I am reluctant to criticize my friends at the Revolutionary Communist Party (RCP, USA) but I do so in the hope that they will correct a mistaken campaign.
They are, after all, the best hope overall – the only hope for an organized force in this country - to lead a movement to overthrow this despicable government and the necessary steps that must be taken, now and after. And when I speak of the government I mean not only Trump, but his vice-president Pence, and this government as a whole based on its plundering the planet and exploiting people, here and abroad. The RCP is the only organized force that I know of even entertaining, and working for, the people to take the stage of history. Everybody else seems committed to some version of riding the bourgeoisie's coattails, where the people's role is at most as spectators, not as participants, genuinely engaged.
Thus, I make these and similar remarks not without a lot of consideration since I have learned so much from the RCP over the years, have worked with many of them through decades in various roles, including most recently as a World Can't Wait's Steering Committee member, have great respect for what they do, the sacrifices they always make to do what they do, and have become what I am in no small degree because of Bob Avakian's works in particular.
It is not easy to do what they do. To declare openly that you are a revolutionary communist alone is hard and most groups don't even dare to do that, let alone all that entails in living up to that! It's in the spirit of agreement that I raise this criticism.
One of the things that I have learned from Avakian is to fight for what you think is objectively true because it is only through that contention between differing versions of the truth, measured against empirical reality and practice (historic and international) that we determine how best to get closer to the truth so that we advance humanity's historic quest for truth.
This is not a matter of sheer rhetoric or the tossing about of differing ideas for the sake of doing that. When humankind first figured out how to use fire and keep themselves warm and cook food, or learned to sail on the sea without capsizing, or fashion arrows that flew through the air, or how to cure diseases such as pneumonia with penicillin, they didn't keep these breakthroughs to themselves but these inventions spread among the people, even before cash rewards existed. Einstein and those before him were not motivated mainly by extrinsic material rewards, but the pleasure of figuring things out.
Let me now proceed to the heart of my disagreement: I do not agree with the RCP's role in trying to organize people in this country around Trump and Pence's fascism. The dispute here does not arise because I disagree with them that Trump and Pence are fascists, because they unquestionably are. Nor do I disagree with them that these fascist measures must be fought tooth and nail. My dispute with them grows out of the RCP making the Trump's and Pence's fascism the leading edge of their organizing others around.
The fact that Trump and Pence ARE fascist and are busy everyday trying to and installing it through various means such as in immigration, prison policies and other institutional measures, in part by executive action and appointments, IS a feature of what they doing. But it is one thing to fight against these measures – which must be done – and another thing to make that effort the heart of what you are doing.
There are a number of dimensions to this. Let me take them in turn.
The first question that arises is: what IS the nature of the situation we face? We need to be clear on this more than anything or else everything else that flows out of our assessment of the situation will be compromised by a mistake made in that primary assessment. Having said that, it is practically axiomatic that you cannot judge things merely on the basis of what everyone or a lot of people ALREADY see and think they know. If correct, your assessment practically by definition is only going to be fully understood by a much smaller number, even conceivably as small as one person or a few people, especially in the earlier stages of a thing.
The very first question that I pose here itself has many different dimensions to it, so it must be first broken down into its parts. I offer these parts initially in no particular order.
First, there are the numerous speeches that Andy Zee has given about why the NO! fascism campaign must be waged and how. Andy is spokesperson for Revolution Books and has delivered a number of keynote addresses on the NO! movement. It seems fair, therefore, to take his words – and those of RCP Chair Bob Avakian - as representative of the leadership of the NO! movement. While I have read through and listened to all but one of several talks by Andy on this topic, I am left unconvinced and frankly bored by his presentations. This surprised me at first because he is not a boring speaker, as I have shared a podium with him on another topic. Mine is a reaction to his delivery but more than that, to the actual content of what he is saying about NO!
We have recognized that there are two windows that are still open that make it possible to do what we are calling for. First is that the Trump/Pence Regime has not, as yet, been able to fully institute fascism. They have made significant progress, they have plans in the works, but there is still an opening. As we and others have pointed out, it would only take one serious international or domestic incident for that window to suddenly slam shut with the regime taking "emergency" measures. And even without such an incident, things can reach a point through executive measures and laws that the regime pushes through, where the window closes in that way—with the result that fascism is consolidated.
In contrast to that analysis, I have written before (e.g., in my 2011 book Globalization and the Demolition of Society) the following: the executive branch of government since Reagan's presidency has step-by-step been concentrating more powers in its hands and moving towards a more fascistic style, regardless of which party holds the White House and regardless of who holds a majority in Congress. Indeed, if you look closely at what have been the policies – and not what the various presidents have said about what they stand for – then you will see that what matters is chronology rather than party or individual. That is, Obama, for example, was worse than Bush Jr., and Bill Clinton was worse than Reagan and Bush Sr., with Obama worse than all of those who came before him from Reagan on. This is true regardless of whether we look at domestic or foreign policy. Obama made no secret that he admired Reagan more than all of his predecessors and Obama's foreign policy was to the right of Bush Sr. Obama's DOJ, for example, went after the one active CIA person who actually publicly condemned the CIA's concerted practice of torture, John Kiriakou, for saying that he objected to torture and that the CIA was in its policy using torture, in a media interview, and imprisoned him for twenty-three months, after Obama's DOJ under Eric Holder revived the Kiriakou investigation after Bush Jr.'s DOJ ended up dropping its lengthy investigation of Kiriakou. Obama also deported more undocumented immigrants than Bush Jr. And so on.
While the media have severely underplayed the fascist measures that Trump and Pence are instituting, the idea that Trump and Pence will get away with this and end up prevailing is itself highly questionable. The picture that the RCP consistently paints of this regime is that Trump and Pence are getting their way. This is strange, not because there is no historical trajectory to point to – which I just did in the last paragraph – but this RCP depiction of Trump and Pence getting their way is belied by opposition to them showing up all over the place, including many in the ruling class itself.
If Hillary Clinton had won the election and not taken her win for granted, paying attention to Wisconsin, for example, what would the RCP be mobilizing people to do against a Clinton Administration? The answer, of course, is that they'd be struggling against the Democrats in the White House and the dire threat of global warming et al. This would make their current stance against fascism seem odd.
Fascism is not the normal way that this country has been ruled. While more and more people are coming to see the qualitative change that the Trump/Pence Regime is bringing, we have a society-wide struggle to wage with people to recognize and come to grips with the reality that with the election of Trump there is a fascist qualitative change in the social, political, and cultural norms of how this society is governed and ruled. The abnormality of Trump consistently gets focused on his narcissistic psychology and/or his financial and other misdeeds, and what is not confronted is the radical tearing up of the norms of society and in its place new fascist norms being cemented into place.
It is true that there is a real difference between fascist norms and bourgeois democracy. But if you are waging a fight which treats fascism as the main danger, what are you mobilizing many people to do: fight to restore and/or protect bourgeois norms? Isn't that at least problematic? It certainly shows up in the numerous talks that Andy Zee has given: in the entirety of what he has said, no really new material is presented and no events, persons, or processes are further newly really illuminated by that analysis. It is almost as if Andy doesn't wholly believe it himself, so much he simply repeats things a lot.
Trump is not blundering. Nor is he on an out-of-control, self-destructive ego trip. Trump is calculating. Trump is moving. He is tearing up the legitimating norms of this country—the principles that politicians are supposed to pay lip service to and the procedures through which government is supposed to proceed—and he is doing this consciously. He is setting the new norms that he believes to be necessary for "American greatness"—a USA up against tremendous challenges and contradictions. Trump, and the regime he leads, stands for unapologetic, violent, lynch-mob-style white supremacy... to replace the systemic and systematic but hypocritically denied white supremacy enforced by the police, the courts, and a thousand other institutions.
In doing so, Trump is calling the bluff of all the established politicians and commentators. He is defending, energizing, and emboldening the core of his base. He is setting his norms, the norms of fascism, in place at a breakneck pace. Yet none of the politicians criticizing Trump and or tut-tutting against racism will dare call Trump the FASCIST that he is. None of them will say that the Trump/Pence regime must go NOW. Let alone concretely proposing how to do that. And meanwhile, the juggernaut rolls on. Waiting and hoping for them, for someone "up there," for someone beside yourself to take action... to stand up... to organize... is worse than wishful thinking; it is irresponsible at a time that demands moral responsibility and political accountability.
This deserves some teasing apart. First, to say that the rest of the ruling class is "tut-tutting" racism and that none of them have called for their ouster NOW is not true. Many are calling (e.g., Tony Schwartz, The Art of the Deal's ghost writer, Al Gore, and others have called for Trump's resignation). It is true that nearly all of them focus on Trump and not both Trump and Pence, but this is a growing political crisis and Pence is neck deep in it too. If Trump is forced to resign and there is a powerful surge from below, do you not believe that the masses will also be anxious to get rid of Pence too? Trump's Manufacturing Council he was forced to disband before the CEOs in it did it first after Trump revealed his true self at his Tuesday, August 15, 2017 press conference.
Second, to say that "the juggernaut rolls on" is peculiar given how much his surprise election has resulted in and intensifies how many leaders and members of the public are outraged, saying so, and doing what many are doing to interfere with this regime. To describe Trump and Pence as a "juggernaut" is to ignore just how much trouble they have gotten into. Look at how many of his administration have been fired or resigned. Look at the fact that most Americans disagree with Trump's tweets. Do you really think the US imperialist empire can stand by and want their secrets let go willy-nilly as Trump has demonstrated time after time? I could go on and on with this point.
Fascism thus tears the mask away of "by public consent" and the interplay of different interest groups and is the transparent rule by the bourgeoisie where dissent is criminalized (even in bourgeois ranks) (this last point not made in the quote above) and rule is not through appeals to fairness or reason, but through open terror.
By this definition, Trump and Pence do cohere various strands and do foment direct brutality. Certainly, this was and is true at Trump's rallies. In his recent speech to police, Trump did just that, saying that police should be more brutal, not less. What kind of response did he get? The police have been besieged rightly so for their murders and brutality towards especially black and brown people and every week it seems another several cases occur. Yet police chiefs and rank and file police's public reaction to Trump's remarks was to reject what POTUS was saying, rather than greet those remarks as welcome or at least be quiet. At best, Trump's words make PR by the police more difficult, not less. This also is not to say that police violence against black and brown people has lessened, because it hasn't, but it is to say that Trump's view is openly dissented with because such remarks makes their jobs harder and less legitimate in people's eyes.
But in recognizing the horrific nature of these Christian fascist forces and what they are aiming to impose on society and the world, it would be a grievous error to overlook or underestimate the degree to which Clinton and the Democrats in general not only have agreement with but are actually implementing significant aspects of the same program and, where they are not actually taking the lead in this, are following, or giving way to, the initiative of the self-proclaimed Right. This stands out very sharply with regard to policies most directly affecting the masses of proletarians, and particularly those concentrated in the inner cities.
The world outlook and the political views and actions of the Christian fascists must be opposed because they serve to uphold and fortify horrendous oppression, exploitation, and plunder, of women, of whole peoples and nations, and of the masses of working people throughout the world. And, for that matter, the same applies to the political views and actions of Clinton and others who are in contention with the Christian fascists for predominance within the ruling structures of the American capitalist imperium.
Is Trump and Pence representative of "a different society?" Or is bourgeois rule and capitalism-imperialism doing it?
Avakian appears to me to be equating the GOP and the Democrats. If so, then, where then does the NO! campaign come out of that?
If you are mobilizing people against capitalism-imperialism, whatever form it takes – whether it is bourgeois democracy or fascist, whether there is a Republican or Democrat (or in some places and at certain times, a social democrat in charge or some other party) then isn't this what you stand for: the ending of capitalism-imperialism?
A friend of mine observed that the RCP is particularly vulnerable to fascism as compared to bourgeois democracy as an organization and individually since fascism ends any due process, and therefore their heightened concern about Trump and Pence's fascism is understandable. But if that is so, and I find this person's observation persuasive though not definitive, then isn't the RCP substituting in part at least its own concerns, however unconsciously, for the movement itself?
There is a history to communists misapprehending fascism and deviating towards forming alliances around a United Front against Fascism with bourgeois democrats. To reiterate a point I made earlier: what matters less here is how one distinguishes fascism from bourgeois democracy than what the bourgeoisie is doing to maintain its rule. If you are going to fool people into thinking they have a choice through the vote, then you are not going to put forward two candidates who are exactly alike because then the ploy does not work: people will see that there is no difference between the two parties and they will rebel. Thus, you are forced to make some distinction between the (in this country two) main political parties. When Obama offered Obamacare – a retread of Romney's plan as Massachusetts' Governor, which was modeled after the conservative think tank the Heritage Foundation plan – the GOP isn't going to position itself to the Left of Obama, but was forced by Obama's actions even further Right. From that perspective and more, Obama bears a lot of responsibility for what the GOP and its social base have become.
Don't be manipulated by the more extreme position of the bourgeoisie into playing on the side of the less extreme bourgeoisie's position. Extremity here is between and among the two parties and driven by their need to move Rightward in general by neoliberalism's nature. Of course, given that trajectory, the GOP will overall have the initiative, but that is the case because the bourgeoisie as a whole is moving Right, not because the GOP somehow is more imaginative in this way or is inherently worse than the Democrats are. Each party has its respective social base and correspondingly must play to its base. If it fails to do this even rhetorically, then it will not do its job.
The fact that the Democrats are more cosmopolitan than the GOP does not necessarily make them better, or the GOP leadership necessarily more narrow-minded by nature. They are both bourgeois parties. They might and do have disagreements with each other but the real differences they have - do we make concessions or clamp down harder - is not based on party and belied by their record in foreign policy where it was Democratic Presidents that escalated the war in Vietnam (JFK and LBJ) and a Republican who drew us out (Nixon), not because they were members of different parties but what the bourgeoisie in Nixon's case was forced to do.
Avakian's words quoted above clash with the NO! campaign. They don't lead to the NO! campaign but rather a campaign from below that targets Trump and Pence for their policies and works to further de-legitimate the bourgeoisie's right to rule and the system they direct, and whose system rules they personify that is destroying the planet. This is not first and foremost because they are fascists but because they represent in their persons capital and stand for a social base and times that capitalism itself has rendered in part antiquated. Trump and Pence's sin from the standpoint of the system is that their governance is hurting, not helping, the system's credibility. This is a crisis for their system first of all and not first of all a crisis of the people. It is a crisis for the people, but it is first and foremost a system crisis.


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Colorado State Patrol says no charges will be…
Crashes and Disasters
Colorado State Patrol says no charges will be filed in connection to death of Trooper William Modén
Modén was struck and killed on June 14 while responding to an accident
By Carina Julig | cjulig@prairiemountainmedia.com | Loveland Reporter-Herald
PUBLISHED: August 8, 2019 at 2:12 pm | UPDATED: August 8, 2019 at 5:45 pm
Colorado State Patrol
Colorado State Patrol Trooper William Modén was struck and killed Friday, June 14, 2019 on I-70 between Limon and Peoria.
No charges will be charged against a pickup truck driver who struck and killed Colorado State Patrol Master Trooper William Modén in a June collision on Interstate 70.
Col. Matthew Packard, the state patrol chief, said the driver who struck and killed Modén was not impaired, had not been using his cell phone and did not have any mechanical defects in his pickup truck that would have led to the collision.
Modén, 37, was killed June 14 while responding to a rollover crash on Interstate 70 near Deer Trail. He was struck by a Ford-250 that was traveling in the left lane. The driver of the Ford F-250, a 58-year-old male who has been not identified stopped at the scene and cooperated with investigators.
Modén and another trooper were investigating another crash that had happened shortly after 8 p.m., said state patrol Capt. Matthew Secor, who led the investigation, said in a video synopsis of the crash that was release Thursday.
The troopers parked their vehicles on the right shoulder of I-70 with their emergency lights flashing, and Modén was standing in the left lane of traffic using GPS equipment to measure the crash sight.
At 9:38 p.m., the driver of the Ford F-250 approached the troopers' vehicles and moved to the left lane of the highway, as required by law. The other trooper saw the vehicle approaching and attempted to warn Modén, who did not respond, the news release said.
As the driver noticed Modén in the roadway, he swerved to avoid the trooper but still struck him. Modén was thrown into the median, and the other trooper immediately began first aid. Modén was airlifted to University of Colorado Hospital, where he was pronounced dead.
According to investigators, the driver was going below the speed limit of 75 miles per hour and was not under the influence of drugs or alcohol.
Modén was wearing a reflective safety vest, and Packard said the safety vest may not make troopers as visible to drivers as the state patrol believed. Though it was not possible to pinpoint a single cause of the crash, Packard said visibility was a factor. The state patrol will be soliciting input on how better to support troopers, Packard said.
Modén was a 12-year veteran of the Colorado State Patrol. At he funeral, he was posthumously promoted to the rank of master trooper.
Modén was the fifth trooper killed on Colorado roads since 2015, and the second this year. Trooper Daniel Groves, 52, was run over in March while helping a motorist on Interstate 76 during a blizzard.
Kelsey Brunner, The Denver Post
Randy Wittmer helps arrange the memorial on top of Trooper William Moden's patrol car outside of the Colorado State Patrol Office Commerce City, Colorado on Monday, June 17, 2019. Wittmer is a volunteer for Aurora Police Department and was freshening up the flowers on the memorial. Colorado State Trooper William Moden was investigating a car crash on Friday, June 14, 2019, when he was struck and killed by a second collision.
Driver of pickup truck that hit, killed Colorado trooper was in left lane, CSP says
Colorado State Patrol trooper struck by driver and killed was helping woman and baby who were going 100 mph, rolled over
Fallen Colorado State Patrol trooper remembered as "knight in shining armor" during service
accidental deaths
Carina Julig
Carina Julig is the crime and breaking news reporter at the Reporter-Herald. She was previously an intern at the Boulder Daily Camera and the Denver Post, and has a journalism degree from CU Boulder. Follow her @CarinaJulig.
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Aurora police officer sentenced to home detention after pleading guilty to DUI, gun charges
An Aurora police officer has been sentenced to home detention after pleading guilty to charges of driving under the influence and prohibited use of a weapon while drunk.
Truck driver killed after collision with train in Logan County
The crash occurred around 5:14 p.m. in Logan County near Highway 113, Cpl. Ivan Alvarado, Colorado State Patrol spokesman, said.
Woman charged, victim in critical condition after hit and run in Denver
An automobile/pedestrian hit and run in Denver left one person with serious injuries, the Denver Police Department said in a tweet on Friday.

redpajama_set_name: RedPajamaCommonCrawl


10 Unique Furniture Makeovers You Need To See To Believe.
There are thousands of furniture makeovers on the interwebs providing us with inspiring tutorials but not like these! I've compiled a list of furniture makeovers that are so unique and stunning, they leave me breathless!
I love finding inspiration for my furniture restorations especially when they have unique elements and some flair. Let's face it, anyone can paint a piece of furniture – well, most anyone but doing it with imagination and unique elements, well, you've got my attention.
I wanted to be sure to include links to their tutorials to these makeovers as well so you can have some direction in recreating your masterpiece. Not every piece might be exactly what you are looking for, but with some tweaking, these makeovers are a great way to get started and break into your stunning restorations.
I hope you find some inspiration as I did. Enjoy!
1 – An Old Dress got A Stunning Lace Makeover – You can give it a budget-friendly yet a stunning makeover. I love the lace elements. This looks like a high-end piece you'd find at an expensive furniture shop.
2 – Hand Painted Floral End Table – There are times when a pop of color is the perfect solution. This hand-painted beauty can be easy replicated – just let your flair flag fly! I love it and can't wait to give it a whirl!
3 – Hand Painted Princess Furniture – Sometimes, you have to feel like a princess. This is one of those times. Yep, I can see one piece like this in my bedroom. The hubby will just have to deal with it!
4 – How A Serpentine Chest Found Its Neutral Bliss – her goal was to relax the room's traditional roots without having to buy new furniture. I think she outdid herself! Everything about this piece speaks of elegance. With simplicity and southern charm, this piece won my heart over.
5 – High-End Lacquered Finishes – There are times when a high-end lacquered piece is just the right fit. The look is achievable and stunning.
6 – How To Restore Your Furniture From Tragic To Magic – Of course, I had to include one of my own. The before picture is astounding. After this vanity was upcycled, all of her glory was revealed.
7 – How To Decoupage Your Furniture – I swoon with joy when I see perfectly decoupaged furniture. This is a perfect example of that. This project only took her about 30 minutes and was under $5 – wow and wow.
I also love stenciling furniture. It makes my heart flutter! Take a look at this beauty! I especially appreciate how easy stenciling furniture is to achieve. The outcome – chic and spectacular!
8 – Masking Tape Creates This Detailed leaf and Vine Design – This is a pretty simple technique of applying masking tape in a leaf and vine motif over a base coat of paint and then painting over that in a contrasting color. Simple maybe, stunning for sure. I can't wait to try this technique.
9 – A Blue Buffet Makeover – I can't stop staring at this buffet. Everything about it is appealing to me from the way it's staged to the color theme. Perfection! I'm green with envy!
10 – Embossing Plaster Dresser – Another beauty from Orphans With Makeup. I adore a dresser with carved or raised details. This technique is on my to-do this and soon. Another photo I can't stop drooling over.
What furniture restorations do you have lined up? I'd love to see more beautiful projects so please leave them in the comments section below.
And as always, thanks so much for stopping by to read 10 Unique Furniture Makeovers You Need To See To Believe. Please subscribe below for the latest updates!
OMG yes. I like them all for different reasons. That high gloss green is stunning and I like your vanity makeover as well. Carved, embossed, and decoupaged ones are very inspiring as well.
Thanks so much Sue. I love being inspired by such creative folks.


After a six-year engagement, Sacha Baron Cohen and Isla Fisher's long-awaited wedding ceremony turned out to be the most intimate of affairs: Just six guests attended the traditional Jewish ceremony on March 15 in Paris.
And those six had to move quickly. In an effort to keep the celebration quiet, the bride and groom gave their loved ones "very little notice" ahead of the nuptials, according to Australia's WHO magazine.
Baron Cohen, 38, and Fisher, 34, have been together for about eight years, have a 2-year-old daughter, Olive. They spent a week at the Hotel Ritz in Paris and were photographed walking around the nearby Place Vendome wearing matching berets.
They are now back in London, where Fisher is filming new movie, Burke and Hare.


The museum's newest permanent gallery, a Naturalist Center, opened in August 2010. Modeled after the Smithsonian Institution Naturalist Center at the National Museum of Natural History, the local Naturalist Center offers similar access to diverse natural history specimens, from taxidermy mounts to animal bones, rocks, minerals, and plants. More than 200 mounted African animals and an outstanding collection of African artifacts provide unique learning opportunities. See an elephant, giraffe and lions in naturalistic settings. The interactive Catawba River Gallery allows kids to "get their hands wet" at the water table and see how they "measure up" to river fish species.
Visit the Vernon Grant Gallery, devoted to the creator of Kellogg's Rice Krispies characters Snap! Crackle! Pop! Families and young children will enjoy a new exhibit, Tinker Tim the Toymaker, with 3-D interactive projects and landscapes inspired by Vernon Grant's 1934 children's book.
The Museum Store offers a variety of unique and eclectic children's gifts, pottery, jewelry and souvenirs.
Closed New Year's Day, Thanksgiving Day, Christmas Eve and Christmas Day.
Admission: Free on Sundays; Tuesday – Saturday, Adult, $5; Senior, $4; Youth ages 4-17, $3; 3 and younger and CHM members, free. Prices and hours subject to change.


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The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Tuckwell, D.S. et al.
Surface loops adjacent to the cation-binding site of the complement factor B von Willebrand factor type A module determine C3b binding specificity.
The interaction of factor B with C3b deposited on the surface of pathogens is the first step in the activation of the alternative complement pathway. The role of the von Willebrand factor type A (VWFA) module of factor B in this interaction has been investigated by generating three chimeras, Ch1-Ch3, in which surface loops of the VWFA module flanking the cation-binding residues were replaced by the corresponding sequences of C2, a factor B-like molecule which does not bind C3b. The location of the three loops was inferred from a homology model based on the structure of the integrin alphaM VWFA module [Ch1, betaA-alpha1 loop: Ch2, alpha3-alpha4 loop; and Ch3, betaD-alpha5 loop; Lee, J.-O., et al. (1995b) Cell 80, 631-638]. The function of the chimeras was studied by means of hemolytic assays and assays of the individual steps of the alternative complement pathway, i.e., binding to the C3b analogue cobra venom factor and factor D cleavage. These experiments showed that Ch1 and Ch3 define regions that are involved in C3b binding whereas Ch2 does not appear to be involved in binding specificity. The inability of Ch1 to register the enhancement of cobra venom factor binding normally seen after factor D cleavage suggested that the betaA-alpha1 loop mediates the conformational regulation of ligand binding affinity. Homology modeling of the chimeras has been used to visualize the surface structures which potentially define the C3b binding site.[1]
Surface loops adjacent to the cation-binding site of the complement factor B von Willebrand factor type A module determine C3b binding specificity. Tuckwell, D.S., Xu, Y., Newham, P., Humphries, M.J., Volanakis, J.E. Biochemistry (1997) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg


text:
The Bear Quartet - 89 (Vinyl)
Regular price Sale price 200 kr
Format: Vinyl album
Cat#: DISKRET 005
Label: Diskret Förlag/Adrian Recordings
1. Halmet
2. On The Map
3. Sweet Beef
4. Least Loved (Of The Unloved)
5. I Was A Weapon
1. I Am Your Sister
2. Reanimation Of The Dead Sea
3. Carry Your Weight
4. Northern
It's beyond doubt that The Bear Quartet is one of Sweden's most influential bands, and when it comes to lyrics, Matti Alkberg and Peter Nuottaniemi are second to none. It's safe to say that The Bear Quartet, despite their hundreds of magnificent songs and lyrics, perhaps is music's best kept secret.
"89" is The Bear Quartets 14th album. On the one hand it has all the typical ingredients from the bands career up until now. On the other, it sounds like nothing they've ever recorded before. The Bear Quartet never looks back and never stands still. And with this album they still follow their own road, this time it leads into the dark woods. It's almost an occult album, dark, but still danceable indie rock. Or in singer Matti Alkberg's own words, it "spans effortlessly over metal, kraut, Finnish tango music, afrobeat and punkrock, without once losing focus or becoming pretentious". And it's true. Traces of Black Sabbath melt with hints of Velvet Underground and Radiohead in the most natural way you can imagine. It's completely brilliant.
© 2020, Adrian Recordings


Universal joints are found in driveshafts and in front axle shaft assemblies. They couple the driveshaft to the differential and either the transmission or transfer case, and couple the inner front axle shaft to the outer stub shaft.
Universal joints, a.k.a "U-Joints", transmit rotary motion between two shafts that are not in a straight line. U-Joints are commonly found in drivelines and front axle shafts. U-Joints are used in drivelines because the angle of the driveline can change while in motion. Front axle shaft use U-Joints because they have to turn as they rotate.
U-Joints are simple to make and relatively inexpensive to mass produce which is why they are frequently designed to be the weakest link in a front axle assembly, as a U-Joint is much cheaper to replace than an axle. With proper care U-Joints can last for years in a rig you don't take off road.
The most common types of U-Joints are 1310 followed by 1330 and 1350. 1 ton trucks will use 1480 and 1485.
Super Joints are made from chromoly steel (SAE Grade 4340) instead of standard carbon steel, which improves the strength of the U-Joint by 50% or more. The two major weak links in a standard U-Joint are the cross and the roller bearing caps. In a Super Joint the cross is replaced with the Chromoly steel alloy while the roller bearings are replaced with caps/bushings or pins.
An Off Road Only U-Joint is a type of Super Joint not made for continuous rotation without regular maintenance due to the bushing needing frequent lubrication. Super Joints that use bushings are for rigs that need raw strength over long service and are used mostly on trail-oriented rigs.


Browse our archive of closed consultations.
DCC has published a response to the consultation.
DCC is consulting on the rationale used and the Device Model Combinations selected for SMETS1 Initial Operating Capability Systems Integration Testing.
DCC is consulting on proposals for improvements to the current SMETS2 DCC Communications Hub (Comms Hub) Firmware Management processes.
DCC is consulting on amendments to the Intimate Communications Hub Interface Specification (ICHIS) and Communications Hub Supporting Information (CHSI).
DCC is consulting on the introduction of an additional service that would provide the ability for customers to request a non-standard delivery of Communications Hubs at the latest firmware version.
Over its lifetime, DCC has engaged extensively with customers and stakeholders on a wide variety of topics and through a range of forums and other media. This consultation presents a range of ideas and seeks views from customers and stakeholders as to how engagement can be improved.
Real time performance monitoring is something that DCC consider is essential in our management of the network and we have been considering ways to enable a 'Performance Monitoring' ability for DCC, to complement our Production Proving capability.


But these shares may not stay undervalued for much longer.
Image source: Flickr user Andreas Poike.
With the stock market in nearly nonstop rally mode during the past six years, investors haven't needed to look far to uncover an abundance of growth stocks. But not all growth stocks are created equal: While some could still deliver extraordinary gains from here, others appear considerably overvalued now, and might instead burden investors with hefty losses.
What exactly is a growth stock? Though it's an arbitrary number, I'll define a growth stock as any company forecast to grow profits by 10% or more annually during the next five years. To decide what's "cheap," I'll use the PEG ratio, which compares a company's price-to-earnings ratio to its future growth rate. Any figure around or below one could signal a cheap stock.
I figured we'd start off this week by going 0-60 in a flash, or at least going off the beaten path, by taking a closer look at Fiat Chrysler Automobiles (NYSE: FCAU).
What's been ailing Fiat Chrysler of late? Look no further than economic slowdowns in Latin America and Asia. Weaker growth in Asia, compounded by currency devaluations and growth struggles in countries like Brazil, clearly have some investors concerned that the automaker's growth could be stymied. Also,it's working with a large amount of debt that could hamper its ongoing efforts.
But skeptics may want to consider letting their foot off the brake for a handful of reasons.
2015 Jeep Cherokee. Image source: Fiat Chrysler Automobiles.
To begin with, Jeep sales are hot. Like scorching hot. Sales of the Grand Cherokee have almost quadrupled between 2009 and 2015 in the United States, and the introduction of the Cherokee in China should pack some serious punch for Fiat Chrysler. Further, production of the Renegade is allowing the company to take a serious bite out of the compact SUV market overseas. Fiat Chrysler intends to exploit Jeep's strength to the fullest extent possible.
Along those same lines, its focus on using overseas assembly plants is helping shorten delivery times, allowing the company to take advantage of cheaper labor, and is reducing supply chain costs. It hasn't been a perfect strategy, especially with the economies of China and Brazil slowing, but it should deliver strong returns over the long run.
Lastly, we're seeing a strong response in the U.S. to falling gas prices, which are encouraging consumers to take the plunge on SUVs and trucks (the Dodge Ram, for instance). SUVs and trucks typically have juicier margins than sedans, meaning savings at the pump are benefiting most automakers.
With profits projected to be in the 8.7 billion euro to 9.8 billion euro range by 2018, and a microscopic single-digit forward P/E, Fiat Chrysler is a stock growth and value investors will want to keep their eyes on.
Next up, I have a cheap growth stock that could set your portfolio up for a hole-in-one: ClubCorp (NYSE: MYCC).
Indian Wells Clubhouse. Image source: ClubCorp.
ClubCorp, as the name implies, is an owner and operator of membership-based golf clubs and courses, as well as business, country, sports, and alumni-based clubs. In recent months, the company's valuation has taken a nasty tumble as heavy rainfall in Texas has "swamped" its earnings potential, and weakness in oil prices is seen as threatening the pocketbooks of ClubCorp's clientele. While there is some merit to these concerns -- ClubCorp has fallen short of Wall Street's earnings forecast for three straight quarters -- there's also plenty of fairway to be seen if you dig deeper.
There are two particular factors that make ClubCorp stand out: its growth strategy and its clientele.
In terms of growth, ClubCorp has a self-described three-pronged strategy that involves organic growth, reinvention, and acquisitions. Organic growth involves marketing to new members and boosting membership prices to grow its top and bottom lines. Reinvention entails sprucing up its clubs with multimillion-dollar investments to make them more attractive to members and their families. Lastly, acquisitions provide an immediate boost to top-line and bottom-line results. In 2015, based on the company's preliminary full-year results, revenue rose 19.1%, and EBITDA hit a record for the fifth consecutive year. In short, the strategy appears to be working.
The second component is ClubCorp's clientele. Membership-based clubs typically are targeting the affluent, who are likely to be less fazed by a recession or downturn in the U.S. economy. Even though the drop in oil prices may be of concern in to members on Texas, the company's broad portfolio of clubs across more than two dozen states more than negates this worry, in my view.
Sporting a PEG ratio of around one, and projected to grow its full-year EPS from $0.05 in 2015 to $0.57 by 2017, ClubCorp could be a solid investment worth considering.
Finally, if you want to make your portfolio really sparkle, consider the cheap growth turnaround story of Dominion Diamond (NYSE: DDC).
Image source: Flickr user Serendipity Diamonds.
Dominion Diamond is the operator of the Diavik and Ekati diamond mines in Canada, and as you can tell from its share price, the company has fallen on tough times recently. Its CEO vacated his role last year, and weakness in overseas markets like China has reduced demand for rough diamonds. Dominion has needed to cut its prices in order to move its product, and the result has been a substantial fall off in top-line and bottom-line results.
Yet it could be just a matter of time before Dominion Diamond is sparkling once again. For instance, a number of charges the company has taken recently are one-time in nature, such as the CEO departure, or for foreign currency translation. These charges don't truly reflect the health of Dominion Diamond's business model.
Secondly, diamond prices as a whole have held up well, likely implying that whatever supply issues are being worked through in China will be short term. Diamond Search Engine's Diamond Price Index has been range-bound for three years -- between 210 and 221 -- meaning the downside pricing pressure Dominion Diamond is currently dealing with is likely only temporary.
We're also seeing pressure from activist investors for Dominion to consider a possible sale, or to boost its already impressive shareholder yield. This is a company with a strong cash position that's on track to bring its Misery main pipe in the Ekati mine online next year, and which could, according to Wall Street, deliver more than $2 in EPS by 2019.
This diamond in the rough could be polished once again very soon.


text:
About MCB
Fen-1 Facilitates Homologous Recombination by Removing Divergent Sequences at DNA Break Ends
Koji Kikuchi, Yoshihito Taniguchi, Atsushi Hatanaka, Eiichiro Sonoda, Helfrid Hochegger, Noritaka Adachi, Yasuo Matsuzaki, Hideki Koyama, Dik C. van Gent, Maria Jasin, Shunichi Takeda
Koji Kikuchi
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, JapanCREST, JST (Japan Science and Technology), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
Yoshihito Taniguchi
Atsushi Hatanaka
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto 606-8501, Japan
Eiichiro Sonoda
Helfrid Hochegger
Noritaka Adachi
Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka-ku, Yokohama 244-0813, Japan
Yasuo Matsuzaki
Hideki Koyama
Dik C. van Gent
Department of Cell Biology and Genetics, Erasmus Medical Center, P.O. Box 1738, 3000, DR Rotterdam, The Netherlands
Maria Jasin
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021
Shunichi Takeda
For correspondence: stakeda@rg.med.kyoto-u.ac.jp
DOI: 10.1128/MCB.25.16.6948-6955.2005
Homologous recombination (HR) requires nuclease activities at multiple steps, but the contribution of individual nucleases to the processing of double-strand DNA ends at different stages of HR has not been clearly defined. We used chicken DT40 cells to investigate the role of flap endonuclease 1 (Fen-1) in HR. FEN-1-deficient cells exhibited a significant decrease in the efficiency of immunoglobulin gene conversion while being proficient in recombination between sister chromatids, suggesting that Fen-1 may play a role in HR between sequences of considerable divergence. To clarify whether sequence divergence at DNA ends is truly the reason for the observed HR defect in FEN-1−/− cells we inserted a unique I-SceI restriction site in the genome and tested various donor and recipient HR substrates. We found that the efficiency of HR-mediated DNA repair was indeed greatly diminished when divergent sequences were present at the DNA break site. We conclude that Fen-1 eliminates heterologous sequences at DNA damage site and facilitates DNA repair by HR.
Homologous recombination (HR) plays a critical role in genome maintenance by repairing double-strand breaks (DSBs) induced by exogenous agents or occurring during DNA replication. In chicken B lymphocyte precursors, HR mediates the diversification of the immunoglobulin (Ig) variable region, a process called gene conversion (7, 31, 33, 45). HR is also essential when transfected DNA is integrated in the genome at specific sites of homology during gene targeting.
HR is initiated by DNA damage, including DSBs and single-strand breaks. It involves interactions between damaged DNA and intact homologous sequences and results in the transfer of genetic information from the intact donor to the damaged recipient. HR-dependent DSB repair has been well studied in the budding yeast by use of the HO restriction enzyme. The initial step involves processing of DNA ends to produce a 3′ single-strand overhang, which is covered by Rad51. The resulting nucleoprotein filament is responsible for homology search, homologous pairing, and strand invasion (D loop formation) followed by DNA synthesis from the 3′ end of the invading strand (46). This HR-dependent repair of HO-induced DSBs requires a number of nucleases (13). Firstly, the 3′ overhang formation at DSBs appears to be carried out by Mre11 and Exo1 and perhaps by other unknown nucleases in mitotic cells (12, 20, 24, 40, 41). Secondly, nonhomologous tails from the 3′ overhang including the HO site should be eliminated. These overhangs interfere with subsequent steps of HR by destabilizing the D loop and precluding 3′-OH-end extensions (26). In higher eukaryotic cells, the end processing of DNA during the initial step of HR is more controversial. For example, mre11-deficient DT40 cells exhibit normal kinetics of Rad51 focus formation after irradiation (IR) (48), indicating that induced DSBs are processed normally in the absence of Mre11. Likewise, exo1-deficient mouse embryonic stem cells show defective mismatch repair but normal HR capability (44).
Fen-1 is a structure-specific nuclease that cleaves 5′ flaps of the branched DNA structures and possesses double-strand-specific 5′-to-3′ exonuclease activity (14, 27). Recently Zheng et al. (51) reported that Fen-1 cleaves DNA bubble structures by 5′ and 3′ incision in vitro. The endonuclease activity of Fen-1 is required for processing the 5′ ends of Okazaki fragments in lagging strand DNA synthesis (42, 43). Fen-1 also contributes to base excision repair (BER) by removing 5′ flap structures formed during gap-filling DNA synthesis (28). This notion is supported by the phenotype of FEN-1-deficient DT40 cells, which are hypersensitive to killing by alkylating agents such as methylmethane sulfonate and hydroxyperoxide (22). Consistent with the important role for Fen-1 in DNA replication and BER, FEN-1−/− mice are lethal during early embryogenesis (19), and even mice heterozygous for FEN-1 display a high incidence of tumorigenesis, presumably due to genome instability (18).
Although mammalian mutants deficient in FEN-1 are not viable, FEN-1−/− DT40 cells are able to proliferate with slightly elongated cell cycle time (22). Thus, FEN-1−/− DT40 cells provide a novel opportunity to analyze in vivo functions of vertebrate Fen-1. DT40 cells are useful for comprehensive analysis of a variety of HR reactions, because a number of phenotypic assays have been developed (15, 31, 50). These assays include the measurement of the rate of Ig gene conversion, sister chromatid exchange (SCE), gene targeting, repair of DSBs created in artificial constructs, and repair of DSBs induced by ionizing radiation (IR) at the late S to G2 phase (1, 2, 4, 32, 34, 35, 36, 37). Using these assays we found in this study that Fen-1 is required for HR between homologous sequences with nonhomologous tails at the DNA break ends while it is dispensable for HR between perfect homologies.
Plasmid constructs.Two XPG disruption constructs, XPG-hisD and XPG-bsr, were generated from genomic PCR products combined with hisD- and bsr-selection marker cassettes (see Fig. S2 in the supplemental material). Genomic DNA sequences were amplified using the primers 5′-TCTGATACATGAACTGACAGATAAGCACAG-3′ and 5′-CGGGATCCGTCTGCTAAAGTAACTCACCACCACAAGC-3′ (for the left arm of the disruption construct) and 5′-CTCGGATCCTTTTCCCAGTACCAGCTTAGGGGTTTGC-3′ and 5′-GAGGGTACCTGAAGCATTTCCTGCTCAGCAGAAAGGTC-3′ (for the right arm of the disruption construct). Amplified PCR products were cloned into the pCR2.1-TOPO vector (Invitrogen). The 2.1-kb NotI-BamHI fragment from the left arm and the 2.5-kb BamHI-KpnI fragment from the right arm were cloned into NotI and KpnI sites of pBluescript KS, respectively. The BamHI site between the two arms was used to clone marker gene cassettes. For the probe used in Southern blot analysis, the genomic DNA was amplified using the primers 5′-GCTACTTCTGTAACAGGACAAATGTTCTTG-3′ and 5′-ATAACCAAACATCACTATCATCAGTGATTG-3′ and was digested with EcoRV to obtain a 1-kb fragment. The expression vector pCR3-loxP-XPG/IRES-EGFP-loxP, in which the XPG and enhanced green fluorescent protein (EGFP) genes are flanked by two loxP sequences, was constructed by inserting an XPG SalI-BamHI cDNA fragment between the SalI and BamHI sites of pCR3-loxP-MCS-loxP (49). Gene targeting substrates and heterologous sequences inserted into S2neo reporter gene were amplified with primers listed elsewhere (see Table S1 in the supplemental material). Expression vectors of chicken FEN-1 and nuclease-dead mutant of FEN-1 were given by Keizo Tano (Research Reactor Institute, Kyoto University, Osaka, Japan).
Cell culture, DNA transfection, and γ irradiation.Cells were cultured in RPMI 1640 supplemented with 10−5 M β-mercaptoethanol, 10% fetal calf serum, and 1% chicken serum (Sigma, St Louis, MO) at 39.5°C. Methods of DNA transfection for producing stable transfectants and genotoxic treatments were as described previously (34). Cell synchronization was achieved by elutriation as described previously (34). 137Cs (Gammacell 40, Nordion, Kanata, Ontario, Canada) (0.02 Gy/s) was used for γ irradiation.
Measurement of SCE levels.SCE levels were measured as described previously (49).
Analysis of Ig gene conversion.FEN-1−/− cells were established from CL18, a subclone of DT40 cells that is negative for surface IgM (sIgM) (3, 22). We confirmed that FEN-1−/− cells retained the same frameshift mutation as do wild-type CL18 cells by sequencing the Ig Vλ region. The rate of Ig gene conversion was assessed by measuring the gain of sIgM expression during a 3-week period as described previously (3).
I-SceI-induced gene conversion and gene targeting.A total of 107 cells were suspended in 0.1 ml Nucleofector Solution T (Amaxa biosystems) and electroporated using an Amaxa system (Amaxa biosystems) at program B-23. For the gene conversion assay, 5 μg of circular I-SceI expression vector (pcBASce) with or without nuclease expression vector was transfected into the cells. For the gene targeting assay, 2 μg of substrate DNA and 4 μg of pcBASce with or without nuclease expression vector was transfected. pBluescript II KS+ was used as a negative control. At 24 h after electroporation, the number of live cells were counted by fluorescence-activated cell sorting (FACS) and the cells were transferred to 96-well cluster trays with or without 2.0 mg of G418 per ml. Cells were grown for 7 to 10 days, and HR frequencies were calculated by the following equation: HR frequency (colonies/cell) = number of G418-resistant colonies/(plating efficiency of transfected cells in the absence of G418 × number of live cells determined by FACS 24 h after electroporation).
Measurement of targeted integration frequencies.To analyze the targeted integration events at the Ovalbumin (4), RAD54 (2), and β-ACTIN loci, each disruption construct was transfected into cells, and Southern blot analysis was performed following selection of clones against appropriate antibiotics. For the CENP-H locus, a CENP-H-EGFP knock-in construct (10) was used, and the targeted events were scored by FACS analysis.
Nucleotide sequence accession number.The chicken XPG cDNA sequences have been submitted to the GenBank database under accession number AB063480.
Reduced kinetics of the Ig gene conversion in FEN-1−/− cells.We have screened nucleases that are required for HR by analyzing the rate of Ig gene conversion in nuclease gene-disrupted DT40 clones. In this assay, intragenic gene conversion between two diverged homologous sequences, i.e., donor pseudo-V (ΨV) and recipient VJλ segments, allows determination of gene conversion events as well as the identification of aberrant events (29). To assess the kinetics of Ig gene conversion, we measured the gain of surface IgM (sIgM) expression, which may reflect elimination of a given frameshift mutation at the recipient VJλ by superimposed gene conversion events (3, 30). Interestingly, FEN-1−/− cells exhibited a 3.2-fold reduction of sIgM gain (Fig. 1A), suggesting a role for Fen-1 in Ig gene conversion. In contrast, gene conversion was not impaired in cells deficient in XPG (data not shown), which belongs to the same nuclease group as Fen-1 (21). Since a defect in Ig gene conversion is often accompanied by the alteration of the usage of donor ΨV segments, we determined nucleotide sequences of the Ig Vλ segment in the cells that acquired sIgM expression. We found that the usage of ΨV segments was different between wild-type and FEN-1−/− cells, while no significant alternation was found in their gene conversion tract length. The ΨV8 segment was used in 78.9% of the gene conversion events in wild-type cells, while all analyzed 49 gene conversion events exclusively involved ΨV8 in FEN-1−/− cells (Fig. 1B). The ΨV8 donor segment shares the highest homology with the VJλ recipient segment among the ΨV segments (3). Thus, we conclude that deletion of FEN-1 reduced the frequency of Ig gene conversion involving ΨV8 by 2.5-fold and completely abolished Ig gene conversion with more-diverged ΨV donor segments. These observations imply that Fen-1 may be involved in HR, particularly between diverged homologous sequences.
Reduced frequency of Ig gene conversion in FEN-1−/− cells. (A) Fluctuation analysis of appearance of sIgM-gain revertants. The abundance of sIgM-gain revertants was determined in parallel cultures derived from sIgM− single cells after 3-week clonal expansion; median percentages are noted above each data set and are indicated by the line. (B) Preference of pseudo-V gene usage as a donor for Ig gene conversion among isolated sIgM-gain populations. The total number of Vλ sequences analyzed is indicated in the center of the charts.
The reduced kinetics of Ig gene conversion in FEN-1−/− cells led us to perform other phenotypic assays of HR reactions. We previously showed that HR-deficient clones such as RAD54−/− cells exhibit elevated IR sensitivity specifically in the late S to G2 phase, when sister chromatids are available to provide exactly matching repair templates for HR (2, 34). We analyzed the sensitivity of synchronized populations of cells to killing by γ radiation using a colony formation assay. Unlike RAD54−/− cells, FEN-1−/− cells showed elevated IR sensitivity in the early S phase but not in the late S to G2 phase (Fig. 2B), indicating that Fen-1 is dispensable for HR between sister chromatids. We next determined the level of microscopically visible SCE events, which display gene conversion associated with crossover between two sister chromatids (32). Consistent with the hyper-recombination phenotype of the budding yeast rad27Δ strain (39), FEN-1−/− DT40 cells showed about 4.5-fold-higher spontaneous SCE levels than did wild-type cells (Fig. 3). When we induced SCE by exposing the cells to 4-nitroquinoline 1-oxide (4-NQO), which mimics UV damage (9), the levels of induced SCE were very similar between wild-type and FEN-1−/− cells (Fig. 3). These data suggest that Fen-1 is not required for HR between identical sister chromatids.
γ-Ray sensitivity of cells at the G1, early S, and late S/G2 phases. (A) Cells of the indicated genotypes were synchronized at the G1 phase with elutriation and released into culture at 0 h. WT, wild type. (B) Wild-type or FEN-1−/− cells were exposed to 2-Gy γ-rays at the indicated cell cycle phase. The number of colonies which appeared after irradiation was divided by that of nonirradiated controls; results are shown as % survival.
The level of induced SCE was indistinguishable between wild-type and FEN-1−/− cells. The histogram indicates the number of SCE per cell in the wild-type, FEN-1−/−, and XPG−/− cells. The values of induced SCE were calculated by subtracting the mean value of nontreated cells from that of 4NQO-treated cells; results are shown at the top of each panel. Black and gray bars indicate spontaneous SCE as well as SCE induced by 0.2 ng/ml 4NQO treatment, respectively.
Defective I-SceI restriction enzyme-induced gene conversion in FEN-1−/− cells.It is believed that Ig gene conversion is initiated by single-strand damage, which is generated as the consequence of AID deaminase-dependent formation of uracil at the Ig V gene (1, 6). To test whether Fen-1 is required not only for Ig gene conversion that is induced by single-strand DNA damage but also for DSB-induced HR, we used an artificial gene conversion substrate DNA, SCneo (16). In the SCneo construct, two mutated neomycin-resistance genes (neoR) that are complementary to each other are localized in tandem. The recipient neoR coding region is disrupted by the 18-bp I-SceI cleavage site including a stop codon (S2neo; Fig. 4A), while the other promoterless intact neoR gene serves as a genetic donor for recombinational repair of the I-SceI-induced DSB. To accurately compare data of wild-type and FEN-1−/− cells, we integrated the SCneo substrate at the Ovalbumin locus in each genotype (11). DSBs induced by transient expression of I-SceI are repaired by gene conversion either from the upstream donor homologous sequences (intragenic gene conversion) or the other sister chromatid (unequal sister recombination) (16). Of note, the 18 nucleotides comprising the I-SceI site in the SCneo recipient sequence should be eliminated during gene conversion-dependent DSB repair to reconstitute a functional neoR gene in the cells. Accordingly, we found that HR-mediated DSB-repair induced by transient expression of I-SceI was reduced more than 10-fold in the FEN-1−/− cells while there was no significant decrease in colony number in XPG−/− cells (Fig. 4B and data not shown). Notably, the reduction in I-SceI gene conversion efficiency was partially reversed by transfection of chicken FEN-1 cDNA into FEN-1−/− cells but not by a nuclease-dead mutant of chicken FEN-1 (Fig. 4B). Overexpression of chicken FEN-1 in wild-type cells enhanced I-SceI-induced gene conversion by 2.87-fold (see Fig. S1 in the supplemental material). These data indicate that Fen-1 is required for efficient DSB-induced gene conversion (Fig. 4B) as well as single-strand-damage-induced Ig gene conversion (Fig. 1), and the nuclease activity of Fen-1 is important for this process.
The reduction of I-SceI-induced gene conversion in FEN-1−/− cells. (A) Experimental method of measuring the frequency of gene conversion by counting G418-resistant colonies. The expression vector encoding I-SceI is introduced into cells carrying SCneo in the Ovalbumin locus. Black and gray boxes in S2neo represent the 5′ untranslated and coding regions of the neoR gene, respectively. The figure is not drawn to scale. Successful gene conversion would reconstitute functional neoR gene. (B) The recombination frequency in the SCneo reporter construct in each genotype is shown as the number of G418-resistant colonies derived from 107 cells transfected with the indicated plasmid. Complementation denotes cotransfection of the I-SceI expression plasmid with expression vector of the disrupted gene in the indicated transfected cells. DN, an expression plasmid for nuclease-dead mutant of chicken FEN-1. The experiments were done more than four times.
Fen-1 is involved in elimination of heterologous sequences at the I-SceI cleavage site.To investigate whether the sequence divergence between donor and recipient was indeed responsible for the reduction of HR frequency in the absence of Fen-1, we examined I-SceI-induced gene targeting as previously studied (8). Wild-type or FEN-1−/− cells carrying S2neo targeted sequence at the Ovalbumin locus were transiently transfected with the donor construct and the I-SceI expression vector (Fig. 5A). We used a series of donor constructs carrying different degrees of sequence divergence at I-SceI site (Fig. 5B). Among these modified targeting constructs, Mneo-1 had the smallest sequence divergence from the intact I-SceI site, differing only at two residues. When successfully targeted, these modified sequences will replace the stop codon in I-SceI site and be translated into four extra (Mneo-1, Mneo-2, Mneo-3), one extra (Mneo-4), one fewer (Mneo-5), or two fewer (Mneo-6) amino acid residue(s) in the neoR gene product compared to the wild-type neoR gene. Using this series of targeting constructs we found that Mneo-1 gave a similar number of colonies when transfected into FEN-1−/− cells and wild-type cells carrying S2neo. Conversely, the gene targeting efficiency in FEN-1−/− cells, compared to wild-type cells, decreased with the extent of heterologous sequence at the site of DNA breaks (Fig. 5C). These data support our notion that Fen-1 facilitates HR by eliminating heterologous sequences at the I-SceI site.
Diverged short sequences block effective recombination in FEN-1−/− cells. (A) Experimental method of measuring the frequency of gene targeting by counting G418-resistant colonies. The expression vector encoding I-SceI is introduced together with WTneo (white box) into cells carrying S2neo in the Ovalbumin locus. Black and gray boxes represent the 5′ untranslated and coding regions of the neoR gene, respectively. The figure is not drawn to scale. Successful gene targeting would reconstitute a functional neoR gene. (B) Base sequence alignment around the I-SceI site in a series of targeting constructs (Mneo-1 to Mneo-6). Mneo-1 donor contains sequences that are two nucleotides shorter (shown by hyphen) than the corresponding sequences of S2neo recipient. Bold characters show inserted point mutations. Boxed characters show a stop codon. (C) The gene-targeting frequency of targeting constructs in FEN-1−/− cells. The indicated targeting constructs (shown at top) were transfected into cells carrying S2neo. The number of diverged sequences (shown at bottom) includes inserted point mutations and missing sequences in the targeting constructs. Relative HR frequencies on the y axis were calculated by dividing the HR frequency of FEN-1−/− cells which appeared after G418 selection by that of FEN-1+/+ cells.
In the present study, we provide the first evidence that Fen-1 is involved in HR reactions in higher eukaryotic cells. Interestingly, only a subset of HR events is affected by loss of Fen-1. Clearly FEN-1−/− cells are not IR sensitive during the G2 phase of the cell cycle and display wild-type levels of induced SCE. However, the HR reaction appears to be affected in FEN-1−/− cells when sequence variation between recipient and donor occurs. Thus, Ig gene conversion, which is a good example of HR between variable sequences, is significantly reduced in FEN-1−/− cells. Moreover, the mutant cells exclusively use the ΨV8 donor segment, which shares the highest homology with VJλ recipient segment.
Lastly, our S2neo reporter assay clearly points to a role of Fen-1 in removing nonhomologous sequences during the HR reaction. In these experiments, which were thoroughly controlled for variations in plating efficiency and sensitivity to the endonuclease expression, gene targeting efficiency decreased with the extent of sequence divergence only in the FEN-1−/− mutants but not in wild-type and XPG−/− cells. One could argue that the HR frequency could be affected by the enzymatic activities of reconstituted neoR gene products. The use of various Mneo constructs may cause variation in the number of G418-resistant colonies, since the introduction of sequence divergence at the I-SceI site results in the changes of amino acids in neomycin phosphotransferase. This was not the case, since each Mneo construct showed similar HR frequencies in wild-type cells (Fig. 5C). Another point of concern is the possibility that HR frequency can be affected by nonhomologous end-joining (NHEJ) activity. As long as DSB ends are ligated precisely by NHEJ, these sites are subject to perpetual digestion due to the constitutive expression of I-SceI restriction enzyme. Either HR or imprecise ligation by NHEJ eliminates the I-SceI site and terminates the reaction. The latter case leads to the apparent decrease in HR frequency due to the improperly reconstituted neoR gene. We excluded this possibility by a plasmid religation assay (37), in which we observed a normal NHEJ activity in FEN-1−/− cells (data not shown). Taken together, these data indicate that the HR defect in FEN-1−/− cells clearly depends on the divergence between recipient and donor sequences. Fen-1 is dispensable for the HR reactions that occur between identical or highly homologous sequences such as two sister chromatids or ΨV8 segment but is required for the recombination between DNAs that have short nonhomologous sequences at the ends. Our findings are also consistent with previous yeast genetics results (25). Fen-1 is localized together with PCNA close to the chromatin at pachytene when meiotic recombination between homologous chromosomes occurs (17). It is tempting to speculate that Fen-1 may also facilitate recombination by removal of heterologous sequences between maternal and parental chromosomes during meiosis in higher eukaryotes.
We observed an elevated level of spontaneous SCE in FEN-1−/− cells, which apparently argues against the involvement of Fen-1 in HR. However, this finding is consistent with results obtained from phenotypic analysis of the yeast rad27Δ strain (39), where the frequency of mitotic crossover is increased and is thought to be a consequence of defective lagging strand DNA synthesis (42, 44). The resulting defect in DNA replication appears to be replaced by HR-mediated repair, because budding yeast mutants deficient in both rad27 and RAD52 epistasis groups are synthetically lethal (5, 38). Likewise, our observation of increased spontaneous SCE in FEN-1−/− cells may reflect enhanced HR-dependent repair due to defective processing of Okazaki fragments and impaired BER. Accordingly, we observed increased IR sensitivity during early S phase, which could be a consequence of defective BER and subsequent replication blocking in FEN-1−/− cells.
How Fen-1 eliminates nonhomology from DNA ends remains elusive. It has been shown in vitro that Fen-1 possesses 5′-to-3′ exonulease as well as structure-specific endonuclease activity. We speculate on three possibilities for the action of Fen-1 based on the biochemical evidence presented so far by others. First, Fen-1 may extend the 3′ overhang with its exonucleolytic activity until the identical sequence is exposed, so that the pairing can occur between the substrate and homologous template DNA. Secondly, the endonuclease activity of Fen-1 may eliminate nonhomologous 5′ flap structures at D-loops after the invasion of 5′ overhang into duplex DNA. This idea is consistent with biochemical evidence that Fen-1 cleaves the 5′ and not the 3′ flap structure of DNA and with the observation that Rad51 can form filaments on 5′ single-stranded DNA and perform strand exchange (23). The third of the possibilities relies on the recent observations made by Zheng et al. (51), in which DNA bubble structures are cleaved by Fen-1 at single- and double-stranded DNA junctions on both ends. This suggests that, under some circumstances, Fen-1 could cleave the 3′ flap structure, which is generated after strand invasion by 3′ overhang. The first and third possibilities are not mutually exclusive and may in fact complement each other. Accumulating evidence has suggested a critical role of Fen-1 for processing DSB ends in the course of HR (25) and NHEJ (47) in yeast. This study sheds light on a previously unknown function of Fen-1 in higher eukaryotic cells: the elimination of imperfectly matched sequences from DSB ends for subsequent HR-mediated DSB repair. Interestingly, Fen-1 also contributes to conventional gene targeting at three different loci (see Table S2 in the supplemental material). Although the role for Fen-1 in this situation is unclear, it is tempting to speculate that Fen-1 functions in removing the heterologous sequences as it does in I-SceI-induced gene targeting. Since overexpression of Fen-1 alone enhanced I-SceI-induced gene targeting (see Fig. S1 in the supplemental material), the challenge for the future will be to seek for the way to improve gene targeting efficiency in vertebrate cells using Fen-1 and to understand how Fen-1 works in conventional gene targeting.
We thank K. Tano for expression vectors of chicken FEN-1 and nuclease-dead mutant of FEN-1 and Y. Kitawaki, Y. Sato, S. Okajima, and R. Ohta for their technical assistance.
Financial support was provided in part by a grant of Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Corporation, by a Center of Excellence (COE) grant for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government, and by grants from The Uehara Memorial Foundation and The Naito Foundation.
Received 21 February 2005.
Returned for modification 5 April 2005.
Accepted 27 May 2005.
↵† Supplemental material for this article may be found at http://mcb.asm.org/.
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Molecular and Cellular Biology Jul 2005, 25 (16) 6948-6955; DOI: 10.1128/MCB.25.16.6948-6955.2005
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The Medical Supplies Division (MSD) of Ministry of Healthcare and Nutrition is the main organization responsible for providing all Pharmaceuticals, Surgical items, Laboratory Items, Radioactive Items, Printed materials, etc. for Government sector healthcare institutions throughout the country. In addition MSD is also responsible for supplying dangerous drugs and essential medical items, which are not available to the privet sector in the open market.
MSD is the central organization where the medical supplies are stored until they are distributed among healthcare institutions. It has a network of stores comprising of with a central Medical Stores in Colombo (MSD) and there are 26 Regional stores at district level (RMSD). In the chain of central medical stores, there are 18 Bulk warehouses at main building, 3 Bulk warehouses at Angoda, 5 bulk warehouses at Wellawatta, one warehouse at Digana and one warehouse at Welisara.
More About MSD . . .
Task of the MSMIS Expansion project is Strengthening the medical supplies chain by expanding the MSMIS system up to the Divisional Hospitals and Medical Officer of Health offices (MOHs) maintained under provincial review (RMSDs).
More About Expansion Project . .


text:
namespace axl {
namespace io {
namespace win {

//..............................................................................

class UsbPcap {
public:
	enum {
		// as suggested by USBPcapCMD

		IoctlOutputBufferSize   = 1024,             // 1K
		DefaultKernelBufferSize = 1 * 1024 * 1024,  // 1M
		DefaultSnapshotLength   = 65535,            // 64K - 1
	};

	enum Mode {
		Mode_Capture,
		Mode_Enumerate,
	};

protected:
	axl::io::win::File m_device;

public:
	bool
	isOpen() {
		return m_device.isOpen();
	}

	bool
	open(
		const sl::String_w& name,
		Mode mode = Mode_Capture
	);

	void
	close() {
		m_device.close();
	}

	sl::String_w
	getHubSymlink();

	bool
	getHubSymlink(sl::String_w* symlink);

	bool
	setSnapshotLength(size_t size);

	bool
	setKernelBufferSize(size_t size);

	bool
	setFilter(uint_t deviceAddress);

	bool
	setFilter(
		const uint_t* deviceAddressTable,
		size_t deviceCount
	);

	bool
	clearFilter();

	size_t
	read(
		void* p,
		size_t size
	) {
		return m_device.overlappedRead(p, size);
	}

	bool
	overlappedRead(
		void* p,
		dword_t size,
		OVERLAPPED* overlapped
	) {
		return m_device.overlappedRead(p, size, overlapped);
	}

	bool
	getOverlappedResult(
		OVERLAPPED* overlapped,
		dword_t* actualSize
	) {
		return m_device.getOverlappedResult(overlapped, actualSize);
	}

	size_t
	getOverlappedResult(OVERLAPPED* overlapped) {
		return m_device.getOverlappedResult(overlapped);
	}
};

// . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

inline
sl::String_w
UsbPcap::getHubSymlink() {
	sl::String_w string;
	getHubSymlink(&string);
	return string;
}

//..............................................................................

} // namespace win
} // namespace io
} // namespace axl

redpajama_set_name: RedPajamaGithub


Elekta Unity Two worlds, one future.
Uniting high-field 1.5T MR imaging, precision radiation therapy and intelligent software without compromise, Elekta Unity provides a tailored solution for the new field of magnetic resonance radiation therapy (MR/RT). The combination of technologies enables you to see and track the target, including changes in tumor position, shape and biology, and provides the real-time information you need to respond immediately—all while the patient is on the table.
UMC Utrecht's use of Elekta Unity today demonstrates the practicality of the Unity workflow to adapt the patient's treatment to his or her daily anatomy using real time, diagnostic quality imaging, integrated with a next generation linear accelerator.
Since receiving CE Mark, Elekta Unity has been used for more than 250 treatments. The treatment regimen for the first patient was 5 fractions of 7Gy given over a 10-day treatment period using a stereotactic IMRT approach.
Shaista Hafeez, PhD: "Game-changing innovative technology"
William A. Hall, MD: "Personalized Radiotherapy"
Jan Lagendijk, PhD: "See what you treat"
Professor Uulke van der Heide, PhD: "A paradigm shift"
Elekta Unity has CE-mark and 510(k) clearance but not commercially available in all markets.
Important Safety Information: Radiation therapy is not appropriate for all patients. Radiation treatments may cause side effects that can vary depending on the part of the body being treated. In some patients, they can be severe. Treatment sessions may vary in complexity and time. Refer to individual product labeling (instructions for use) for more complete information on product safety and effectiveness for its intended use.


text:
Shopping During Coronavirus Pandemic: Grocery Stores Change Operations To Help Seniors
Filed Under:Coronavirus, groceries, seniors
SACRAMENTO (CBS13) – Some local grocery stores are stepping up to help seniors. Raley's says it's selling the essentials in a bag each morning starting at 7 a.m. It'll be a mix of fresh and canned food.
The bag is $20 and there's a limit of one per family. They're being offered on a first-come-first-serve basis.
Raley's hopes to have the service up and running on Saturday.
Some stores are setting aside special hours for seniors and those with health conditions.
Stores urge people to stop hoarding, saying there is enough food for everyone.
"Our supply system in America is very, very strong. It's very strong, but when we get the hoarding and all the stock up from individuals, it makes it very difficult to be able to manage," said Safeway NorCal Division President Brad Street.
Street and San Jose Mayor Sam Liccardo tried to ease people's fears and remind them to not overbuy.
"Hoarding hurts our neighbors…it's important that food be available for everyone who needs access to food when they are able to go shop," said Liccardo.
Starting Thursday, on Tuesdays and Thursdays, every Safeway from the time it opens until to 9 a.m, will be reserved for seniors 65 years or older and those at-risk only.
It's an idea that shopper Candace Levers thinks is great.
"I think there's a little too much panic happening and I think a lot of that concern was about the stock and the supply chain. Clearly, looking at this, there's no problem," she said.
"With this being very new, we're all learning," said Street. "So as we're learning and going through this, I think that we'll have to speed that up a little bit, yes."
Safeway isn't the only store opening first to seniors, Whole Foods Market stores in the U.S. and Canada are opening one hour early so people 60 and older can shop first. The adjusted hours are posted on the store's web page.
Target will open an hour early every Wednesday for who it calls "vulnerable shoppers."


text:
Author: Kristopher Poskey
Kristopher Poskey is an active duty member of the United State Army. As an academic junior, he began his college career at Texas A&M where he studied Forensics and Investigative Sciences. In his spare time, Mr. Poskey continues to study astronomy, cosmology, international security, astrophotography, and political science. Mr. Poskey writes for various individuals and organizations.
Posted on November 8, 2012 December 23, 2015 by Kristopher Poskey
Book Review: About Time: Cosmology and Culture at the Twilight of the Big Bang
When introducing his book "About Time: Cosmology and Culture at the Twilight of the Big Bang," author Adam Frank tells us that he is setting out to "unfold the grandest conception of the universe we human beings have been able to imagine and explore. At the same time embracing our most intimate and most personal experience of the world — the very frame of human life."
"This book is about time, both cosmic and human."
For those interested in the complex journey of humanity through the cosmos, Frank does not fail in his quest to unravel the unique web of 'time' into a thread of understandable science. That is, if you can take a partially solved puzzle and write a book that connects the proverbial dots of known science and cultural anthropology with the partially understood theories of cosmology and related sciences.
Mission accomplished by Frank.
Upon first receiving this book, I was hopeful that Frank would present the material of thousands of years of science in a unique and interesting way; setting his writing apart from the hundreds of other astronomy books I've read. Frank, being a seasoned writer and astrophysics professor, did not disappoint. Frank takes you on a conversational journey, filled with real life examples, both personal and historical, to share his view of some of the most multifarious ideas being considered in our galaxy today.
The first few chapters are a review of compound science related to our galaxy, but Frank quickly dives into a discussion of how culture has been affected by the world around it. From there Frank draws a picture from intricate ideas and theories of how society fits in the larger puzzle of cosmology. All while focusing on the measurement of time.
If you are looking to take your perspective of cosmology to a new and deeper level, allow Adam Frank to steal some of your time and read his book "About Time". Frank will surely have you viewing your society, history, and clock in a whole new perspective. Not to mention putting you on the forefront of scientific theories and cultural progress being considered in the world of cosmology.
Adam Frank is Professor of Astrophysics at the University of Rochester and a regular contributor to Discover and Astronomy magazines, and is the co-founder of National Public Radio's popular 13:7 Cosmos & Culture blog. He won an American Astronomical Society Prize for his scientific writing. His first book was The Constant Fire: Beyond the Science vs. Religion Debate.


I'm writing at around 4AM, drinking coffee while my dogs snooze on the other furniture. Today, my sweet retired Bianca turns thirteen. How amazing that is to me. She's still in great health, still has lots of spirit and is full of her usual joy. How I love that crazy dog!
Olga, my 8-year-old working guide has a urinary tract infection. No wonder she's been peeing all the time and anywhere. sigh. She's on meds finally, so it will get better soon. Still, my application for training continues. Olga hasn't really been a strong worker, and I haven't been as 100 percent confident in her as with some other dogs. But she is a sweetheart, a completely good girl, good companion, never any trouble but the off and on house relieving.
so, how's the process going?
That application seems to be moving the fastest. They've sent reference forms to those on my list and my friends have returned those already. I'm sure they've contacted GDB by now, but of course, I have no idea how that went. I have my medical appointment on the 20th of march, and my friend's son will do the video, as soon as I can tie him down to do it. Yes, GDD needs a video, because being a small school, they can't easily send people out here to do an interview.
It's funny, once upon a time, GDD had a bad rap in the community of guide dog handlers, but over the last few years, I've heard good things about them, and I've seen some good dogs. and damn1 they still train goldens. I want a golden!
That process seems a bit slower. But they did indicate to me that they've decided not to send out personal reference forms. I imagine that's because of my long time history of being a solid handler–39 years now. I have their medical forms and of course will get them filled out next month. There will be a home interview, but as of yet, I haven't heard from anyone regarding that. It's probably the fun weather.
My guide dog alma mater. It still boggles my mind that I'm considering going elsewhere. Never dreamed GDB could do anything that would cause me to choose another training school. I already had follow up scheduled and I requested it to be a home interview instead after submitting a retrain app. That is happening on March 9. Nancy Denier, from the Oregon campus will be here. I got along well with her when I worked at GDB, so fingers are crossed.
Still, my conscience troubles me. I am so deeply unhappy and troubled by the changes at GDB. and yesterday, they issued the news that they've finally hired a new CEO. she has no human services or blindness field experience. she does have animal experience, since she's been some kind of executive with a bay area humane society, and she has good business background. but that doesn't mean she'll be any good as a CEO when it comes to making decisions and planning direction that is for the good of students and grads. Last year, I protested the changes with letters and signing petitions. Now, it feels as if I should protest with my business. In other words, take myself and my support elsewhere. I've seen GDB go through many changes in 39 years, but what they did last year upset me too much, and I feel there is no true graduate services and support anymore.
On the other hand, GDB knows me, inside and out, when it comes to knowing what type of dog I need with my arthritis and all. They have the best dogs, and I love their training methods. It's scary starting over somewhere new and having to explain everything about my physical condition all over again.
Oh well, I shall go forward with my applications and see where it leads me. I wonder if I should also apply to guide dogs of America.
Mmmm, time for more coffee. Feel free to follow this blog and to comment as you desire.
I'm wishing you nothing but the best of luck with whichever school you pick. I It's strange breaking away from the proverbial GDB fold, but for me it was a great idea, and I don't seem to have many regrets. Have you looked into GDF for Goldens? I understand they put out some good ones. Anyway, please keep us posted on how all the aps go. And also, happy Birthday Bianca dog!!
Hey shanna, I wish I could take your path and owner train or hire a trainer, but that's not practical for me now. Hmmm, GDF, maybe I should consider them too. Thought of GDA, but I can't go there for reasons I won't say on a public blog. BTW, where is Crunches?


text:
Q: Java LED programming Just wondering if there are any Java API's that enable you to control the LED's found on desktop/laptop cases?
Or, if not, is it at all possible?

A: If you're talking about the LEDs on the front that indicates the power state and HDD busy state, I'm afraid there's no way to play with them. AFAIK they are directly controlled by the controllers in the mainboard, and are not exposed to any software above BIOS.
If you want to plug in custom set of LEDs to your machine and control them with Java, then you can connect them to a serial or parallel port and use Java native methods (which essentially talk to C or C++ code) to control them. AFAIK, this is because the JVM doesn't have direct APIs to talk to underlying hardware. This can become quite tricky as Windows Vista and later requires a kernel mode driver to communicate with ports and are blocked for all user-mode software. So you C++ code should talk to kernel mode drivers.
Another way is to disconnect your LEDs from the PC and communicate via a custom protocol over WiFi or Bluetooth. As mentioned by @Makoto,  you can use arduino or a similar board and communicate via either a wireless or a wired technology.

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