 Year’s Eve (early) Countdown. It was my first time in that area and at the Exploratorium. The celebration was great for kids – from games, small prizes, fresh popcorn, a balloon drop, the Little People, and a DJ, there were endless activities for them to enjoy. Charlie and Jack also loved the Exploratorium itself with its tunnels, climbing walls, water stations, toddler area, train sets and gigantic musical instruments. We’ll definitely be back here again!
Charlie LOVED the shapes light-up box. He had fun changing the patterns and getting the pieces to fit. He also enjoyed the train station a lot which is directly behind him in this picture.
These little fellas below are only five days apart. It’s so fun to watch them interact!
Check out my friend, Christine’s, take on the Skokie Exploratorium as well! This is a place I highly recommend if you have younger kiddos.
Aging of the skeleton is associated with increased prevalence of osteocyte apoptosis in mice and humans. Work leading to this application shows that the skeletal syndrome that ensues with aging is mimicked by osteocyte specific deletion of the gap junction protein connexin (Cx) 43. Mice lacking Cx43 in osteocytes exhibit increased osteocyte apoptosis and accumulation of empty lacunae, and reduced OPG levels, and Cx43- deficient osteocytes express lower levels of the survival-associated microRNA (miR) miR21. In addition, bones from old mice exhibit reduced Cx43, OPG, and miR21 expression. We showed in vitro that apoptotic osteocytes release high mobility group box protein1 (HMGB1), which reduces OPG expression and increases osteoclast recruitment and differentiation through activation of receptors for advanced glycation end products (RAGE). HMGB1 also activated toll-like receptor 4 (TLR4). However, whether activation of HMGB1 receptors RAGE or TLR4 has a role in the skeletal phenotype of Cx43-deficient or old mice is not known. The mechanism by which HMGB1 is released by apoptotic cells is not known. A potential mechanism could involve opening of Pannexin1 (Pax1) channels in cells undergoing apoptosis. Whether this mechanism operates in osteocytes undergoing apoptosis is not known. The long-term goal of our studies is to improve the management of the adverse skeletal effects of aging by targeting osteocyte apoptosis and resorption. The specific objective of this application is to define the signaling pathways involved in the elevated osteocyte apoptosis and bone resorption in aging. We propose that the bone fragility syndrome that ensues with aging is due to increased osteocyte apoptosis as a consequence of reduced expression of osteocytic Cx43, OPG, and miR21. We hypothesize that low OPG and the consequent increase in the RANKL/OPG ratio acts as a permissive event for osteoclast development; whereas low miR21 reduces anti-apoptotic kinase signaling and activates caspases, with the consequent Panx1 channel opening and HMGB1 release, directing osteoclasts to areas with accumulated apoptotic osteocytes. To test this hypothesis, we will pursue a combination of in vivo and in vitro studies that include the use of novel genetically modified mice, and established and primary osteocytic cells.
Aim 1 will examine the role of Cx43/miR21 on osteocyte apoptosis with aging.
Aim 2 will investigate the role of HMGB1 in osteoclast recruitment and differentiation in Cx43 deficiency and aging.
Aim 3 will explore the consequence of osteocytic Panx1 removal on HMGB1 release and osteoclast recruitment. Successful completion of these studies will provide the molecular basis for the in- creased osteocyte apoptosis in the absence of Cx43 and in old animals. In addition, these studies will establish the molecular link between dying osteocytes and targeted bone resorption. Moreover, they will offer the basis for treatments in which the effect of increased osteocyte apoptosis on osteoclast recruitment are counteracted by targeting the HMGB1-RAGE/TLR4 system.
Increased bone fragility with aging has been associated with accumulation of apoptotic osteocytes and empty lacunae in mice and humans. In this application, we propose to advance in our understanding of the molecular mechanisms by which osteocytes from old individuals are less susceptible to survival signals, thereby setting the stage for improved management of bone fragility with aging, a growing public health concern. These studies are relevant to the NIH mission because they will provide evidence for the effectiveness of pharmacological intervention to restrain targeted osteoclast recruitment, thus preserving bone micro- architecture and strength.Write a positive tweet. Possible types: OPTIONS:
- negative
- positive

A: @Danielle_Jane14 stay home &amp; we can chit chat haha 


input question: Write a random tweet?

A random tweet: @byronhill Do they take checks? 


IN: OPTIONS:
- negative
- positive
Write a tweet that is negative.

OUT: I eat rice with my kfc chicken.....WTF who doesn't! Feels fat....  but never will be. Going to work. Lol gunna sing with queenie all shift


Q: negative (OPTIONS:
- negative
- positive)
A: WTF is up wit TwitPic it's not letting me upload 


Q: Write a negative tweet.

A: Cleaning 


input question: Write a random tweet?

A random tweet:
@keza34 ooooo who's the phsyco?? And hi mom I'm ill  have fluEuropean Council President Charles Michel said EU leaders agreed to cooperate on energy after a long day of talks. However, a consensus was not reached on capping gas prices. A news item on the Deutsche Welle website presents latest developments.
European Council President Charles Michel said early Friday morning that European Union leaders “agreed to work on measures” that would combat rising energy prices.
The 27 leaders of EU nations had gathered at a two-day summit in Brussels aimed at overcoming differences between countries to combat the continent’s energy crisis.
The meeting dragged on into Friday morning as divisions between some countries could not be bridged. A consensus was not reached on capping the price of gas.
“We brought ourselves together,” German Chancellor Olaf Scholz said after the discussion.
“We have named precise parameters that energy ministers can use to work out the concrete details unanimously,” Scholz said, adding that EU leaders could meet again if energy ministers, who are due to meet in Luxembourg on Tuesday, cannot reach an agreement.
Hungary’s prime minister Viktor Orban said on Friday that the proposed price cap, if sealed, would not apply to long-term gas supply deals like the 15-year deal that Hungary has with Russia’s Gazprom.
This doesn't make sense to me. [Less than half](https://en.wikipedia.org/wiki/List_of_IndyCar_Series_drivers) of the IndyCar grid is American. Why can foreigners come to America and race but Americans can't go somewhere else? What about the likes of Tsunoda or any other Asian driver that competes in Europe? What about the drivers who couldn't succeed in F1 but now race in IndyCar?

The real reason we don't have an American driver is that there are not enough Americans who care about F1 for American companies to sponsor a team for $millions because it has an American driver. It's all about the money and marketability.Purchase: I first took this bit out on trial from Sandridge Saddlery. When I tried it out on my horse was comfortable with the bit so, I bought it and it cost me $200.00.
Likes: This bit provided comfort and acceptability for my horse. He was much more in-tuned to what I was asking him than in his regular snaffle. This bit does not pinch the corners of the mouth as other snaffles do so, no need for bit guards.
Dislikes: So far I have been extremely pleased knowing that my horse is happier with this mouthpiece. The only thing I don't like about the bit is the high cost and that is only comes in 16mm width, but it was worth it for me and my horse.
Quality: Eggbutt shape, double jointed snaffle with loose rings(rings are stainless steal). Mouthpiece is made with Aurigan,85% copper and are guaranteed nickel-free. High quality product that is durable and gentle for your horse.
Summary: A truly wonderful bit, highly recommended for any horse ridden in a snaffle. Extremely durable and well made. I will definitely only buy Herm Sprenger.Okyeame Kwame appeared on stage cladded in an all-white African apparel with a chain of Kente amidst contemporary choreographers who acted as Okyeame performed his classic song ‘’Sika’’.
Okyeame Kwame has once again proven why he is revered as Ghana’s most ‘’versatile’’ musician when he put up an outstanding performance to entertain the audience at the launch of the Preparation of a Long Term National Development Plan for Ghana at the Conference Centre, Accra.
The programme which was organized by the National Development Planning Committee saw in attendance the President, John Dramani Mahama, Former Presidents, John Agyekum Kufour and Jerry John Rawlings, past and present Ministers, Chiefs and other respected state men and women.
Okyeame Kwame appeared on stage cladded in an all-white African apparel with a chain of Kente amidst contemporary choreographers who acted as Okyeame performed his classic song ‘’Sika’’. The characters included Pastors