The Historical Immersion Project (HIP) is a collection of mods for Crusader Kings II which are designed to be able to work together in any combination. As the name suggests, all of its modules share a common focus upon historical immersion, while also aiming to provide improved balance and new mechanics and flavor.
HIP is not currently available on Steam Workshop because of conflicts between the modular installer and the limitations of the Workshop system. However, the team do have a Steam group where players can get notifications of new releases and keep track of other HIP players.
EMF is the core overhaul mod in HIP. It is based on (but replaces) the now defunct Project Balance. EMF focuses on providing historically plausible, coherent new mechanics and flavor for your CK2 experience. It also improves upon, and occasionally fixes, certain aspects of the vanilla game experience.
SWMH is first and foremost a comprehensive map overhaul, we have gone to great lengths to bring alive the medieval world as contemporary accurately as possible. Secondly it includes substantial work on history and cultural related features. All this work has been conducted with a philosophy of keeping as close to the core features as possible, in order to maximize compatibility with other mods.
VIET (Vanilla Immersion events and traits) is a mod that offers tons of new flavor events that provide variety (and the occasional surprise) to your game play. This is mod is, however, not included with current versions of HIP anymore. Support and integration for the mod has been dropped after 2015 after the original creator temporarily left the CK2 modding community. However, the reboot Viet Events Reborn should be compatible with HIP even though it's not integrated.
LTM is a graphics overhaul mod for the SWMH map. The mod replaces and adds lots of map related materials, both to the terrain map and political maps, such as new textures, borders, rivers, shaders, trees, terrain, etc., with assets of higher quality, variety, accuracy, and discernibility. LTM for vanilla is a lite edition however, this means that it only replaces existing vanilla assets but does not add any additional content nor does it make any improvements to the vanilla map, that being said, LTM 'lite' still makes the vanilla map far more clear and pretty than what is originally.
The Alyssa is a very classy-looking hip bag - not a traditional style fanny pack - worn with a matching or purchased belt. Convert it to a crossbody/shoulder bag with a sophisticated chain strap, or change up the look for the evening to a clutch with a matching wristlet. The Alyssa Hip Bag will get you through the day with a mere change of the strap and without having to move things from one purse to the other for your different activities or wardrobe style.
Dress it up with a metal flap edge and magnetic snap, or go understated with a turn lock. Designed for leather, faux leather/vinyl, and cork with a cotton lining. If you choose to use quilting cotton or cotton canvas for the exterior, increase the amount of SF101 required. If using cotton, your bag will be slightly less structured. This bag is perfect for showing off that beautiful fabric you "just had to have."
How about a classy shoulder bag? The testers were thrilled with the new Karys pattern, claiming it was a quick make. And their creativity in fabric and hardware choices, along with their excellent skills, will inspire you to make one, too! Take a look at their makes along with all the details.
Thank you Patricia. ClearlyI can see so much effort goes into your patterns, you are meticulous and understand that the smaller detail is where it all counts. I truly appreciate the quality we receive. - Elena F. on Facebook - Read the full review
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Feature Papers represent the most advanced research with significant potential for high impact in the field. FeaturePapers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer reviewprior to publication.
The Feature Paper can be either an original research article, a substantial novel research study that often involvesseveral techniques or approaches, or a comprehensive review paper with concise and precise updates on the latestprogress in the field that systematically reviews the most exciting advances in scientific literature. This type ofpaper provides an outlook on future directions of research or possible applications.
Abstract:Osteoarthritis (OA) impacts millions of people and places a high burden on healthcare systems in the United States. Current treatment modalities have limitations and do not address underlying pathology. Lately, there has been an immense growth in the use of biologics, including perinatal allogenic tissues for orthopedic regenerative medicine applications. Amniotic tissue is an exciting new alternative for such applications. Despite several published studies that reported its use for treatment of ophthalmic conditions and complex wounds, there are limited clinical studies evaluating its safety and efficacy in treating patients suffering with knee or hip OA. In this manuscript, I focused on three prospective clinical studies which evaluated the safety and efficacy of amniotic tissue in patients suffering with moderate knee or hip OA. The results from these studies presented the scientific community with much needed, well-executed, and prospective clinical trials. Though these trials demonstrated that administration of amniotic tissue in knee or hip joint is safe and potentially effective, more multi-center, prospective, double-blinded, randomized controlled trials are warranted to further establish the efficacy of amniotic tissue to mitigate symptoms of knee and hip OA to ultimately justify its clinical use.Keywords: osteoarthritis; knee osteoarthritis; hip osteoarthritis; regenerative medicine; biologics; amniotic tissue; amniotic fluid; amniotic membrane; amniotic suspension; amniotic-fluid-derived stem cells
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Taking a deeper look into the BMP2-activated pathway, BMP2 activates the pathway by binding to two receptors: bone morphogenetic protein receptor type Ia (BMPRIa) and bone morphogenetic protein receptor type II (BMPRII). BMPRII then phosphorylates BMPRIa at three separate locations, and an interacting protein called casein kinase 2 (CK2) is released. CK2 signals to induce osteoblastogeneis, adipogenesis, osteoclastogenesis, and chondrogenesis . A mimetic peptide, CK2.3, binds to CK2, which blocks its interaction with BMPRIa at a specific phosphorylation site [22,23]. Stimulation of osteoblast and osteoblast precursor cells with CK2.3 was found to significantly increase mineralization, which is indicative of preliminary bone formation. Furthermore, CK2.3 increased osteoblast activity in extracted calvarial and extracted BMSCs. Injection of CK2.3 via tail veins of mice led to increased trabecular BMD. Mineralization apposition rate (MAR), another measure for bone formation, was also significantly higher in mice injected with CK2.3. .
Basal level mineralization was higher in primary cells extracted from POA than primary cells extracted from POP. A von Kossa assay was used to determine mineralization potential between cell populations with the two skeletal diseases. *** denotes p < 0.001.
Cells isolated from POP did not respond to BMP2 stimulation, while POA did. (A) Five female patients were analyzed. Cells from all patients responded significantly to BMP2 compared to unstimulated cells. (B) Five other female patients diagnosed with osteoporosis were analyzed, and their cells showed no mineralization response compared to unstimulated cells (p < 0.05). a = statistically significant from control.
Cells isolated from both POA and POP responded to CK2.3 stimulation. (A) Cells from five female POA were analyzed, and significantly responded to CK2.3 stimulation compared to unstimulated or control cells. (B) Cells extracted from five female POP were analyzed, and all patients significantly responded to CK2.3 treatment compared to the control. CK2.3 could be a potential therapeutic product for osteoporosis (p < 0.05). a = statistically significant from control.
BMP2 is approved by the FDA for fracture healing in osteoporotic patients. However, it has recently been shown that prolonged treatment with BMP2 decreases the BMD in osteoporotic patients. Here, we showed that the BMD of POP decreased significantly in correlation with their increasing age . In addition, the cells isolated from POP did not respond to BMP2 stimulation when assessed for mineralization potential. There is a variety of reasons as to why this could be occurring. For BMP2 to elicit its mineralization response, it must bind to its two dimerized receptors (a type Ia and a type II receptor). BMP2 will either bind preferentially to the type 1 receptor and recruit the constituently active type II receptor or it will bind to an already dimerized complex of receptors . Previously, Turgeman et. al. had shown that human BMP2 (hBMP2) restored osteogenic potential of osteoporotic stem cells and that hBMP2 adenoviral vector increased osteogenic potential in a senile osteoporotic mouse model .
There are several limitations to this study. While a number of POP and POA were X-rayed and their BMD was quantified, only a select few had a cell population harvested from them. Further studies need to be done in order to verify the difference in BMP2 response between POP and POA. In addition, the means of BMD quantification through SPA is relatively novel, and while it is cost-effective and efficient, it does not provide the same level of detail as a density X-ray absorptiometry (DXA) scan. Only osteoblast-specific markers were investigated in this study because osteoblast activity and matrix deposition were of interest. In the future, it would be crucial to also investigate osteoclast activity and regulation as there is extensive crosstalk between osteoblasts and osteoclasts. This could be done through immunofluorescently staining for tartrate-resistant acid phosphatase (TRAP), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), and metalloproteinases (MMPs). Only femoral heads from female patients were utilized because both osteoporosis and osteoarthritis affect the female population more than the male population. In the future, we would like to investigate the effect of both BMP2 and CK2.3 in the male population to determine if this effect is mirrored. 2b1af7f3a8