This may seem so simple, but when it's clever, pretty and connects to mom's coffee, it's a good idea. A morning without coffee does not a good morning make. No one is happy if mom does not get that infusion of caffeine. So, make it a pretty mug and make sure the coffee is brewed when she wakes, M'kay? Thanks. This handmade Morning Hug in a Mug comes from Etsy but you could easily find something with a similar sentiment at your local TJ Maxx or Target. We love the Turqouise to brighten up an early morning.
Mom hair. don't care – what we do care about is that indentation that the hair tie causes around our wrist and The Grommet solves this problem. It also does allows you to be fashionable when you want to have a hair tie on you for evenings out. The price is bit steep at $24.95, but if you look at is a piece of jewelry, it makes the price point better. And, it's a gift, you're not buying it anyway, right?
Um, who doesn't need one of these? Yes, please! This one is priced really cheap too.
When we saw this Growing Wishes Kit we couldn't pass up the positivity share. It's something mom can do with her kids, on her own or with extended family. Plant wishes at the start of the year centered around the themes of love (forget-me-not), clarity (daisy), happiness (happiness), joy (baby's breath), strength, and friendship (sweet pea) is such a great idea. Definitely one of the best $20 gifts you can get or give to start off your 2017.
The Instant Pot is the forgetful mom's saving grace. It's the #epicfail's fail safe. The lazy mom's win for the week. You can cook a piece of frozen meat from the freezer within the hour. Make risotto without fail and throw something together in a matter of minutes when you didn't remember you had guests coming over. It's a win-win gift. The best part? You can keep it simple or go elaborate with your meals and you're still a success with this machine. Just remember, Pinterest is your friend for recipes or you can use their Instant Pot App. Amazon is running deals off an on through the holiday season, so keep an eye out if this is of interest to you or a mom in your life.
Meeting Grandma for lunch and want to send her off with a recent photo of her favorite grandchild? Have a last minute kid project that requires a few photos? In the need of printing out a photo for a photo gift last minute? Done deal with the HP Sprocket. And, it fits in your purse. Find it on QVC right now as a bundle and they break it down into smaller payment options.
A piece of jewlery that represents a mother and her children is always a win. This nestling birds necklace from Uncommon Goods is a super sweet option.
A subscription box for the first few months (or all year long) is a great way to treat your favorite mom. Roost Crate is the perfect gift for a mom in your life that loves perusing farmer's markets but never finds the time. Every month the box comes jam packed with artisinal finds and goodies. The best part is it's a small business out of Upstate New York owned by a fellow mom, and we love that.


text:
ABOUT KEN SHELDON
Ken Sheldon is a novelist, composer, playwright and performer. Formerly the West Coast bureau chief for Byte Magazine, his writing has appeared in publications ranging from Acoustic Guitar to Yankee Magazine. He writes music for children and adults and created the bestselling Sing Along and Learn series published by Scholastic. His writings appear under his own name, and also as suspense novelist Michael Manley and Yankee humorist Fred Marple.
Michael Manley is the nom de plume of the late Stanley Michael Miastkowski and Kenneth Manley Sheldon. Stan was a search and rescue worker who participated in dozens of rescue and recovery operations, including operations following the September 11 attacks in New York. He was a broadcast and print journalist for nearly 35 years, including stints as a columnist for Esquire, PC World and Byte Magazine. Stan passed away in 2009. Ken continues to write as Michael Manley in his honor.

redpajama_set_name: RedPajamaCommonCrawl


Home > Papers > Pilot Randomized Trial of Integrated Cognitive-Behavioral Therapy and Neuromuscular Training for Juvenile Fibromyalgia: the FIT Teens Program.
Pilot Randomized Trial of Integrated Cognitive-Behavioral Therapy and Neuromuscular Training for Juvenile Fibromyalgia: the FIT Teens Program.
J Pain. 2018 Sep; 19(9):1049-1062.


text:
Ryan Burr Goes To Overtime
The Tuesday edition of NASCAR Now had wrapped-up at 6PM when host Ryan Burr simply told viewers he was not done. Without explanation, Burr extended the program by fifteen minutes.
While the first thirty minutes of this show consisted of mediocre scripted content, the best part of the show happened when Burr was released to talk live with Andy Petree and Boris Said. Burr is an ESPNEWS veteran and one of his strengths is working live in an interview setting.
Boris Said was on the phone and proved to be a big asset to the extended telecast with his road racing perspective. Said provided a good critique of the Montreal rain race and helped fans to understand the real circumstances with some of the problems the teams experienced. This time, Said really came through in the crunch.
Andy Petree has been working hard this season and has a very good perspective on the inner-workings of the sport as things begin to get serious. As ESPN has learned from the very successful Monday edition of this program, conversation with informed NASCAR veterans is a big hit with the fans. This was a great example.
Tuesday is not a very good day for the NASCAR Now gang and interviews with Ron Fellows and Scott Riggs did not serve to spice-up the program. Unfortunately, Fellows has never been a good TV interview despite being an outstanding individual. A couple of questions to Fellows about his sports car wins might have helped this interview along.
David Newton returned to report that Robbie Loomis and the Petty bunch might run two cars full-time and one car for Kyle part-time next season. Burr tried to hype the tension between Carl Edwards and his crew chief at Pocono, but Newton didn't bite and said it happens all the time. "Good stuff," said Burr. Not really. Burr did not ask Newton about either Ryan Newman or Martin Truex Jr. That would have been good stuff.
After Monday's show with the four ESPN pit reporters, the information in this single-anchor show was lacking. Tim Brewer's Tech Tip was no help since it was information fans had seen before. The opportunity to provide a more topical feature on someone or something going-on in the NASCAR community usually exists on slow Tuesdays like this one.
With little manpower in the Mooresville, NC area ESPN has stepped away from the pre-produced features of last season and instead substituted interviews from the various shops. While this might speak to the news of the day, it does very little to expose NASCAR fans to what the teams are actually doing as they gear-up to travel to Watkins Glen. The lack of "ground troops" in the Mooresville area is hurting ESPN.
Three more shows before qualifying gets underway on Friday should leave a lot of time for NASCAR Now to offer previews of the Truck, Nationwide and Sprint Cup races. This is a very long weekend of racing with a lot of it live on the ESPN and ABC family of TV networks.
If the information comes along about why this show ran long and messed-up the DVR's and TiVo's of NASCAR fans nationwide, we will certainly pass it along.


Many individuals get stressed out in managing their investment portfolios and their finances. In some months, your investments are doing good and the next month you may be losing money. Fortunately is that there is manner in which a person can minimize their anxiety and stresses in looking after their finances.
Get sound guidance from a great monetary professional. There are lots of financial specialists that can provide you great suggestions on how to manage your financial resources. Listen to what they have to say and choose for yourself the best route you can take regarding your investments and finances.
Develop a spending plan to manage your expenses. A budget plan will enable you to distribute your paycheck that will pay all of your expenses and will avoid you from spending your money on things that you do not require.
Prepare for any emergency situations that might come up. Put aside a small quantity of a loan from your weekly income into an emergency situation fund. The function of the emergency situation fund is to provide instantaneous cash for unexpected, unexpected occasions. When something occurs, you will have something to fall back on.
Learn to handle your posts practices. The more you invest in things that you do not require, the less loan you will have for the future. There is nothing wrong with buying things that seem nice at the time. The point is that you require to invest your loan sensibly.
Stay out of debt. Settle your charge card expenses and try to get rid of your debts. There likewise any credit therapists you can talk to that will help you develop a strategy to get out of debt.
These are some of the methods to manage your anxieties and tensions of dealing with your financial resources. Even if you do not make a great deal of money, there are ways to lower your expenditures and establish a sound spending plan. The secret is to know how to handle the cash you do have.


At least four members of the security forces and nine civilians were killed when a car bomb was detonated near a security convoy on the western outskirts of Kabul.
At least 11 more people were wounded in the attack.
Taliban spokesman Zabihullah Mujahid claimed responsibility in a tweet.
Meanwhile, at least 10 police officers were killed and 11 were wounded in a three-hour attack by Taliban militants on a checkpoint in northern Kunduz Province, provincial council member Ghulam Rabbani Rabbani said.
In southern Kandahar Province, Taliban militants stormed a checkpoint in the Arghistan district, killing eight officers, a spokesman for the provincial governor, Aziz Ahmad Azizi, said.
Eleven Taliban militants have also been reportedly killed in the fighting.
Taliban militants have stepped up attacks on Afghan security forces and government facilities in recent months.
At least 32 members of the Afghan security forces were killed on December 10 in several Taliban attacks across the country.


Battlegrounds. Barack Obama and Mitt Romney campaigned in the same state for the first time this week, staking claims from opposite ends of Ohio. Also contested this week: hockey's Stanley Cup, which was settled in favor of the Kings, and Greece's place within Europe, which has yet to be resolved.
All are welcome to join in this week's quiz, regardless of financial deficits or currency concerns. And there are no harsh austerity measures either; we'll continue to provide the full complement of twelve questions.


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text:
Q: how to change current path for upload when working with ajax The following problem appears:
I have a drag and drop area for file uploading and a normal form:
Drag and drop:

Drag and Drop Images Here

Below a normal form:
    <form class="sfmform" action="" method="post" enctype="multipart/form-data">
         Upload Files

            <input type="file" name="file" id="file" />

            <input type="submit" class="Button Primary" name="upload" value="Upload" />

    </form>

This is how i handle the upload with php:
    if($_SERVER['REQUEST_METHOD'] == "POST") {
   // file is ready to be uploaded
   $tmpFilePath = $_FILES['file']['tmp_name'];
   $newFilePath = $dir.'/' . $_FILES['file']['name'];
   if(move_uploaded_file($tmpFilePath, $newFilePath)) {
   //echos successful upload
   }
}

The variable $dir changes everytime; i read this from the current url like this:
// read actual dir from url
$actual_link = "http://$_SERVER[HTTP_HOST]$_SERVER[REQUEST_URI]";
$strArr = explode("=",$actual_link);
$CurrentPath = $strArr[1];

if(isset($_GET['dir'])) {
$dir = $CurrentPath;
}

So if the url string is like this: example.com/sfm?dir=uploads/sfm/root/folder1
$dir has the value: uploads/sfm/root/folder1
The problem: uploading with the normal form puts the file in folder1
But uploading with drag and drop puts the file ALWAYS in root.
Both follow the same php for uploading like above.
Probably, when uploading via drag and drop, he can not read the value from $dir
This is my ajax call:
function uploadFormData(formData) {
$.ajax({
url: "sfm",
type: "POST",
data: formData,
contentType:false,
cache: false,
processData: false,
success: function(data){
    $('#drop-area').append(data);
}
});
}

The php code for uploading is in the same file as the drag and drop div with the form. The file is called: sfm.php
Why is uploading via drag and drop not possible in subfolders?
Update:
this is the complete javascript:
$(document).ready(function() {
$("#drop-area").on('dragenter', function (e){
e.preventDefault();
});

$("#drop-area").on('dragover', function (e){
e.preventDefault();
});

$("#drop-area").on('drop', function (e){
e.preventDefault();
var sfmfile = e.originalEvent.dataTransfer.files;
createFormData(sfmfile);
});
});

function createFormData(sfmfile) {
var formFile = new FormData();
formFile.append('file', sfmfile[0]);
uploadFormData(formFile);
}

function uploadFormData(formData) {
$.ajax({
url: "sfm",
type: "POST",
data: formData,
contentType:false,
cache: false,
processData: false,
success: function(data){
    $('#drop-area').append(data);
}
});
}

A: Here is exactly how you can pass the $dir value with your formData in ajax call as :
function uploadFormData(formData) {
   formData.append('dir', <?php echo $dir; ?>);
    $.ajax({
        url: "sfm",
        type: "POST",
        data: formData,
        contentType: false,
        cache: false,
        processData: false,
        success: function(data) {
            $('#drop-area').append(data);
        }
    });
}

A: Solution already found. This is how it should be:
function uploadFormData(formData) {
$.ajax({
url: "<?php 'sfm?dir='.$dir; ?>",
type: "POST",
data: formData,
contentType:false,
cache: false,
processData: false,
success: function(data){
    $('#drop-area').append(data);
}
});
}

The path must be defined in the url of the ajax

redpajama_set_name: RedPajamaStackExchange


Hello parents and students. Welcome back to another great year! I had a great summer, and I hope you did, too!! We will be having our winter concert December 20th, and our spring concert May 15th. The winter performance will be all grades K-3 9:50-11:30 in the gym. The spring concert will be grades K-2 10:00-11:30 in the gym. The 3rd grade will be performing in the evening at 6:40 in the gym. I am looking forward to seeing you all again!
Also, here are some links related to music and the brain, for those of you who may be interested.
The Counting Music activity shows you how to count rhythms, and connects your knowledge of fractions and length to musical notes. Simply enter the notes and it counts the music with you.


Instagram has introduced two new marketing tools—stories insights in Business Tools and full-screen ads in stories.
More than 150 million Instagrammers use ephemeral stories feature since it was introduced last year. One-third of the most viewed stories on Instagram are from businesses. More than 70% of Instagram's users follow businesses.
Instagram Business Tools will include insights on stories in weeks to come. The business profiles will get 4 options for individual stories within Business Tools: reach, impressions, replies and exits. The businesses will be able to get an idea from the insights and they can learn how to create more relevant content that resonates with the audience.
Instagram stories feature and along with it these business tools will be rolled out to everyone globally in coming weeks. Instagram plans to launch more of such features in future.


With the advent of the internet and e-commerce websites, gone are the days where you'd have to travel to a gift shop in your locality to pick out gifts for people, be it for their anniversaries, birthdays, or any other special occasion. However, we must admit that there is no better way of picking up a gift than actually seeing it for yourself before picking it up. While it also minimises any chances of breakage or spoilage, the process of personally going to choose and buy it adds a personal touch, which is of utmost importance when gifting. What if we told you that we stumbled upon one such gift shop in Borivali that has maintained itself as is since time immemorial? Yes, Planet Shoppe in Borivali West is a tiny gift shop that is your one-stop solution to everything gifting (when we say everything, we mean it). The outside of the shop is stacked with greeting cards (remember buying cards for your friends' birthdays) for every occasion and every type of person (best mom, best dad, world's best sibling and more) starting at only INR 50! Push open a door fully covered in keychains to enter and you will be teleported to a another planet (see what we did there) full of gift items that we wish we could gift ourselves. We found soft toys starting at INR 200, decor show pieces (INR 65-INR 2,000), perfumes (both Indian and imported brands), imitation jewellery, air diffusers and board games from your childhood (think Monopoly, Game Of Life, Jenga and many more) too. For those who love their morning dose of coffee, check out their massive collection of mugs (INR 299 upwards) lined against the wall. They also house watches of well-known brands (for those who still believe in the magic of watches over cellphones). After having seen all beautiful and colourful gift items in their neatly arranged, cosy vibe shop, we looked up only to be surprised more- a huge collection of charms, windchimes and dreamcatchers was awaiting our attention and we couldn't get our eyes off them, and we did end up picking up a nice peacock-blue dreamcatcher for INR 549. Quirky keychains in various designs and shapes start at INR 95 (who doesn't love cute keychains) here. For those who are spoilt for choice after checking out the collection and can't zero in on a single item, their chocolate gift boxes and collection of chocolates will surely get your attention. We found everything at this gorgeous shop between INR 5 and INR 5,000. Love the old-world charm and the idea of gift-picking? Head here for the perfect experience that you've been missing.


Your customers are mobile, so why isn't your advertising? Mobile PPC provides high quality, targeted traffic from day one, giving your local or online business the sales it needs for continual growth.
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From social platforms like Facebook Ads to search advertising on Google AdWords, we can ensure your business's marketing message is visible to mobile users on any platform and device.
From new keywords to new platforms, your dedicated account manager will always be available to suggest improvements and optimisations for your mobile advertising campaign.
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In the context of Big Data, Open Data and information exchanges and analysis, first you have to specify and create your content and its formal structure.
The CAM editor is the leading open source toolkit for building and deploying information exchanges and Open Data APIs using XML or JSON with SQL. The CAM toolkit provides an intuitive approach using a WYSIWYG visual structure editor to dramatically simplify the process of developing and managing XML business information exchanges and schema, including the use of JSON. This gives developers control, insights and analysis that are needed for consistent, interoperable and reliable exchanges.
The CAM toolkit also automates the tasks of generating supporting artifacts such as business documentation, cross-reference spreadsheets, models (UML, XMI), XML Schema, JAXB data bindings and test XML instances generation including SQL data extracts.


Singer, Songwriter, Producer and Arranger N.I.K.K.I. Da Jukebox has decided to emerge onto the music scene with her single "Love Again". She appears on Independent Artist Radio (IAC) with "Love Again" peaking at No. 1 for 10 consecutive weeks on Cashbox Radio and is currently still in the top 10 in the R&B genre. Love Again is currently available for download on Itunes as well as IAC.
Born Nicole Marie Whitehead, she has now branded herself as N.I.K.K.I. Da Jukebox. She was coined this name from Berklee College of Music in Boston, where she majored in Vocal Performance. N.I.K.K.I. Da Jukebox has no limits as to what she can do vocally. After taking a listen to her songs, you will become a fan of hers. "She is truly a catalog artist that appeals to all ages and that's rare to come by these days". She knows her audience and strives to have commercial appeal. You will know that Da Jukebox is on the scene to stay….and she is very confident that there is nothing to stop her drive. Her goal is to set a standard amongst her peers, because she has brought something new to the arenas; which are vocal arrangement styles that are outside of the box, coupled with harmony structures that are her own. Da Jukebox is destined to be a successful Pop icon. In her own words, "she is putting her claim to fame directly in the hands of the people that make the difference, which are music lovers and club goers." She understands that the music industry successes those who dare to be different, this is why it's important that she remains true to herself. Her EP has a song that everyone can attest to. Da Jukebox skillfully wrote and produced her soon to be released EP that shows her uniqueness along with her partner C.I.U., who she co-owns the independent record label "The Bottom Line Entertainment, a local premier entertainment company in Metropolitan, Atlanta. Together they have produced, written or appeared on projects with major artists; (Bubba Sparxx, Goodie Mobb, Rock City), and video games, (Midway Sports: NBA Ballers & NBA Ballers Phenom), local commercials, and songs for sports affiliates; (King of the Hoops, Streetball, etc..). She currently produced a basketball focused EP called "Put It on the Line – Game Time" with artist and partner C.I.U., available for download on Itunes. She is a dedicated member of the quad group "Project TBL, where you get a chance to hear the many vocal styles and arrangements that Da Jukebox evokes, together making Project TBL an upcoming Pop Sensation whose sound is directly a cross between the Fugees and the Blackeyed Peas.
Consequently, being the woman empowerment fan that she is, she gives women hope and inspiration that encourages them to open up and not be ashamed of their feelings on all levels. If one had to give words that describe N.I.K.K.I. Da Jukebox, it would be first, Confident, Determined, Honest, Loyal, Dynamic and securely True to the Game! Da Jukebox often says some of the numerous mixtapes she appears, "Nobody has the ability at this time to do it like Da Jukebox…." And "I'm coming like a thief, it's a takeover, I'm here to give the whole industry a makeover". N.I.K.K.I. Da Jukebox is the definition of an artist: and that is a person whose creative works shows sensitivity and imagination…therefore, take a listen to "Love Again" and become a believer yourself.
Raindrops are the burdens that came with your relationships that you weathered.
I need to know what's going on!
Dancing with the Stars and having a good time doing it.
I wanna go all night long!
I'm asking for another chance at Love.
N.I.K.K.I. Da Jukebox performing live at Smith's Olde Bar, Atlanta, GA (corner of Piedmont Ave and Monroe St). December 12th, 9pm Sharp.
N.I.K.K.I. Da Jukebox performing live at Smith's Olde Bar, Atlanta, GA (corner of Piedmont Ave and Monroe St). Come out and Experience Da Jukebox in Action.
Outstanding work! Keep doing your thing.
* Your song 'Love Again' has just been added to THE ART GALLERY station!
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* Your song 'Raindrops' has just been added to The PLuna Music Station station!
* Your song 'Love Again' has just been added to stars station!
* Your song 'Love Again' has just been added to KABRL Smooth Traxx station!
* Your song 'Love Again' has just been added to 2009 RnB/Soul Songs Sorted! station!
* Your song 'Raindrops' has just been added to crimson station!
* Your song 'Love Again' has just been added to Regina C Radio Station station!
* Your song 'Love Again' has just been added to F.T.H. station!
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* Your song 'Love Again' has just been added to Inet Jazz 365 Radio A New Age of Music station!
* Your song 'Almost There' has just been added to MUSIC IS TRUTH station!
* Your song 'Love Again' has just been added to The JazzXpress Caravan station!
* Your song 'Talk 2 Me' has just been added to eYe station!
* Your song 'Love Again' has just been added to IF YOU'RE NOT THE LEAD DOG... station!
* Your song 'Talk 2 Me' has just been added to Inet Jazz 365 Indie Radio station!
* Your song 'All Night (featuring Project TBL)' has just been added to KABRL Smooth Traxx station!
* Your song 'Talk 2 Me' has just been added to KABRL Smooth Traxx station!
* Your song 'Dancing With the Stars' has just been added to SMACK station!
* Your song 'March On' has just been added to eYe station!
* Your song 'Love Again' has just been added to We Bring Music station!
* Your song 'March On' has just been added to Hood Tales station!
IAC Your song 'Love Again' has just been added to Hood Tales station!
EP has outstanding production from super producer N.I.K.K.I Da Jukebox and grammy award winning producer Ricciano Lumpkins.
"Put It On The Line – GAME TIME" by C.I.U aka "Mr. Put It On The Line" released by the Bottom Line Entertainment (TBL-ENT) is a complete classic!
"Put It On The Line" embodies the spirit of a champion from childhood to high school to college and ultimately the success of a NBA superstar.
"King Of The Court" is an up tempo guitar driven track with a catchy chant hook that will appeal to die hard basketball fans that live for this sport.
"All The Way" is an energizing song that truly makes you believe you are unstoppable and you have what it takes to go all the way and win the championship.
"This Is Our Year" is the new "We Are The Champions" It will soon be the playoff anthem. Every season teams claim that this is their year, but whose year is it really?
The combination of the ear catching track, flawlessly sung hook and powerful motivating lyrics are truly something special.
"For The Love Of The Game" – Features verses from TBL-ENT recording Artist Tre-Doh and N.I.K.K.I Da Jukebox. Each artist explosively expresses why they love the game of basketball.
"We Did It Again" is dedicated to those champions that keep on winning. For some reason they just can't lose.
"Victory Tonight" has a vintage throwback sound that grabs your attention as soon as it comes on. It's a confident song that makes you feel invincible. Lisa Denise is featured on the hook and bridge and victoriously delivers the vocals.


time out • n. 1. time for rest or recreation away from one's usual work or studies: she is taking time out from her hectic tour. ∎ (usu. timeout or time-out) a brief break in play in a game or sport: he inadvertently called for a timeout with two seconds remaining. ∎ (also timeout or time-out) an imposed temporary suspension of activities, esp. the separation of a misbehaving child from one or more playmates as a disciplinary measure: it's the third time this week he's been in time-out. 2. (usu. timeout) Comput. a cancellation or cessation that automatically occurs when a predefined interval of time has passed without a certain event occurring.
"time out." The Oxford Pocket Dictionary of Current English. . Encyclopedia.com. 23 Apr. 2019 <https://www.encyclopedia.com>.


text:
The Conversion Gradient at HIS4 of Saccharomyces cerevisiae. II. A Role for Mismatch Repair Directed by Biased Resolution of the Recombinational Intermediate
Henriette M. Foss, Kenneth J. Hillers and Franklin W. Stahl
Genetics October 1, 1999 vol. 153 no. 2 573-583
Henriette M. Foss
Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229
Kenneth J. Hillers
Franklin W. Stahl
Salient features of recombination at ARG4 of Saccharomyces provoke a variation of the double-strand-break repair (DSBR) model that has the following features: (1) Holliday junction cutting is biased in favor of strands upon which DNA synthesis occurred during formation of the joint molecule (this bias ensures that cutting both junctions of the joint-molecule intermediate arising during DSBR usually leads to crossing over); (2) cutting only one junction gives noncrossovers; and (3) repair of mismatches that are semirefractory to mismatch repair and/or far from the DSB site is directed primarily by junction resolution. The bias in junction resolution favors restoration of 4:4 segregation when such mismatches and the directing junction are on the same side of the DSB site. Studies at HIS4 confirmed the predicted influence of the bias in junction resolution on the conversion gradient, type of mismatch repair, and frequency of aberrant 5:3 segregation, as well as the predicted relationship between mismatch repair and crossing over.
Gilbertson and Stahl (1996) drew attention to several properties of recombination at the ARG4 locus of Saccharomyces cerevisiae that are not implicit in the canonical model for meiotic double-strand-break repair (DSBR). Each of these had been reported separately in earlier work at ARG4 or at other loci or was implied by previous observations. The occurrence of all of them in a single cross encouraged us to rationalize them within a single model. Here we identify deviations from the canonical model and test predictions of a modified model, including those applying to the origin of the conversion gradient, which have been addressed in recent publications (Alaniet al. 1994; Kirkpatricket al. 1998; and see Hillers and Stahl 1999).
The centerpiece of the canonical DSBR model is a double-Holliday-junction intermediate (Figure 1). This intermediate (joint molecule) arises via invasion by the two overhanging 3′-ended single strands into the same chromatid, followed by DNA synthesis primed by the invading ends. This feature of the model is recommended by its simplicity and by the physical demonstration of some of its salient features (e.g., Schwacha and Kleckner 1995).
The crosses performed by Gilbertson and Stahl (1996) were designed to test central predictions of the canonical DSBR model: (1) Hybrid DNA (hDNA) should be formed on each side of a DSB; (2) this hDNA, detected with appropriate markers as heteroduplex DNA, should be found in separate haploid products of a single meiosis; and (3) in a fraction of such tetrads, the heteroduplex-containing chromatids should be reciprocally recombinant (crossed over) for markers flanking the heteroduplex regions.
To facilitate the testing of these predictions, the crosses of Gilbertson and Stahl (1996) had the following features (Figure 2): (1) Markers were inserted close to and on opposite sides of the DSB site (to reveal the expected heteroduplexes, these markers were small palindromes, which are semirefractory to mismatch repair (MMR) when in heteroduplex with the wild type); (2) one of the two palindromes was in ARG4, which permitted phenotypic screening for tetrads manifesting conversion; and (3) auxotrophic markers flanking the ARG4 region permitted the identification of tetrads in which conversion at the DSB site was accompanied by crossing over.
The data collected by Gilbertson and Stahl (1996) differed from the simple predictions of the canonical model in several ways. First, tetrads that had heteroduplex DNA for both palindromes were found, but few of them showed the heteroduplexes on separate chromatids, and those that did were all crossovers. [Gilbertson and Stahl (1996) noted that their failure to find evidence for steps h and i of the canonical model (Figure 1) is, in fact, a corollary of the long-standing observation that "aberrant 5:3's" are rarely observed in S. cerevisiae for the well-documented ARG4 gene; for review see Szostak et al. (1983).] Conversely, among the noncrossover tetrads that were doubly heteroduplex, the two heteroduplexes were invariably located on the same chromatid, a feature not predicted by the DSBR model. These observations raised two questions: first, in terms of Figure 1, how are opposite-sense resolutions effected while same-sense resolutions are avoided and, second, how does the joint molecule give rise to noncrossovers?
—The canonical DSBR model. A DNA duplex chromatid (a) is cut on both strands (b) and then resected on both sides of the break in the 5′-3′ direction. The resulting 3′-ended overhangs (c) bind a RecA-like protein and invade a homolog chromatid (d). DNA synthesis primed by the invading ends completes the joint molecule (e) in which the two participants are tied together by a pair of Holliday junctions. The joint-molecule intermediate is resolved back to duplexes by resolvase-catalyzed cutting of the junctions. When the junctions are cut in the opposite sense (left), crossovers result. (f) The noncrossing strands were cut at the left junction (vertical cutting), while the crossing strands were cut at the right junction (horizontal cutting). (g) The cutting was horizontal-vertical. When the junctions are cut in the same sense (right), noncrossovers result. (h) The junctions were cut horizontal-horizontal, and in (i) they were cut vertical-vertical. Same-sense resolutions can result in "aberrant 5:3 tetrads," in which each of the noncrossover chromatids has received information from the other at a given site. Such tetrads would arise for markers on either side of the DSB, as shown in h and i. The rarity of these tetrads at ARG4 of yeast casts doubt on the concept that noncrossovers typically arise from cutting of the two Holliday junctions. The segments of hDNA indicated in the joint molecule (e) have not been experimentally confirmed (e.g., Schwacha and Kleckner 1995).
A second notable feature of the data of Gilbertson and Stahl (1996), reported previously by others (e.g., Porteret al. 1993), was that a conspicuous fraction of the events appeared to be "one-sided"; i.e., in about half of the tetrads that manifested conversion for the palindrome on one side of the DSB, the palindrome on the other side showed normal 4:4 segregation. These may have been tetrads in which resection from the DSB had been so lopsided that one of the palindromes was not included in the joint molecule. However, Sun et al. (1991) reported that 68% of the DNA that enjoyed a DSB was resected >440 bp. If resection lengths at ARG4 are exponentially distributed, ∼85% of the resections would be expected to reach the palindrome markers of Gilbertson and Stahl (1996; Figure 2). If resections have a minimal length, as they seem to have at another locus (Bishopet al. 1992), all of the resections might include the markers of Gilbertson and Stahl (1996). For simplicity, therefore, we assume that all resections proceeded beyond those two markers. If that assumption is correct, the canonical model predicts that both markers will give rise to 5:3 tetrads (half conversions, Figure 1) except when MMR intervenes. This prediction implies that MMR must account for 4:4 as well as 6:2 tetrads, i.e., that both restoration- and conversion-type MMR occurs.
—The cross of Gilbertson and Stahl (1996). The segregating diploid was marked with small palindromes close to the DSB site on each side. The DSB site is in the promoter region of ARG4. The palindrome marker on the "right" side of the DSB site was in the 5′ end of the coding region of ARG4. These palindrome markers make relatively poorly repairable mismatches when in heteroduplex with their wild-type allele, allowing for the detection of half conversions (5:3 segregations) as well as full conversions (6:2 segregations). Strains carried nutritional markers flanking ARG4. One nutritional marker was 4.8 kb to the left of the ARG4 DSB site; the other marker was 8.6 kb to the right of the DSB site.
An additional feature of the data observed and addressed by Gilbertson and Stahl (1996) concerns a relationship between crossing over and MMR. Gilbertson and Stahl (1996) observed that, in addition to the relative shortage of doubly unrepaired heteroduplex among crossovers, there was a relative excess of 6:2 tetrads (full conversions) associated with crossing over. Specifically, for aberrant segregations presumed to arise by DSBs at the ARG4 site, the following relations were seen: 5:3 on both sides of the DSB were crossovers 0.10 of the time; 5:3 on one side and 6:2 on the other were crossovers 0.46 of the time; 6:2 on both sides were crossovers 0.68 of the time. The apparent correlation between full conversion and crossing over was rationalized by Gilbertson and Stahl (1996) with the assumption that junction cutting occurs preferentially in crossovers and, as proposed previously by Alani et al. (1994) and by Schwacha and Kleckner (1995), triggers a late round of mismatch repair. Junction cutting creates ends, which, they presumed, stimulate MMR.
—Gilbertson and Stahl's (1996) modification of the canonical theory. The finding by Gilbertson and Stahl (1996) of the tetrads diagrammed in d drove home the point that most noncrossovers at ARG4 are not the result of cutting two Holliday junctions and provided support for the idea of resolution mediated by topoisomerase or by the cutting of one junction followed by sliding of the other. In the absence of MMR and of any resection of the 3′-ended strands, as illustrated here, all aberrant segregations are half conversions (5:3 tetrads).
—Early MMR. Mismatch repair guided by the ends of the invading strands (a) can remove invading DNA, which is shown arbitrarily on the right side of the DSB (b). Synthesis then completes the joint molecule (c). While a marker on the left of the DSB will segregate 5:3 (half conversion), one on the right will segregate 6:2 (full conversion). MMR tied to invading ends leads to full conversions only, not to restorations (4:4 segregation). A half-converted marker on the left of the DSB would yield the forbidden aberrant 5:3 if resolution-producing noncrossovers were by cutting both junctions, but not if it were by topoisomerase or by cutting of only one junction.
Prompted by their data, Gilbertson and Stahl (1996) presented a slightly modified version of the canonical DSBR model. In Figure 3, their model is diagrammed for the instance in which MMR of heteroduplexes fails for both of the palindrome markers. Gilbertson and Stahl (1996) proposed that noncrossovers arose primarily by topoisomeric resolution of the joint molecules. They noted that cutting of one junction followed by sliding of the uncut junction to that unligated site would give the same products. Thus, crossovers, presumed by Gilbertson and Stahl (1996) to arise in the canonical manner, i.e., f or g in Figure 1, suffer more cut junctions than do noncrossovers and therefore undergo more MMR than noncrossovers.
Our modification of this model is based on two proposals: (1) To account for the rarity of same-sense, but abundance of opposite-sense, resolutions of Holliday junctions (Figure 1), we propose that each junction has a structural asymmetry that biases which strands are cut; and (2) retaining the conventional assumption that strand ends not only stimulate MMR but direct it to occur on the discontinuous strand, we follow the suggestion of Alani et al. (1994) that MMR is often directed not by the discontinuities at the DSB site (Figure 4) but rather by cuts at the Holliday junctions (Figure 5). A relationship between MMR and crossing over is implicit in these proposals if crossovers, but not noncrossovers, are derived from joint molecules in which both junctions are cut. A further implication is that junction-directed MMR will result in either restoration of 4:4 segregation or full conversion (6:2 segregation), depending on the direction of junction-cutting and the location of the affected mismatch relative to the DSB. Restoration-type repair could account for Gilbertson and Stahl's (1996) one-sided events; it could also contribute to gradients of aberrant segregation frequencies (conversion gradients) such as those observed, for example, in the HIS4 and ARG4 genes.
—Crossing over and late MMR guided by junction cutting. MMR keyed by cutting of the two Holliday junctions in the favored sense can result in restoration (4:4) of a marker on the same side of the DSB as a cut junction (left), or full conversion (6:2) of a marker on the other side of the DSB from the cut junction (right) as illustrated for the right-hand marker.
Our primary modification of the DSBR model is forced by the first proposal, that a structural asymmetry dictates which strands of a Holliday junction are cut. The only apparent asymmetry in the canonical intermediate (Figure 1e) is the disposition of the newly synthesized DNA. At one junction, the new DNA is on a Crick strand, while at the other junction it is on a Watson strand. We propose that this new DNA, or its synthesis, dictates both Watson strands to be cut (or left uncut, depending on the direction of the bias) at one junction and both Crick strands to be cut (or not) at the other junction. Strict adherence to this rule will generate crossovers of either type f or type g in Figure 1, but not both. In an alternative scheme mentioned by Gilbertson and Stahl (1996), one of the junctions is cut at random, while a "machine" then constrains the cutting of the second junction to be opposite that of the first. This scheme predicts crossovers of type f and type g in equal frequencies.
The existence of a bias, as well as its sense, is implied by a feature of the Gilbertson and Stahl (1996) data. Those authors attempted to "locate the exchange" that unlinked the flanking markers. They did so in the manner proposed by Fogel et al. (1979), by asking whether the minority marker at a site segregating 5:3 had become unlinked from the flanking marker located on the same side of the recombination-initiating site. That tactic was devised at a time when the Aviemore model (Meselson and Radding 1975), in which a single Holliday junction represented a crossover, held sway, and it made some sense within that context. In the DSBR model, however, crossing over is the result of the combined mode of resolution of two Holliday junctions. In this context, therefore, linkage (or lack of linkage) between the minority marker at a site segregating 5:3 and a more distant marker on the same side of the DSB does not locate the exchange, but, instead, tells which strands are cut to give the required opposite-sense resolution.
Gilbertson and Stahl (1996) examined 5:3 segregants for the palindrome on the right side of the DSB and noted that, among crossovers, the minority marker tended to remain linked to its flanking marker on the right. The linkage was 84%, instead of the 50% expected from the hypothesis of unbiased cutting. Similarly, for tetrads 5:3 at the marker to the left of the DSB, among crossovers the minority marker tended to remain linked to its flanking marker on the left. This result indicates that the mode of resolution is indeed nonrandom and that the preferred mode involves the cutting of those chains that were newly synthesized at the junction— resolution f is favored over resolution g. Others observed a bias in the same direction (Fogelet al. 1979; White and Petes 1994; Hillers and Stahl 1999).
The identification of a bias in junction cutting allows us to explore the potential consequences of MMR triggered by junction cuts. In Figure 5, we illustrate MMR in the context of crossing over, with resolvase cutting in the favored orientation. The strand discontinuities introduced by resolvase determine the strands upon which excision will occur during MMR. Junction-directed MMR can result in either restoration or full conversion as illustrated for MMR occurring (arbitrarily) on one strand or the other of the upper duplex. Other patterns can arise if both duplexes are repaired or if MMR is triggered both by the DSB ("early repair"), as illustrated in Figure 4, and by junction cuts ("late repair"). Note that early repair alone generates no restorations and that late repair triggered by "unfavored" junction resolution (Figure 1g) can do so only for mismatches beyond the DSB. The assumption, adopted in Figures 5, 6, 7, 8, 9, that MMR occurs after junction resolution, implies a competition between cut junctions for the right to direct the repair of a given mismatch, making it likely that proximity of a mismatch to a junction increases the likelihood that its repair will be directed by that junction (see also calculations and discussion). Thus, among crossovers resolved in the "favored" mode, mismatches far from the DSB would be more likely to undergo restoration-type repair than conversion-type repair, while among crossovers resulting from "unfavored" resolution such mismatches would be more likely to undergo conversion-type repair.
If the observed relative paucity of noncrossovers among tetrads with full conversions reflects reduced opportunity for late MMR, noncrossovers must suffer fewer junction cuts, i.e., one or none, than do crossovers, which suffer cuts at both junctions. We propose that noncrossovers arise from the resolvase cutting of one Holliday junction accompanied by sliding of the other junction. Within the constraints of our model, the choice of single junction-cutting-with-sliding rather than topoisomerase is a forced move—the recovery of noncrossover tetrads with full conversion on one side of the DSB and normal 4:4 segregation on the other side argues for MMR potentiated by junction resolution. Possible segregation patterns resulting from such MMR directed by "favored" resolution of the junction on the left are illustrated in Figure 6, which arbitrarily allows both continuous and discontinuous repair tracts (see below).
—The possible outcomes of late MMR in noncrossovers. MMR keyed by cutting of one Holliday junction, in the favored sense, can, in principle, have any of the following three outcomes: it can result in restoration (4:4) of a marker on the same side of the DSB as the cut junction (left), full conversion (6:2) of marker on the other side of the DSB from the cut junction (middle), or both restoration and full conversion (right).
—Noncrossing over with MMR directed by resolvase nicks in the absence of early MMR. (A; variation 1) A joint molecule (a), with heteroduplex on both sides of the initiating DSB, can be cut at either junction with equal probability to give b or c. The cuts shown are the ones favored by the model, wherein resolvase action is guided by the newly synthesized DNA. The uncut junctions slide to the sites of the cut junctions to give d and e. With probability (1 - L)2, MMR fails to operate at both heteroduplexes, yielding the trans-heteroduplex (f). With probability L, MMR operates on the mismatch farther from the strand end, removing DNA from the mismatch to the end, giving rise to g and h. Resynthesis gives the products i and j. With probability (1 - L)L, MMR fails for the site far from the end but succeeds for the site closer to the end, removing DNA from that site to the end (k and l). Resynthesis then gives the products m and n. (B; variation 2) a-f are as in A. In g and h the two mismatches have been independently repaired, with probability L2. In i-l, one or the other has been repaired, with probability (1 - L)L.
The combination of location-dependent late repair and favored junction resolution suggests a mechanism for the restoration-conversion mix of repair proposed by Detloff et al. (1992) to account for the dependence of steep conversion gradients on efficient MMR. The authors proposed that the observed gradients represent an increasing likelihood for restoration-type repair with increasing distance of the mismatch from the DSB. Thus, to effect a gradient, efficient MMR must cause full conversion for mismatches close to the DSB while masking mismatches nearer the Holliday junction through restoration-type repair. Defects in MMR would prevent half conversions from becoming undetectable restorations and would, consequently, result in longer, shallower gradients. We propose that, at the DSB site, MMR of well-repairable mismatches is directed exclusively from the DSB, resulting in full conversions and preempting restoration-type repair. With increasing distance from the DSB, mismatches would become more likely to escape early repair and would, therefore, become subject to junction-directed restoration-type repair. This hierarchical relationship between early and late repair would result in a conversion gradient. We envision that such a gradient would add to the effect conferred by heteroduplex rejection (Hillers and Stahl 1999).
—Noncrossing over with MMR directed by resolvase nicks, following early MMR. When early MMR has repaired one or both mismatches, as diagrammed here, variations 1 and 2 are equivalent. The nascent joint molecule (a) can be repaired at both mismatches (probability E2), giving product (b), or at one mismatch [probability E(1 - E)], giving joint molecules (c or d). These joint molecules can be cut by resolvase at either junction, giving intermediates (e) whose junctions slide to give unligated products (f). If MMR fails (probability 1 - L), these intermediates are recovered as ligated products. If MMR succeeds (probability L), the products recovered are those in g.
Adopting the first proposal outlined above, that Holliday junction resolvase preferentially cuts the pair of strands, one of whose members was newly synthesized in the neighborhood of the junction during formation of the joint molecule, we derive expectations for the distribution of tetrad types from the data of Gilbertson and Stahl (1996), based on the second proposal, that at least some of the discontinuities that trigger MMR must be created by Holliday junction resolvase. We outline the possible consequences of such late MMR as well as of the early MMR that can occur after the invasion step, before DNA synthesis completes the joint molecule. Expected frequencies of tetrad classes are expressed in terms of the probability of repair of a given poorly repairable mismatch by the early or late pathways. In assigning numerical values to these probabilities it is not our intention to find the best fit, but simply to ascertain (1) whether or not there is a set of values that allows the model to approximate the data and (2) whether such a set implies a substantial contribution of late MMR to total MMR of poorly repairable heteroduplexes as proposed in the model. Should there be such a set, we would consider the model a candidate for experimental test and refinement.
The predicted consequences of early and late MMR overlap but do not coincide. Early MMR produces only full conversions (6:2) and never restorations of 4:4 segregation (Figure 4). Late MMR, on the other hand, can generate restorations as well as full conversions. A mismatch on the same side of the DSB as the cut junction that directs the MMR results in restoration of normal segregation, while MMR for a mismatch on the far side of the DSB results in full conversion (Figure 5). When early MMR has acted at both marked sites, late MMR is preempted. When early MMR has acted at only one site, late MMR can act only at the other site. When early MMR has failed at both sites, late MMR can act at either or both sites.
In our calculations, we make the following simplifying assumptions: (1) All junction cutting is effected by cutting the two strands in one of which there is newly synthesized DNA near that junction; (2) all mismatches of Gilbertson and Stahl (1996) are equally correctable; (3) the palindromes of Gilbertson and Stahl (1996) are sufficiently close to each other that the difference in their distances from the two Holliday junctions is not a factor; (4) the marker excised by MMR is always the one that is cis to the strand end; (5) late MMR occurs after resolution of the joint molecule, which for noncrossovers means after sliding the uncut junction to the location of the cut junction [this assumption is forced by consideration that late MMR prior to junction sliding would result in aberrant 4:4 rather than normal 4:4 segregation (restoration)]; (6) in early MMR, corrections of the two mismatches are independent of each other; and (7) among crossovers, late MMR, too, occurs independently for each of the two mismatches, because repair is triggered by junction cuts on separate chromatids. Among noncrossovers, on the other hand, late MMR for the two mismatches is triggered by a single junction cut, which may or may not affect both mismatches. We therefore present our calculations for each possibility. In variation 1, we presume that MMR excises DNA between the site of either mismatch and the discontinuity created by Holliday junction resolution. Such a rule is suggested by the in vitro properties of the MMR system of Escherichia coli (Grilleyet al. 1993). In variation 2, the removal need not be continuous. Such a possibility is suggested by the demonstration in yeast (Kirkpatricket al. 1998) of tetrads in which a site segregating normally is flanked by sites segregating 5:3. Earlier data supporting the same view are summarized by Fogel et al. (1981). The difference in the two variations affects the formalizations of the models only for noncrossovers and only when neither mismatch has been repaired by early MMR.
—Crossing over with or without early MMR. Variations 1 and 2 are equivalent. The nascent joint molecule (a) can undergo early repair at both mismatches (probability E2), giving product (b), or at one mismatch [probability E(1 - E)], giving joint molecules (c). The joint molecules are cut in the favored crossover pattern (d). The resulting resolved duplexes can be ligated without MMR [probability (1 - L)2], giving products (e), or their mismatches can be repaired from either cut junction to give f or g {probability of each is [1 - (1 - L)2]/2}. If early MMR fails [probability (1 - E)2], the joint molecule (h) is cut (in the favored pattern) to give a pair of duplexes, each member of which has a heteroduplex region and two strand interruptions that can direct MMR (i). MMR on one duplex only (j) has four possible outcomes, each with a probability (1 - L)2[1 - (1 - L)2]/2. MMR on both duplexes (k) has four possible outcomes, each with probability [1 - (1 - L)2]2/4. All opportunities for MMR may fail, giving type l with probability (1 - L)4.
Figures 7, 8, 9 are pictorial representations of the model, showing the steps in junction resolution and associated MMR with their associated probabilities. These figures formalize the assumptions and their algebraic consequences. Figures 7 and 8 describe noncrossovers in the absence and presence of early MMR, respectively. Figure 9 describes crossovers. E is the probability of early MMR of a given poorly repairable mismatch; L is the probability of late MMR of a given poorly repairable mismatch stimulated by a given junction cut. The pathways shown in Figures 7, 8, 9 permit us to calculate expectations for the relative frequencies of the tetrad classes observed by Gilbertson and Stahl (1996). The predictions of the two variations of the model are presented in Table 1.
To compare the calculated probabilities with observed numbers (Table 2), we normalized the calculated probabilities to account for the fact that Gilbertson and Stahl (1996) enumerated only those tetrads in which segregation at the right palindrome was aberrant. The normalized probabilities were then multiplied by the observed total number of noncrossovers or of crossovers, respectively, to get the expected numbers for each observed tetrad class. The relative rarity of tetrads that manifest full conversion simultaneously for both of the palindrome markers suggests that late MMR is more frequent than early MMR, and we see that major features of the data of Gilbertson and Stahl (1996) are accommodated when L = 0.6 and E lies between 0 and 0.1. According to our model, these small E values characterize only poorly repairable mismatches. Well-repairable mismatches close to the DSB typically become full convertants via early repair.
Predicted probabilities of the tetrad classes
Calculated frequencies compared with frequencies from Gilbertson and Stahl's (1996) Table 3
The observed values for 4:4, 6:2 and for 5:3, 6:2 noncrossover tetrads are bracketed by the predictions of variations 1 and 2, suggesting that they are generated by a mix of the two variations.
In comparing the model with the data, we ignored the fact that a fraction of the crossovers enumerated by Gilbertson and Stahl (1996) are incidental to the conversions at the palindrome sites. We also ignored the evidence that some (∼16%) of the crossover resolutions break our assumed rule for junction cutting. Additionally, by writing a model with symmetric probabilities, we have ignored asymmetries reported by Gilbertson and Stahl (1996): (1) MMR more often corrected in favor of the wild-type allele of the palindrome markers; (2) mismatches for one palindrome appeared to be corrected more often than mismatches for the other palindrome; and (3) initiations were more often on one chromosome than the other. These asymmetries do not bear directly on the issues examined here. Furthermore, our calculations, which average out such asymmetries, are compared with combined data from two types of crosses (one parent carrying both palindromes or each parent carrying one palindrome), which also average out asymmetries.
Our calculations led to underprediction of the 4:4, 5:3 class. The discrepancies are in the same direction for both noncrossovers and crossovers and for variations 1 and 2, so that no mixture of the two variations will relieve the problem. Heteroduplex rejection (see Hillers and Stahl 1999) is likely to contribute to the 4:4 segregant class. Also, our assumption that resection is always greater than the 130-bp distance from the DSB site to the left palindrome may be wrong, so that some of the 4:4 segregants are truly "no events." Alternatively, we may note that in both of the variations of the model the (4:4, 5:3) tetrads arise when the site nearer to the relevant cut junction (on the left) is repaired without involvement of the more distant site. That consideration suggests that our assumption that each marker triggers MMR without regard to its position relative to the other marker and/or distance from the points of junction resolution was too simple.
Gilbertson and Stahl (1996) suggested that "one-sided events" (aberrant segregation on one side of the DSB and 4:4 segregation on the other) reflect early, reversible interactions of the cut chromatid with its sister. The considerations presented here do not rule out such possibilities but do offer a testable alternative. If one-sided events represent mismatches rendered undetectable by restoration-type MMR, these mismatches should become detectable as an increase in the frequency of aberrant segregation when MMR efficiency is reduced. Experiments by other workers failed to demonstrate a significant increase in aberrant segregation frequency for well-repairable markers near the high end of the conversion gradients in ARG4 and/or HIS4 when MMR was reduced by a mutation in the MSH2 gene. For markers far from the DSB site, however, aberrant segregation frequencies were increased by mutations in genes governing MMR (Alaniet al. 1994; Hunter and Borts 1997). These data are compatible with the proposal that poorly repairable mismatches near the DSB, and well- or poorly repairable mismatches far from the DSB, escape "early" conversion-type MMR directed from the DSB and thereby become subject to restoration-type MMR directed by junction cuts.
The study by Hillers and Stahl (1999) permits further tests of our model. First, the prediction that junctions should be cut predominantly in the favored direction is supported by the data—among crossover tetrads, 57-60% had type-f resolution at HIS4 (Table 4, Hillers and Stahl 1999). The weakness of the bias as compared with that at ARG4 implies a relatively high frequency of random junction cutting at HIS4, offering the opportunity to test other aspects of the model. For example, increased randomness in junction cutting should cause increased frequencies in "same sense" resolutions (as in Figure 1i) as well as in type g resolutions. In fact, Hillers and Stahl (1999) found ∼40 tetrads of type i whereas Gilbertson and Stahl (1996) found none in an ARG4 analysis approximately as large. (Note that, if unfavored resolutions result from the loss of guiding signals in the meiotic cell, the model predicts approximately equal numbers of type g and type i resolutions. The observed inequality suggests that additional factors are involved in junction resolution.)
A relative excess of tetrads of types g and i is predicted to result in a shallower conversion gradient, possibly contributing to the relative shallowness of the gradient at HIS4 as compared with ARG4 (Detloffet al. 1992). The data of Hillers and Stahl (1999) allow us to determine the distribution of conversion-type repair for DSB-distant mismatches among resolution types. Hillers and Stahl's (1999) Table 4 shows that, among half conversions at the 5′ marker, the frequency of full conversions for a well-repairable 3′ marker was 35/82 = 0.43 for combined tetrads of type g + i, in contrast to 22/150 = 0.15 for tetrads of type j + h, and 6/73 = 0.08 for tetrads of type f. These data and similar, though scant, data for a poorly repairable marker support our suggestion that, by their penchant for conversion-type repair, tetrads of types g + i diminish the slope of the conversion gradient.
Our model predicts the following: type i resolutions direct full conversions only; type g resolutions direct predominantly full conversions, triggering restorations only from junction cuts on the far side of the DSB; type j resolutions direct restorations and conversions in approximately equal numbers; type f resolutions direct predominantly restorations, triggering full conversions only for mismatches beyond the DSB; and type h resolutions can direct restorations only. The observation that the frequency of conversion-type repair is lowest for resolution type f, intermediate for type j + h, and highest for type g + i supports half of this prediction; support for the other half calls for a reverse correlation with respect to restoration-type repair. To test this latter prediction, we examined the resolution types identified in Hillers and Stahl's (1999) Table 4 for evidence of restoration-type repair.
Restoration-type repair, as well as heteroduplex rejection, can manifest itself indirectly as an increase in aberrant segregation events in response to reduced MMR. The contribution to this increase from heteroduplex rejection (assumed to occur independently of subsequent junction resolution) should be identifiable. In tetrads of type gIII + iIII, which by definition did not undergo heteroduplex rejection, the effect of reduced MMR could reflect only the minimal restoration-type repair expected for tetrads of type g, whereas in the full class of type g (or g + i) tetrads such an effect should represent both heteroduplex rejection and restoration-type repair. It follows that any increase in the effect of reduced MMR in tetrads of types j + h and f over tetrads of type g (or g + i) may be attributed to the relatively greater incidence of restoration-type repair predicted for tetrads of types j + h and f. Table 3 confirms a minimal incidence of restoration-type repair in tetrads of type g + i, a greater incidence of heteroduplex rejection (last three rows), presumably occurring in all tetrad types, and a progressively larger incidence of restoration-type repair in tetrad types j + h and f, respectively, as predicted. The negligible evidence for restoration-type repair in tetrads of type gIII implies that, for the crossovers in these experiments, proximity to the directing junction is the primary factor governing the type of repair (full conversion vs. restoration) of DSB-distal mismatches.
Resolution-dependent increases in aberrant segregation frequency in response to reduced MMR
Thus, the results of Hillers and Stahl (1999) support the crucial tenets of the model: (1) junction cutting directs mismatch repair; (2) junctions cut in the favored sense direct restoration-type repair, while junctions cut in the unfavored sense direct conversion-type repair; and (3) the relationship between junction resolution and mismatch repair holds for all resolution types (Figure 1), suggesting that noncrossovers as well as crossovers are derived from the joint molecule intermediate. Finally, the correlation between the strength of the resolution bias and the steepness of the conversion gradient, together with the correlation between favored resolutions and restoration-type repair, indicate a major role for restoration-type repair in the formation of the conversion gradient.
H.M.F. gratefully acknowledges the patient explanations of yeast genetics provided by Eric Foss. This work was supported by grant GM-33677 from the Institute for General Medicine of the National Institutes of Health and MCB-9402695 from the National Science Foundation. F.W.S. is American Cancer Society Research Professor of Molecular Biology.
Communicating editor: P. J. Pukkila
Received September 15, 1998.
Accepted May 6, 1999.
Alani E.,
Reenan R. A.,
Kolodner R. D.
, 1994 Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics 137: 19–39.
Bishop D. K.,
Park D.,
Xu L.,
Kleckner N.
, 1992 DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell 69: 439–456.
Detloff P.,
White M. A.,
Petes T. D.
, 1992 Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae. Genetics 132: 113–123.
Fogel S.,
Mortimer R.,
Lusnak K.,
Tavares F.
, 1979 Meiotic gene conversion: a signal of the basic recombination event in yeast. Cold Spring Harbor Symp. Quant. Biol. 43: 1325–1341.
Strathern J. N.,
Jones E. W.,
Broach J. R.
Lusnak K.
, 1981 Mechanisms of meiotic gene conversion, or "wanderings on a foreign strand," pp. 289–339 in The Molecular Biology of the Yeast Saccharomyces: Life Cycle and Inheritance, edited by Strathern J. N., Jones E. W., Broach J. R.. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Gilbertson L. A.,
Stahl F. W.
, 1996 A test of the double-strand break repair model for meiotic recombination in Saccharomyces cerevisiae. Genetics 144: 27–41.
Grilley M.,
Griffith J.,
Modrich P.
, 1993 Bidirectional excision in methyl-directed mismatch repair. J. Biol. Chem. 268: 11830–11837.
Hillers K. J.,
, 1999 The conversion gradient at HIS4 of Saccharomyces cerevisiae. I. Heteroduplex rejection and restoration of Mendelian segregation. Genetics 153: 555–572.
Hunter N.,
Borts R. H.
, 1997 Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev. 11: 1573–1582.
Kirkpatrick D.,
Dominska M.,
, 1998 Conversion-type and restoration-type repair of DNA mismatches formed during meiotic recombination in Saccharomyces cerevisiae. Genetics 149: 1693–1705.
Meselson M. S.,
Radding C. M.
, 1975 A general model for genetic recombination. Proc. Natl. Acad. Sci. USA 72: 358–361.
Porter S. E.,
, 1993 Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break. Genetics 134: 5–19.
Schwacha A.,
, 1995 Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83: 783–791.
Sun H.,
Treco D.,
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, 1991 Extensive 3′-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation site. Cell 64: 1155–1161.
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, 1983 The double-strand-break repair model for recombination. Cell 33: 25–35.
, 1994 Analysis of meiotic recombination events near a recombination hotspot in the yeast Saccharomyces cerevisiae. Curr. Genet. 26: 21–30.
Volume 153 Issue 2, October 1999
You are going to email the following The Conversion Gradient at HIS4 of Saccharomyces cerevisiae. II. A Role for Mismatch Repair Directed by Biased Resolution of the Recombinational Intermediate


I love dips. For me there is nothing better than taking a chip, veggie or a piece of bread and smothering it with whatever dip I have come across. I especially love dips that star hot and melty cheese in them.
But sometimes I need a break from my melty cheese dips and want something a little bit different. Jim and I stumbled on the combination of feta and roasted red peppers after he had had a similar dip while at a friends party. Jim found a basic recipe online and whipped this up and I was hooked on the combination. After a few tweaks and revisions, we found the below recipe to be our favorite way to make this stellar combination.
This dip is amazing served with warm pita bread cut into triangles (you can get pita bread at almost every grocery store, usually by the deli counter) and can be served as an appetizer or a light dinner. We recently paired this dip with seasoned pearl (Israeli) couscous and it was a hearty and filling meatless meal.
The best part? This dip only takes 10 minutes from start to finish and you only have to dirty up the food processor to make it. An amazing dip, fast prep and only a few dishes to wash? Sign me up!
Serve with warmed pita bread.
This recipe can easily be doubled or even tripled if you are feeding a crowd or want leftovers. It tastes even better the next day and requires no warm up to dig in!
If you do want to make a large batch of this but have a small food processor, you may want to make a single batch each time and combine all batches into a large bowl to avoid breaking your food processor. Since you are making the same thing, you won't even need to wash the food processor in between batches.


North America and China are each receiving another Overwatch expansion team.
As expected the Mayhem are making big changes this offseason.
Stay up to date on all the changes happening this offseason to your favorite Overwatch League teams.
This brings the total up to four players released by Boston within the last few days.
ShaDowBurn, Joemeister and DayFly are no longer calling Philly home.
The announcement everyone expected is here.
Seoul joins the ever growing list of teams to make big roster changes.
NYXL have removed a coach and now a main tank.
Roster changes continue to pour in from across the league.
Kalios, Snow and Avast are no long members of the team.
NYXL makes big changes to their coaching ahead of the second season of Overwatch League.
Earn new a legendary skin, player icon and sprays.


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Welcome to Foothills at Old Town Apartments
Our leasing office is now open for in-person tours by appointment only. Please see our video/virtual tour and call or email us to schedule an appointment time that works for you.
Foothills at Old Town Apartments is a modern, pet-friendly apartment community in Temecula, California near I-15 and I-215. Foothills at Old Town Apartments offers 1-bedroom, 2-bedroom and 3-bedroom luxury apartments for rent, including unique tri-level townhomes that feature two-car garages with direct access. Enjoy an impressive selection of amenities, such as kitchens with upgraded appliances, granite countertops, contemporary cabinetry and crown molding.
You will find that Foothills at Old Town Apartments is set amongst the serene landscapes of the Santa Rosa Mountains and the scenic Temecula Valley wineries. Residents have convenient, easy access to shopping, dining and entertainment at Temecula Town Center and Promenade Temecula. Foothills at Old Town Apartments is close to major employers and schools such as Pechanga Resort & Casino, Abbott, Temecula Valley Hospital, Medline, Kaiser Permanente, Mt. San Jacinto College (MSJC Temecula Valley) and the highly-rated Temecula Valley Unified School District (TVUSD). Nearby I-15 and I-215 provides easy access to downtown San Diego, Riverside and the greater Southern California area.
Enjoy the convenience of a stylish community at Foothills at Old Town Apartments with amenities that include a resort-style pool and spa, fitness center, ample BBQ and seating areas, clubhouse, coffee bar and more. Those who appreciate the charming ambiance of Old Town Temecula and its nostalgic boutiques, fine dining and live theater will love living at the Foothills at Old Town Apartments.
Contact us today to see what is available!
Call us: (951) 676-7545 / Email us: [email protected]
Or stop by: 28845 Pujol St, Temecula, CA 92590
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Foothills at Old Town Apartments
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Jeff Harman - Oceus Networks, Inc.
Jeff Harman is Chief Operating Officer for Oceus Networks. In this role, Mr. Harman leads the execution of the company's strategic plan and provides the operational leadership to enable the company's success and growth.
Prior to coming to Oceus Networks, Mr. Harman had over 22 years of industry experience in the delivery and management of technology systems, networks, and services across the Federal Government. He previously worked for CACI International as a Senior Vice President Operating Group Manager, directly managing over $200M in annual revenue with clients in the Defense Information Systems Agency (DISA), the United States Combatant Commands, the U.S. Navy, and the Department of Homeland Security. In his role ,Mr. Harman was responsible for the Enterprise IT Services and Solution core competency and was the developer of the CACI IT Service Management framework.
Prior to joining CACI, Mr. Harman held leadership positions for Teaming Associates, BBN, and GSI. Mr. Harman served in the U.S. Air Force prior to joining GSI and holds a Bachelor of Science degree in Information Systems.


» Why do you keep hearing so much about Linux and open source?
» How can software be free? What's the catch?
» Does open source make sense for your business?
Read on and find out about your options.
Is Open-Source software a trend or a fad? Let's first define what is meant by open source and closed source and how they differ.
There are several models or approaches for developing software applications. The most common model is closed source, better known as commercial software.
Closed-source programs are owned by someone (or some organization) and distributed through a variety of retail channels including the owner's website. If the program is in the form of shareware, a fully functional version of the program can be installed and run. There may be a limited period of time after which the software will disable itself.
The concept of shareware started out as a way for independent software developers to distribute their programs and make some money off of their efforts. As the concept gained acceptance and as some of these developers became successful, some software development companies adopted the idea.
Another approach is to create a demonstration (demo) version of the software. Demo versions are usually designed to expire after some period of time and/or may have limited features to prevent full use of the software. Demos are usually distributed by commercial enterprises.
In either case, the source code is not usually included. The buyer pays for the right to use the program but does not own it. In some cases the software is actually free, ie. freeware, which means the author is not seeking compensation for his/her efforts but retains exclusive rights to the source code.
True-open-source development requires that a community of software engineers band together to work on the software. The idea is that more minds create better software. Open-source programs always include source code for those interested in peering into how the program does what it does and possibly contributing to the development effort.
The software and source code are available without cost or obligation (yes, really!). Open-source models vary by source-code-license terms. Source-code licensing only matters if you intend to modify or reuse the source code in any way. These issues are not relevant to most of us.
The topic of source-code licensing is fairly detailed and complex. There are several widely used licenses placing restrictions on how the source code may be used. These restrictions are not pertinent to this article but if you're interested in learning more there is an in-depth article at the Free Software Foundation.
There has been increasing focus on the issue of open source over the last few years largely due to the lawsuits involving Microsoft products. Microsoft Windows, a closed-source, operating system, has come under pressure from Linux, an open source one. Similarly, Microsoft Office, a closed-source, office productivity suite, has been under fire from OpenOffice, an open source one (which is the foundation for Sun's StarOffice).
An interesting question is whether or not open source provides innovative ideas. If open source is to have staying power, it must generate new ideas that improve software programs not just copy someone else's work. Historically, the open-source communities have improved and extended existing concepts.
For example, The Apache Foundation was the first to implement the concept of virtual web hosts (multiple websites hosted on a single computer). Linux was the first operating system to run on everything from a wrist watch to a mainframe. StarOffice was the first office suite to run on any desktop platform (PC, Mac, Unix workstation, etc.). How can open communities of software developers achieve such feats? It's simple, they aren't burdened by the need to generate revenue or protect market share. And, many minds can solve difficult problems with relative ease.
What about quality, reliability and security?
The characteristics of software vary widely whether developed using an open or closed model. Many open-source packages are rock solid and better than their closed-source counterparts. Examples include the Apache web server, Linux operating system , SendMail email server, and MySQL database. At the opposite extreme, there are open-source projects that were abandoned before reaching maturity.
Any enterprise-wide software selection needs to be carried out using discipline and research. With closed source, the watch words are "buyer beware". With open source, they are "user beware".
So what drives these open-source communities and how does anyone make money?
Many open-source contributors conduct a labor of love though some receive compensation through companies that advocate open-source tools such as Sun, IBM, HP, Red Hat, etc. For many software developers, contributing to open source software is a personally rewarding experience and an opportunity to learn new techniques and tools. Such projects can be found at SourceForge, The Mozilla Foundation or The Apache Foundation.
This leaves open the question of how major firms like IBM, Sun and Red Hat can "sell" open-source software. You can buy Linux, StarOffice and other open-source programs from such firms. Well, not really. You are buying the packaging, documentation, technical support, convenience and, perhaps some value-added features but the open-source software is free and can always be downloaded from the project website. If anyone tries to sell you open-source software and claims it cannot be downloaded for free, they're not being completely honest.
Back to the original question, trend or fad? Microsoft is sending it's lawyers after open source. A sure sign that it's worried. IBM and Sun are pouring millions of dollars into open source. A sure sign that they find it easier to switch than fight. Open source is here to stay.
We're not suggesting that you sell all your software-company stocks. There are many ways that software companies can make money by leveraging open source. Take a look at Apple Computer. They tossed their operating system, embraced the FreeBSD open-source project, added many valuable features and, created Mac OS X. It's worth every penny they charge for it!
If you want to know more about how open source can benefit your business, read our article called "Are You Throwing Money Away?".
Open-source software development is a community activity. Groups of people form virtual teams and create great software.
The most well-known, open-source software project is Linux.
The Open-Source movement gained momentum and respect in the market for network servers. This is most often a combination of Linux and Apache though many other options are available.
Gradually, the open-source movement has migrated to the desktop challenging Microsoft Windows and Office. Linux and OpenOffice are the usual suspects but again, other options are available.
Today, Linux is showing up on Personal Digital Assistants (eg. Sharp Zaurus), television set-top boxes (see the TV Linux Alliance) and, other electronic devices.
Thus, we have many Linux variants. They have much in common but also provide uniqueness targeted at specialized applications.
We encourage you to consider open-source alternatives the next time you evaluate a software purchase. An excellent news site for open-source activities is LinuxWorld.


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Israeli Police Chief To lgnore Sex Harassment Allegations Submitted Anonymously
Jewish Sex crimes
Israeli Police Chief To lgnore…
The declaration by Israel Police Commissioner Roni Alsheich that he will no longer probe anonymous complaints of sexual harassment in the force has raised the ire of the Justice Ministry's police investigation unit, that announced Sunday it would continue to look into all such allegations regardless.
"The department is authorized to investigate complaints leading to suspicion of the commission of a crime by a policeman even when they come from unidentified sources," a department source said. "Every complaint that reaches the department will be investigated as has been done until now."
The department also called on policemen and policewomen who feel personally threatened or who have witnessed sexual crimes against policewomen to report them – even anonymously.
Department officials spoke to Haaretz after a report Sunday on Channel 2 about Alsheich's declaration last week.
"Anonymous letters have turned into a culture of settling scores in the police force, and as such, from now on the police will not deal with anonymous letters that raise suspicions of violations by policemen," Alsheich reportedly said. "In an organization that requires reporting by policemen, there is no need for such letters."
Alsheich's decision is rather problematic given the recent spate of cases of senior police officers coming under fire for apparent sexual harassment.
The case of former Jerusalem police chief Nissan "Niso" Shaham, for example, began with an anonymous complaint that eventually led to an indictment for sexual assault, sexual harassment, fraud and breach of trust.
Similarly, the cases of former officers Hagai Dotan, Kobi Cohen and others who were forced to leave their jobs all began with an anonymous letter that was investigated and led to revelation of more concrete evidence.
Last week, Brig. Gen. Yael Eidelman, the commissioner's adviser on women's issues, opened a conference at the Police Academy in Beit Shemesh to mark International Women's Day. She spoke at length about the advancement of women in the force and also mentioned its lack of tolerance for sexual harassment.
Immediately afterward, Alsheich took the podium and right away began to speak about the issue of anonymous complaints made by police personnel about a variety of matters, stressing that anonymous complaints about sexual harassment would also not be investigated.
Within the force Alsheich's remarks were taken as criticism both of policewomen who have complained and of police personnel who became aware of incidents of harassment and passed the information on to the relevant authority anonymously.
"A policeman or policewoman who witnesses or receives information about sexual harassment or another violation, even a significant one, will not [report] it openly," said one officer.
"If the policewoman isn't prepared to complain, then why should I come and raise the problem. The policewoman affected may claim, out of fear, that the reported incident never happened.
So should I report? Should I not report?"
In private conversations Commissioner Alsheich broached the issue some time ago, after deciding to reinstate Maj. Gen. Roni Ritman as commander of the Lahav 433 fraud investigation unit, despite recommendations that Ritman be appointed to a different position.
Ritman was accused last year of sexual harassment but no evidence to back the claims were found and he returned to the force in December.
"I don't have to 'sacrifice' him to the Molech," Alsheich said, in a reference to the ministerial investigative department and the media.
The police spokesman said, "The Israel Police works on different levels to increase the reporting of violations and to support the complainants.
These include improving the processes involved in revealing failures to report and surveys to identify problematic cultures in specific units …
"The commissioner's policy and the message conveyed to the policemen about the importance of reporting violations in real time have proven themselves and eradicated the phenomenon of 'anonymous score-settling' that often hurt the complainants themselves."
Category: Jewish Sex crimesBy Joe Levin March 14, 2016
Tags: Israel PoliceJewish Sex crimesRoni Alsheich
PreviousPrevious post:Prince George's County, MD – Maryland Policeman Killed In 'Unprovoked Attack'NextNext post:Chief Rabbi Yitzhak Yosef: Keep Children Away From Secular Family
Police drop investigation into sexual abuse claims against Rabbi Chaim Halpern
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Modeling agent accused of sexual assault to be freed to house arrest
Pedophile was ignored in Israel, then arrested in the US
Nimrod Shalom, Sentenced to Seven Years in Prison For Transmitting Sexually Explicit Video of a MinorNimrod
Orthodox schools' board distances itself from accused Rabbi Halpern


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A radical new approach to science fiction skirmish wargaming, built on the same core mechanics as hit sci-fi battle game, Horizon Wars. Zero Dark lets you play solo, co-op, player-versus-player or even team-versus-team with the same core rules.
No weapons tables. No faction limitations. Build your heroes from scratch and equip them to suit your play-style and existing miniatures collection. Take on the unpredictable and dangerous Red Force. And test your mettle as your team explores the mysteries of the Fallen Earth in the pursuit of lost secrets in Operation Gemini.
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Blue-storyteller A June 14, 2021 9:23 pm UTC
Hello, does the game support 3 player games?
Sascha S July 11, 2021 9:19 pm UTC
There is a versus mode with several different symmetrical missions, that pits 1:1 and the AI controlled "Red Force". So technically there is a third player present.
IMO you could easily adapt the system and also:
The teams of heroes (usually up to 4) can be controlled by several players on one side, too. So you could go with 3 heroes and fight the AI controlled Red Force, or build teams, or, ...
Robey J July 13, 2021 8:20 am UTC
In a way. The game is designed to be played solo, co-op or PvP. You can easily play it with three player co-op, with each player controlling one or more heroes. You can also play TvT, with two players sharing a team on one side.
In terms of having three teams simultaneously... The game doesn't explicitly support that kind of play.
Anthony G December 02, 2020 4:38 pm UTC
Could this be adapted to the Star Wars world? I am looking to repurpose my Imperial Assault minis and this seems like it could be the game. I like small "outer rim" missions as opposed to the typical battles legion offers. Thanks.
Robey J January 06, 2021 12:40 pm UTC
Definitely, although there are no rules for the Force. One of my patrons is doing exactly this.
I'm currently working on some rules to adapt the game to internal spaces with a grid layout, which would also give you more utility for your IA tiles, too.
Andrew M August 17, 2020 3:55 pm UTC
I ordered this as a result of reading the review in Miniature Wargames, which often looks at niche publications that tend to be overlooked elsewhere, and, better still, gives more than a cursory description that is little more than a 'heads up'. The editor, John Treadaway, is very well versed in SF gaming, and his thoughtful comments - clearly based on some study of the book, convinced me to give it a try. I've yet to read more than the opening pages, but am impressed by the quality of production, and look forward to giving it serious attention when time and other projects allow.
Thanks, Andrew! I'm talking to John about ZD having a couple of feature articles in the magazine in the near future, including an exclusive mission. As I had to teach myself layout and desktop publishing from scratch to make the book, I'm particularly pleased that you like the layout.
Dwight F May 11, 2020 12:46 am UTC
Does it cover 15mm?
David K May 29, 2020 12:51 pm UTC
Yes - the rules cover 28/32mm and 15mm with the units of measurement and base sizes being the only differences I can think of off the top of my head.
Steve S March 28, 2020 5:16 pm UTC
WARGAME VAULT STAFF
Precinct Omega Publishing has a fairly active Facebook page, probably could ask over there for the best answer.
Peter L March 26, 2020 12:56 am UTC
Is this compatible with Over the Horizon or is this a new rulesset? Thanks
Adam A April 01, 2020 11:10 am UTC
No, this is a separate game. Similar mechanics, different scale and operation level.
Steve A.
Absolutely the best solo skirmish system I have played! Elegant yet detailed in the systems approach. Totally addicted. The author has an excellent knack for story telling as well! Can't wait for more from this publisher! [...]
Sascha S.
I couldn't have asked for more! Cinematic game play, easy but elegant character creation and nearly unlimited possibilties for settings/ miniature ranges. Had been a while since I enjoyed solo tabletop gaming so much. Such an amazing [...]
Felix S.
In my opinion it's the perfect set of rules for playing co op and singleplayer tabletop games without miniature ristrictions. I especially like the innovative dice system and the way units are activated without counting rounds and troublesome mark [...]
This great is just a great game and a lot of fun. I have been playing it solo unfortunately doing to the current global situation but even solo is great fun a lot of tactical decision and open to a lot of customisation. You can certainly adapt any mini [...]
Anthony G.
This is an absolutely amazing sandbox skirmish game. It plays amazing solo and co-op and I can finally play a Star Wars in the style I want to play. You can use about any mini so this ruleset will cover star wars, generic sci-fi, modern and futuristic [...]
Robey Jenkins
David Sondered
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Klimkin explained why the Ukraine to become an EU member
The Minister of foreign Affairs of Ukraine Pavlo Klimkin said that Ukraine should become a member of the European Union, not to be a country – supplier of agricultural products and labour. He told reporters in Brussels.
The Minister noted that after the introduction of a visa-free regime for citizens of Ukraine in relations with the EU, Ukraine's European integration is not going to stop.
"It's nice when in the pocket have a biometric passport, and of course, you cross the border, but now needs to work on ambitious ideas. I believe that absolutely can not stop. You can, of course, by telling ourselves how well we have done what we have achieve, but I believe that this is not a reason to celebrate. This is a reason to move on," – said Klimkin.
"I think, like all Ukrainians, that Ukraine must join the European Union and the purchase is gradual, of course – all the benefits of the four freedoms," – said the Minister of foreign Affairs of Ukraine.
In his opinion, accession to the EU Ukraine needs a clear plan, which Ukraine must "harmonize with the European Union and to understand where we will help."
"But the logic needs to be ambitious than to clearly say that in the future we see this as an ambitious goal, and now we have to move on. If we ask a less ambitious goal, we will always put ourselves in a situation where we will deal with separate issues. We should be the ultimate goal. It is, of course, must be achieved through a clear understanding of what to do," said Klimkin.
According to the Minister, "if we don't do now for European reform, which are incorporated in the Association Agreement, if we do not use these opportunities, in the end, we can expect the fate of the country, which is a supplier of agricultural products and labour."
"Or we go by Association, performing all necessary reforms and going the European way, or is it the other way. And I think that we have to choose the European path and European Union", – said the head of the foreign Ministry of Ukraine.
Recall Klimkin also said that the foreign Ministers of countries-EU members at an informal luncheon "Friends of Ukraine in the EU + Ukraine" agreed on the continuation of sanctions against Russia.
In Ukraine created a shortage of cigarettes – the experts
"Gazprom" appealed a billion-dollar fine in the Ukraine
In Chernihiv, a lone gunman wounded two commandos
In London, a car crashed into a crowd of people
A restart of the Cabinet, "swing" with autogas and scandalous crash: the end of the week in Ukraine
The EU has reacted to the detention of protesters in Russia
The claim in the Hague was the first step of Ukraine to bring Russia to justice – Poroshenko
Göteborgs-Posten (Sweden): the Swedish flag — a problematic symbol
Groysman: Ukraine is ready to accompany every project of Israeli business "turnkey"
Klimkin explained that means enhanced Association of Ukraine with EU