text:
0 Members and 1 Guest are viewing this topic.
it turned out that the Daka were next to useless. I guess the whole thing was really just Ganishka's or the GH's excuse to have the apostle bag made so that Ganishka could break the world with it later.
I thought the scene where a naked Schierke stumbles on a sleeping Guts felt like something out of a much lesser and creepier manga. I don't want kiddie sexual tension in my Berserk, Miura. The schoolgirl crush thing was kind of cute until that scene.
For that matter the prisoners bound for Daka production would have been a great opportunity to counter the one actual sexist element of Berserk, All Naked Ladies Are Reasonably Hot. Because I'm really very sure that the hotness level of the women wouldn't be a factor in their suitability for making Daka, and if that's most of the point of Ganishka's army taking conquered women prisoner it would be highly foolish to only take the cute ones. Even the trolls had a better excuse for only finding/taking sexy looking women; you could make the argument that practically all the girls in the farming village could be built like that or that the trolls only liked the cute ones (similarly you could argue only the cutest girls would be around/take part in the naked stuff in the heretics' orgy). But Ganishka's army has been rolling over the entire country, so you'd now have to argue that either there are literally no ladies who are fertile but aren't nicely built or that the army puts them all somewhere you can't see them. Not that we ever really see many of these doomed women, but the ones we do see have a very narrow range of body types. The 'little sister' during the rescue is the only one I saw on a casual flip through that would look out of place as a pinup. (I forgot the apostle bag is way back in vol 27! dang.)
Maybe I'm just being naive or something, but I didn't take that scene where Schierke got spun around in her towel by Casca and ended up naked leaning on a sleeping Guts as being all that sexualized. I mean I know it's playing on the fact that she has a crush on Guts and that situation would be very embarrassing for a young girl, especially one who's a bit on the reserved side, like Schierke is, but it all just struck me as more silly/goofy. I thought seeing her bare behind was kinda funny. Also, I think showing her bare bottom gives the reader more of a sense of how embarrassed/exposed Schierke feels in that moment. Other events within that scene are pretty comedic, so that's how I took it.
It's also worth noting that Guts doesn't care or even seem to notice that she was undressed, but he still gets scorched.
Well said. I think the reaction this scene often gets is primarily from American audiences. We tend to be a bit on the prudish side, second-guessing how other cultures approach nudity -- and really, anything even remotely sexual. But this is meant to be a funny scene, not sexually charged or titillating.
That's true, the Daka were surely a great troop booster for normal warfare and useful up til that point. Even if Ganishka didn't need them for the capture of Wyndham.
It still seems weird that he was all excited to pit them against the apostle forces in Wyndham just for them to immediately get wiped.
It's just hard to imagine Ganishka didn't have any idea what to expect with the apostle forces. And I suppose it would be foolish in war not to put out everything you've got even if you don't think it's gonna do much
For that matter the prisoners bound for Daka production would have been a great opportunity to counter the one actual sexist element of Berserk, All Naked Ladies Are Reasonably Hot. Because I'm really very sure that the hotness level of the women wouldn't be a factor in their suitability for making Daka
I always found it to be a pretty generic ecchi kind of scene. Like I said, the angle that we're shown it, with her ass turned towards us while she's slightly curved forward and stuff... I mean sure, the panel is sandwiched between hilarious panels and it's the catalyst to her funny reaction so it's not completely gratuitous but I think that one drawing in particular isn't really funny (or supposed to be funny); it's pretty much the definition of fan service to me.
And I'm from a country whose tourism is based on asses and boners so it's not culture shock at work here, it's just how I interpret it.
Except that doesn't sound like the kind of "service" the fans of Berserk would look forward to. Just like seeing Farnese's breasts once every 12 volumes isn't what keeps the readers coming back. It's just that the Japanese don't have the same rapport to nudity than some western countries do.
That might play more of a role in your interpretation of the scene than you think it does. I mean we see Puck's ass all the time and no one cares. Did volume 15's cover bother you as well?
There's something to the vulnerability of a nude girl while the "camera" points at her ass in that position that bothers me. It's not just the nudity itself, it's the angle, her position, the manner in which he exposes her to us. I saw it and immediately thought it was a typical erotic manga scene, while the previous page doesn't bother me at all (and we're shown more of her, in terms of anatomy). In Puck's case, he's a tiny humanoid fantasy creature that's always nude, I'm not bothered by it.
Well, like I said, I think your cultural background may influence how you perceive the scene more than you think it does. The cover with Puck that I mentioned has almost the exact same pose in it, but no one's bothered by it.
Of course, you're free to disagree. But to suggests it's "fan service" or that this is meant to be erotic is kind of ridiculous in my opinion.
But I do think that pose, even within a context, is used purposefully erotically in that page. Being the great visual storyteller he is, I think Miura knew of more than one way to communicate what he did without showing us her nude behind in that position. And given the character, and the age she appears to be, I have a problem with it.
I think you might be taking it too seriously dude.
But I do think that pose, even within a context, is used purposefully erotically in that page.
What would the purpose be, though? To titillate the reader in the midst of a comic scene? It doesn't make sense.
Well, it's not as though comedy + titillation is an unheard of combination, but it's pretty much always silly titillation. The titty bullet dodge scene from Highschool of the Dead might be fanservice but I don't think it's supposed to actually get anyone hot, despite all the lovingly animated bosom jiggles. It's supposed to make you laugh.
I might call Schierke's butt fanservice in the sense that I'm sure there are readers out there that went "aah!! I got to see Schierke's butt!"
I am definitely of the opinion that it's just supposed to make you laugh at/with the awkwardness of Schierke's situation. Not least because it's really not a flattering/sexy drawing. And also because the default non-westernized setting for bathing nudity in Japan is non-sexual. You wouldn't, for example, mistake the naked girls bathing in Totoro for fanservice.
Seems like a specious comparison to me. I was trying to appeal to Eluvei's common sense regarding author intent, not argue whether it's theoretically possible.
For the sake of comparison I checked out the similar sequence from volume 6, where Casca wakes up nude and attacks Guts in a comical manner, and the panel she realizes she's exposed never did, and still doesn't, appear fanservicey to me.
She's just sitting there blank-faced. In Schierke's case, we're "forced" to look at her butt, which I don't think is a stretch to say is the only thing in the foreground, and then her tiny blushing face.
In a vacuum I'd still see that panel and think it's something that can only be seen as perverted due to the pose alone, but that's unfair to Miura.
To go back to your comparison with Casca, since Schierke's still a kid, she doesn't have breasts. Therefore her nakedness has to embarrass her differently, and to show her rear-end is logical in that regard (because the front would just not be Ok). You mention the pose, but it's not like she's arching her back or something, she's lifting herself from a prone position because she just fell down.
Man, I never thought I'd ever have to talk so long about this specific panel. That's not exactly what I have in mind when I think of discussing Berserk.


text:
Most women experience some unpleasant or uncomfortable symptoms during their menstrual cycle. For some women, the symptoms are significant, but of short duration and not disabling. Other women, however, may have one or more of a broad range of symptoms that temporarily disturb normal functioning. These symptoms may last from a few hours to many days. The types and intensity of symptoms vary in individuals. This group of symptoms is referred to as premenstrual syndrome, or PMS. Although the symptoms usually cease with onset of the menstrual period, in some women, symptoms may last through and after their menstrual periods.
According to the American College of Obstetricians and Gynecologists, nearly 85 percent of women, during their reproductive years, experience at least one of the common symptoms associated with PMS. It is estimated that 5 percent of women have symptoms so extreme that they are considered disabled by the condition.
In general, women most likely to experience PMS symptoms are between the ages of 20 and 40—and particularly women from this age group who have one child and have a history of depression in their family.
The following are the most common symptoms of premenstrual syndrome. However, each individual may experience symptoms differently. Symptoms may include:
Psychological symptoms
Lack of control
Difficulty in concentrating
Severe fatigue
Decreased self-image
Emotional hypersensitivity
Crying spells
Sleep disturbances
Fluid retention
Edema (swelling of the ankles, hands, and feet)
Periodic weight gain
Oliguria (diminished urine formation)
Breast fullness and pain
Respiratory problems
Eye complaints
Visual disturbances
Gastrointestinal symptoms
Abdominal cramps
Pelvic heaviness or pressure
Skin problems
Neurodermatitis (skin inflammation with itching)
Aggravation of other skin disorders, including cold sores
Neurologic and vascular symptoms
Syncope (fainting)
Numbness, prickling, tingling, or heightened sensitivity of arms and/or legs
Easy bruising
Heart palpitations
Muscle spasms
Decreased coordination
Painful menstruation
Diminished libido (sex drive)
Appetite changes
Food cravings
Hot flashes
The symptoms of PMS may resemble other conditions or medical problems. Consult a health care provider for diagnosis.
The cause of premenstrual syndrome is unclear, but seems to be related to fluctuations in estrogen and progesterone levels in the body, and does not necessary denote disabled ovarian functioning. Social, cultural, biological, and psychological factors have been identified as possible contributors of PMS.
For some women, making simple lifestyle changes helps to reduce the occurrence of PMS symptoms. These changes may include:
Regular exercise (three to five times each week)
A well-balanced diet. It is generally recommended that women with PMS increase their intake of whole grains, vegetables, and fruit, while decreasing their intake of salt, sugar, caffeine, and alcohol.
Adequate sleep and rest
Not smoking
Aside from a complete medical history and physical and pelvic examination, diagnostic procedures for PMS are currently very limited. Your health care provider may consider recommending a psychiatric evaluation to, more or less, provide a differential diagnosis (to rule out other possible conditions). In addition, he or she may ask that you keep a journal or diary of your symptoms for several months to better assess the timing, severity, onset, and duration of symptoms.
Specific treatment for PMS will be determined by your health care provider based on:
Your age, overall health, and medical history
Extent of the condition
Current symptoms
Your tolerance for specific medications, procedures, or therapies
Expectations for the course of the condition
Your opinion or preference
Counseling with your health care provider regarding symptoms can often increase understanding and lead to activities for stress management. Other possible treatments for managing PMS symptoms may include:
Diuretic use prior to the time symptoms are usually noted (to reduce fluid retention)
Prostaglandin inhibitors (i.e., nonsteroidal anti-inflammatory medications, or NSAIDs, such as aspirin, ibuprofen) to reduce pain
Oral contraceptives (ovulation inhibitors)
GnRH agonists (used to temporarily stop ovarian production of estrogen and progesterone to relieve symptoms)
Changing the diet (to increase protein and decrease sugar and caffeine intake)
Vitamin supplements (i.e., vitamin B6, calcium, and magnesium)
Regular exercise
Antidepressants (or other medications)

subset: commoncrawl


text:
Broadway star Sandra Joseph, from Phantom of the Opera, talks to Omega's George Kaufman about overcoming fear on and off the stage.
George: You've said when you were nine years old you saw the play Annie and decided you wanted to be in the theater when you grew up. Eventually, you played the leading lady in The Phantom of the Opera on Broadway, a dream come true. What was the magic that happened that night when you were nine?
Sandra: I believe God speaks to us through the longings of our heart and this particular means of self-expression—being on stage singing and acting—was what called to me. It was a yearning I couldn't even describe. But the idea of getting up in front of people was terrifying. It took many years. I didn't perform as a kid. It wasn't until I was in high school that I did my first show.
George: I recall a conversation I read a New York Times feature where a grandmother asked her 9-year-old granddaughter, "What do you want to be when you grow up?" The granddaughter said, "Grandma, I don't even know what I want to be for Halloween."
Sandra: It's funny how passion and desire strikes some of us at a young age. For me, it happened before I had any idea whether or not I could sing or act. Martha Beck calls it precognitive knowing—the idea that there are some points in our life where we just know something in an inexplicable way. I had no reason to believe I could ever become a singer or actress. I was a kid in Detroit with not a lot of money. No one in my family had ever been to New York or to college. It made no sense externally, and yet, I remember feeling so deeply that it was possible for me. I have no idea why.
George: Was it encouraged at home?
Sandra: I was blessed with supportive parents, and a father who had done some acting himself locally around Detroit, but he was practical. He worked, raised two daughters, and encouraged me wholeheartedly. If I had any belief in a future of possibility or magic, it's because of him.
George: Now you are supporting other people, doing for them what your father did for you.
Sandra: My greatest joy is supporting people who not only want to perform professionally, but anyone who longs for a means of self-expression. Many of us are stifled creatively. We have an innate desire to be seen and heard, and to connect, but we were wounded as young people. One unkind remark in childhood can render you permanently paralyzed and mute. It takes tremendous courage to dive back in. Creative expression in any form is risky to the ego. It will make you question your worth: "What if I fail? What if I'm no good?" "What if I make a fool of myself?"
George: You were terrified, but this is what you decided to do for a living. How do you manage being in the public eye?
Sandra: When you love something even the slightest bit more than you fear it, the love will always win. There are times when I'm scared stiff to put myself out there, but I had to master walking into fear. Making friends with that feeling is my path to awakening. And that's what I love helping other people learn to do. When you stand up in front of an audience, anything can happen. If you can stay open to that vulnerability and become steady in that groundlessness, the courage you cultivate will sustain you in every aspect of your life.
George: In 2007 you were diagnosed with a brain-stem tumor on the cranial nerve that controls the left side of the tongue. For someone who relies on her voice for a living, this must have been very frightening. Did the practice of being present help?
Sandra: My college acting teacher used to say, "Don't play the end of the scene at the beginning." That's how I try to live with this, by staying rooted in the present moment. Today, the tumor is tiny and benign. If I project forward and think about the fact that it could become cancerous, I can spin myself into all sorts of fear. But if I stay focused on the here and now, I feel great. I'm in a healthy body that's growing stronger every day. It's really about training my mind.
George: Do you still get what people euphemistically call butterflies, but is really controlled terror?
Sandra: Absolutely! I've learned a number of techniques to manage anxiety. I follow a whole process to prepare myself—whether it's for a performance or an MRI—including visualization, meditation, and breathing techniques. The same practices I use to deal with stage fright I use elsewhere in my life and can be used by anyone. Whether you want to sing a solo in church, give a presentation at work, or simply strengthen your courage muscles, they work in all kinds of fearful situations.
George: These tools for performance are actually tools for life?
Sandra: Putting yourself through the terror of getting up in front of people is a wonderful training ground for living. You learn to become comfortable with all your emotions. You learn to adjust to how things are rather than how you think they should be. You learn to replace self-criticism with self-compassion. Isn't that what we all need to be doing every day in our lives?
Performing gives you an opportunity to merge your internal world with the external world and express your most authentic self. In my workshops, I simply open up a safe space for people to be seen and heard and I watch them come alive. I think many of us are waiting for permission to shine. We don't believe we deserve to. But if you don't express what is within you, a little part of you dies every day. And you rob the world of your unique gifts. No one else has what you have to offer. No one else has been cast in the role of You.
George: People often think they don't have anything to contribute, or nothing new to say, especially when it comes to creative expression. But if they look inside I think they find that unique aspect of who they are that differentiates them from everybody else in the world.
Sandra: We try too hard to be unique, when the fact is, we are each an individual universe and every one of us is fascinating. There's an improv exercise where everyone closes their eyes and visualizes a box in front of them. Each person unwraps the box, takes the lid off, and looks inside. In a room of 100 people, every person finds something different inside that box. We just don't trust our imaginations.
George: We have a tendency to listen to our self-critic and question our self-worth. If somebody tells us something bad about our art, we instantly assume it to be true. And if somebody says good things about our art, we tend not to trust the statement.
Sandra: Science has shown that we have a negativity bias: we're like Velcro for negative comments and Teflon for positive ones. It's why an actor who receives a dozen good reviews will only remember their one bad one. We need practices that help us tip the scales in the other direction.
George: You must have had your share of positive and negative reviews as you played Christine in the Phantom of the Opera over such a long period of time. Critics aside, what did Christine have to teach you?
Sandra: I played the role for ten years, and it was my job each night to learn to see the unmasked Phantom with total acceptance and love. I needed to learn how to see my unmasked self the same way. Most of us feel there are parts of ourselves we need to cover up in shame. It's a continual growth process to drop the mask of ego and see who you really are through eyes of compassion and love.
I also love the metaphor that behind the mask we are all the same, each one a part of the invisible web that connects all life. What we see on the surface is such a tiny aspect of all there is. There is so much we can't comprehend, so much beauty that we miss. We get so caught up in our to-do lists, our accomplishments, and our striving we forget to stop and marvel at the mystery. We can begin by dropping the mask in our interactions with each other and seeing we're more alike than we are different.
George: Did you have anything to teach Christine?
Sandra: After more than 1,000 performances, I had to teach her how to be present. If I was not in the moment and listening—awake and aware—then my performance would fall flat and the audience would feel it. Every night, I tried to convince myself that the show was happening for the first time so that the audience would get the performance they deserved to see.
George: Your thoughts about looking behind the mask remind me of a story from Ram Dass. He would do something to impress his teacher, who would see right through him but love him just the same. Like Ram Dass, I think you're talking about unconditional love.
Sandra: What a gift when someone else sees us with total acceptance and compassion. It gives us the freedom to begin to see ourselves that way. I believe that a happy person is one who has seen themselves fully and deemed themselves worthy. When you see all that you are and start to love yourself, laugh at yourself, and be kind and compassionate to yourself, that's when true happiness begins to grow.
© 2012 Omega Institute for Holistic Studies


text:
Buildings and bins I'm looking for the manufacturer of steel buildings - probably built in the 70s - that have "Chief" as the logo on the end of the building. David Legg Waynetown, IN
Contact Chief Industries, Building Div., Box 2078, Grand Island, NE 58802, 308/382-8820.
I have a Samson building by Fairford Industries, Moose Jaw, Saskatchewan, Canada, that needs repair. Ray Mulder Firth, NE
Contact one of Fairford's U.S. distributors: Shield Industries, Box 687, Hutchinson, KS 67504, 800/798-1968; or Norwood Sales, 102 Sunflower Ave., Cooperstown, ND 58425, 800/446-0316.
I have several Stor Mor grain bins and would like to know where to find parts for them. William Duncan Americus, KS
Contact MFS York/Stor Mor, Box 2105, Grand Island, NE 68802, 800/247-6621.
Running gear parts I am in need of parts for a 47 Kewanee wagon gear. Is there another company that handles them since Kewanee is no longer in business? Marvin Umbanhowar Rankin, IL
Go to your Bush Hog dealer or call Bush Hog Parts Dist., 7303 Vine St. Ct., Davenport, IA 52806, 800/304-6234, for a dealer near you.
Implement parts We have a Niemeyer Sohne power harrow, model TE 450. Can you find a supplier or dealer we can buy parts from? Richard Dragt Waddell, AZ
Contact Krone Niemeyer, Box 1896, West Memphis, AR 72303-1896, 870/732-4270.
I'd like to find parts for a Crustbuster grain drill. Randy Newholm Kansasville, WI
Contact Crustbuster Speed King, Box 1438, Dodge City, KS 67801, 316/227-7106.
We are looking for parts for our Noble hoe drills and have come to a dead end. Please help! Dale Seeman Redstone, MT
Contact Wil-Rich Mfg., Box 1030, Wahpeton, ND 58078, 701/642-2621.
Sprayers large and small I am looking for parts for a field sprayer made by Kuker-Parker Industries. Gary Simmons Elkhart, KS
Contact Master Mfg., Box 3806, Sioux City, IA 51102, 712/258-0108.
I have a droplet sprayer called "Ride and Beautify." It was made by Western Manufacturing in Marshalltown, IA. I now need replacement parts for it. Ken Halverson New Ulm, MN
Contact Handy Industries, 702 S. 3rd Ave., Marshalltown, IN 50158, 800/247-7594.
You can reach us in three ways: 1) firstname.lastname@example.com;
2) Farm Industry News, Edit. Dept., 7900 International Dr., Suite 300, Minneapolis, MN 55425; and
3) www.farmindustrynews.com (click on e-mail). We assume all letters to be for publication and reserve the right not to publish due to content or space limitations. To publish your letter or e-mail, we must receive your name and address.
Intertec Subscriber Privacy Notification: Intertec Publishing makes portions of our magazine subscriber lists available to carefully screened companies that offer products and services directly related to the industries we cover. Any subscriber who does not want to receive mailings from third-party companies should contact the Intertec subscriber service department at 800/441-0294 (U.S.), 913/967-1707 (outside the U.S.).


text:
Hello darlings!
I am writing now with one big melancholy in me when remembering the greatest concert I have ever been to so far! I don't know how many of you know Roger Waters, but he is a former member of Pink Floyd and actually the mastermind behind the band and of my favorite artists. This was probably the last chance for me to see him performing ''The Wall'' entirely, so I came here.
This is what I wore on the concert day, something comfy. You can see photos from the concert below:
The Wall symbolizes fear and isolation so this album tells the story of a restless man ever since childhood. There were projections on that wall which was built slowly during the concert, and towards the end of the last song, the whole thing was torn down. The album is very conceptual and the show was like no other, story telling and filled with emotions and different moods...it was just perfect!
And one last crappy photo after the concert, with The Wall behind me.
Hope you enjoyed the photos, catch you soon!
Wearing: New Yorker shorts, dad's T shirt customized, Mondex tights, no name sneakers.


text:
Justification by Faith
Citizenship in any kingdom demands certain things, and in the kingdom of God, citizenship demands righteousness. We cannot attain this righteousness on our own, for it must be imputed to us by the great King of this kingdom. Those who ...Read More
Counting It All Joy
Dr. R.C. Sproul has often said that while anyone can believe in God, it takes real faith to believe God. Trusting in His goodness during a severe illness, times when others sin heinously against us, the death of a ...Read More
The Millennium, Part II
Postmillennialists do not deny that there will be tares in God's kingdom until Jesus returns (Matt. 13:24–30). Still, Dr. Keith A. Mathison notes that "at the end of the age, the Son returns to a field of ...Read More
Counting It All Joy
Our future hope, rightly understood, does not make us callous to the needs and importance of this present life. Instead, it makes us live today with confidence, sure of the Lord's presence as we courageously face the unknown. "This ...Read More
The Reality of Our Sin
All of us understand that there is something fundamentally wrong with us. Even the best of our deeds often result from the worst of intentions. Wickedness is indeed presently all-pervasive. Yet it will not always be this way. Those who ...Read More


text:
So much going on, so much progress, so little time left!! We are racing the clock and the calendar; the tiny house house conference is upon us, and we are in the final push.
Some quick pix.
Loft ceiling with interior siding:
First wall for the bathroom:
Since these pictures were taken we have nearly finished the interior siding and trim and are getting ready to install the bathtub and build walls, stairs and kitchen counters.
It has been a little over a year since we started the build, a year tomorrow since La's papa was killed in a car accident, and just over a year and a half since La started to draw her blueprints.
I never knew a year could simultaneously go by so quickly and so slowly.
We will try to be more diligent in our updates. In the interim, please enjoy La's TEDTalk from last year. It is short and sweet. Almost like her, except she is nearly to her mama's height.
Love and gratitude to all of you who have been following us on our journey.


text: Holding a hanger, this pro-choice activist says "We won't go back". Demonstrators assembled in front of the U.S. Supreme Court steps in Washington D.C. on Wednesday, March 2, 2016 as the Court heard oral arguments in the Whole Woman's Health v. Hellerstedt case. This case involved a Texas law requiring that clinic doctors have admitting privileges at local hospitals and that clinics upgrade their facilities to standards similar to hospitals. If the law is allowed to go into effect it could effectively shut down all but about 10 clinics in the state. It is the first major controversial case the court has handled since the death last month of Justice Antonin Scalia. (Photo by Jeff Malet)


text:
Moundi_conn needed a new logo design and created a contest on 99designs.
A winner was selected from 97 designs submitted by 35 freelance designers.
'Conn-tact Fitness'
i'm a professional athlete an my business partner an me have decided to branch off an form our own PT company.
We are both very well accredited and live near the beach in eastern sydney so we will be targeting anyone from youth to 40-50 age bracket.
We already have clients that are keen for group fitness session and also 1 on 1 sessions. we need a strong logo that represents our professional approach and that shows that were dedicated, know what were on about and most of all have fun in the process
We are targeting also at selling our shirts and fitness equipment with the Logo on it so the males and females mainly from 18-40yrs are also into the fashion side of things so that would be unreal if its really UNIQUE and FUN type logo!
- something that is unique
- a picture that appeals to woman e.g not a big muscle man but maybe a normal outline of a woman an man that don't represent big muscular figures
- something thats easy to read and understand for people that may see us out in public training clients
- 'Conn-tact Fitness' has to really pop out and we want a small slogan to go with it saying: "SHOCK THE BODY TO MAKE THE BODY"....
- please feel free to make the slogan a strong type design that goes with the fact that we are both well know athletes that have tattoos and resemble a very athletic and hardcore attitude..
- we have tribal type tattoos so some type of tribal incorporation could be really catchy!
- as with colours a plain black or white background is what were looking at putting the logos on so BRIGHT colours that POP and stand out on them will be great!
- Please feel free to be as creative as possible with the script in the slogan and the Conn-tact Fitness as the main eye catcher!!!
Find out how a design contest works or learn more about our logo design services.


text:
Highly Commended in Natural Health Magazines 2016 International Beauty Awards
Neal's Yard Remedies are three times Highly Commended in Natural Health Magazines 2016 ... Read more ►
WINNER: Beauty Baby Awards 2015
Neal's Yard Remedies are three times WINNERS of the 3rd annual Beauty Baby Awards ... Read more ►
We have won TWO GOLD awards in the FreeFrom Skincare awards 2015.
These are fantastic awards as they were founded to encourage and reward Skincare products that ... Read more ►
Best Innovative Product - Frankincense Intense
Our amazing Frankincense Intense™ has been awarded 'Best Innovative Product' ... Read more ►
Ultimate Natural Beauty Bible Award
Neal's Yard Remedies are three times WINNERS of the Ultimate Natural Beauty Bible Award Winner ... Read more ►
Winner of Best Organic Range
We have been awarded WINNER in the Best Organic Range and HIGHLY COMMENDED in the Ethical Range ... Read more ►
Best Natural & Organic Brand Award
Great news - Shortlist Beauty Awards have awarded us 'Best Natural & Organic Brand' in their ... Read more ►
Frankincense Intense is a winner!
We have been lucky enough to receive a 'highly commended' recognition for Frankincense ... Read more ►
We are winners again!
Our White Tea Facial Mist has been awarded Best Facial Spritzer in the Skin Deep Beauty Awards ... Read more ►
Award-winning Mineral Make-up
Our Mineral Makeup has been awarded 'BEST MINERAL MAKEUP TREAT FOR SENSITIVE SKIN' in the ... Read more ►
We feature in Natural Health Magazine November Issue!
In this month's Natural Health Magazine we have a full page feature with Susan Curtis our ... Read more ►
Beauty Awards Winner 2013!
Jane and Adele from our PR Team attended the 2013 Beauty Awards and we're delighted to announce ... Read more ►
Top Sante Best Beauty Award 2013
In the October issue of Top Sante we featured in a spread of the top 43 best beauty buys. We won ... Read more ►
The PR team have been hard at work!
We recently launched our new Organic Herbal Teas with the talking point of the event was our ... Read more ►
We have won TWO GOLD and TWO SILVER
We have won TWO GOLD and TWO SILVER awards in the FreeFrom Skincare awards. These are fantastic ... Read more ►
We are winners!
We are on a winning streak… Rejuvenating Frankincense Cleanser has just been awarded Woman & Home ... Read more ►
That's right…we won!
We have won TWO AWARDS for the RSVP Magazine Beauty Awards. RSVP is a hugely popular monthly ... Read more ►
We won for the 5th Year running!
We have just been awarded by Natural Health Magazine BEST NATURAL RANGE 2013 for the 5th year ... Read more ►
Best New Certified Organic Skincare Product 2013
Rejuvenating Frankincense Facial Oil has won the prestigious CEW award for Best New ... Read more ►
We Won!
Just 3 years after we launched our Bee Lovely and Help Save the Bees campaign, the EU have ... Read more ►
Neal's Yard Remedies Wild Rose Beauty Elixir
A natural, organic radiance booster ... Read more ►
The Natural & Organic Awards 2011
The Natural Products Achievement AwardWinner: Peter Kindersley, Founder of ... Read more ►
Elle UK
Loved by Elle "We're big fans of their award-winning products, all made with natural, ... Read more ►
The Times
Citrus Hand Softener "A tiny dab of this thick cream keeps your hands moisturised all ... Read more ►


text:
ownCloud is a software suite that provides a location-independent storage area for data (cloud storage).
owncloudAUR is available in the AUR.
- First of all set up the LAMP stack as described in the corresponding Wiki article.
- Install the owncloudAUR package as described in AUR#Installing_packages.
- Add the following lines into /etc/httpd/conf/httpd.conf (php5 should have been configured during the LAMP stack setup):
Include /etc/httpd/conf/extra/owncloud.conf LoadModule php5_module modules/libphp5.so Include conf/extra/php5_module.conf
Uncomment extensions in /etc/php/php.ini
gd.so xmlrpc.so zip.so iconv.so
Depending on which database backend you are going to use uncomment either one of the following extensions in /etc/php/php.ini
sqlite.so sqlite3.so pdo_sqlite.so
mysql.so mysqli.so pdo_mysql.so
now restart the apache server with:
# rc.d restart httpd
and open http://localhost in your browser. You should now be able to create a user account and follow the installation wizard.
Custom configurations
Filesize Limitations
With the default configuration ownCloud only allows the upload of filesizes less than 2MB. This can be changed by changing the following line in /etc/php/php.ini to your liking.
As of version 4.0 this is no longer necessary! The maximum upload size is now set via the ownCloud gui
upload_max_filesize = 2M
As of version 4.5, upload limits are set in /usr/share/webapps/owncloud/.htaccess. This won't work if PHP is set up to run as CGI, so you need to change the limits in /etc/php/php.ini. You also need to change open_basedir.
upload_max_filesize = 512M post_max_size = 512M memory_limit = 512M open_basedir = /srv/http/:/home/:/tmp/:/usr/share/pear/:/usr/share/webapps/
Running owncloud in a subdirectory
By including the default owncloud.conf in httpd.conf, owncloud will take control of port 80 and your localhost domain. If you would like to have owncloud run in a subdirectory, then skip the 'Include /etc/httpd/conf/extra/owncloud.conf' line altogether and just use a symbolic link like so:
ln -s /usr/share/webapps/owncloud/ /srv/http/
Filling ownCloud with data
Small Files
Always use WebDAV or the web interface to add new files to your ownCloud. Otherwise they will not show up correctly, as they do not get indexed right.
Consider installing and enabling php-apc to speed up WebDAV.
When using SABnzbd, you might want to set
folder_rename 0
in your sabnzbd.ini file, because ownCloud will scan the files as soon as they get uploaded, preventing SABnzbd from removing UNPACKING prefixes etc.
Big Files
WebDAV isn't suitable for big files, because it fills up all the RAM and CPU.
With the current version, it looks like, there is no good way of copying huge amounts of data to your ownCloud.
Here's a Workaround:
copy the files directly to your ownCloud and do a full re-scan of your database (you could use the Re-scan filesystem add-on for example).
But beware that this will not work as easily in the future, when end-to-end encryption gets added to ownCloud (this is a planned feature).
Important Notes
- When using a subdomain (like cloud.example.xxx), make sure it is covered by your certificate. Otherwise, connection via the owncloud client or webdav might fail.
- If you are planning on using OwnCloud's sync-clients, make sure to have NTP installed and running on your OwnCloud server, otherwise the sync-clients will fail.
- Add some SSL encryption to your connection!


text:
0 Members and 1 Guest are viewing this topic.
Egypt (AINA) -- Osama Araban, a Muslim man riding a Harley-Davidson motorcycle, went on a rampage last week in Egypt, killing 63-year old Coptic Christian Abdo George Younan, in the village of Bagour, before traveling onwards and stabbing with intention to kill two other Copts in two different villages, at least 10 km apart (AINA 9-18-2009).Read the complete story here:http://www.aina.org/news/20090921172742.htmLord have mercy.
How in Mor's good nameone hundred fifty four postsNo Rachel Weisz picSelam
Page created in 0.084 seconds with 25 queries.


text:
Between Katniss and Tris
Back in March 2011 I reported exclusively that Jennifer Lawrence was the first choice to play Katniss in The Hunger Games. At one point however, they were also interested in Saoirse Ronan, particularly after her performance in Hanna (click here for a refresher) but that she would have to really, REALLY dazzle producers to take the job away. That obviously didn't happen and Ronan went on to win the lead role in The Host, Stephenie Meyer's follow-up to Twilight, at that time a reasonably coveted part...
Until Tris Prior came along in Divergent.
Timing sucks, doesn't it?
For many of you, Ronan IS Tris. But seeing as she already committed to the lead in The Host, another potential dystopia franchise, straddling both was impossible. And now it's Shailene Woodley who will be Dauntless. Classic Hollywood Sliding Doors moment.
The first trailer for The Host was released earlier this week. I didn't read the book so I don't know how well this reflects the source material but from an uninitiated viewer's perspective, um, this doesn't look so good. And it certainly doesn't seem like it will stand up next to The Hunger Games or Divergent which makes it all even more disappointing. That Saoirse couldn't be Tris because of something that might be lesser. Then again, Twilight became a phenomenon on a low quality product so...
Interestingly enough, from the 2 minute preview, Ronan does appear to have strong chemistry with her Host love interest Max Irons who broke up with Emily Browning at some point during filming. My smutty senses are tingling. Are my smutty senses full of sh-t?
Here are Ronan and Irons with co-star Jake Abel at the Twilight 5 premiere the other night and Ronan shooting scenes for The Host last night.


text:
Alumni50 needed a new logo design and created a contest on 99designs.
A winner was selected from 4 designs submitted by 2 freelance designers.
INS UK and Ireland
I am the CEO of a medical company (http://www.pointofcare.ie) who is assisting in the launch of an international affiliate of a large nursing organisation called Infusion Nurses Society (http://www.ins1.org). We are building a social network community of nurses who want to specialise in infusion medical care. Infusion medical care is the delivery of medicines by IV (intravenously). These nurses will work with patients that have serious diseases like MS, Rheumatoid Arthritis, Chrons Diseases etc..
Qualified Nurses that have an interest in specialty infusion care that live in the Ireland or the UK.
We have permission to use the INS logo at http://www.INS1.org, we would like the tagline removed and the words UK and Ireland to be added. We need the background to be white instead of grey tinted.
reference http://www.ins1.org
Find out how a design contest works or learn more about our logo design services.


text:
Next Game: GPR Away v Saracens Sat. Feb. 16th ko 3.00pm live on BT
Quote:Blue Oyster Cult - there's something I haven't heard in a while...
Quote:Cockerill quote - [www.planetrugby.com
Leicester scrum-half Ben Youngs, who left the field with a minor shin injury in the second half, could be cited after he appeared to knee an opponent deliberately while he was on the ground.
Exiles coach Toby Booth said the England number nine's actions were "unnecessary" but Cockerill believes Young's actions were not intentional.
"It was in the heat of the battle," he said...
Quote:Actually I think you'll find that that's exactly what you can do. What you're supposed to do in fact!Saint Dom
He needs to learn that he can't ride with the hunt and run with the hounds...
Total users online:
Most users online:
Users on this site:


text:
Message Board
Jerrilyn Farmer Message Board
Talk about the novels, new and used books that Farmer has written!
Author Farmer's Book Reviews
Mumbo Gumbo
Morrow, March 2003, 23.95, 256 pp. ISBN 038097889X Mad Bean Events is one of the industry's most well known event planners but with the economy in a downward spiral and the international scene so frightening, business is hurting. Co-owner Madeline Bean has only one more affair to cater before she faces an empty calendar. Greta Greene, the producer of the famous quiz show Food Freak, offers her a temporary job as a writer for the production beca...
Perfect Sax
Morrow, Jan 2004, 22.95, 304 pp. ISBN 0380978903 Maddie Bean's catering and events planning business is becoming very chic with the rich, powerful and famous in Las Angeles and Hollywood. Her firm is catering an event to raise funds for the Woodburn School of Music so that gifted children who can't afford the fees can obtain a scholarship. The gala is a smashing success and Maddie is justifiably proud of her role in the affair. She leaves th...


text:
Produce by overdriving, short circuiting, bending and just messing up a v-tech speak and spell typed unit. Very fun easy to mangle with some really interesting results.
This sound has not been commented on yet, be the first to comment!
Please log in to comment
Share url:
920 x 245
481 x 86
375 x 30
We use cookies to ensure you get the best experience on our website. By browsing our site you agree to our use of cookies.
For more information check out our cookies policy.


text:
The Wabash Center for Teaching and Learning in Theology and Religion will celebrate the opening of its new home with an open house and ribbon cutting this weekend. Founded in 1996 by a grant from Lilly Endowment Inc., the Wabash Center has become internationally recognized for its service to theology and religion faculty in colleges, graduate schools, and seminaries.
Housed in Wabash College's historic Hovey Cottage since its founding, the Wabash Center has moved into a 4,000 square-foot office and conference facility to better meet the needs of over 150 scholars who attend workshops and consultations on the Wabash campus each year.
The new facility is situated on the southeast end of the Wabash College campus on South Grant Avenue directly across from the Fine Arts Center. An open house is scheduled for 1 p.m. to 3 p.m. on Saturday, May 10 at which time staff will give tours of the building and discuss the Wabash Center's programs. A formal ribbon cutting ceremony will take place at 6 p.m. on Sunday evening, May 11. The public is cordially invited to attend.
"The new Wabash Center building gives us new space for conversations and work," said Wabash Center Director Nadine Pence (left). "The design brings under one roof our resource, work, and classroom space, as well as making it possible to have occasional meals and receptions."
The one-story, L-shaped building has been designed with hospitality as its centerpiece, owing to the long-standing Wabash Center tradition of welcoming scholars from across the United States and Canada. In addition to four offices for Wabash Center professional staff, the building includes a 25-seat conference room; two smaller breakout meeting rooms; space for five administrative staff; a large, open reception area; and a kitchen. The most striking feature of the new Wabash Center building is its semi-circular patio and garden area, through which visitors will walk as they enter the new facility.
"This new building is a wonderful conversation and work space for the many visiting faculty who come to the Wabash campus each year," said Pence. "Its design is open and inviting; the building material is warm and receptive."
Created and sustained by grants from Lilly Endowment Inc., the Wabash Center for Teaching and Learning in Theology and Religion seeks to strengthen and enhance education in North American theological schools, colleges and universities. The Center helps build enabling environments for good teaching and learning through workshops and conferences, grant-making, and consultants' program. These programs support the initiatives of faculty and institutions that enhance the teaching of theology and religion, allowing for thoughtful reflection on the vocation of teaching.
Browning Day Mullins Dierdorf Architects designed the new facility.
For more information on the Wabash Center for Teaching and Learning in Theology and its programs, contact Director Nadine S. Pence at by email or by phone at 800-655-7117. Learn more about the mission and programs of the Wabash Center.


text:
Hi all,
I recently upgraded to 5.2.5420.20141215 from the latest stable version.
I remember that in the old version, you could select a folder from the drop down menu on the far left where it says "All Music". I don't seem to be able to do that now?
What i mean is that when adding a folder in "Media Folders" it would come up in the drop down menu on the left and then just sort out the different artists in that folder in the accordion below.
I'm sure there's a setting somewhere but i can't seem to find it.
Would appreciate any help.
Also, some songs just won't get added inside the different letters of the accordion, which i believe worked fine before.
I've added a picture in case i'm not clear enough.


text:
YCD Multimedia, a leading global provider of smart digital signage solutions, announced Version 5.0 of its cloud-based content management system – YCD|CMS SaaS. The new version greatly improves core features while adding new tools, including all new built-in editors, new and enhanced content management with authorizations and remote control, and a host of user interface enhancements.
With the new built-in HTML 5-based editors users can now create and edit layouts, playlists, and schedules right from the CMS for a more efficient workflow and quicker turnaround from authoring to display.
YCD|CMS's already powerful content management capabilities have been bolstered with a host of remote station control and monitoring features such as real-time playback status, zone, layout, playlist and videowall details, and remote control capabilities such as player restart, weekly/monthly automatic sync, and automatic alerts and notifications. Enhanced content management pages now allow users to delete playlists, schedules, and layouts with or without associated media to preserve and optimize player media storage.
Lastly, user interface enhancements of YCD|CMS SaaS solution include keyword search columns in playlist, schedule, layout, and package management pages, plus a quick search widget for quickly finding stations and an indication icon for RAMP (YCD's Retail Advertising and Merchandising Platform).
"YCD|CMS SaaS 5.0 reflects our customers' requirements for a cost-effective and highly efficient content management system, bringing a higher level of functionality within our platform to better accommodate our customer workflows and business infrastructure," says Noam Levavi, YCD's CEO. "The new version is optimized to meet the evolving digital signage needs of various industries, extending our leadership position in the global market in providing digital merchandising and digital ambiance solutions built on effective customer communication."
YCD|CMS Software as a Service (SaaS) solution addresses authoring, scheduling, managing, and distributing content easily, quickly, and accurately without having to disrupt existing IT or management infrastructure. It uploads ads, promotional messages and dynamic content and creates audio and video playlists. It schedules playback up to a year in advance for any number of locations and ensures synchronized audio and video content playback across multiple screens or locations. In addition to the cloud–based service (SaaS), YCD|CMS is also available as an on-premise solution.
The five times weekly e-newsletter that keeps you up-to-date on the latest industry news and additions to this website.


text:
No one can guarantee that young adolescents will grow into responsible and competent adults. Your influence on your young teen, however, is enormous. Yes, on a bad day the smelly sneakers and mood swings may push you to your limits. But it is critical to remain involved. It's when you are ready to throw up your hands in frustration that you most need to hang in.
Learning as much as you can about the world of early adolescents is an important step toward helping your childand youthrough the fascinating, confusing and wonderful years from 10 through 14. As middle school teacher Emily Hutchison from Texas puts it, early adolescence is "never dull, never boring." Stay tuned to the life of your young teen and enjoy this special time.


text:
CANR alum Kaitlin Ricketts interns at Meadowset Farm and Apiary
Until last April, University of Delaware alum Kaitlin Ricketts didn't know much about sheep cheese. Now, her job revolves around it. Ricketts, who graduated from UD in the spring of 2012 from the Department of Animal and Food Sciences with a concentration in pre-veterinary and animal biosciences, is the farm intern at Meadowset Farm and Apiary in Landenberg, Pennsylvania. Meadowset, a farm that focuses on practicing sustainable farming to produce all of their products, is a sheep micro dairy owned by Tom Schaer and Barbara Dallap Schaer—both of whom are large animal veterinarians. Meadowset sells sheep cheese, eggs, lamb, honey and other various farm products available at the farm's store. The cheese can also be found Va La Vineyards in Avondale, Pennsylvania, and at the restaurants Talula's Table in Kennett Square and Talula's Garden in Philadelphia. Ricketts explained that the micro dairy, which milked 28 sheep last season, has two different styles of sheep cheese: pecorino and tomme. "The pecorino, which is an Italian style cheese, is very comparable to a parmesan, and the other one is a tomme, which is a washed curd cheese which reduces the acidity making it a milder cheese," said Ricketts. Ricketts said that while her official title is 'Farm Intern,' she has various responsibilities on the farm. "My duties range everything from just your every day feeding to watching to see what the animals' health levels are, and I'm also running the farm store on the premises so I'm dealing with people directly, selling products and trying to market our cheese a little bit." This last part has been the most eye opening for Ricketts, as she explained that she did not take a lot of food-agriculture classes while at UD. "I've been going around to local natural food markets and dropping off samples of lamb and trying to make sales there which is pretty new to me," said Ricketts. "I'm kind of learning that all on my own." What she did have while at UD was a lot of hands on experience working at a dairy, which she said was one of the main reasons she came to study at the College of Agriculture and Natural Resources. "I grew up in the suburbs of Baltimore so there was no farming background," said Ricketts. "I came to Delaware because of the Ag school and because of the farm being right there. That was a big draw to me and I started working on the UD Dairy farm my sophomore year so that's where my interest really started." Ricketts, who also raised seeing eye dogs for the Puppy Raisers of the University of Delaware (PROUD) organization on campus, fed the calves and milked the cows while at the UD farm, all the while trying to pick up as much knowledge as she could from Richard Morris, dairy manager, and the rest of the UD farm staff. Explaining that her original plan was to go to veterinary school, Ricketts said she eventually realized that vet school just wasn't in the cards at this point and time in her life. "Working on the farm and being in classes like professor Tanya Gressley's 'Dairy Production' sort of opened up my eyes to the fact that there are probably other things out there that can make me just as happy as being a veterinarian," said Ricketts. "Vet school isn't for everyone and I just kind of hit a wall one day and had that realization that there are others things that I think I need to look into before I say, 'Yeah, I'm going to go to vet school.'" Still, sometimes working on the farm comes as a shock to her. "If you would've told me my freshman year that I was going to be working at a dairy farm making cheese I would've said you're crazy," said Ricketts. She said that her favorite part about working on the farm is getting to work outdoors. She also said that she enjoys getting to have her old sorority, Sigma Alpha, come out to the farm to do service projects and that those in the sorority who are interested in pursuing veterinary careers get to learn first hand from the farm owners. Ricketts said that Tom and Barbara Schaer are "great people and they're very enthusiastic about what they do so it's kind of hard to not love your job when you're working for people like that." "A lot of the girls in Sigma Alpha are still very much in the mindset of going to vet school so them talking to Tom and Barb I think is helping them figure things out too," said Ricketts. "So that's been really exciting for me, the past couple of weeks being able to connect everything that I've had in my life the past couple of years." Article by Adam Thomas


text:
Capcom's most successful video game is no longer Street Fighter II, with the SNES fighter's 6.3 million copies now bettered by Resident Evil 5.
Resident Evil 5 has now sold 6.5 million copies since its release in 2009.
Third in line is the hugely disappointing Resident Evil 6 which has some how blundered its way to 5.2 copies sold since its release in 2012.
It's worth pointing out that Street Fighter II Turbo for the SNES has also sold an impressive 4.1 million copies, and given its release a year after the original would have cannibalised sales.
Capcom has seen more than 60 games sell over one million copies, the latest being Monster Hunter 4 which has moved over 3 million copies in just a matter of months.
Source: Capcom Investor Relations


text:
When Project Progress to be shown in higher management, milestone chart is the best form while the team or lower a level bar chart is preferred way.
How about if nothing is mentioned in the question or to be presented in townhall meeting where higher management and lower staffs along with project team is present.
Manish can you explain elaborately!
Project Progress Report
Discuss PMP doubts, tips and lesson learned. iZenBridge makes PMP® Certification easy
3 posts • Page 1 of 1
- email@example.com
- Participant
- Posts: 74
- Joined: Tue Jul 11, 2017 9:28 am
Re: Project Progress Report
In such scenario,I wud prefer the most summarised view as top management would preside over the town hall meeting.hence milestone chart wud be apt.
However,this should be defined a part of schedule management plan via project schedule.
However,this should be defined a part of schedule management plan via project schedule.
Re: Project Progress Report
I second Niraj on this as a Townhall meetings are generally called for updating the organizational status to the staff which may include the mix of all level of employees. As such, presenting a high level overview and not specifics like a bar or gantt chart is preferred.
3 posts • Page 1 of 1
Who is online
Users browsing this forum: No registered users and 18 guests


text:
There's a big bit of news for houseboat buyers and sellers in Seattle--we've finally got financing for houseboats/barges in rental marinas such as Seattle Marina and Commercial Marina. This has been the number one factor holding back houseboat sales in the past. Buyers had to pay cash for the full price of the houseboat, which was too great of a barrier for most.Thanks to Linda Bagley of Special Agents Realty for the heads up. We don't have the final official stats yet, but here are the likely terms:
Seattle Metropolitan Credit Union will be lending on houseboat "vessels".Qualified borrowers will be able to finance up to 75% of the purchase price, and sales tax can be financed. This is important for buyers, as sales tax can add a 10% upfront cost to a vessel purchase.
Interest rates are likely to be 6.625%-7.125%, on a 30 year amortized loan with a 10 year balloon. This means you'll make payments on the home like a 30 year loan, but the balance will be due after 10 years. At that point, you'll need to make a full payoff, or find alternative financing. This is a great way for a first time buyer to get a foot in the door.
These houseboat vessels must be in moorage with a long-term lease, and an inspection/survey will be required to verify the condition of the vessel. Like all financing the buyers will need to go through an application process to verify their eligibility for financing, but this is a huge step forward for the houseboat vessel community.
Like what you read?
Want to know when we have important news, updates or interviews?
Join our newsletter today!
Send to your friends!


text:
One Year Later: Our NEW ROMO! + Thanks to Original Backers
Hi all -
It's been a really tough but fun year for us. We learned so much from our first Kickstarter project - what worked, and what didn't.
We knew... Read more
The android and updated iOS apps are live!
Hey robot fans! The android app and updated iOS apps are now live! Download and play!
P.S.-- Here are some awesome Romo pictures people tweeted/email us!
Bots are arriving around the world!
Hey Romo fam-
We're emailing today because robots are showing up on people's doorsteps around the world. Huzzah!
The little bots in this batch of 1400 taught our whole team... Read more
Update #10, Shipping Robots
Hey Guys,
Its official, robots are being shipped. We got a few out the door on Saturday and already have 100 boxed and ready to go right now, with more... Read more
February 28th Update
Hey Romo Users,
We know you're anxiously waiting for your robots.
An update: Last week 2000 circuit boards arrived at our workshop in Vegas. We pulled them out and... Read more
The 2012 Update
Fellow robot lovers,
The last time we reached out to you, we had just finished building 100 special edition pre-Christmas robots. Now that those first Romos have found happy homes, we... Read more
We are building Christmas robots!
Hello robot family,
Sorry for the radio silence over the last couple weeks. We have been hard at work ordering parts, soldering motors, laser-cutting acrylic, and assembling robots! Barring major... Read more
Meet Romo in Seattle Wednesday, Nov. 16
If you are in Seattle on Wednesday the 16th, you are invited to come meet Romo in person! We are getting together with the guys from the popular Seattle Kickstarter... Read more
Romo in Color!
We're excited to announce that Romo is now in color!
If you want a color other than clear (is that a color?) just add $10 to your order. And as... Read more
Romo has something to say!
Tweet our Kickstarter! Like us on Facebook! Let us know what cool things you think Romo should do!
Btw, we're using the Dragon Mobile SDK for voice recognition.
Thanks to all of you, we reached our goal in just under 72 hours! We love your enthusiasm and all of the feedback! Please let us know if you have... Read more
Teaser to Romo Kart
Wow! Backers already. Thanks guys!
Here's a teaser image to the Romo Kart game we're working on. Other games in the pipeline include Sumo and Jousting!


text:
Project #11 for NEPatsFan01
Budjetti $30-100 USD
Project #11 for NEPatsFan01 - No others need bid
* 30 Teen Health and Wellness Articles
* The articles must be 300 to 500 words in length and must pass copyscape
* Free of grammatical errors, etc.
* You will have 3 days to satisfactorily complete the project.
* Upon payment of the fee I will have full ownership, including copyright, to the articles.
* You will not be able to resell or reuse these articles.
* Escrow with payment upon completion of the project.
Thanks Erin!


text:
This is definitely one of the riskier posts I've written. I've been a Google Apps customer for a couple of years, and I've even done consulting work for Google.
But Google has a right to know this information, and so do their channel sales partners, because it will serve them well, and enable them to help their customers. Without breaking any non-disclosure agreements, I'm going to attempt to describe why Google Apps still loses deals, even when selling to big enterprise companies that are absolutely fed up with Microsoft.
5 Reasons
- 1. Government agencies still have serious security concerns: It's an open secret. There have been a series of well-known Google Apps deployments in both the government sector and the corporate sector that have been terminated early. The government deals have largely fallen apart over security concerns, but for every high-level government deal that Google loses, they seem to win a smaller one.
- 2. Microsoft is starting to really care about Google Apps competitor Skydrive: From 2007 to 2011, Microsoft's SkyDrive product was under-promoted and under-supported. About three months ago, that changed. They're branding it as a cross between Google Apps & DropBox, and they've combined some of the best features of both, along with the Microsoft Office interface that has been popular since, well, before the Internet.
- 3. Most partner websites stink: With a few exceptions, there aren't many Google Apps partners that have websites that excel at content marketing, which is exactly what prospective Google Apps customers need. One that seems to get the picture that robust resource centers and marketing automation are "table stakes": Appirio.
- 4. Google's lack of commitment to uptime, at least until recently: It's 2012. Having 99.9% uptime isn't really anything to be proud of. As an IT admin, if you told me that my company will not have access to their email, calendar, or documents three hours per year, during the work day, I wouldn't be too impressed. In recent months, Google has made strides against this by raising the bar to a 99.99% uptime agreement - but they do limit their liability to a 15-day credit, and they haven't put this to the forefront of their messaging. Also, their track record has been, well, only okay. In 2010, Gmail maintained uptime of 99.984%, which is similar to phone lines. About a year ago, Google also dropped the "scheduled maintenance clause" from its service level agreement (SLA), and Microsoft and Salesforce quickly followed suit.
- 5. Lack of partner-driven video case studies: It's 2012. Nothing helps a customer own a very tough "change concept" (i.e. doing a multi-million dollar Google Apps deal) like seeing other companies in their industry do the same thing, and tackle all of the complex organizational change management. Try finding some Google video case studies on customer success that include a featured partner. It's tough. And it doesn't build a lot of buy-in for Google's sales prospects in their partner-driven ecosystem.
Also read:
Full Bio
Adam Metz is the VP of Business Development at Metz Consulting the social concept, a social customer management-consulting firm, based in Oakland, California. Metz has consulted with companies since 2006 on how to acquire, manage, monetize and retain customers from the social web. Metz's customer community, at http://metz.customerhub.net has nearly 500 members, and offers a no-cost 9-hour training course on social customer relationship management.Metz's second book, The Social Customer, was released on 9/16/11 and has hit #1 on the Amazon marketing charts. Adam's first book, There Is No Secret Sauce, has sold or downloaded over 3000 copies, and is currently in its third printing. He has additionally published an eBook, The Metz Way.Metz specializes in social media marketing and social customer relationship management (social CRM) for awesome consumer brands and loves lifestyle, travel, apparel and consumer-packaged goods (CPG) companies.Metz has consulted with nearly 100 consumer and B2B companies, including Hershey's Chocolate, Waggin' Train Pet Food, Wente Vineyards (top 30 winery) Pirate's Booty, MBT Shoes, Maestroconference, Obama Girl (Barely Political), Lynda.com, Passport Resorts, Hollywood Park Racetrack, The San Francisco Convention and Visitor's Bureau, Mighty Leaf Tea, Timbuk2 bags, and dozens of others. Adam Metz also worked on the first social media program for Pulitzer-Prize winning author Thomas Friedman.Metz has lectured at the University of California, Berkeley, the University of Washington, and University of California, Santa Cruz and has given keynote talks at numerous conferences and associations including the California and Minnesota Chapters of the American Marketing Association, the San Francisco Chamber of Commerce, the Western Association of Convention & Visitors Bureau Technology Conference, and the Hospitality Sales & Marketing Association.Metz lives in Oakland, California with his fiancee Susan.


text:
Today we are busy making Monster Valentines.
We are using scraps of fake fur and old sweaters to cut out monster shapes. We glue our fuzzy fabric scraps onto paper hearts and add all sorts of appendages.
The kids are really having a blast glueing on googly eyes, adding horns and big teeth! These Monster Valentines are just the perfect thing for my silly monster loving boys.
Our first Valentines Day swap is hosted by our favorite local family resource blog Hilltown Families, so fun.
We got a list of families to send homemade Valentines to, and cant wait to see what everyone sends us.


text:
Franklin County, Massachusetts Genealogy
United States Massachusetts Franklin County
This is a historical and genealogical guide to the county of Franklin. You will find help with town histories, vital records, deeds and land records, city directories, cemetery records and cemeteries, churches, town records, newspapers, maps, and libraries.
- 1 Franklin County Massachusetts History
- 2 Franklin County Massachusetts Genealogy Resources
- 2.1 Vital Records
- 2.2 Cemetery
- 2.3 Census
- 2.4 Emigration and Immigration
- 2.5 Land Records
- 2.6 Probate Records
- 2.7 Other Court Records
- 2.8 Maps
- 2.9 Military Records
- 2.10 Franklin County Massachusetts History and Genealogy Websites
- 3 Franklin County Massachusetts Libraries and Genealogy Societies
- 4 Franklin County Massachusetts Genealogy References
Franklin County Massachusetts History
Brief History
Franklin County was long settled by the time it was set off as its own county in 1811. Early settlers made their way into the region first along the Connecticut River. It was a crossroads for migrations from eastern Massachusetts, Rhode Island, and Connecticut, and the gateway to Vermont and New Hampshire's river valley settlements. The county has always been sparsely settled. Franklin's county government was abolished on 1 July 1997, but its former jurisdiction is used for state offices as a district.[1]
Historical Data
The basic data are from the historical county boundary series[2] with additions from various sources.
|2 Dec. 1811
|Franklin County set off from the northern third of Hampshire County. [Mass. Acts, 1811, Ch. 61, p. 467]
|7 Feb. 1816
|Small loss when part of Orange annexed to Athol, Worcester Co. [Mass. Acts, 1816, Ch. 62, p. 71]
|28 Jan 1822
|Loss when part of New Salem was combined with Pelham, Hampshire Co., to create the new town of Prescott, Hampshire Co. [now extinct]. [Mass. Acts, 1822, Ch. 34, Sec. 1, p. 614]
|21 Feb. 1822
|Gained when part of Rowe was combined with the Gore in Berkshire Co. to create the new town of Monroe in Franklin Co. [Mass. Acts, 1822, Ch. 93, Sec. 1, p. 707]
| 5 Feb. 1830
16 Mar. 1837
|Small loss when part of New Salem annexed to Athol, Worcester Co. [Mass. Acts, 1830, ch. 33, p. 300 and 1837, Ch. 80, Sec. 1, p. 70]
|2 Apr. 1838
|Gain when part of the territory known as Zoar in Berkshire Co. was annexed to Charlemont and Rowe [Mass. Acts 1838, Ch. 56, Sec. 1, p. 344 and Ch. 57, Sec. 1, p. 345]
|2 Feb. 1849
|Border between Whately and Williamsburg, Hampshire Co., clarified - no change. [Mass. Acts, 1849, Ch. 3, p. 198]
|27 Apr. 1911
|Border between New Salem and Prescott, Worcester Co. [now extinct], redefined - no change. [Mass. Acts, 1911, Ch. 340, Sec. 1, p. 310]
|28 Apr. 1938
|Large gain when Quabbin Reservoir created and "drowned" four towns. New Salem annexed parts of Enfield, Greenwich, and Prescott, all in Hampshire Co. [Mass. Acts, 1827, Ch. 321, Sec. 1, p. 384; 1938, ch. 240, Sec. 1, p. 188]
Record Loss
There is no known history of courthouse disasters in this county.
Towns and Cities
Charlemont (1765) | Colrain (1761) | Conway (1775)
Deerfield (1677) | Erving (1838) | Gill (1793)
Greenfield (1775) | Hawley (1792) | Heath (1785)
Leverett (1774) | Leyden (1809) | Monroe (1822)
Montague (1775) | New Salem (1775) | Northfield (1723)
Orange (1810) | Rowe (1785) | Shelburne (1775)
Shutesbury (1761) | Sunderland (1714) | Warwick (1763)
Wendell (1781) | Whately (1771)
County Histories
Works written on the county include:
- Biographical Review: this volume contains biographical sketches of the leading citizens of Franklin County, Massachusetts (Boston, 1895), 668 pp.
WorldCat (Other Libraries); FHL book 974.422 D3b and film 1320725 Item 1.
Digital version at Internet Archive.
- Theophilus Packard, A History of the Churches and Ministers, and of Franklin Association, in Franklin County, Mass., and an appendix respecting the County (Boston, 1854), vii, 456 pp.
WorldCat (Other Libraries) and [Index; FHL fiche 6206740.
Digital versions at Internet Archive and Google Books.
- Francis Nims Thompson, "The Probate Court and its Judges" in History and Proceedings of the Pocumtuck Valley Memorial Association, 7 [1921-1929]: 631-653.
WorldCat (Other Libraries); FHL has to v. 6 only.
Digital version at Ancestry ($).
Franklin County Massachusetts Genealogy Resources
Vital Records
In Massachusetts, the original vital records (of births, marriages, and deaths) have been created and maintained by the town or city in which the event occurred. In very early colonial times, copies of these records were submitted to the county, but that practice died out long before this county was established. There were marriage intentions commonly recorded in the bride's home town and additional recordings maybe found in the groom's home town and their current residence.
Massachusetts was the first state to bring a unified state-level recording of these events (but not marriage intentions) in 1841 (Boston excluded until 1850). The associated records of divorce and adoption are handled by the courts. The state has maintained a state-wide index to divorces since 1952, but adoption records will require more researching to discover.
It is easiest to start with the state vital records for events since 1841, though realize the original record is with the town or city. More details can be found on the Massachusetts Genealogy Guide page.
- 1666 - 1970 Massachusetts, Delayed and Corrected Vital Records, 1753-1900 at FamilySearch — index & images
|Tombstone Transcriptions Online
|Tombstone Transcriptions in Print
|List of Cemeteries in the county
|Family History Library
|MAGenWeb Archives
|Billion Graves
|Tombstone Project
|Billion Graves
|See Massachusetts Cemeteries for more information.
- 1865 - Massachusetts State Census, 1865 at FamilySearch — index and images
Emigration and Immigration
- 1837 - 1965 - Maine & Massachusetts Case Files of Deceased and Deserted Seamen 1837-1965 at FamilySearch - images
Land Records
Land transfers, commonly called deeds, are recorded on the county level in Massachusetts. Not all deeds were recorded as is common practice today. The earliest transactions were charters or grants from the English Crown. Once local government was established, the colony would grant land to settlers directly or to towns to dole out. Some towns first start out as proprietorship and records were recorded there. Once towns were established, deeds were recorded on the county level.
Franklin District Registry of Deeds
30 Olive Street - Suite 2
Greenfield MA 01301
Phone 413-772-0239
Records are available at the Registry. Their records ONLINE are:
- Recorded Land [i.e. deeds], 1951-present.
Note: Index back to 1951, but records online back only to 1958. Record images back to 1787 can be found under "Search Criteria" by selecting "Unindexed Property Search," but you need to know the volume and page. Records before 1812 are copies from the Hampshire County records.
- Recorded Plans, 1800-present.
- Registered Land [i.e. land court], 1900-present.
- Registered Land Plans, 1899-present.
- Hampshire County Land records abstracted, v. 1-4 plus index, 1663-1786, at FHL films 1769542-1769543.
Note: These are the Indian deeds that for the area that became Franklin County.
- Deeds, v. 1-485, 1787-1902, index, 1787-1889, 1890-1899 (Massachusetts Land Records, 1620-1986), at FHL film 893536 (1st of 217) and New England Historic Genealogical Society (to v. 431).
Note: v. 223 (1859) missing.
- Deeds, v. 1-485, 1787-1902, index, 1787-1889, 1890-1899 (Massachusetts Land Records, 1620-1986), at FamilySearch, browsable but not indexed.
Probate Records
Probate and Family Court is organized on a county level in Massachusetts since the creation of the counties. The main records genealogists seek are testate (wills), intestate (administrations), guardianships, and divorces (since 1922), though there are many more that are valuable to any researcher, too. See a further discussion of the topic in general on the Massachusetts Genealogy Guide.
Franklin Probate and Family Court
PO Box 590
425 Main Street
Greenfield MA 01302
Phone 413-774-7011
The original records are either at the courthouse or at the Judicial Archives in Boston. Their located has not been researched.
- The Massachusetts Society of Mayflower Descendants has online the Franklin Co., Mass., Probate Guide and Index, 1812 to 1925. From this page, select where in the alphabet you want to start. That brings you to a page for that section with a link to the page of the index by the first name on that page.
- 1635 – 1991 Massachusetts Wills and Probate Records 1635-1991 at Ancestry.com — index and images, $
- Franklin County Probate files, #1-18089, 1812-1915, at FHL film 1787376 (1st of 394).
- Franklin County Probate: records, v. 1-49 (1812-1866), v. 1-71 (1828-1894) [no description for second series]; dockets, #1-18800 (1812-1921); index, 1812-1925, 1926-1965, at FHL film 854379 (1st of 45), New England Historic Genealogical Society, and Massachusetts Archives (to v. 49).
Other Court Records
The court system can appear to be complex. The system was reorganized in 1686/1692, 1859, and 1978. Described below are the most commonly used records for history and genealogy, but realize that this list is incomplete. For more detailed information regarding court structure, see Understanding the Massachusetts Court System.
Older records are held by:
Supreme Judicial Court Archives
(administration - records stored in several off-site facilities and the Mass. Archives)
16th Floor, Highrise Court House
3 Pemberton Square
Boston MA 02109
Phone 617-557-1082
Email firstname.lastname@example.com
Quarterly Court of General Sessions of the Peace
This court was active from 1812 to 1827. The court heard criminal cases and had authority over county affairs that included levying taxes, reviewing town bylaws, highways, licensed liquor, regulated jails, supervised the administration of the poor laws, and appointed some county officials.
There are no records microfilmed. The original records are either in the county courthouse or at the Judicial Archives. Their location has not been researched.
Inferior Court of Common Pleas
This court was active from 1812 to 1859. The court heard all civil cases over 40s unless a case involved freehold or was appealed from a justice of the peace.
- Court of Common Pleas, dockets, 1823-1865, records, 1812-1858, at FHL film 854382 (1st of 220).
- Court of Common Pleas, records, v. 16-17, 1844-1847, at New England Historic Genealogical Society.
Superior Court
The Quarterly Court of General Sessions was merged into the Inferior Court of Common Pleas in 1827, and that court was reorganized in 1859 to created the Superior Court as the new lower (i.e. trial) court. It covers both criminal and civil matters.
- Superior Court, records, 1859-1867, at FHL films 901086-901087.
- Superior Court, divorce record books, 1888-1933, at FHL films 2196180-2196181 and Massachusetts Archives.
- Superior Court, divorce docket, 1888-1923, at FHL film 1769526.
Supreme Judicial Court
The Supreme Judicial Court was established by the Massachusetts Constitution of 1780 that combined the former Governor and Council with the Superior Court of Judicature creating the highest state court. This court hears appeals, writ of error, capital offenses, and crimes against the public good. That included divorces until that action was moved to the lower court in 1887.
- Supreme Judicial Court: Index, 1816-1888; Docket books, 1816-1888; Record books, 1816-1889 (inc. divorce) at Massachusetts Archives and FHL film 901088 (1st of 6) (records to 1871 only).
Justice of the Peace
- Records of Philip Phillips, J.P. of Ashfield, 1790-1792, at FHL film 902898 Item 5.
- Record of Henry Bassett, J.P. of Ashfield, 1816-1838, at FHL film 902898 Item 6.
Naturalization Records
Naturalization records were created on a variety of governmental levels from the Federal down to the city at the same time. The county records for all levels are outlines below. For more information, see the Massachusetts state page for more on naturalization.
No federal records as yet digitized at NARA.
|Superior Court
|Judicial Archives
|Index at courthouse
| Records, 1907-1945, at Mass. Arch. RR
Petitions, 1907-1945, FHL film 2195582 (1st of 11)
Declarations, 1906-1945, FHL films 2195580-2195581
Index, 1811-1991, FHL film 1769521-1769526, 1769527
| Greenfield
District Court
|District courthouse
|Records, 1891-1906, and Index, 1891-1906, FHL films 1765478-1765479
| Orange
District Court
|District courthouse
|Final declarations, 1899-1906, FHL film 1769564
There are so many published maps of interest to genealogists and historians that this list will not be recreated here. The focus is with resources you can access online and in the Family History Library.
- Henry Francis Walling, Map of Franklin County, Massachusetts (1858) at the Norman B. Leventhal Map Center, Boston Public Library.
- 1895 map of Franklin County.
Military Records
Revolutionary War
- 1775 - 1783 - Massachusetts, Revolutionary War, Index Cards to Muster Rolls, 1775-1783 at FamilySearch — images
- 1805 - 1845 - Massachusetts Revolutionary War Bounty Land Applications, 1805-1845 at FamilySearch — index and images
Franklin County Massachusetts History and Genealogy Websites
- The Franklin County MA GenWeb Project, an member of The MAGenWeb Project, an affiliate of The USGenWeb Project.
- The USGenWeb Archives Project for Franklin County.
- FamilySearch.org FamilySearch Catalog for Franklin County.
- Massachusetts Genealogy Franklin County
- Kindred Trails Franklin County Massachusetts Genealogy.
- Cyndi's List for Franklin County.
- GenealogyInc for Franklin County.
- GenealogyTrails for Franklin County.
- Linkpendium for Franklin County.
Franklin County Massachusetts Libraries and Genealogy Societies
Memorial Libraries
PO Box 53
6 Memorial Street
Deerfield MA 01342
Phone 413-775-7125
Email email@example.com
This library is located at Historic Deerfield in association with the Pocumtuck Valley Memorial Association Library.
For information on additional archives and repositories, see
- List of Massachusetts Archives, Libraries, Publications, Historical & Genealogical Societies
- Massachusetts Archives for information on additional archives and repositories
- List of Massachusetts Archives, Libraries, Publications, Historical & Genealogical Societies
Family History Centers
Family history centers provide one-on-one assistance and free access to premium genealogical websites. In addition, many centers have free how-to genealogy classes. See family history center for more information. Search the online FHC directory for a nearby family history center.
Franklin County Massachusetts Genealogy References
- ↑ Abolished County Governments - Secretary of State, Acts of 1996, Ch. 151, Sect. 567.
- ↑ Massachusetts Atlas of Historical County Boundaries


text:
Are you a graduate who is looking to pursue a career in the education sector?
Are you looking for the perfect experience to support a future PGCE or Schools Direct application as well as gain financial reward?
Secondary schools in Basildon are looking for Cover Supervisors to work within their schools. This role would suit a confident graduate who has previous experience (in a voluntary capacity or otherwise) working with students, perhaps in a secondary school, primary school or youth work setting. The successful graduate will be motivated and able to converse, liaise and engage with people of all ages including pupils aged 11 - 16, fellow colleagues and teachers.
Highlights of the cover supervisor role:
The role of a cover supervisor is to deliver pre-set work in the absence of the classroom teacher. The role commands a certain level of flexibility as you may be delivering and supervising classes varying in size, ability and age. You may also be at various schools in the Basildon area so the networking opportunities are not only endless but the experience you will gain is perfect for an inspirational teacher. The successful cover supervisor will be covering a range of subjects to gain a full 360 degree, well rounded experience.
This role will suit a recent graduate who has some experience of engaging with young adults aged 11 - 16. A graduate who is confident in their approach and has a professional manner would be ideal.
This role would also suit a more experienced cover supervisor - someone who has previously fulfilled the role in a secondary school or someone who is passionate about working within a secondary school.
This is an excellent chance to join Teaching Personnel's team of teaching staff and deliver a professional and quality learning experience to young minds.
If you think you would be a well suited fit and you would like to apply for one of these positions then please do not hesitate to send your CV to me at the Chelmsford Branch of Teaching Personnel.
All applicants will require the appropriate qualifications and training for this role. Please see teachingpersonnel.com/faqs for details.
All pay rates quoted will be inclusive of 12.07% statutory holiday pay.
Teaching Personnel is committed to safeguarding and promoting the welfare of children. All candidates must undertake or have undertaken a valid enhanced Disclosure and Barring Service (DBS) check. Full assistance provided.
For details of our privacy policy, please see teachingpersonnel.com/privacy-notice


text:
Cell ablation is a powerful tool for studying cell lineage and/or function; however, current cell-ablation models have limitations. Intermedilysin (ILY), a cytolytic pore-forming toxin that is secreted by
Dechun Feng, Shen Dai, Fengming Liu, Yosuke Ohtake, Zhou Zhou, Hua Wang, Yonggang Zhang, Alison Kearns, Xiao Peng, Faliang Zhu, Umar Hayat, Man Li, Yong He, Mingjiang Xu, Chunling Zhao, Min Cheng, Lining Zhang, Hong Wang, Xiaofeng Yang, Cynthia Ju, Elizabeth C. Bryda, Jennifer Gordon, Kamel Khalili, Wenhui Hu, Shuxin Li, Xuebin Qin, Bin Gao
Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via
Juhyun Lee, Peng Fei, René R. Sevag Packard, Hanul Kang, Hao Xu, Kyung In Baek, Nelson Jen, Junjie Chen, Hilary Yen, C.-C. Jay Kuo, Neil C. Chi, Chih-Ming Ho, Rongsong Li, Tzung K. Hsiai
Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders.
Mahalakshmi Shankaran, Chelsea L. King, Thomas E. Angel, William E. Holmes, Kelvin W. Li, Marc Colangelo, John C. Price, Scott M. Turner, Christopher Bell, Karyn L. Hamilton, Benjamin F. Miller, Marc K. Hellerstein
Increased sodium influx via incomplete inactivation of the major cardiac sodium channel NaV1.5 is correlated with an increased incidence of atrial fibrillation (AF) in humans. Here, we sought to determine whether increased sodium entry is sufficient to cause the structural and electrophysiological perturbations that are required to initiate and sustain AF. We used mice expressing a human NaV1.5 variant with a mutation in the anesthetic-binding site (F1759A-NaV1.5) and demonstrated that incomplete Na+ channel inactivation is sufficient to drive structural alterations, including atrial and ventricular enlargement, myofibril disarray, fibrosis and mitochondrial injury, and electrophysiological dysfunctions that together lead to spontaneous and prolonged episodes of AF in these mice. Using this model, we determined that the increase in a persistent sodium current causes heterogeneously prolonged action potential duration and rotors, as well as wave and wavelets in the atria, and thereby mimics mechanistic theories that have been proposed for AF in humans. Acute inhibition of the sodium-calcium exchanger, which targets the downstream effects of enhanced sodium entry, markedly reduced the burden of AF and ventricular arrhythmias in this model, suggesting a potential therapeutic approach for AF. Together, our results indicate that these mice will be important for assessing the cellular mechanisms and potential effectiveness of antiarrhythmic therapies.
Elaine Wan, Jeffrey Abrams, Richard L. Weinberg, Alexander N. Katchman, Joseph Bayne, Sergey I. Zakharov, Lin Yang, John P. Morrow, Hasan Garan, Steven O. Marx
Magnetic resonance–guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma–bearing FVB/n and BALB/c mice. We observed a 5-fold and 50-fold enhancement of liposome and drug concentration, respectively, within MRgFUS thermal ablation–treated tumors along with dense accumulation within the surrounding tissue rim. Ultrasound-enhanced drug accumulation was rapid and durable and greatly increased total tumor drug exposure over time. In addition, we found that the small molecule gadoteridol accumulates around and within ablated tissue. We further demonstrated that dilated vasculature, loss of vascular integrity resulting in extravasation of blood cells, stromal inflammation, and loss of cell-cell adhesion and tissue architecture all contribute to the enhanced accumulation of the liposomes and small molecule probe. The locally enhanced liposome accumulation was preserved even after a multiweek protocol of doxorubicin-loaded liposomes and partial ablation. Finally, by supplementing ablation with concurrent liposomal drug therapy, a complete and durable response was obtained using protocols for which a sub-mm rim of tumor remained after ablation.
Andrew W. Wong, Brett Z. Fite, Yu Liu, Azadeh Kheirolomoom, Jai W. Seo, Katherine D. Watson, Lisa M. Mahakian, Sarah M. Tam, Hua Zhang, Josquin Foiret, Alexander D. Borowsky, Katherine W. Ferrara
Optical imaging of whole, living animals has proven to be a powerful tool in multiple areas of preclinical research and has allowed noninvasive monitoring of immune responses, tumor and pathogen growth, and treatment responses in longitudinal studies. However, fluorescence-based studies in animals are challenging because tissue absorbs and autofluoresces strongly in the visible light spectrum. These optical properties drive development and use of fluorescent labels that absorb and emit at longer wavelengths. Here, we present a far-red absorbing fluoromodule–based reporter/probe system and show that this system can be used for imaging in living mice. The probe we developed is a fluorogenic dye called SC1 that is dark in solution but highly fluorescent when bound to its cognate reporter, Mars1. The reporter/probe complex, or fluoromodule, produced peak emission near 730 nm. Mars1 was able to bind a variety of structurally similar probes that differ in color and membrane permeability. We demonstrated that a tool kit of multiple probes can be used to label extracellular and intracellular reporter–tagged receptor pools with 2 colors. Imaging studies may benefit from this far-red excited reporter/probe system, which features tight coupling between probe fluorescence and reporter binding and offers the option of using an expandable family of fluorogenic probes with a single reporter gene.
Ming Zhang, Subhasish K. Chakraborty, Padma Sampath, Juan J. Rojas, Weizhou Hou, Saumya Saurabh, Steve H. Thorne, Marcel P. Bruchez, Alan S. Waggoner
Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.
Melissa C. Hanson, Monica P. Crespo, Wuhbet Abraham, Kelly D. Moynihan, Gregory L. Szeto, Stephanie H. Chen, Mariane B. Melo, Stefanie Mueller, Darrell J. Irvine
Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator–like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the
Diana L. Bernstein, John E. Le Lay, Elena G. Ruano, Klaus H. Kaestner
Adoptive transfer of tumor-reactive T cells can successfully reduce tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported. A noninvasive method to track engineered cells with high sensitivity and resolution would allow observation of correct cell homing and/or identification of dangerous off-target locations in preclinical and clinical applications. Human deoxycytidine kinase triple mutant (hdCK3mut) is a nonimmunogenic PET reporter that was previously shown to be an effective tool to monitor whole-body hematopoiesis. Here, we engineered a construct in which hdCK3mut is coexpressed with the anti-melanoma T cell receptor F5, introduced this construct into human CD34 cells or PBMCs, and evaluated this approach in multiple immunotherapy models. Expression of hdCK3mut allowed engrafted cells to be visualized within recipient bone marrow, while accumulation of [18F]-L-FMAU in hdCK3mut-expressing T cells permitted detection of intratumoral homing. Animals that received T cells coexpressing hdCK3mut and the anti-melanoma T cell receptor had demonstrably higher signals in HLA-matched tumors compared with those in animals that received cells solely expressing hdCK3mut. Engineered T cells caused cytotoxicity in HLA/antigen-matched tumors and induced IFN-γ production and activation. Moreover, hdCK3mut permitted simultaneous monitoring of engraftment and tumor infiltration, without affecting T cell function. Our findings suggest that hdCK3mut reporter imaging can be applied in clinical immunotherapies for whole-body detection of engineered cell locations.
Melissa N. McCracken, Dimitrios N. Vatakis, Dhaval Dixit, Jami McLaughlin, Jerome A. Zack, Owen N. Witte
Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic
Joachim Albers, Claudia Danzer, Markus Rechsteiner, Holger Lehmann, Laura P. Brandt, Tomas Hejhal, Antonella Catalano, Philipp Busenhart, Ana Filipa Gonçalves, Simone Brandt, Peter K. Bode, Beata Bode-Lesniewska, Peter J. Wild, Ian J. Frew