting commission to be set up and for what could be considered as proper accounting standards for public bodies. CIPFA is also concerned with the whole range of local authorities. In Clauses 23 to 28 we will look further at the extension of those powers to local authorities.
As the noble Lord, Lord Higgins, said, it is possible to argue that the Financial Reporting Advisory Board is sufficient and, while Opposition Peers agree that it may be seen as being an independent authority, it is only advisory. We do not feel that it is strong enough to be able to lay down these guidelines. Therefore, we support these amendments, and feel it is an important issue within the context of the Bill.
Lord McIntosh of Haringey: I have to say at the outset that we do not accept the need for a national accounts commission. The amendments are presumably designed to ensure independence in the standards-setting process. Indeed, both the noble Lord, Lord Higgins, and the noble Baroness, Lady Sharp, have said that.
The Government cannot have made it sufficiently clear that the existing provisions of the Bill ensure that the Treasury has little discretion in the setting of accounting policies. That is in contrast to the present system of appropriation accounts where the Treasury has almost total freedom to determine the policies to be followed.
We believe that our proposals provide a robust and professional framework for determining accounting policies. They require resource accounts and whole of government accounts, which are not covered by the amendment, to follow generally accepted accounting practice, modified only as necessary to take account of the specific context of departmental accounts and to present a "true and fair view". That really means that the Accounting Standards Board, which is the guardian of GAAP and the "true and fair view", sets the rules, not the Treasury.
All accounting policy issues are subject to the oversight of the independent Financial Reporting Advisory Board. I was pleased to have the recognition of the noble Lord, Lord Higgins, that it is indeed independent. This process is designed to ensure that any adaptations to GAAP are fully justified. It provides a further check on Treasury discretion.
The FRAB prepares reports on its own activities, setting out its views on Treasury proposals that have been put forward. Those reports are submitted to Parliamentthis is the issue raised in relation to parliamentary scrutinyso that all Members can see how the process has been working. The Treasury agreedagain, I am not sure whether we made this adequately clearthat in response to a recent report by the Public Accounts Committee, the FRAB should submit its reports directly to the PAC and Treasury committees rather than through the Treasury.
The requirement that resource accounts present a "true and fair view" is the benchmark against which the Comptroller and Auditor General undertakes his independent audit, providing a further scrutiny of the detailed accounting policies. In order to obtain unqualified audit opinions, accounts will have to satisfy the Comptroller and Auditor General that they meet the highest standards.
The amendment involves the setting up of a new accounting standards-setting body which would be in competition with the Accounting Standards Board. We do not believe that a separate standards-setting body or separate statements of national accounting practice are needed. The Government are content to follow, as far as possible, the standards issued or approved by the Accounting Standards Board, which already apply to all private sector bodies and many parts of the public sector. Introducing separate standards for any government accounts could lead to confusion and a divergence between the requirements placed on departments and those placed on other bodiesprecisely the situation that the RAB is intended to end.
The suggestion that the Comptroller and Auditor General should determine the duties of the commissionwhich is what the amendment requireswould give him powers which it would be inappropriate for an auditor to possess and would threaten his independence. Responsibility for the preparation of accounts must lie with the bodies preparing the accounts. In the case of government departments and whole of government accounts, the responsibility must lie with the Treasury to ensure consistency across departments and the wider public sector.
To abrogate that responsibility to the proposed national accounts commissionwhich I have already argued is unnecessarywould lead to a confusion of responsibility. It would result in conflicts between the requirements of budgeting and public expenditure control operated by the Treasury and accounting requirements.
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text: [ Some Gifts Break Too Soon! [VIDEO] By Sean Ericson December 28, 2011 I love the motorcycle that you rebuilt and gave me for Christmas! Hold my beer and watch this! Read More Category: Gone Viral, Videos Tags: crash, fail, motorcycle, ouch Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


text:
Yesterday I decided to put CyanogenMOD on. I had it on my 1st Gen. Note and I loved it! Problem is, the app they provide for installation does not yet support Note 3, so I went down the old road of doing it manualy. Never done it before though, so something was bound to happen.
Problem caused by impatience and ignorance
In short, i did the following -
1) Installed CF AutoRoot, which, of course, installed SuperSU
2) Installed MobileOdin
3) Put CM11 on my SD card
4) Booted into stock OS and attempted to install CM using MOdin
5) Failed to install - ODIN kept saying its not meant for my phone (i go the hlte image and the image was supposedly meant for hltexx etc.)
6) I followed to instructions to delete a line from the install script which would allow me to install the same image with no problems.
7) Last step obviously unzipping and rezipping file
8) Phone gives another big FU and says this is not the right image now
And this is where I firmly believe i messed up
8) Frustrated, i uploaded an unzipper folder
9) Picked the file 'boot.img' as targer file in Mobile Odin (Why? Why did I do that?)
Result - boot process is stuck at the Samsung SM-N9005 etc. logo with the top two lines saying:
Set Warranty Bit : kernel
After a good 15-20s pause the phone just shuts down.
What the verdict? This thing is salvageable or should I start weeping?


text:
Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 160168, 10 pages
Expression Profiling and Proteomic Analysis of JIN Chinese Herbal Formula in Lung Carcinoma H460 Xenografts
1College of Basic Medicine and School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China
2Zhejiang California International Nanosystems Institute, Zhejiang University, Hangzhou 310058, China
3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
4Department of Pharmacology and Winship Cancer Institute, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
Received 28 March 2013; Revised 8 July 2013; Accepted 17 July 2013
Academic Editor: Aiping Lu
Copyright © 2013 Luyu Zheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Many traditional Chinese medicine (TCM) formulae have been used in cancer therapy. The JIN formula is an ancient herbal formula recorded in the classic TCM book Jin Kui Yao Lue (Golden Chamber). The JIN formula significantly delayed the growth of subcutaneous human H460 xenografted tumors in vivo compared with the growth of mock controls. Gene array analysis of signal transduction in cancer showed that the JIN formula acted on multiple targets such as the mitogen-activated protein kinase, hedgehog, and Wnt signaling pathways. The coformula treatment of JIN and diamminedichloroplatinum (DDP) affected the stress/heat shock pathway. Proteomic analysis showed 36 and 84 differentially expressed proteins between the mock and DDP groups and between the mock and JIN groups, respectively. GoMiner analysis revealed that the differentially expressed proteins between the JIN and mock groups were enriched during cellular metabolic processes, and so forth. The ones between the DDP and mock groups were enriched during protein-DNA complex assembly, and so forth. Most downregulated proteins in the JIN group were heat shock proteins (HSPs) such as HSP90AA1 and HSPA1B, which could be used as markers to monitor responses to the JIN formula therapy. The mechanism of action of the JIN formula on HSP proteins warrants further investigation.
1. Introduction
Nonsmall cell lung cancer is a major cause of cancer-related mortality worldwide and is highly resistant to treatment by classical cytotoxic agents including platinum-based drugs. Traditional Chinese medicine (TCM) aims to correct maladjustments and restore the self-regulatory ability of the body without antagonizing specific pathogenic targets. TCM has been used to treat human diseases and has a long history of safety and efficacy. The approaches used in systems biology and pharmacogenetics are similar to the practices of TCM [1]. The JIN formula is an ancient herbal formula recorded in the classical TCM book Jin Kui Yao Lue (Golden Chamber). This formula is composed of Ophiopogon japonicus (30 g), prepared Rhizoma pinelliae (15 g), Ginseng radix (30 g), Glycyrrhiza radix (12 g), peach kernel (15 g), unprepared Coix lacryma-jobi seeds (30 g), Chinese wax gourd seed (30 g), and Phragmititis caulis (30 g). TCM theory indicates that lung cancer is related to Qi and Yin deficiencies, Qi insufficiency in the spleen and lungs, or pathological changes because of Qi stagnation, blood stasis, and phlegm and toxin accumulation. The JIN formula can replenish both Qi and Yin, strengthen the spleen and lungs, and clear the lungs. The JIN formula can also remove phlegm and activate blood circulation to remove stasis. This study focuses on the efficacy of the JIN formula in vivo in a murine xenograft lung cancer model. This study explains the underlying mechanism of the JIN formula by microarray and proteomic analysis.
2. Materials and Methods
2.1. Cell Line and Culture Conditions
Human lung carcinoma (NCI-H460) cells were obtained from the Cell Line Bank (Shanghai, China) and used in the described experiments. The cell line was cultured in Dulbecco's modified Eagle's medium (Gibco, USA) with 10% fetal bovine serum, 100 U/mL penicillin, and 100 mg/mL streptomycin in a cell culture incubator at 37°C under 5% CO2. The cells were used within 2 passages to 4 passages at the log phase of growth. Aliquots of the cell line were frozen at −80°C until use.
2.2. Experimental Animals
Balb/c athymic (nude) mice (male, 6 wk to 8 wk, ) weighing 21 g to 25 g were purchased from the Animal Center of the Academy of Military Medical Sciences (Beijing, China). The mice were housed under specific pathogen-free conditions according to the guidelines of the Institutional Animal Care and Use Committee of Nanjing University of Chinese Medicine. The animal room was controlled for temperature (°C), light (12 h light/dark cycle), and humidity (%). All laboratory feed pellets and bedding were autoclaved.
2.3. Xenograft Model
The tumor regression model was successfully applied in nude mice to evaluate antitumor activity. This model was used to evaluate the suppression of solid tumor growth by the JIN formula. A total of 1 × 107 NCI-H460 cells in 0.2 mL of culture medium were injected subcutaneously into the flank of each mouse by using a 26 ga needle. After 7 d of observation, a solid tumor mass was excised from the mice inoculated with NCI-H460 cells. When the tumor volume in the nude mice reached approximately 50 mm3, the xenografted tumor models were randomly distributed into four groups: NCI-H460 + saline (mock group), NCI-H460 + 12 mg/mL/d JIN formula (JIN group), NCI-H460 + 20 μg/mL/d diamminedichloroplatinum (DDP) (DDP group), NCI-H460 + JIN formula + DDP (coformulated group, same dosage as in other groups), and saline (control group, without tumor). Six mice were included in each group. The JIN formula was orally administered daily for 15 d, and DDP was injected abdominally for 15 d. A group with no tumor was administrated orally with saline and served as a control group.
2.4. Antitumor Activity In Vivo
All animals were monitored for activity, physical condition, body weight, and tumor growth. The body weight of each animal was measured once every 3 d. The longest () and shortest () tumor diameters (mm) were obtained, and the formula for an ellipsoid sphere () was used to calculate the tumor volume every 2 d. The tumor weights were also measured on the basis of the tumor regression on the final day of the experiment after the animals were sacrificed. The antitumor activities of the treatments were expressed as follows: inhibition rate , where and are the tumor weights of the mock and treatment groups, respectively. The xenografted tumors and other vital organs of the mice were harvested, fixed in 4% formalin, embedded in paraffin, and cut in 4 mm sections for histological study.
2.5. Preparation of Total RNA
Total RNA from the xenografted tumor was isolated with TRIZOL reagent (Invitrogen Life Technologies). We pooled an equal amount of cancer tissues from six individual mouse xenografts in each group (JIN, DPP, JIN + DDP, and the mock groups) to save cost. The RNA was eluted in RNase-free water, and the integrity was verified by electrophoresis on 1.2% agarose gel and visualized with ethidium bromide staining. The concentration was quantified by ultraviolet absorption with a nanodrop spectrophotometer (BioLab Ltd.).
2.6. Expression Profiling Array
The total RNA from the experimental samples was used as a template and reverse-transcribed to generate cDNA. The cDNA was then converted into biotin-labeled cRNA probes by using Biotin-16-dUTP (Roche) by in vitro transcription with the TrueLabeling-AMP linear RNA amplification kit (SuperArray Bioscience). Before hybridization, the cRNA probes were purified with the ArrayGrade cRNA Cleanup Kit (Superarray Bioscience).
The Oligo GEArray microarray series (OHS-044) (SuperArray Inc.) was used to quantify the expression of the 113 genes involved in the 15 signal transduction pathways in cancer (mitogen-activated protein kinase (MAPK), Wnt, hedgehog, signal transducers, and activators of transcription, stress/heat shock, inflammation/nuclear factor-kappa B, survival, androgen/estrogen, and transforming growth factor-beta (TGF-β) pathways, etc).
Purified cRNA probes were hybridized with the membranes at 60°C overnight with slow agitation in a hybridization oven. The hybridized membranes were washed once in saline sodium citrate buffer solution I (2x, 1% sodium citrate/sorbitol buffer) and once in solution II (0.1x, 0.5% sodium dodecyl sulfate (SDS)). Membranes were incubated with alkaline phosphatase-conjugated streptavidin. Thereafter, the membranes were washed and incubated with the CDP-Star chemiluminescent substrate. Detection was performed by exposure to X-ray film. Membrane images were analyzed by the web-based GEArray Expression Analysis Suite software. The relative expression level of each gene was determined by comparing the signal intensity of each gene in the array after background and normalization corrections. For comparison, at least 1 spot intensity had to be more than twice the background intensity, and the spot intensity ratios had to be higher than 2 (for upregulation) or lower than 0.5 and higher than 0 (for downregulation).
2.7. Quantitative Real-Time Polymerase Chain Reaction (PCR)
PCR primers were designed by using the Primer 5.0 software (Primer, Canada) based on the special design criteria for real-time PCR primers (Table 1). The forward and reverse primer sequences and lengths of amplified gene products were as follows. The RNA samples were reverse-transcribed by using Moloney murine leukemia virus reverse transcriptase (Epicentre). An oligo-dT primer was used to prime the reverse transcription. Beta-actin was selected as the reference gene for the normalization of results. Quantitative real-time PCR was performed by using Rotor-Gene 3000 real-time PCR (Corbett Research) with SYBR green (Molecular Probes) as the detection system. The results were analyzed by Rotor-Gene 6.0 software (Corbett Research). Relative expression levels were determined in three repeat experiments (, mean ± standard deviation).
2.8. Sample Preparation for Proteomic Analysis
For the proteomic analysis, we pooled an equal amount of cancer tissues from six individual mouse xenografts in each group (JIN, DPP, and the mock groups) to save cost. Cancer tissues were snap-frozen in liquid nitrogen and stored in a −80°C freezer. To extract proteins, the cancer tissues were grinded under liquid nitrogen with a mortar and pestle, and tissue lysis buffer was added. The solution was then sonicated on ice with an ultrasonic processor (Bioblock Scientific, France) for 90 min. The tissue lysis buffer contained 50 mM Tris (pH 7.4), 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 1x cocktail (0.5 mM Na3VO4, 50 mM NaF, 1x phosphatase inhibitor cocktail, and 5 mM phenylmethanesulfonyl fluoride). The homogenate was then centrifuged at 12,000 g for 1 h at 4°C. Supernatant was collected, and protein concentration was determined by bicinchoninic acid assay. Each sample (70 μg) was separated on 12% SDS polyacrylamide gel. Gels were stained with colloidal coomassie brilliant blue. Twenty-seven individual bands were removed and subjected to gel trypsin digestion by using the In-Gel Tryptic Digestion Kit protocol (Pierce Biotechnology, Rockford, IL, USA). The bands were then analyzed by tandem mass spectrometry (MS/MS).
2.9. Mass Spectrometric Analysis
Tryptic peptide mixtures were separated by Ettan multidimensional liquid chromatography (LC) nanoflow/capillary LC system (GE Healthcare, Pittsburgh, PA, USA) equipped with a trapping column (Dionex/LC Packings μ-Precolumn Cartridge P/N 160454 C18 PepMap 100; 5 μm, 100 Å, 300 μm internal diameter × 5 mm; Sunnyvale, CA, USA) and nanocolumn (Dionex/LC Packings P/N 160321; 150 mm × 0.075 mm inner diameter, C18 PepMap, 3 μm, 100 Å; Sunnyvale, CA, USA). The mixtures were then analyzed by using LTQ-Orbitrap (Thermo Finnigan, Bremen, Germany) with a nanospray configuration. The precursor ion scan mass spectra (m/z 300–1600) were obtained in the orbitrap with a resolution of R = 60,000 at m/z 400, and the number of accumulated ions was 1 × 106. The five most intense ions were isolated and fragmented in a linear ion trap (number of accumulated ions: 3 × 104). The resulting fragment ions were recorded with a resolution of R = 15,000 at m/z 400.
2.10. Mass Spectra Analysis
The Extract-MSn of BioWorks V3.2 (Thermo Electron, Inc., Waltham, MA, USA) was used to generate the mass spectrometry (MS) peak list with the default parameters. The Interactive Chemical Information System peak detection algorithm was used. The SEQUEST algorithm (Thermo Fisher Inc.) was used for the SEQUEST database search, and the spectra were searched against the IPI.HUMAN.v3.58.fasta protein database (79,794 entries) (http://www.ebi.ac.uk/) by using the BioWorks program V3.2 (Thermo Electron, Inc., Waltham, MA, USA). In the Turbo SEQUEST search parameter setting, the threshold for data generation was 10,000, and the precursor mass tolerance for data generation was 1.4 Da. For the SEQUEST search, peptide tolerance was set at 3 Da, and fragment ion tolerance was set at 0.01 Da. PeptideProphet [2] was used to assess the tandem mass spectra quality. The threshold score for accepting individual tandem mass spectra was , which corresponds to a 0.5% error rate in our dataset. One missed tryptic cleavage was permitted.
Carboxyamidomethyl cysteine (Cys_CAM) (+57) was included as a fixed modification for iodoacetamide reduction and alkylation. Given that the proteins were prepared by polyacrylamide gel electrophoresis, cysteines might react with free acrylamide monomers to form propionamide cysteine (Cys_PAM). We included an optional 14 Da in the search to account for potential Cys_PAM. The mass difference between Cys_PAM and Cys_CAM is 14. Methionine oxidation (+15.999 Da) was selected as another optional modification for the database search. Proteins with ProteinProphet P value greater than 0.9 and more than two unique peptide hits were considered as true hits. A randomized database of the IPI.HUMAN.v3.58.fasta was used as a decoy database to calculate the false discovery rate of protein identification. The Perl script used for randomization was obtained from http://www.matrixscience.com/downloads/decoy.pl.gz. The false discovery rate (0.568%) was calculated by the ratio of the number of matches in the randomized database to the number of matches in the IPI.HUMAN.v3.58.fasta database. Keratins were removed from the protein list because these proteins often represent contaminations from sample handling.
The MS/MS data from the cancer and control samples were analyzed by the PeptideProphet and ProteinProphet program for statistical validation by using TPP4.31 [3, 4]. To identify the differential protein expression between two experimental groups (e.g., Sample A versus Sample B), we used the spectral counting method with a Bayesian mixture model [5]. Spectral counts are the average of duplicate LC-MS/MS runs and normalized to the total spectra (5000 × total spectra of the protein/sum of all total spectra of the proteins in the dataset). Significantly differentially expressed proteins were identified with a posterior probability of >0.95 by using the Bayesian mixture model, and the spectral count difference was great than 10. GoMiner [6, 7] was used to find statistically represented gene ontology (GO) biological processes (level 3) with (i.e., ).
2.11. Western Blot Analysis
Cells were lysed in NP-40 buffer (1.0% NP-40, 10 mM hydroxyethyl piperazine ethanesulfonic acid, pH 7.4, 150 mM NaCl, 5 mM NaF, 2 mM Na3VO4, 5 mM Na4P2O7, 10 g/mL aprotinin, 10 g/mL leupeptin, and 1 mM phenylmethylsulfonylfluoride). Equal volumes of cell lysate were subjected to SDS-polyacrylamide gel electrophoresis (12.5% gel). Proteins were then electrotransferred into a nitrocellulose membrane (GE Water and Process Technologies, USA). The membranes were blocked in a solution of 5% nonfat dry milk in Tris-buffered saline—Tween 20 buffer (20 mM Tris, pH 7.6, 500 mM NaCl, and 0.5% Tween 20) for 30 min followed by incubation with a primary antibody for at least 2 h. The membrane was then washed and treated with horseradish peroxidase-conjugated anti-mouse immunoglobulin or anti-rabbit immunoglobulin as indicated. Immunodetection was performed by using West Pico (Pierce Chemical, Rockford, IL) or West Dura (Pierce Chemical) followed by imaging on an Image Station 2000R (Eastman Kodak, USA).
2.12. Statistical Analysis
The data were analyzed by SPSS 19 software and presented as mean ± standard deviation. The significance of the difference between the mean of the mock and treatment groups was analyzed by using one-way ANOVA followed by Dunnett's t-test correction and paired t-test. Statistical significance was determined at the level of and .
3. Results
3.1. The JIN Formula Has Similar Effects as the Standard DDP Treatment but Is Less Toxic Than DDP
To study the toxicity of the JIN formula, we treated NCI-H460 xenografts that were grown subcutaneously in nude mice with saline, JIN formula, DDP, and JIN formula + DDP (coformulated group) for 15 d. A control group with no tumor was also included. One mouse in the mock group died on the 11th day of treatment. A mouse in the DDP and coformulated group died on the 15th day before sacrifice. Other mice in these two groups significantly lost weight and displayed slower activities and dry skins. All mice in the JIN group were alive and had stable weights, normal activities, and moist skins (Figure 1).
This result indicated that herbal treatment and chemotherapy prolonged the lifespan of the mice. However, chemotherapy is toxic to the mice, whereas herbal treatment showed little toxicity compared with the saline group as demonstrated by the body weight loss.
All treatment groups (DDP, JIN, and JIN + DDP) showed inhibited growth of the NCI-H460 cell-transplanted solid tumor compared with the mock group (Figure 2). Significant differences in the final tumor weights () and volume () were found between each treatment group and the mock group after sacrifice (Figure 2). The tumor weights of mice treated with DDP, JIN, and the coformula were inhibited by 63.99%, 55.03%, and 65.79% (), respectively, after 15 d of treatment compared with those of mice administered with saline only.
3.2. Histological Changes Induced by JIN Formula Treatment
Histological examination showed that the tumors of the mock group were solid masses composed of densely arranged cells without distinct cell differentiations. The cells were heteromorphic and had large nuclei that contain vesicles and obvious nucleoli. Reverse proportions between the nucleus and cytoplasm, high rates of mitosis and angiogenesis, infiltrative growths of tumor cells, and large areas of necrosis and hemorrhage were observed. No significant difference in cell morphology was found between each treatment group and the mock group. However, the tumor cells in the treatment group were less densely arranged, with patchy sparse cell arrangements, enlarged intercellular spaces, vacuoles in the cytoplasms, scattered intense stains in nuclei, scattered pyknosis of tumor cells, and varying degrees of degeneration. Tumor cell metastasis was not found in the lungs and liver (data not shown). The results indicated that the formula can promote the degeneration and death of tumor cells and induce apoptosis, thus inhibiting the growth of lung cancer. These data suggested that the JIN formula could be safely administered as a novel therapeutic agent. Optimization of the dose and dosing schedule might yield a higher antitumor efficacy (Figure 3).
3.3. Gene Expression
To investigate preferentially altered signal transduction pathways in H460 xenografted tumors treated by herbal formula, the Human Q Series Signal Transduction in Cancer Gene Array, which includes marker genes with functions related to cell signal transduction pathways, was used. In the JIN group, the CDKN1C gene was upregulated and the PTCH2, TCF7, and WSB1 genes were downregulated with twofold differences in ratios, as shown by the t-test. The results were reconfirmed by real-time PCR with CDKN1C and PTCH2 primer pairs (Tables 2-3, Figure 4). The expression of these genes indicated the preferential change in the hedgehog and TGF-β signaling pathways in H460 xenografted tumor regulated by the JIN formula.
Furthermore, the coformula treatment of JIN and DDP also inhibited the stress/heat shock pathway, which involves the HSF1, MYC, and FOS genes (Table 4).
3.4. Proteomic Analysis of Cancer Cells Treated with JIN and DDP
We conducted a comprehensive mass spectra analysis of the JIN formula, DDP, and mock groups. We identified 1,131, 831, and 1,326 proteins in the JIN formula, DDP, and mock groups, respectively. By using Booth's Bayesian mixture model to compare the spectral count data for shotgun proteomics [5], we identified 40 (corresponding to 36 proteins) and 178 peptides (corresponding to 84 proteins) that were differentially expressed between the mock and DDP groups and between the mock and JIN formula groups, respectively (see Supplementary Tables 1 to 4 available online at http://dx.doi.org/10.1155/2013/160168). We found that the expression of the HSP90AA1 and HSPA1B proteins was significantly reduced in the JIN group compared with that in the mock group. HSPA1B was also significantly reduced in the DDP group compared with that in the mock group.
GoMiner analysis revealed that the differentially expressed proteins between the JIN and mock groups were enriched in GO:0006977 (DNA damage response signal transduction by p53 class mediator resulting in cell cycle arrest), GO:0006915 (apoptosis), and GO:0016032 (viral reproduction) (Table 5). By contrast, the differentially expressed proteins between the DDP and mock groups were enriched in GO:0065004 (protein-DNA complex assembly) and GO:0006414 (translational elongation) (Table 6). These results suggested that the JIN formula and DPP act on different biological processes.
We identified proteins and protein families that were downregulated in the JIN group compared with these in the mock group. These proteins include several histone family proteins and two heat shock proteins (HSPs), namely, heat shock 70 kDa protein 1β (HSPA1B) and HSP 90 kDa alpha, class A member 1 (HSP90AA1). Several proteasome subunits (PSMA3, PSMA7, and PSMA8) and cellular structural proteins (Lamin A/C, keratin 18, tubulins, transgelin, etc.) were upregulated by the JIN formula relative to the mock control group. We selected HSP90AA1 for validation by Western blot, which shows that HSP90AA1 was downregulated by the JIN and DPP treatments (Figure 5). The downregulation was more significant in the JIN treatment group compared with that in the DPP group.
4. Discussion
Chinese or oriental herbal medicine has long been used for treating cancer. Single herbs are seldom used alone compared with herbal formulae, which uses the synergy and interactions among various phytochemicals present in different herbs to achieve therapeutic efficacy and targets multiple biological and pathological processes while minimizing side effects.
TCM formulae are rich in potential cancer chemopreventive and therapeutic agents. However, rigorous and systematic evaluations are necessary to establish the efficacy of herbal formulae and transform traditional herbal practices into evidence-based medicine. We evaluated the anticancer activities of the JIN formula, which is an ancient herbal formula recorded in the classic TCM book Jin Kui Yao Lue (Golden Chamber). The results showed that the JIN formula significantly delayed the growth of subcutaneous human H460 xenografted tumors in vivo relative to the mock control group.
Gene array analysis of signal transduction in cancer showed that the JIN formula acted on multiple targets in the MAPK, hedgehog, and Wnt signaling pathways in the H460 xenografted tumor. JIN upregulated two tumor suppressors, namely, CDKN1C and interferon regulatory factor-1 (IRF-1). Abnormal cell cycle regulation is the important reason of excessive cell proliferation and tumorigenesis. Cell cycle progression is regulated by balanced interactions between cyclins and cyclin-dependent kinases (CDKs). The suppressive effect of cyclin-dependent kinase inhibitors (CDKIs) on cyclin/CDK complexes is among the many mechanisms that control normal cell cycle progression. Cell cycle progression is negatively regulated by proteins from two families, the inhibitors of cyclin-dependent kinase 4 (INK4) family [CDKN2A (p16), CDKN2B (p15), CDKN2C (p18), and CDKN2D (p19)] and the CIP/KIP family [CDKN1A (p21), CDKN1B (p27), and CDKN1C (p57)]. The protein encoded by CDKN1C is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and the Beckwith-Wiedemann syndrome, thus suggesting that this gene is a tumor suppressor candidate [8]. The anticancer mechanisms of the JIN formula may seek a new breakthrough by the further study of this protein family. IRF-1 was originally identified as a regulator of IFNα/β. IRF-1 expression is considerably upregulated during viral infections and stimulations by the interferon family. Increasing evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. In human tumors, IRF-1 is deactivated to prevent apoptosis and cell cycle arrest by genetic mechanisms [9].
The downregulated genes PTCH2, TCF7, and WSB1 are related to the embryonic signaling pathways Hedgehog and Wnt. The inappropriate reactivation of these pathways in adult cells promotes tumor growth [10]. Many studies showed that lung tumors are caused by the activation of these embryonic regulatory pathways [11, 12]. Hedgehog signaling plays a key role in a variety of processes, such as embryogenesis, maintenance of adult tissue homeostasis, tissue repair during chronic persistent inflammation, and carcinogenesis. Hedgehog signals protect cancer cells, particularly cancer stem cells [13]. Hedgehog signaling is frequently activated in esophageal cancer, gastric cancer, and pancreatic cancer due to transcriptional upregulation of Hedgehog ligands and epigenetic silencing of HHIP1/HHIP gene, encoding the Hedgehog inhibitor. However, Hedgehog signaling is rarely activated in lung cancer due to negative regulation by the canonical WNT signaling pathway. The Wnt pathway may serve as a potential target in the development of therapeutic agents. The blockade of the Wnt pathway may be considered in formulating new treatment strategies in lung cancer [14]. Given the current and increasing availability of drugs that inhibit Hh and Wnt signaling, an understanding of the role of Hh and Wnt in lung cancer pathogenesis might lead to the development of new therapies. Furthermore, the co-formula treatment of JIN and DDP also targeted the stress/heat shock pathway, specifically for the HSPA4, HSF1, MYC, and FOS genes.
HSPs are encoded by several gene families and have essential roles in cell survival, tumorigenesis, and tumor progression. The HSP70 family proteins, which are named according to their approximate relative molecular mass, contain at least eight members that are almost ubiquitously expressed [15]. More than 99% of the amino acids of the two major HSP70 proteins, namely, HSP70-1a and HSP70-1b (encoded by the HSPA1A and HSPA1B genes, resp.), have been identified. These proteins are initially found in cells under stress [16, 17]. HSP70 is closely involved in programmed cell death protection through interactions with several key regulatory proteins, along with HSP90 and several cochaperones. HSP70-1 proteins are overexpressed in many types of tumor, and this over-expression is often correlated with tumor malignancy, progression, poor prognosis, and metastasis [16]. The overexpression of HSP70-1 induces cell transformation [15]. However, the expression and regulation of HSP70-1 in lung cancer cells are rarely studied. Our analysis showed that HSPA1B, which also belongs to the HSP70 family, was highly expressed in the mock group. After JIN formula treatment, the expression of HSPA1B was downregulated significantly. Cancer metastasis was not observed in the lungs, liver, and brain of mice from the JIN group, thus suggesting that distant tumor metastases was prevented by the JIN formula.
HSP 90 kDa (HSP90) is a molecular chaperone that maintains the function of numerous intracellular signaling nodes utilized by cancer cells for proliferation and survival. HSP90 is also involved in a number of human pathological states such as ischemia and autoimmune diseases. Lung cancer progression is also influenced by HSP90. HSP90α is a cytoplasmic protein that is highly conserved in the process of biological evolution. The HSP90 chaperones in humans are encoded by two distinct genes, namely, HSP90α and HSP90β. Differences in their respective modes of regulation have been observed; HSP90α is more inducible than HSP90β. HSP90α is required for the conformational maturation and stability of multiple oncogenic kinases that induce signal transduction and proliferation of lung cancer cells. HSP90α is also important in modulating tumor cell apoptosis. Moreover, HSP90α facilitates the migration and proliferation of tumor cells and is associated with the poor prognosis of specific cancers. Changes in the proteins encoded by HSP90 may be caused by changes in the nature and expression of HSP90α. These changes may participate in the development of lung cancer. Considering the increased role of HSP90α in tumor cells, the expression of the antiapoptotic response of HSP90 in lung cancer incidence and the process of encoding HSP90α and HSP90AA1 in single nucleotide polymorphisms may be interrelated and associated with lung cancer. HSP90 is an adenosine trisphosphate- (ATP-) dependent molecular chaperone that maintains the active conformation of clients in coproteins of cancer cells. The inhibition of HSP90 leads to the inhibition of tumor growth and metastasis [17]. HSP90 is also detected on the plasma membrane of tumor cells and its expression is correlated with metastatic potential [18]. In the current study, we discovered that HSP90AA1 was highly expressed in the mock group. This study is the first to report the downregulation of HSP90AA1 by the JIN formula relative to the mock group. HSP90AA1 might serve as a potential prognostic marker or a candidate therapeutic target of H460. HSP90AA1 might also be a viable marker for H460 without distant metastasis.
We found that GO:0044237 (cellular metabolic process) and GO:0006139 (nucleobase, nucleoside, nucleotide, and nucleic acid metabolic process) (Table 5) were enriched by differentially expressed proteins in the JIN group compared with the mock group. HSP90AA1 and HSPA1B were downregulated by the JIN formula. Aldolase A (fructose-bisphosphate) was upregulated in the JIN group compared with that in the mock group. HSP90AA1 is related to GO:0034621 (cellular macromolecular complex subunit organization), GO:0072395 (signal transduction in cell cycle checkpoint), and GO:0044249 (cellular biosynthetic process, etc.). HSP90 is an active ATP-dependent chaperone involved in the assembly and regulation of signal transduction pathways by activating specific client proteins [19]. HSP90AA1 plays an important role in each step of the cell cycle and tumor formation. The function of HSP90 is reflected by the polo-like kinase stability. The inhibition of HSP90AA1 in HeLa cells results in cell cycle arrest either at the G2 stage or metaphase-anaphase transition [20]. Our results suggested that the JIN formula acted on the maintenance of the cell cycle and signaling processes. The potential mechanism of the JIN formula is shown in Figure 6. Further investigation should be conducted to reveal the detailed mechanism of the JIN formula.
Authors' Contribution
X. Zhang, H. Fu, and B. Lin designed the research; L. Zheng, M. Jiang, W. Zhang, H. Zhang, F. Xiong, Y. Yu, M. Chen, J. Zhou, X. Dai, and M. Wang performed the research; L. Zheng, M. Jiang, and W. Zhang contributed equally; Y. Tang, M. Jiang, G. Cheng, and J. Duan designed the herbal formula; L. Zheng, M. Jiang, W. Zhang, H. Zhang, B. Lin, and X. Zhang analyzed the data; and L. Zheng, B. Lin, H. Fu, and X. Zhang wrote the paper.
The authors thank the members of the Fu Laboratory of the Emory University and Jiangsu Key Laboratory for their research on the TCM formulae and the Nanjing University of Chinese Medicine for their assistance and enlightening discussions. This study is supported in part by the National Science and Technology Pillar Program in the 11th Five-year Plan of China (Grant no. 2006BAI11B08-01, for H. Fu and X. Zhang), Priority Academic Program Development of Jiangsu Higher Education Institution (for X. Zhang), and the Ministry of Science and Technology of China (Grant no. 2006DFA32950, for B. Lin).
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Denver Post writer Adrian Dater reported yesterday that third year center Matt Duchene is still out indefinitely with a knee injury. This is not the news the Avalanche were hoping for heading into the stretch run out of the All-Star break. The Avalanche's 26-23-2 record is good for 54 points and ninth place in the Western Conference.
The Avalanche have 31 games remaining in their season, at least one fewer than everyone else in Western Conference. To secure a playoff spot, they probably need to win over 20 of those games. That is going to be extremely difficult without Matt Duchene.
The bright spots for the Avalanche must continue to perform. Even more emphasis is going to be put on the talents of breakout center Ryan O'Reilly, rookie Gabriel Landeskog and Peter Mueller who recently returned to the line up. T.J. Galiardi playing at the top of his game could also be a huge asset to the club.
The underachievers on the team are going to have to step up. Paul Statsny leads the team in salary, but has not played great the last two seasons. With Matt Duchene out for the foreseeable future, he needs to start scoring again. Milan Hejduk's slump is also worrying for the club. If does not reach the 20 goal mark, will this be the Czech's last year in the NHL?
On the defensive side, everyone needs to step up. Jan Hejda and Erik Johnson lead this list. However, the defense has committed too many costly turnovers overall leaving the goalies out to dry.
Speaking of goalies, Semyon Varlamov will start in net tonight against Edmonton. He was demoted to the back up role, but after Giguere's two losses he appears to be back in the mix. I think Giguere gives the team the best chance to win down the stretch, but he still should not play too many games and tire himself out.
So will the Avs prevail? Only if everyone on the team steps up and most likely only if Matt Duchene is not out of the line up too much longer. If they are out of the playoffs, it's a sign that this team has not taken big enough steps in the right direction.


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New year, new layout. If you read this blog through RSS or something similar, check it out at the main site.
Update on my book resolution from 2011:
I only read 45 books, which I am still happy about. I could have rushed through 5 books in the last 2 days but I didn't want to.
You can see what I read and where I went wrong (Hello, February and November) here.
I'm going to continue to track what I read this year because I think it's interesting, but I'm not making any resolutions. If you find it interesting, too, follow here.
My sister is big on resolutions but I don't really make them. She kind of pressured me into telling her my goals for the year, though, so here they are:
- convocate
- get a full time teaching job for September
- move out
- go to at least 3 new countries (Europe trip in July for graduation hopefully...it's in the works.)
What are yours?
And now, here is DJ Earworm's latest mash-up of the 25 biggest hits of 2011 for the US.
I did a post about him last year.
Of his new mashup, he says, "2011 gave us songs of regret and anger, pride and perseverence, and lots of fire. When someone's taken everything from you, what do you do?"
Once again, the focus is on the positive. Even with the world going boom, people are still partying and dancing. My favourite lyric is "I got my pop, I got my dance, I got that rock and roll/ You can take everything but you can't take my soul."
I think that sums it up nicely.
So far my 2012 has been spending time relaxing with friends and family, getting ready to go back to school and start a new job, and looking forward to the year. I think it's going to be a good one!


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The Cerny Brothers, Tyler Lyle
Bootleg Bar
2220 Beverly Blvd
Los Angeles, CA, 90057
Doors 8:00 PM / Show 9:00 PM
This event is 21 and over
Miner is a Los Angeles/Silverlake folk-rock group formed in 2012 from the creative nervous breakdown of songwriter Justin Miner, which led him to take an extended break from the music world. He subsequently left Los Angeles to travel the jungles of Central and South America and the redwoods of California's central coast. He returned home rejuvenated, built a small studio in his bedroom with one microphone, and recruited family members (wife Kate Miner, brother Jeremy Miner) to sing and stomp, and Miner was born. When the recording was finished, Justin uploaded first single "Hey Love" to Soundcloud, and within a few days it unexpectedly reached #2 on the Hype Machine single charts. Justin quickly recruited some friends and put together the current live lineup, which includes Justin Miner (vox, guitar), his wife Kate Miner (vox, mandolin, ukulele, harmonica), his brother Jeremy Miner (banjo, lead guitar), his cousin Amanda Koosed (keys), and longtime friends Justin Krook (bass) and Dave Schechtman (drums & percussion).
Miner finds a unique groove within the recent indie-folk revival while still further blurring the genre lines between singer-songwriter, folk, and rock. They self-released a six-song EP called "Hey Love" in September, currently only available at shows. They are now writing new material for their debut album and continuing to perform live.
The Cerny Brothers have been playing music together since they were just young bucks, coming up together in a rural Illinois town. While the music itself has taken on different forms over the years, it has always had one simple and cellular foundation in which it is firmly based: brotherhood. That's right; there are no gimmicks or posturing to be found here. Their kinship is legitimate. It's one that has stood up against the test of time, carrying them from their adolescent and early adult years in the Midwest, to their long journey west to their current base, Los Angeles.
Since the release of their debut album Dream (recorded and produced by Eric Fink of nationally acclaimed act The Giving Tree Band at Crooked Creek Records), brothers Robert and Scott have been hard at work in Los Angeles. In a short amount of time, they have been building a loyal following and turning heads with their energetic, yet intimate live shows. After initially performing as a duo, the brothers were honored to welcome drummer Cody Fontes and upright bassist Gabe Davis to the family.
The music, rooted in a time-honored blend of Folk and Americana styles, has been shaped by long instilled values of hard-work, dedication, and honesty. The Cerny Brothers play music that inspires a sincere and genuine connection between them and their fans – a connection that is unique, timeless, and simply cannot be ignored.
A recent transplant fom Atlanta, GA to Santa Monica, CA, Tyler Lyle has self-released five independent projects in the last four years. A self-described 'old soul', Tyler's lyrics carry the weight and understanding that go far beyond his twenty-five years. His latest album, The Golden Age & The Silver Girl, is a collection of songs written in and in the aftermath of a relationship. Recorded in one day, the day before Lyle boarded a plane for the superior California weather, the album is a singular statement; an over-exposed Polaroid of a point in time with affecting lyrics, carnival-esque folk production and an honest self-awareness that makes this an instantly relatable classic. The Golden Age & The Silver Girl was self-released on digital platforms on February 7th, 2012.
Upcoming Events
Bootleg Bar
- Sorry, there are currently no upcoming events.


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Guild Wars 2
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- Boards
- Guild Wars 2
- Thinking of getting this, convince me (honest opinions please)
Reasons why I enjoyed WoW (and WoW style games).
- The class and race diversity. I enjoyed how it's hard to have to identical characters in the game.
- The fact that you can play as a DPS/tank/healer specs, and that there were varying ways to play specs.
- The diversity of the game. You can go and solo play quests by yourself, or do PvP/raids with others. Or simply go off and meander and build up professions to make money.
- I love the open world style of WoW, LoL style games where you're stuck in a dungeon/limited area bore me a ton
What I didn't like about WoW
- You had to constantly stay playing to keep atop the game
- The monthly fee
- The constant crappy "upgrades" to the game (like cata and that pandaria crap).
So I'm looking in to guild wars 2. I'm intrigued by it greatly. So it's up to you guys to sway me either way, does it sound like GW2 is something that I would enjoy and if not, is there another recommendation you have? Please be honest, don't just piss and moan that the game sucks if you don't like it.
GT = xxCARLSONxx
PSN = xvCARLSONvx
OkFirst, by and large don't ask trollfaqs on whether you should get a game, especially an MMO. Just read a broad consensus of reviews and watch some youtube videos. That's all you need to do. People here will only give u agenda based opinions, with the rare genuine one thrown in.
Secondly, why did you think WOW went downhill after WOTLK?
first of all. ignore brackie.
second. read this topic.
CAPCOM = Conning All Players Cash Over Morals
No worries though, I'm almost certain GW2 is for you, since no one has taken the xxCARLSONxx tag. ...
Well maybe, but you definitely got XxXcArLsOnXxX in the bag.
Brackie posted...
OkFirst, by and large don't ask trollfaqs on whether you should get a game, especially an MMO. Just read a broad consensus of reviews and watch some youtube videos. That's all you need to do. People here will only give u agenda based opinions, with the rare genuine one thrown in.
I just lost interest with how much they changed everything. At the risk of sounding like an ass, I liked how you had to actually stick to a rotation, and alter it with different boosts that equipment provide. It felt like once Cata came out, the game was catered to the casual player and took the pride of playing well away. I went from being one of the best ret/holy paladins on the server (honestly not trying to brag), to having people who were mediocre in wotlk/bc become on par with me in cata. That pride of being good was diluted in cata.
GT = xxCARLSONxx
PSN = xvCARLSONvx
Kagerasu posted...
No worries though, I'm almost certain GW2 is for you, since no one has taken the xxCARLSONxx tag. ...
You're implying I'm childish because I wanted my GT to be my last name? Maybe I should have went with kushedout420, or ownedyou01205054623. Sorry, but I'm not a stoner and I don't live in the matrix
GT = xxCARLSONxx
PSN = xvCARLSONvx
tehdud posted...
first of all. ignore brackie.
You wish you were me.
NCpwn: That's cool. D3 was a fun game.
Xeeh Bitz best hits: http://www.gamefaqs.com/boards/938738-guild-wars-2/64689532
ahahahaha good one
CAPCOM = Conning All Players Cash Over Morals
carlsoto posted...
Ok, so I used to really enjoy playing WoW (before things got messed with post WoTLK) and I enjoyed it alot. I also played SWTOR, and I enjoyed it, but not nearly as much as I had hoped. I'm looking for a new MMORPG to play and haven't found one I like. I tried Diablo 3 as a substitute, but that got too repetitive and boring for me.
Firstly, ignore tehdud..guy has a serious axe to grind and has daddy issues..but lets not go there. I will try to answer your initial query as succinctly as I can:
Going by what you said about WOW:
-There are 5 different races all very unique from each other and there is a reasonable amount of customisation on offer from faces, hairs, body size and even a biography which influences your pesonal story.
- The game does not have a traditional trinity in that every player can tank/dps/heal depending on what skills/traits and weapons you use. Some people have found it unique and freeing , some people find that you are a jack of all traits, master of none. At the start i wasn't sure, but now that i am used to it, personally i would find it hard to go back to the old system.
- Like most MMO's you can do you own thing, go off and solo, do achievements, jumping puzzles, dungeons, world bosses, pvp, W v W. There is soemthign to do for everyone. hardcore raiders from previous games have complained that there is not enough end game or raid style things to do, but sections of the community are glad there isn't..Have to wait and see where the game goes in reagrd to this.
Goin on your negatives of WOW:
Well firstly, no monthly fee so thats not an issue. You don't have to keep grinding to get best gear or else you fall behind either. They ahve recently introduced a new tier that si currently restricted to a back piece and rings which has divided the community but initially the margins are so small, that they won't make a major difference to your numbers or performance.
As for upgrades, so far there has been new content monthly ranging from really cool liek the October halloween one to poorly implemented like Novembers Lost shores which was bugged, poorly thought out and generaly a bit of a misfire. December will have the wintersday stuff and Jan and feb promises to have a whole expansions worth of content put together ..we shall see.
Generally, I really like the game however i have a few criticisms of it. You cannot dual at this stage, there are still a lot of bugs, no guild halls, pvp is limited to 5 maps atm, some classes seem a lot more usefull and playable than others at this stage, some of the bosses have ridiculous hp and seem cheap and unfair...
But overall, I really like it..MMO wise I can't see anything coming up other than Titan to touch it imo..
CruxisInhibitor 4 years ago#10
Honest opinion without going into depth on all the fundamental issues the game design poses, it's not a good time to play. It's really a premature game and feels bad when you get right down to it. It seems to center around shallow gear grind as the meat of gameplay. There are no roles in combat, skills are static, and specs are super-homogenized. Combat just doesn't feel on par with how it should be to retain a player base depth-wise. Wait a few years or at least till the first expansion comes out. ArenaNet has no clue what they're doing right now, the community is volatile, and the game is in limbo for a lot of people until they introduce some Quality of Life changes. Come back in a year or so, then maybe i can recommend. Otherwise, on merit, this game is 100% better than WoW, if only because of questing structure and content delivery.
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- Thinking of getting this, convince me (honest opinions please)
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