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Marina Pinto Kaufman is a member of the Human Rights Watch Americas Advisory Committee, Human Rights Watch Middle East Advisory Committee, and the Human Rights Watch Women's Rights Advisory Committee. She "is one of the founders of the Human Rights Watch film festival. She has also served on the Board of B'nai Jeshurun since 1997." [1] She is also the chair of Storahtelling, an organization that "promotes Jewish cultural literacy through original theatrical performances and educational programs for multi-generational audiences." [2]
External links
- "Biography", Accessed December 2006.


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Listen free for 30 days
After Divorce
After Divorce, What to Do, What Not to Do is for men and women transitioning from separation and divorce into a new life. There are countless books that claim they can walk you through the divorce process step-by-step, from beginning to end. Everything from custody battles to division of property is discussed in these books, but few offer advice for the emotional side of divorce. And for those of you that believe the psychology of divorce should be left to the psychologists. Does this theory still hold true if said psychologists have never been through a divorce?
Michael Eads is not an attorney or psychologist. He's just an ordinary guy who went through separation and divorce and made all the mistakes ordinary people make. This book is for recently divorced people in that scary, dark space after separation and divorce. It is for those people who have reached a crossroads and are wondering which way to turn. Think of Michael Eads as a friend who understands and empathizes as to not only what you're going through, but how you feel. So take a deep breath right now knowing that somehow you will get through this, and that you will be okay.
What listeners say about After Divorce
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- Amazon Customer
- 20-02-17
Not very useful
I found this book to state the obvious in most areas and not be particularly helpful. I found the views to be somewhat outdated. Given that the author is an older gentleman perhaps this goes some way to explain this.
To summarise, after divorce, get a hobby, wait ages before having another relationship, avoid social media and internet dating and forgive your ex.. There- just saved the time reading/listening to this!


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text: A Friend's Homecoming My friend and I have been catching up on social media about his homecoming to the Philippines after 3 years here in Kuwait. He first came in May 2011, after a year his wife was granted family visa. Their baby… December 16, 2014 · by Author · 5


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As expected LG has unveiled the LG G Flex 2 in press conference held at the CES, Las Vegas. Equipped with a 5.5-inch touchscreen that has a 23 degree arc, the device will initially launch in Korea later this month with other countries following suit.
The new curved phablet now features a display size of 5.5-inches, with resolution also bumped to Full HD, resulting in a pixel density of 403 ppi. The display is protected by LG's in-house DuraGuard glass technology.
It will be powered by octa-core 64-bit Qualcomm Snapdragon 810 processor clocked at 2 GHz, backed by the Adreno 430 GPU, and 2 GB of RAM.
The handset sports a a 13 MP rear shooter with OIS+, a dual LED flash, and the laser auto focus system.The G Flex 2 also comes with the option of expandable memory on top of the 16 GB of 32 GB already available, by up to 128GB.


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Herb Garfinkel in Newport News, VA can. State Farm: Ray Garfinkel in Richmond, Virginia, VA – State Farm: Ray Garfinkel Address: 3311 West Broad Street Suite 201, Richmond, VA 23230, united states phone: +1 804-288-5470. Sign In Register.. and his involvement in the community through the different tools of Ray's website. All of the.
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A lawsuit filed in 2007 led to Circuit Court Judge David Rains' ruling in 2009 repealing the state law that authorized the tax on wages for most people working in Jefferson County and a related.
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Ray Garfinkel State Farm Insurance. 3311 West Broad Street Suite 201 – Richmond, Virginia 23230 . Nick Anderson – State Farm Insurance.. 3407 W Broad St – Richmond, Virginia 23230 (804) 353-2406 .


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300LEDs/M SMD2216 Hign Lumen LED Strip Lights
Model: SYS-2216-300LN
brief: CRI >90 Great for creating a bright and soft light fixture, can be used widely
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As Christmas approaches, why not get into the festive spirit by decorating your home and conservatory. Here are a few inspirational ideas that can come in handy, so turn on your Christmas playlist and let's get started.
Frosty the Snowman
In this month's issue of Country Living Magazine, they share their idea of what it means to "Dream of a White Christmas". Imagine bringing frosty white snow, icy blue lakes and beautiful winter nights into your conservatory. Below we've shared a few accent pieces, accessories and Christmas decorations to make your home breathtakingly beautiful, whilst you enjoy a warming mug of hot chocolate.
The fire is so delightful
Warm up your home with this copper opulence look by Cox & Cox. To lift a neutral colour scheme, warm copper tones are perfect, contemporary and on trend. Why not introduce it into your conservatory to create a classic and bold appearance, mix it with a pop of gold to highlight and you have modern theme for hosting guests and celebrating this joyous occasion.
I'm dreaming of a white Christmas
Everyone loves a classic at Christmas, whether it's your favourite festive song or movie, with the same traditional Christmas decorations that get unboxed year after year, you can't go wrong. At Marston & Langinger, we adore a fluffy Christmas tree with the traditional bold colours: berry red, eucalyptus green and copper that was done by the Ideal Show Homes. They assembled a room set that emphasized a stunning yet timeless space with decorations that compliment each other, creating a family and heartwarming atmosphere that no one can refuse. We love these details below, they accentuate the most traditional elements.
All details and photos credited to Cox & Cox, we just love their luxurious decorations and beautiful festive themes.


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- Publication date
- 18th December 2014
- Closing date
- 19th February 2015
- Policy areas
- Electricity - wholesale markets
- Enforcement
- Gas - wholesale markets
- Status
- Closed (with decision)
We are consulting on proposed changes to two documents that describe how we monitor, investigate and enforce the requirements in "REMIT" - the EU regulation on wholesale energy market integrity and transparency. Our proposals will affect companies and individuals who are connected to or involved in wholesale energy markets. We want your views on some changes to:
1. the REMIT Procedural Guidelines. These explain how we take action under our REMIT powers, and
2. the REMIT Penalties Statement. This explains when and how we would impose a penalty if a company or individual breached REMIT.
The changes we are proposing came from:
• changes to our wider enforcement policies and procedures
• looking at the approach to regulation in financial markets
• what we have learnt through using our REMIT monitoring and enforcement powers, and
• the need to encompass imminent new powers that will allow us to take action if REMIT market participants fail to register or submit REMIT data.
The REMIT Enforcement Regulations requires us to consult on our proposed changes. Please send us your views by 19 February 2015. We would like to issue an updated REMIT Procedural Guidelines and REMIT Penalties Statement in summer 2015.
Consultation document
Subsidiary documents
Response documents


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Peek into the past at the Ximenez-Fatio House in St. Augustine! This unique site is part-museum, part-historic site, and part-archaeological dig. Experience it all when you visit and learn about this home's vast history, starting in the late 18-century and continuing to today. Best of all, this site is just an eight-minute walk from Agustin Inn. Find out why this home has been rated as one of the top attractions in St. Augustine year and year!
There's plenty to explore in the historic district of St. Augustine, from the Ximenez-Fatio House to the Oldest Store Museum. Discover it all within our free online Vacation Guide! We've listed our favorite museums and historic sites in town. Our online Vacation Guide is accessible from any device with an internet connection, so you'll rarely be without it. Ditch the bulky travel books and stop scouring the web. Get recommendations from a source you can trust. Access our free Vacation Guide today!
About the Ximenez-Fatio House
The Ximenez-Fatio House was built in 1798 by Andres Ximenez, a merchant who used the building as a storefront as well as his home. Though the house has served many purposes through the year, it's most famous for being one of the most popular boarding houses in town. During its years as a boarding house, it was known as "Miss Fatio's," after Louisa Fatio who purchased the home in 1855. She was the last of three successful women owning and operating a boarding house during the mid-19th century.
Today, the house is known as one of the best-preserved and most authentic representations of St. Augustine in the late-18th and 19th century. Visitors to the home can tour the many rooms, hearing the stories of travelers to the area and their experiences in the Nation's Oldest City.
Visit the Ximenez-Fatio House
The Ximenez-Fatio House is open from Tuesday to Saturday from 11:00 a.m. to 4:00 p.m. Tours are held every 30 minutes, starting at 11:00 a.m. Admission to the museum is $10 for adults and $8 for seniors, students, or anyone with a military discount. Families can get into the museum for $20.
Stay at Agustin Inn
After you've toured the fascinating rooms of the Ximenez-Fatio House, return to the beautiful Agustin Inn for a night of rest and relaxation. Our cozy bed and breakfast is located in the center of downtown St. Augustine, just a short walk from the best attractions in the city. We have a wonderful selection of guest rooms, each accompanied by an exquisitely comfortable bed covered by our 100% cotton sheets. For convenience, towels, aromatic lemon verbena soap and shampoo, and free Wi-Fi are available in each of our rooms.
Check our availability and book today! We look forward to having you.
Are you looking for more articles about various sites in St. Augustine? Browse through our many blogs! We've written about iconic attractions in town, like the Spanish Military Hospital Museum and the Villa Zorayda Museum.


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Are you looking for a fitness class class to attend? Join your local boot camp fitness program in California!
Fitness boot camps in California offer the best workout to transform your body. California boot camp workouts give you a fun exercise program and help you lose weight fast. Our fitness camps in California are offered indoors and outdoors. Our world class fitness instructors will give you an exciting workout that will sculpt your body and give you the flat stomach and firm body you've always wanted. If your goal is weight loss, the California Adventure Boot Camp will guarantee your results. Simply follow our complete body makeover plan and the results just appear! Maybe you want to look good in a bikini. Maybe your goal is to gain self confidence. Or it may be as simple as wanting to feel great and get a fit body! Regardless, California fitness boot camp class is how you reach your personal goals. Log on to our official site to get information on boot camp costs, various price options and schedules.
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If you are interested in starting a California fitness boot camp business, we can show you a step-by-step blueprint about operating a fitness boot camp business. You can run an Adventure Boot Camp business or the new IMPACT fitness boot camp business. Certain restrictions apply!


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Cloudflare has 23 datacenters base from wikipedia April 2013 one of the famous band Metallica.com is powered by cloudflare. The intelligences of your website increase as you partner with cloudflare specially if you update your account into pro because the SSL is included with plenty of great benefits. But if you are new in using cloudflare basic services can give you great benefits in your website. Sometimes their a down time problem in the services so better to pause the cloudflare instead of deleting the services.
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ADAM9 is a membrane-anchored metalloprotease that is markedly up-regulated in several human carcinomas. Here, we show that ADAM9 is similarly up-regulated in mouse models for prostate, breast, and intestinal carcinoma. To assess whether ADAM9 is critical for the pathogenesis of prostate carcinoma, one of the most common cancers in men, we evaluated how loss of ADAM9 affects tumorigenesis in W10 mice, a mouse model for this disease. In the absence of ADAM9, most tumors in 50-week-old W10 mice were well differentiated, whereas littermate controls expressing wild-type ADAM9 had predominantly poorly differentiated, and in some cases significantly larger, tumors. Moreover, gain-of-function experiments in which ADAM9 was overexpressed in mouse prostate epithelium resulted in significant abnormalities, including epithelial hyperplasia at 4 to 6 months of age, and prostatic intraepithelial neoplasia after 1 year. A potential underlying mechanism for the role of ADAM9 in prostate cancer emerged from cell-based assays: ADAM9 can cleave and release epidermal growth factor and FGFR2iiib from cells, both of which have pivotal functions in the pathogenesis of this disease. Taken together, these results suggest that ADAM9 contributes to the pathogenesis of prostate cancer and potentially also other carcinomas, raising the possibility that ADAM9 might be a good target for antitumor drugs.
- Metalloprotease-disintegrin
- Prostate cancer
Cell-to-cell communication is vital for development and adult tissue homeostasis. However, dysregulated or inappropriate cell-to-cell communication can contribute to the pathogenesis of diseases such as cancer. Several key components of the cell-to-cell signaling machinery, including all ligands of the epidermal growth factor receptor (EGFR) as well as other growth factors, cytokines, and their receptors, are synthesized as membrane-anchored proteins whose function can be modulated by proteolytic cleavage and release from the cell ( 1). The enzymes that are responsible for this process, which is called protein ectodomain shedding, are frequently members of the ADAM (a disintegrin and metalloprotease) family of membrane-anchored metalloproteases ( 1, 2). Protein ectodomain shedding functions as a molecular signaling switch that can activate or inactivate the released substrate protein and has emerged as a particularly important regulator of the function of EGFR ligands ( 1).
The ability of ADAMs to affect the function of growth factors and receptors raises questions about whether dysregulation of ADAMs might contribute to tumorigenesis. Recently, overexpression of ADAM9 has been reported in several human carcinomas, including breast ( 3), liver ( 4, 5), pancreas ( 6), and gastric cancer ( 7). The goal of this study was to address whether ADAM9 might play a causative role in tumor development. In situ mRNA analysis showed that ADAM9 is highly expressed in epithelial cells of mouse models for prostate, breast, and gastrointestinal carcinoma. More detailed analysis of prostate tumors revealed high levels of ADAM9 mRNA in well-differentiated carcinomas, but only low or undetectable levels in poorly differentiated carcinomas. This prompted an evaluation of how loss of ADAM9 function affects tumorigenesis in the W10 mouse model for prostate cancer ( 8), and how gain of function through transgenic overexpression of ADAM9 affects epithelial cells in the mouse prostate. The loss-of-function experiments suggest that ADAM9 is critical for tumor progression past the well-differentiated state, whereas gain-of-function experiments provided additional evidence for a causal role of ADAM9 in tumorigenesis. In cell-based assays, ADAM9 cleaves and releases membrane proteins with known roles in prostate epithelial proliferation and transformation, FGFR2iiib and EGF, establishing potential mechanisms for its role in carcinogenesis.
Materials and Methods
Materials. PCR reagents were from Promega (Madison, WI), restriction enzymes from NEB (Beverly, MA), goat anti-mouse ADAM9 ectodomain antibodies from R&D Systems (Minneapolis, MN), and rabbit antisynaptophysin antibodies from Zymed Laboratories (San Francisco, CA).
In situ hybridization. Tumor sections from three mouse carcinoma models were used for ADAM9 expression analysis by mRNA in situ hybridization as previously described ( 9, 10). In the prostate cancer model (called W10 hereafter), the SV40 large T antigen is expressed in glandular epithelial cells of the prostate under control of the probasin promoter ( 8). In the breast cancer model, expression of the polyoma virus middle T antigen in mammary epithelium is driven by the murine mammary tumor virus promoter (MMTV-PyMT; ref. 11), and in the intestinal cancer model a germ line mutation in the adenomatosis polyposis coli gene (Apc) leads to multiple intestinal neoplasias (Min; ref. 12).
PB-ADAM9 transgenic mice. The complete mouse ADAM9 cDNA coding sequence (bp 14-2,551; ref. 10) was amplified by PCR with primers that introduced a 5′ EcoRV site and a 3′ NotI site, inserted into the SK-PB plasmid, which contains a rat probasin (PB) minimal promoter (kindly provided by Dr. N.M. Greenberg, Baylor College of Medicine, Houston, TX) and sequenced to rule out mutations. Transgenic mice were generated by pronuclear microinjection of QiaexII (Qiagen, Valencia, CA) purified PB-ADAM9 cDNA into fertilized C57BL/6J × CBA-f2 eggs. Founder animals were identified by PCR on genomic DNA from tail biopsies with ADAM9 primers that only amplify transgenic ADAM9 cDNA, but not genomic DNA (forward primer, bp 734-757: 5′-CGCTTAGCAAACTACCTGGATAGC-3′; reverse primer, bp 1,489-1,513: 5′-CTGGCAATCTTTACAACAGTCGCC-3′). All histopathologic comparisons were between pairs of heterozygous transgenics and nontransgenic littermate controls. All animal experiments were approved by the Institutional Animal Care and Use Committees of the Memorial Sloan-Kettering Cancer Center and the Hospital for Special Surgery.
Generation of W10/Adam9−/− mice. Transgenic W10 females ( 8) were crossed with Adam9−/− males (mixed SV129-C57BL/6 background) to generate F1 W10/Adam9+/− mice and nontransgenic Adam9+/− littermates. For tumor studies, W10/Adam9+/− mice were bred with Adam9+/− mice to obtain the following genotypes: W10/Adam9+/+, W10/Adam9+/− and W10/Adam9−/−. All offsprings were genotyped by PCR on genomic DNA to detect the W10 transgene as described ( 8), and by Southern blot to detect the targeted ADAM9 allele ( 13). Male littermates containing the W10 transgene that were either Adam9+/+, Adam9+/−, Adam9−/− were saved and analyzed at 50 weeks of age.
Histopathologic analysis and immunostaining. Transgenic PB-ADAM9 mice and littermate controls from three different lines were sacrificed at 4, 6, and 12 months of age, and W10/Adam9+/+, W10/Adam9+/−, and W10/Adam9−/− were sacrificed at 50 weeks of age. The urogenital tract was removed en bloc and fat and connective tissue were trimmed off. Individual prostate lobes were isolated and fixed overnight with 4% paraformaldehyde for histologic analysis. A portion of the urogenital tracts of 4-month-old PB-ADAM9 mice were embedded in OCT Tissue-Tex (Sakura Miles, Elkhart, IN), frozen, cryosectioned, and subjected to immunofluorescent staining for ADAM9. Antisynaptophysin immunostaining was done on paraformaldehyde-fixed sections using the Vectastain ABC kit (Vector Laboratories, Burlingame, CA).
Cell-based protein ectodomain shedding assays. Expression plasmids for alkaline phosphatase–tagged EGFR ligands and the ectodomain shedding assay have been described previously ( 14, 15). The FGFR2iiib cDNA was amplified by PCR using full-length human FGFR2iiib cDNA as template (kindly provided by D.M. Ornitz, Washington University, St. Louis, MO) and ligated into the pAPtag5 expression plasmid (Genehunter, Nashville, TN). The AP-FGFR2iiib deletion mutant (A363-Y376) was generated by overlapping PCR. All expression constructs were sequenced to rule out undesired mutations. Expression constructs for ADAM9 and the catalytically inactive E>A mutant were described previously ( 10, 16).
Up-regulation of ADAM9 in mouse models for prostate, breast, and intestinal cancer. To examine whether ADAM9 is up-regulated in mouse tumor models, we determined its expression by mRNA in situ hybridization at different stages of the W10 mouse model for prostate cancer, in which the SV40 large T antigen is expressed in prostate epithelium under control of the probasin promoter ( 8). Several histologically well defined states of prostate cancer are observed in mouse models for prostate cancer, including high-grade prostatic intraepithelial neoplasia, well, moderately, and poorly differentiated carcinoma ( 17). Whereas ADAM9 was only weakly expressed in prostates from wild-type (WT) mice ( Fig. 1A-C ) or in W10 mice with prostatic intraepithelial neoplasia (data not shown), we observed high expression of ADAM9 in epithelial cells of well-differentiated tumors ( Fig. 1D-F), characterized by densely packed, well-formed glands. This pronounced expression of ADAM9 was no longer seen at more advanced states of prostate cancer, such as in poorly differentiated tumors ( Fig. 1G-I) or in metastatic carcinoma ( Fig. 1J-L). The expression pattern of mouse ADAM9 at different states of the W10 prostate cancer model is consistent with a gene chip analysis of ADAM9 expression at different states of human prostate cancer, which revealed a significantly increased expression of ADAM9 in nontreated primary prostate tumors compared with nonneoplastic prostate, whereas no significant increase was seen in metastatic prostate cancer compared with nonneoplastic prostate. 5
When we examined ADAM9 expression in a second mouse carcinoma model—breast tumors from 4-month-old MMTV-PyMT mice—we found very high ADAM9 expression in tumor cells (an acinus distended by tumor cells is shown in Fig. 1M-O), whereas little expression of ADAM9 was evident in the surrounding mammary tissue, or in high grade, poorly differentiated sections of solid tumors (data not shown). ADAM9 is expressed in a region that is similar to one that was previously described as early carcinoma resembling human ductal carcinoma in situ with early invasion in tumor sections from MMTV-PyMT mice ( 18). In a third mouse carcinoma model—intestinal tumors from Apc/Min/+ mice—ADAM9 was highly expressed in adenomas with strong epithelial proliferation, whereas little ADAM9 was expressed in adjacent apparently normal villi ( Fig. 1P-R). Thus, ADAM9 expression was strongly up-regulated in epithelial cells of three different mouse carcinoma models.
More well-differentiated tumors are seen in W10 mice lacking ADAM9 compared with W10 littermate controls. To determine whether loss of ADAM9 affects development of prostate cancer or its progression, we crossed Adam9−/− mice with W10 mice, a model for prostate cancer ( 8). Through appropriate matings, we generated W10 mice lacking ADAM9 as well as littermate controls carrying one or both WT alleles of ADAM9 (see Materials and Methods). At 50 weeks of age, prostates of all mice were harvested and weighed in a double-blinded manner. We found that 5 of 22 W10 mice with one or both WT alleles of ADAM9 (W10/Adam9+/+ or W10/Adam9+/−) had tumors weighing >200 mg at 50 weeks, whereas all tumors in the 18 W10/Adam9−/− mice analyzed weighed <200 mg (P < 0.05, t test; Fig. 2A ).
To determine whether ADAM9, which is highly expressed at the well-differentiated carcinoma state, might affect the progression of prostate cancer to poorly differentiated carcinoma, we did a double-blinded analysis of the tumor histology of representative sections of tumors from 50-week-old W10/Adam9−/−, W10/Adam9−/+, and W10/Adam9+/+ mice. The lesions were classified as well-differentiated carcinoma when gland formations lined with epithelial cells were present throughout the tumor sections, as moderately differentiated carcinoma when focal to extensive areas of solid cell nests and fused glands were mixed with well formed glands, and as poorly differentiated carcinoma when large areas of the tumor were composed of more solid sheets or nests, with rare gland formation ( Fig. 2B, top, shows examples of each tumor state). This analysis revealed that 58% of tumors from W10/Adam9−/− mice contained only well-differentiated carcinoma, 42% of tumors contained some moderately differentiated carcinoma, whereas none had areas of poorly differentiated carcinoma (n = 12; Fig. 2B, bottom). On the other hand, 50% of tumors in littermate controls (W10/Adam9+/+ or W10/Adam9+/− mice) contained poorly differentiated carcinoma, 33% contained moderately differentiated carcinoma whereas 17% contained only well-differentiated carcinoma (n = 12; Fig. 2B, bottom). Thus, there was significantly more well-differentiated carcinoma and less poorly differentiated carcinoma in W10 mice in the absence of ADAM9, compared with controls with one or both copies of WT ADAM9.
Transgenic overexpression of ADAM9 in mouse prostate results in abnormal acinar epithelium and high-grade prostatic intraepithelial neoplasia. The high expression of ADAM9 in epithelial cells of three mouse carcinoma models coupled with the results of the loss-of-function studies prompted us to assess how transgenic overexpression of ADAM9 affects prostate epithelial cells. For this purpose, we generated three independent mouse lines that overexpress ADAM9 under control of the minimal probasin promoter (PB-ADAM9). PCR and Western blot analysis confirmed that overexpression of ADAM9 was restricted to the dorsolateral prostate lobes in all three lines (data not shown). Urogenital tracts from 4-, 6-, and 12-month-old male PB-ADAM9 mice and nontransgenic littermates were collected for further analysis. In 4- and 6-month-old PB-ADAM9 mice, histopathologic analysis of dorsolateral prostate lobes uncovered disorganized prostate ducts with areas that seemed to lack a proper epithelial lining and lumens filled with rounded cells ( Fig. 3A ). These abnormalities were not seen in any sections of prostate glands of WT littermates ( Fig. 3D). Immunofluorescent analysis of adjacent cryosections stained with anti-ADAM9 antibodies confirmed high ADAM9 expression in transgenic glands and in cells filling the lumen of these glands ( Fig. 3B).
Prostate ducts with a similar appearance as those seen in 4- and 6-month-old PB-ADAM9 mice (disorganized epithelia, lumen filled with cells) have also been described in transgenic mice overexpressing a dominant-negative form of the FGFR2iiib under the probasin promoter ( 19). In prostates from these animals, increased expression of the neuroendocrine marker synaptophysin was observed in the smooth muscle area adjacent to the basement membrane. When prostates from 4-month-old PB-ADAM9 mice and WT littermate controls were stained with antibodies against synaptophysin, we observed a clear increase of stained cells within the smooth muscle areas adjacent to the basement membrane in PB-ADAM9 mice compared with nontransgenic littermates (compare Fig. 3C and F).
When we inspected prostates of 12-month-old PB-ADAM9 mice, we observed considerable epithelial cell hyperplasia with stratification of the nuclei ( Fig. 3G and H), whereas prostates from nontransgenic littermates did not have any evident abnormalities ( Fig. 3I and J). In some sections of PB-ADAM9 prostates, more severe abnormalities could be seen, including extensive layering of the acinar epithelial cells, cells with increased nuclear to cytoplasmic ratio, variability in nuclear shape, condensed chromatin, prominent nucleoli, and appearance of mitotic figures. These abnormalities are consistent with the changes associated with prostatic intraepithelial neoplasia, considered to be a precursor of invasive prostate carcinoma in humans.
ADAM9 cleaves FGFR2iiib and epidermal growth factor in cell-based assays. The similarities between the histopathologic changes seen in 4-month-old PB-ADAM9 animals ( Fig. 3A-C) and in mice expressing a dominant-negative FGFR2iiib under control of the probasin promotor ( 19) raised the question whether overexpressed ADAM9 could cleave and potentially down-regulate FGFR2iiib. If this were the case, ADAM9 might affect signaling via FGFR2iiib in a similar manner as overexpression of a dominant-negative receptor. To address this possibility, we cotransfected WT ADAM9 or a catalytically inactive E>A mutant together with FGFR2iiib in Cos-7 cells. Overexpression of ADAM9 resulted in a strong increase in ectodomain shedding of FGFR2iiib into the supernatant, whereas overexpression of the inactive ADAM9E>A control did not ( Fig. 4B ). ADAM9-dependent shedding of FGFR2iiib was only weakly enhanced by phorbol 12-myristate 13-acetate (PMA), a phorbol ester that is commonly used to stimulate ectodomain shedding. No shedding was observed when a mutant FGFR2iiib lacking 14 membrane-proximal amino acid residues (del 363-376aa) was cotransfected with ADAM9 WT, strongly suggesting that FGFR2iiib is cleaved in its juxtamembrane region ( Fig. 4B).
The EGFR signaling pathway has also been implicated in the pathogenesis of prostate cancer ( 20– 22), and proteolytic processing of EGFR ligands is important for regulating the function of these growth factors ( 1, 23– 25). Because ADAMs participate in the shedding of six of seven EGFR ligands ( 15), we tested whether overexpression of ADAM9 triggers the release of one or more of these proteins. When ADAM9 WT was overexpressed in Cos-7 cells together with different EGFR ligands, we observed a significant increase in the release of EGF, but not of HB-EGF, transforming growth factor-α (TGF-α), betacellulin, amphiregulin, or epiregulin ( Fig. 4C). ADAM9-dependent shedding of EGF was only weakly enhanced by treatment with PMA, and was not seen in the presence of the overexpressed catalytically inactive ADAM9E>A mutant ( Fig. 4C). The apparent mass of soluble EGF released by ADAM9 differed from that of endogenously released EGF, indicating that ADAM9 has a different cleavage site than the endogenous EGF sheddase (most likely ADAM10; ref. 15).
Membrane-anchored peptidases can function as critical regulators of cell-to-cell signaling. This study was initiated because the membrane anchored metalloprotease-disintegrin ADAM9 is highly expressed in several human carcinomas ( 3– 6). We found that ADAM9 is also prominently expressed in epithelial cells undergoing neoplastic changes in mouse models for prostate, breast, and intestinal cancer. In addition, the more detailed analysis of different tumor states in the W10 mouse model for prostate cancer uncovered highest expression of ADAM9 in well-differentiated tumors of the prostate. The observed up-regulation of ADAM9, a cell surface peptidase with a potential role in cell-to-cell signaling, raised questions about whether the enhanced expression is merely correlative, or whether it might also have a causative role in tumorigenesis. To address this, we did loss-of-function experiments with W10 mice crossed with mice lacking ADAM9, and gain-of-function experiments by transgenic overexpression of ADAM9 under the prostate specific probasin promoter (PB-ADAM9 mice).
The loss-of-function experiments revealed a critical function of ADAM9 in prostate cancer growth and progression in W10 mice. Remarkably, most of the tumors in W10/Adam9−/− mice were well-differentiated carcinomas, whereas most of the tumors in littermates with one or both copies of WT ADAM9 contained significant areas of poorly differentiated carcinoma. Moreover, 5 of 22 W10 mice with WT ADAM9 had large or very large tumors. No poorly differentiated or very large tumors were seen in W10 mice lacking ADAM9. These results suggest that prostate tumor initiation or progression is delayed in W10/Adam9−/− mice, or that tumor progression is possibly even arrested at the well-differentiated tumor state, which is the state where ADAM9 shows the highest expression in the W10 tumor model. These findings raise the possibility that ADAM9 has a critical role in the transition to more poorly differentiated carcinomas.
Gain-of-function experiments provided additional evidence for a causal role of ADAM9 in tumorigenesis. We found that PB-ADAM9 mice at different ages had significant abnormalities compared with age matched littermate controls. Specifically, at 4 and 6 months of age, transgenic animals of three different lines invariably displayed areas of structurally abnormal and disorganized acinar ducts that were filled with round epithelial cells, with a concomitant increase of synaptophysin-positive cells in the adjacent smooth muscle surrounding the ducts. After 1 year, the dorsolateral prostate lobes of mice from all three lines displayed high-grade prostatic intraepithelial neoplasia lesions, with crowded epithelial cells showing nuclear and nucleolar enlargement.
Taken together, the gain- and loss-of-function studies provide independent lines of evidence for a role of ADAM9 in carcinogenesis. Whereas the loss-of-function studies establish a critical role for ADAM9 in an in vivo tumor model, the gain-of-function experiments show that overexpression of ADAM9 alone is sufficient to trigger preneoplastic changes, including high-grade prostatic intraepithelial neoplasia. Further studies will be necessary to determine whether transgenic overexpression of ADAM9 at the well-differentiated carcinoma state in W10 mice accelerates tumor growth and progression. Nevertheless, it is tempting to speculate that ADAM9, which is highly expressed at the well-differentiated carcinoma state in W10 mice (see Fig. 1D-F), might contribute to cell proliferation and promote neoplastic changes in W10 mice in a similar manner as when it is overexpressed in normal prostate epithelia in PB-ADAM9 mice.
The early lesions observed in PB-ADAM9 mice share striking similarities with the disorganized prostatic ducts in mice expressing a dominant-negative FGFR2iiib in the prostate to disrupt FGF-7 signaling ( 19). Because changes in the FGF signaling pathway are believed to be critical for the development of prostate cancer ( 26), we tested whether ADAM9 can cleave FGFR2iiib in cell-based assays. We found that overexpressed ADAM9 enhances shedding of FGFR2iiib from cells, which is consistent with a model in which ADAM9 overexpressed in prostate epithelium could release and thus down-regulate FGFR2iiib. In addition, the soluble ectodomain of FGFR2iiib has been reported to function in a dominant-negative fashion and disrupt FGF signaling in vivo ( 27). In PB-ADAM9 transgenics, cleavage of FGFR2iiib by ADAM9 could, therefore, conceivably contribute to the early changes seen at 4 and 6 months by disrupting FGFR2iiib signaling. This notion is also supported by the observed up-regulation of the neuroendocrine marker synaptophysin in PB-ADAM9 mice, which was also seen in transgenic mice expressing the dominant-negative FGFR2iiib.
With respect to the possible role of the FGFR2iiib at later states of tumorigenesis, it is noteworthy that this receptor is frequently down-regulated during progression of human prostate cancer and animal tumor models to malignancy, such as in the TRAMP model ( 28). This down-regulation of FGFR2iiib is considered a feature of malignant stroma-independent epithelial cells ( 29, 30). On the other hand, transfection of WT FGFR2iiib into malignant prostate cancer cells is sufficient to inhibit growth and promote differentiation ( 31, 32). In the context of the loss-of-function experiments in W10 mice, it is tempting to speculate that less FGFR2iiib might be shed from Adam9−/− epithelial cells than from Adam9+/+ cells. Less FGFR2iiib shedding in Adam9−/− cells could conceivably lead to an accumulation of FGFRiiib, providing one possible explanation for the higher percentage of well-differentiated carcinomas in 50-week-old W10/Adam9−/− compared with littermate W10/Adam9+/+ controls.
Whereas the changes observed in 4- and 6-month-old transgenic PB-ADAM9 mice resemble those seen in animals expressing a dominant-negative FGFR2iiib, the development of prostatic intraepithelial neoplasia in 1-year-old transgenic PB-ADAM9 mice suggests that additional mechanisms might be affected by overexpression of ADAM9 in prostate epithelium ( 33). Because ADAMs have also been implicated as regulators of EGFR ligands, we asked whether ADAM9 can shed various EGFR ligands. We found that overexpression of ADAM9 leads to a clear enhancement of EGF shedding, but not of any of the other EGFR ligands tested here, including HB-EGF, which was previously reported as a substrate for ADAM9 ( 34). Whereas the reason for this discrepancy remains to be determined, the unequivocal ability of ADAM9 to cleave EGF has potential implications for its role in prostate cancer. EGF is present in large amounts in human prostatic fluid ( 35), is up-regulated in benign prostatic hyperplasia and tumors ( 36), has been implicated in the proliferation of epithelial and stromal prostate cells ( 37), and is expressed in epithelial cells in the TRAMP mouse model for prostate cancer ( 38), which is similar to the W10 model. Moreover, chronic systemic treatment with EGF induces prostate growth in young rats ( 39), and EGF has a role in androgen-independent transactivation of the androgen receptor, which in turn is thought to contribute to androgen-independent tumor growth ( 40, 41). Because ADAM9 can shed EGF in cell-based assays, we hypothesize that it might also increase EGF release and, thus, EGFR activation when it is overexpressed in prostate epithelial cells. In theory, the combination of EGFR activation and inactivation of FGFR2iiib could both promote epithelial cell proliferation, which in turn might raise the likelihood of acquiring additional deleterious mutations in the transgenic PB-ADAM9 mice. Likewise, ADAM9-dependent release of EGF at the well-differentiated state of prostate cancer in W10 mice could also contribute to progression of prostate cancer in this model, although ADAM9 might also have other mechanisms of action.
Taken together, these results provide the first evidence for a causal role of ADAM9 in the pathogenesis of cancer. ADAM9 is up-regulated, directly or indirectly, in three different mouse tumor models, in several human carcinomas, and its expression is also known to be induced by the oncogene c-myc ( 42). ADAM9 deficiency delays or prevents prostate tumor progression to advanced states in a mouse prostate cancer model, and dysregulated expression of ADAM9 initially disrupts epithelial-stromal homeostasis in the prostate epithelium, and later leads to prostatic intraepithelial neoplasia lesions. Cell-based studies show that ADAM9 has the ability to process and shed FGFR2iiib and EGF, both of which have well-established roles in prostate cancer. Moreover, ADAM9 could also have other yet to be identified substrates or other functions that contribute to its role in tumorigenesis, such as roles in cell-to-cell interactions or signaling via its cytoplasmic domain. These findings suggest that ADAM9 might, therefore, be a novel target for the treatment of carcinomas in which this enzyme is highly expressed.
Grant support: Koch and Pepsico Funds (C.P. Blobel, H.I. Scher, and L. Peduto) and by NIH grant GM64750 (C.P. Blobel).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
We thank Dr. A. Koff (Memorial Sloan-Kettering Cancer Center, New York, NY) for providing W10 mice and for helpful comments while preparing the manuscript, Drs. B. Fingleton and L. Matrisian (Vanderbilt University, Nashville, TN) for providing tumors from MMTV-PyMT and Apc/Min/+ mice, Dr. S. Higashiyama (Ehime University, Ehime, Japan) for providing alkaline phosphatase–tagged EGFR ligands, Dr. Steve Swendeman for advice, and Brian Hutchinson and Katia Bozhilova for excellent technical assistance.
↵5 W. Gerald, Memorial Sloan-Kettering Cancer Center, personal communication.
- Received March 30, 2005.
- Revision received July 14, 2005.
- Accepted August 9, 2005.
- ©2005 American Association for Cancer Research.


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Topics include New Mobility, Combined Supplies, High Effectivity Applied sciences for Army, New Supplies on Expert Commerce. Common Motors holds a 20{777b46bc017f520322f4fe1c8523ce7c72011a27ef509825f195f481c071ab54} stake in Industries Mécaniques Maghrébines Common Motors and Shanghai Automotive Business Corporation (SAIC), and has two joint ventures in Shanghai General Motors and SAIC-GM-Wuling Car Each additionally maintain an equal 50{777b46bc017f520322f4fe1c8523ce7c72011a27ef509825f195f481c071ab54} stake in General Motors India Non-public Restricted And General Motors holds a 94{777b46bc017f520322f4fe1c8523ce7c72011a27ef509825f195f481c071ab54} stake in GM Korea and SAIC Group holds a 6{777b46bc017f520322f4fe1c8523ce7c72011a27ef509825f195f481c071ab54} stake.
GM, for example, has been lowering outsourcing contracts and as an alternative has employed greater than eight,000 software program developers , whereas Bosch is seeking to employ 14,000 software program engineers in 2016 alone to develop features for the linked car as part of its push into the Web of Things.
The replacement of Singer by Customary was simply the rise of one company and the decline of another, as evidence that open competitors might still change the construction of the British automotive industry. With its vast land space and a hinterland of scattered and remoted settlements, the United States had a far greater need for automotive transportation than the nations of Europe.
In this test, a full reconstruction of the lateral panels of different automobiles was achieved to evaluate the capability of Kinect sensors to perform in semiconstrained environments and over giant objects exhibiting advanced surface reflectance characteristics.
The Germans had been ardent admirers of Henry Ford and his methods, which they termed Fordismus, however Ford never succeeded in turning into a power within the German automotive world. The hot button is to take a web page from companies like Apple and Samsung on the right way to use digital services to take care of premium pricing out there. All Star Dodge Chrysler Jeep Ram is home to a broad collection of new Chrysler, Jeep, Dodge, and Ram automobiles in Denham Springs. Discover alternative batteries for energy sport vehicles made by manufacturers including Yamaha, Honda and Harley-Davidson on this department.


text: #12066 | 2018-09-19 Gentofte, Denmark Data Scientist For an enterprise client in the Energy sector, we are looking for a Data Scientist. The Data scientist will support a number of projects in working with big data and with onboarding to the clients data lake. The data scientist makes value out of data by proactively fetching information from various sources and analyzing it. Discover the information hidden in vast amounts of data, and help us make smarter decisions to deliver even better products Applying data mining techniques, doing statistical analysis, and building high quality prediction components integrated with our systems Selecting features, building and optimizing classifiers using machine learning techniques Enhancing data collection procedures to include information that is relevant for building analytic systems Processing, cleansing, and verifying the integrity of data used for analysis Doing ad-hoc analysis and presenting results in a clear manner Requirements: Must have worked with Azure cloud and have solid experience with big data technologies such as Spark, NiFi, Hadoop, Hive, Kafka, CKAN. Ability to code in Python is a must, proficiency in C# or java is recommended Have extensive experience with data science and data analysis activities Have worked with machine learning and other AI techniques SAP experience is an advantage since SAP can potentially be a source for many data points Start: 1. October 2018 Duration: 2 months Work location: Gentofte, Denmark Requirements: Min. 5 years of professional IT experience. Job type: Freelance Job is closed Sorry, we are no longer seeking consultants for this project. Please click "Freelance jobs" to see the list of current projects. If you are a client looking for this type of profile, use the "Review a consultant CV" form on our other website. < Back to available freelance jobs


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Carol Pearson will become Endometriosis UK's first Patient Leader, an exciting new volunteer role for the organisation. Carol has stepped down from Endometriosis UK's Board of Trustees where she was a Trustee from 2008 - 2010 and 2011 – 2015, and served as Treasurer.
Carol has worked with the Endometriosis UK team to develop a new volunteer Patient Leader role for the organisation, ensuring that the voice of those with lived experience of endometriosis continues to shape our work.


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Prayer Counseling
This kind of prayer ministry, by the leading of Holy Spirit, focuses on the healing for the innermost hurts; exploring the deep emotional hurts either from childhood or other unresolved issues and traumas. Prayer counseling helps to address challenges that are potential for keeping us stuck in life. Repeated problematic patterns are recognized; root causes are identified; the effects of trauma on our lives are uncovered and addressed; and, healing is appropriated through the power of the principles from the Word of God.
It's about transforming and strengthening the 'inner man' for a life of peace, joy toward the fulfillment of destiny.
"Miracles can happen at an instant! Miracles can happen over a period of time! All of it is God at work in and through us!"
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Toward a National, Friction-Free Scientific Data Superhighway
Time 05/08/18 10:30AM-11:45AM
Room Grand 5-9
Session Abstract
At the 2017 Global Summit, Dr. Larry Smarr from UCSD provided a detailed look at the Pacific Research Platform as an NSF-funded research project which extends NSF-funded campus Science DMZs to a regional model establishing a science-driven, high-capacity, data-centric "freeway system" built on the CENIC/Pacific Wave backbone to University of California campuses, major private California research universities, several supercomputer centers and additional institutions outside of California. As part of its project scope, the Pacific Research Platform plans to help lead the effort over the next few years to explore and expand sustainable methods to scale to a national research platform.
One year later at the 2018 Global Summit, Dr. Smarr, along with several leaders from the R&E networking community, will share their perspectives and approaches to the creation of additional regional research platforms across the country. Also of particular interest to these efforts is the release of the National Science Foundation's 2018 Campus Cyberinfrastructure Program Solicitation that includes targeted investment in the national coordination of advanced network performance and outreach to further scientific research. With a goal to continue to grow the interest of community stakeholders to join a national coalition of the willing, this panel will share its insights into next steps as we build toward the vision of a national, friction-free, high performance, end-to-end science-driven superhighway.
Speaker Larry Smarr University of California - San Diego
Moderator Louis Fox CENIC (Corporation for Education Network Initiatives in California, The)
Speaker Wendy Huntoon KINBER (Keystone Initiative for Network Based Education & Research)
Speaker James Deaton GPN (Great Plains Network)
Presentation Media
Speaker James Deaton GPN (Great Plains Network)
Speaker Wendy Huntoon KINBER (Keystone Initiative for Network Based Education & Research)
Primary track Advanced Networking


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What do you do when you're a columnist and the publishing syndicate you're contracted with is keeping more than its fair share of profits from the merchandising of your cartoons and other creative output? You start your own boutique syndicate – or at least, that's what longtime writer, artist, and East Sider Jane Adler decided to do. Adler, who grew up in Providence, moved to New York, and later moved back home to settle down with her husband, was "discovered" by North America Syndicate – now King Features Syndicate – while working full-time as a freelancer for the Providence Journal "more than 20 years ago," she estimates. In doing so, Adler joined the ranks of legendary columnists and cartoonists like Erma Bombeck and Jules Feiffer. She later founded Whitegate Features Syndicate, with contributor contracts giving 50/50 merchandise profits – "So what happened is that all of the other syndicated columnists came to my syndicate," she says.
Adler has worn myriad professional hats, from oil painter to plant shop owner, to art director for Trinity Repertory (then Trinity Square), to hostess for PBS television, to the owner of her own advertising agency, Adler Advertising. She was one of the only women at the time to be voted into the Art Directors Club of New York. Her best-known syndicated column is the weekly "Indoor Gardening," which combined drawings of plants with her signature wit and curiosity. Her current pursuit is photography.
"I'm just glad I was in [the publishing] business when it was terrific," Adler says. "Everybody wanted to do what I was doing." Like many others, she laments the changes that have hurt the industry since the Internet became popular and widespread. "I like reading on a newspaper — feeling the physical thing."
Adler is also active in a number of community organizations, including serving as head of Communications and PR at Lifelong Learning, where she is also a board member and organizes its popular brown bag lunches. She is the membership chairman of the Pottery and Porcelain Club and serves as a board member and Membership and Activities Chairman of the Providence Village, which is "neighbors helping neighbors."
In their free time, Adler and her husband enjoy life in Providence. "I've had a wonderful career," Adler muses. "I've traveled, met presidents — just everything was wonderful."
Adler's latest photography show will be up at the gallery at St. John's Episcopal Church in Barrington until "at least March."


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Whether you're a local nonprofit reaching individuals in a small community or a national organization reaching individuals across the country, Google Grants can help tap into thousands (or even millions) of people who use Google's search engine every single day.
Google stated in 2017 that it processes trillions of searches every year and that 15 percent of the searches seen every day are new. The wealth of content available for nonprofits to capitalize on within their Grant account is astounding. Remember, search is about being found the moment you are being sought. Thousands upon thousands of keywords are ready and waiting to be queried on and used to display advertisements. But be aware that not all content is weighted equally, and nonprofits need to be vigilant to only bid on keywords that are general to nonprofits and, more importantly, specific to their organization's mission, programs, and services.
Here are 12 Ways a Google Grant Can Help Your Charity Reach Your Fundraising Goals via Digital Marketing
- Drive more donors to give to your organization.
PRO TIP: Include a fundraising-centric ad within your brand campaign to appear on your branded search terms. The biggest misconception about brand search is that individuals will donate anyway because the organization's site will show up organically. Unfortunately, the average web user won't go past the initial ads to click on the organic results. Don't make your donors hunt for your donation form.
- Better understand who is donating and what they are searching before they donate. The terms and phrases donors search are usually not branded or fundraising-centric. For example, a food bank donor might search "child hunger," "volunteer at local food bank," or "food and hunger."
PRO TIP: Always have a donation call-to-action (CTA) as one of your sitelink extensions, as this allows the user to guide themselves to additional landing pages that best match their intended destination. This will make it easy to keep giving to your cause top of mind and easily accessible. Make it easy for donors to give!
- Raise awareness about your organization and its mission locally, nationally, internationally, or a combination of all three.
PRO TIP: Set your location at the campaign level. Branded keywords should be visible everywhere while local, program-specific keywords should be geo-located.
- Increase newsletter sign-ups, volunteer registrations, phone calls, contact form fills, and more.
PRO TIP: Include CTAs for each within your sitelink extensions. Google will allow four per ad to show at once, and these can be set at the account, campaign, and ad group level. Although sitelinks require little maintenance, these should be tracked and optimized on an ongoing basis.
- Set up tracking in the Grant and on your website to measure these conversions and learn more about what is driving them from within the Grant.
PRO TIP: Use Google Tag Manager (GTM) to manage tags or snippets of JavaScript that need to be placed on your website and donation platform. GTM is a user-friendly solution that has streamlined the process of creating tags to send user interaction data to Google Analytics. GTM has several built-in tags for Google Analytics, AdWords conversions, and remarketing, as well third-party tags.
- Link your Google Grant to Google Analytics to track donors' journeys through your website after they click your ad. You can also collect demographics and other data about them.
PRO TIP: Take the time to set up e-commerce tracking. This will enable better attribution!
- Determine the effectiveness of different messaging in search ads with A/B testing.
PRO TIP: Plan out thoughtful and strategic A/B tests so that the results can benefit the overall marketing strategy.
- Understand what search queries donors interested in your organization are entering into Google's search bar.
PRO TIP: Evaluate the donor-centric search queries and assess whether a modified version would be beneficial to include as a callout extension. Callout extensions are similar to sitelinks, but without the link. Callout extensions can be used to draw attention to unique selling points or facts about your organization.
- Use search query insights to create new content pages based on search terms, improving Quality Score, relevancy, and engagement with donors.
PRO TIP: Go beyond your brand and leverage inbound marketing to introduce your organization as a thought leader for a particular topic. Inbound marketing is focused on attracting customers through relevant and helpful content and adding value at every stage in your customer's buying journey. With inbound marketing, potential customers find you through channels like blogs, search engines, and social media. This approach is designed to address the needs of prospects by providing relevant content for what he or she has searched for. Inbound marketing not only attracts qualified prospects, but subsequently builds trust and credibility for your organization.
- Drive donors to more relevant landing pages deeper within your site that others may not reach. This will provide more relevant content and more meaningful interactions with you.
PRO TIP: Use your website's sitemap to create an outline for your account. You want to make sure you are leaving no stone unturned if applicable.
- Maximize your account by setting campaigns to max conversion bid strategy (if appropriate for your account goals) and go beyond the $2 max bid cap.
PRO TIP: Ensure that you have a subdomain set up on your donation platform so that you can send traffic directly to a donation form from the Grants. Most nonprofit donation pages are hosted within their CRM — not on their main website. This means that your donation pages may have a URL that is different than your main website domain, such as YourTownFoodbank.org versus Secure3.Convio.net. Google requires that all destination URLs match the domain used to set up the Grant account. We
recommend that sub-domains be set up (when applicable) so that traffic can be sent directly to a form, rather than a landing page. For example, give.YourTownFoodbank.org versus Secure3.Convio.net. Being able to bid more than the $2 will help increase revenue during the holiday giving season while potentially decreasing your supplemental paid search budget.
- Utilize Expanded Text Ads (ETAs) and Responsive Search Ads (RSAs).
PRO TIP: Google has added more elements to their search ads and increased their character counts, which means that you can now use 300 characters in your headlines, descriptions, and paths. That said, make sure you're using the latest and greatest ETAs in order to take advantage of the new character limit. Also, Google's machine learning can now benefit your ad copy by mixing and matching up to 15 headlines and four descriptions. Rather than write ads individually, you can now use the power of machine learning to determine what combinations of headlines and descriptions work best!
Ready to learn more? Check out our new white paper: "Google Grants Without the Stress."
Get More Insights Into:


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Getting the right company structure, contracts, and forms can be a nightmare when you don't have the money to afford a food law firm. Unfortunately, there's no getting around them. This list of online legal form provider will help you find all the legal documents you need. You no longer have to worry about paying thousands of dollars for legal consultation again.
Thompson Reuters Legal Forms is a comprehensive online legal forms library brought to you by Thomson Reuters where you can easily search more than 600,000 litigation and transactional forms from major national treatises, jurisdictional and practice area titles, regulations, and statues.
HotDocs allows you to transform your frequently used documents and forms into intelligent templates that enable the superfast production of custom documentation. HotDocs is the pioneer and the global market leader for document automation technology, with over one million users in 7,000 client organizations across more than fifty countries.
MegaDox provides a wide variety of high-quality templated legal documents for both individuals and SME. The major focus of their document collection is asset protect (tangible and intangible), families, and futures.
Public Legal contains a huge collection of free legal forms. It also provides links to top law firms, various law schools, government agency websites and more. It's an excellent resource for students, business owners, legal professionals, and anyone who is interested in the legal profession.
The Easy Forms has created an easy way to get state-specific legal forms. The forms are available for immediate download and can be tweaked to your needs or filled in with no changes to make a legally binding agreement.
LexisNexis Automated Forms
LexisNexis Automated Forms uses HotDocs software to put accurate, signature-ready legal forms at your fingertips in minutes. Interactive templates ask you vital questions and use your answers to create a customized form – complete with grammatically correct pronouns and verbs and all paragraphs properly numbered.
Docracy is the home thousands upon thousands of contracts and other legal documentation so if you don't have a lawyer you can choose from their battle tested stock. This is the website I use to get legal documents for everything from web design contracts to agency agreements. My favorite feature is the fact that you can sign electronically and have a legally binding agreement in seconds.
Socrates provides legal documents that can be used for real estate, business, personal and contractors. The products of Socrates are reviewed and approved by attorneys, accountants, and industry experts. Customers can also purchase a bankruptcy kit and view all the bankruptcy debit and credit products.
Small Business Legal Forms lets you get a hold of sophisticated, reusable legal forms as an alternative to both the high cost of legal fees for standard business forms and contracts. At the same time, they claim to have a higher quality documentation library than other legal form providers online.
LawDepot provides free legal documents, forms, and contracts. Whether you're interested in protecting your estate, managing a rental property, setting up a business, or any other situation requiring legal forms, LawDepot's extensive library of documents and legal resources are able to assist you with your legal needs.
Find Legal Forms has attorney-prepared, up-to-date forms legal forms at a fraction of the price an attorney would charge. If you're unhappy with your form purchase for any reason at all, you can contact them within 60 days for a full refund.
Rocket Lawyer is a popular resource that provides online legal services to individuals and small to medium-sized businesses. Its services include; incorporation, estate plans, legal health diagnostics, and legal document review. You can easily create and customize legal documents. The site also provides a way to consult with attorneys on legal issues through its On Call service.
U.S. Legal Forms (USLF) is the leading publisher of State Specific legal forms over the Internet. Whether you are an attorney, small business, or consumer; USLF has something you can use. They pride themselves on their fast results, reasonable price point, and accuracy of their documentation.
Nolo provides online legal forms, lawyers, information, and law books & software. Consumers and small business owners can handle many legal matters themselves with Nolo's comprehensive do-it-yourself resources.
LegalZoom gives you the legal solutions you need to start a business, run a business, file a trademark application, make a will, create a living trust, file bankruptcy, change your name, and handle a variety of other common legal matters for small businesses and families. With LegalZoom doesn't stop there, they also incorporated the ability to speak with a lawyer or tax professional for more in-depth legal advice.
The Entrepreneur Magazine Legal forms are what we call instant access to hundreds of business forms, templates, and contracts online. You can find documents for almost every kind of business such as orders, partnership agreements, loan agreements, applications, and bill of sale.
Onecle has a collection of business contracts, lease agreements, licensing agreements and other legal documentation, forms and agreements. pretty much everything you'd need to manage a company. You can also find attorneys through its lawyer directory which can be browsed by practice area and states.
Your Free Legal Forms is a large database of free legal and business forms including contracts and agreements, leases, non-disclosure and confidentiality agreements, LLC and incorporation checklists, employment agreements, and other consumer and business legal documents, as well as lawyer-contributed articles on important legal issues.
Free Legal Document has an extensive range of free online legal forms which can be printed or downloaded and used as templates. However, free legal forms are not intended as a total replacement for legal or professional counsel. There are situations where you have to consult with a lawyer.
Printable Contracts has more than 350 sample contract templates you can view, download and print for free. There are contracts and agreements for many home and business arrangements, including home maintenance services, modeling and photography contracts, rental contracts, event contracts and more.


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LACOSTE: The Big Leap
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BETC Paris has released this TV spot as part of their "Life Is A Beautiful Sport" campaign for Lacoste.
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The Bucks County Department of Corrections is preparing to launch internet-based Attorney/Offender official client video visitation by the end of May 2017.
More details will be sent in the coming weeks, but I wanted to give you a heads-up prior to your association's monthly meeting to this new method of requesting and having an internet-video-based visitation with an incarcerated offender within all the DoC's facilities.
As we move closer to the go-live date, a flyer with details and instructions will be sent for your information and distribution. These informative flyers will also be handed out at DoC facilities when attorneys arrive to register and visit.
Clarke B. Fulton, Captain of Administration
Bucks County Department of Corrections
1730 South Easton Road
Doylestown, PA 18951


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6D, meet the web. Web, this is 6D.
There are a ton of great online tools for tracking Sunday's legislative election. Here, we run through a few of the best.
In case you've been living under a rock, elections are this Sunday! Are you ready to wet el chiquito?
Most of the action will be in person, of course. But here's your roundup of the digital tools you can't do without on 6D.
Before the vote
- Get to know the people you'll be voting for at EligeTuCandidato.org, an excellent initiative by Transparencia Venezuela. There's a goldmine of information about the candidates, including their career highlights, proposals, promises, and whether or not they've taken part in a coup d'état. They also have many candidates' Twitter handles so you can holler at them. There's even a handy list of cara'e tabla candidates, the ones who use public money for their own campaigns.
- Get a reminder on the voting process at ComoVotar.com, Venezuela Inteligente's great simulator. The more familiar we all are with the process, the faster it's going to go. Be sure to mark three ovals on the voting machine and only then press VOTE, this is the only step in which miembros de mesa won't be able to help you!
- Voting for the opposition, right? But are you sure you know how to pick the right Unidad card. This should be a no-brainer, but the government's playing dirty and it's counting on you to get confused. So, do tell everyone you know about "abajo, a la izquierda, en la esquina, la de la manito".
- Get in touch with fellow voters to attend the verificación ciudadana together. You can register as user at esdata.info and directly contact people in your voting center.
- Make a list of family and friends of voting age. Call them (don't Whatsapp, call!) and ask them how they'll get to their polling stations. Offer help if you can.
Bonus points: join Votojoven's Defensores del Voto initiative.
At the voting station
- Keep calm and vote. Don't wait for the Toque de Diana, 'cause it might not come.
- Remember your list? Call those people again and tell them to go out and vote! Be ruthless, spare nobody.
- Do attend the verificación ciudadana. The machines whose paper trail will be audited have to be chosen after all of the mesas have been closed.
- If you see something you shouldn't be seeing, like two people behind the voting machine or voters being intimidated, make sure to take note: when, where, who was involved? Remember the voto asistido has to follow a very specific procedure, explained in this video.
- Report any irregular activity you noticed. We recommend making the denuncia in two channels: through the MUD's official network of activists, called La Fuerza es la Unión, and through Transparencia Venezuela's Dilo Aquí website.
After the vote
- Head home, get a beer (or 12) and get ready for baranda time.
- Chill. Remember the government cannot simply steal the election and cover its tracks, the system makes numerical fraud impossible to pull off if there are witnesses. Go on, re-read at Quico's article and go through his slides with a cold beverage in your hand.
- Read this handy guide on what to do if the government starts blocking websites. Download it here.
- Don't spread rumors, however optimistic or pesimistic they may be! Let's be patient.
Remember: call, vote, verify and report. Thank you for putting your granito de arena for Venezuela's future.
Did you find this helpful? I'm sure thousands of other people will, too. Share it!
Caracas Chronicles is 100% reader-supported.
Support independent Venezuelan journalism by making a donation.Donate


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At least 30 journalists are thought to have either been killed or gone missing in Mexico since President Felipe Calderon took office nearly 4 years ago.
Journalists covering the Mexico drug war say their lives are in danger as traffickers threaten to violently silence them.
This Thursday, a 21 years-old photographer have been killed and another severely injured in the northern city of Ciudad Juarez.
Local authorities say that while the incidents could have been a case of mistaken identities, it is also possible that photographers were directly targeted by drug cartel hitmen
Al Jazeera's Mariana Sanchez reports from Mexico city.


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Website launches, talks and events, cool projects with ace clients, and a growing team – it all happened in 2018 …
Brand new for 2018
New Adventures
A visual feast of a website for Sir Matthew Bourne's peerless dance theatre company. This was also the year in which Sir Matthew announced New Adventures' next brand new production … Romeo and Juliet, which will premiere and tour the UK in Spring 2019. Exciting times!
Bristol Old Vic
Guiding a 250-year-old theatre and heritage venue into the digital age. A milestone year for this beloved 252-years-old-actually institution, Bristol Old Vic reopened its doors following a major capital renovation/building project in September. And it is pretty special – we wrote a bit about the opening in Bristol Old Vic's grand unveiling, including some photos which don't do the place justice, so visit!
Welsh National Opera
A dual language website celebrating this national opera company's 200+ people. This neat, clean and easy to use website hides a tonne of smart work under the hood, including some clever Tessitura API integration. It was also our first dual language website. Josh and I put together some helpful tips about planning for a multi-language website.
Midlands Arts Centre
An easy to use website (and seriously fun identity) for one of the UK's best-loved arts centres. We've been working with MAC since launching their website over 5 years ago, and towards the end of last year we revamped their visual identity.
This year saw the biggest change to the website since it first went live – with a complete design change to match the new brand identity, and a load of functionality tweaks and improvements. (Using the same base as the original website, meaning what's essentially a whole new site took a fraction of the time/budget to create. All the wins!)
Errr, Supercool – In the summer, we set this very website live. It explains a bit more about us and what we do, and we've whittled-down nigh-on 15 years worth of projects (!) into a more succinct selection of case studies.
Out and about
In March, James teamed-up with Caroline Aston, Audience Insight Manager at Chichester Festival Theatre, to talk to folks at the Ticketing Professionals Conference in Birmingham about preparing for your next big on-sale.
The talk was super-popular – and "brutally honest and brave" – so James and Caroline were asked to do an encore in May, at UK Theatre's Box Office Conference in London.
If you missed out on both talks, here's our write-up: Preparing for your next big on-sale.
July saw new(ish) team member, Kate Mroczkowski learning about The Power of Play at the AMA Conference in Liverpool: Let's play – what I learnt at this year's AMA Conference.
In September, James was on stage again – this time at Leeds Town Hall, as part of a Spektrix Conference panel discussion about digital innovation in the arts.
He talked about our work with Midlands Arts Centre, who welcome over 1,000,000 visitors, and host nearly 400 performances, 900 films and 1,300 creative courses every year. That's a lot of listings – which is where our powerful search with instant results comes in handy.
Kate was in Liverpool talking about cross and up-selling online at the Ticketsolve User Forum in October, and we were on the road again in November. This time James and Kate popped to Manchester for the 2-day Tessitura European Conference (of which we were a sponsor). And finally, another AMA outing – James was in London for the AMA's Digital Day earlier this month.
Cool projects, accessibility a-go-go, and a growing team
As well as new launches, and day-to-day upkeep and iterative improvements to websites, we got to work on loads of ace one-off projects with clients. Here're just a few of them:
Scottish Ballet's Make A Wish campaign to thank Scotland for 50 years of support. We gathered hundreds of wishes – from a chance to dance with the Company to a flash mob on a ferry – and tens of thousands of votes. An esteemed jury, including Dame Darcey Bussell and Susan Calman, will be picking their top five wishes, which Scottish Ballet will make come true in 2019.
We worked with New Adventures to create a Swan Lake timeline, celebrating 23 years of the iconic show. And with the functionality to build timelines now baked-in to the site, the New Adventures team can build timelines for all shows.
James and I were lucky enough to attend the swanky, star-studded Gala performance of Swan Lake at Sadler's Wells in December. And, wow! If you want to see men mind-bogglingly-convincingly transformed into swans, it's on tour across the UK until May.
We harnessed the power of Spektrix's donations web component to create one-click 'add to basket' donations for Chichester Festival Theatre's Ageless campaign. It was a Giving Tuesday success, with a considerably higher average donation amount than last year's campaign. (A simple case of helping people understand how their donations will help, and offering suggested gift amounts.)
Long-time accessibility advocates, this year we worked with Bristol Old Vic, Buxton Opera House, Chichester Festival Theatre and Midlands Arts Centre to further improve their respective online offers for assisted performances. Accessibility's a big part of our work so it's great to have Sally McGrath – developer, accessibility specialist extraordinaire, and maker of cool robot stuff – on the Supercool team.
In November the very-newest Supercooler, developer Pete Nelson, made sure that our 4 client venue on-sales for Ian McKellen's 80th birthday tour in 2019 went smoothly; including a ticket ballot for Chichester Festival Theatre.
Some nifty TNEW styling and integration has just gone live on City of Birmingham Symphony Orchestra's website, making donating and becoming a member online infinitely easier to do.
Finally, we've done loooooads of exciting work with the awesome team at Town Hall Symphony Hall (THSH) in Birmingham over the past year, including using some smart data analysis to make improvements to their online fundraising.
And in perfect timing for Christmas, we've launched a simplified Name A Seat integration for THSH. You can now donate and name seats in Symphony Hall online without the need to fill-in a paper form – and it all integrates seamlessly with Spektrix. Smooooth.
To celebrate, THSH have a £5 raffle to win your very own seat dedication – enter by midday on Friday 21 December.
We're looking forward to continuing to put our collective design, tech and data skillz to good use in 2019 – including on brand new website projects with Eden Court, Sheffield Theatres, and Traverse Theatre.
In the meantime, have a relaxing festive season – warmest winter wishes from the team at Supercool!


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FDA Grants New England Farmers' Holiday Wish
You spoke; the U.S. Food and Drug Administration listened. The FDA announced today that it will redraft significant portions of its recently proposed Food Safety Modernization Act Produce Safety Rule and Preventive Controls Rule.
This is big news! As drafted, the rules could have forced thousands of small farms across New England out of business and caused environmental damage to farmland, water, and wildlife. Thanks to comments from small-scale farmers and farming advocacy groups, local food lovers, and conservation advocates, including CLF members, we have another opportunity to help FDA draft rules that make our food safer and protect sustainable agriculture. As I've noted before, rulemaking is the federal government's most inclusive democratic process. Today, the FDA proved this point.
The FDA plans to release newly drafted rules sometime early next summer. In a statement released today, FDA Deputy Commissioner Michael Taylor explained that the FDA will redraft key provisions of the rules, including "water quality standards and testing, standards for using raw manure and compost, certain provisions affecting mixed-use facilities, and procedures for withdrawing the qualified exemption for certain farms." The FDA will complete its review of the comments it received to determine the full scope of redrafting. CLF will continue to track these rules and work to protect family farms, sustainable agriculture, and locally grown food.
We commend the FDA on its decision. Thank you to CLF members for adding your voice to this important process. New England farmers couldn't have asked for a better holiday gift.


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1. Re: Need help on AN66444JoMe_264151 Aug 1, 2017 11:48 PM (in response to jilic_874441)
Welcome in the forum!
Change some settings:
In system view set the heap size to 0x0200
in Project->Build settings->Arm GCC...->Linker set both "Use newlib nano" and "Use newlib nano float formatting" to true.
2. Re: Need help on AN66444jilic_874441 Aug 2, 2017 7:55 AM (in response to jilic_874441)
Hi, thank you thequick reply.
Sorry, i did not make my problem clear.
The IIR Filter code are not being utilized. I would like help on how to make use of the IIR Filter code to perform the low pass filter.
The "iVcds_acc" value does not correspond to the actual input value. I think additional code are needed to implement the filter.
I can understand the correlated double sampling (CDS) but am at a total lost on the IIR Filter portion.
3. Re: Need help on AN66444JoMe_264151 Aug 3, 2017 12:30 AM (in response to jilic_874441)
Can you please post your complete project or a shortened version that shows the error so that we all can have a look at all of your settings. To do so, use
Creator->File->Create Workspace Bundle (minimal)
and attach the resulting file.
4. Re: Need help on AN66444BoTa_264741 Aug 3, 2017 8:42 AM (in response to jilic_874441)jimbies, Look on this output conversion code (counts to volt): fVcds = ADC_DelSig_1_CountsTo_Volts(iVout1); If you replace "iVout1" with "iVcds_acc", the output to terminal will show averaged value. (well, it is my guess without seeing all code)
5. Re: Need help on AN66444jilic_874441 Aug 3, 2017 10:33 AM (in response to jilic_874441)
Thank you all for the reply.
I did replace "iVout1" with "iVcds_acc" but the value is much lower that my actual input. It looks like something is missing in the "/* IIR Filter*/" code segment.
I have attached the project file, which is actually the example file from AN66444, The only change that I have made is the output code - from UART to LCD Display.
6. Re: Need help on AN66444BoTa_264741 Aug 3, 2017 1:11 PM (in response to jilic_874441)jimbies, I am not at computer right now. My guess is that you not need correlated data sampling (CDS), so following code modification should work: { ......... /* IIR Filter*/ iVcds_curr = iVout1; iVcds_acc += (iVcds_curr - iVcds_acc) >> 4; } /*Display output in desired format on UART*/ fVcds = ADC_DelSig_1_CountsTo_Volts(iVcds_acc);
7. Re: Need help on AN66444jilic_874441 Aug 3, 2017 8:53 PM (in response to jilic_874441)
iVcds_acc += (iVcds_curr - iVcds_acc) >> 4; is giving an output = 7.573.
iVcds gives an output = 4.622 which I have verified with a multimeter to be correct.
Being bad at filter equations, I am not able to figure out what is wrong. Any tips would be most helpful.
8. Re: Need help on AN66444VasanthR_91 Sep 26, 2017 2:00 AM (in response to jilic_874441)1 of 1 people found this helpful
could you please check IIR filter implementation appnote AN2099 (http://www.cypress.com/file/127091/download ). Please check the psuedo code under "PSoC 4 and PSoC 5LP Filter Implementation" for low pass implementation.
Best Regards,
9. Re: Need help on AN66444jilic_874441 Sep 26, 2017 2:36 AM (in response to jilic_874441)
Hi VSRS,
Thank you.


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Good Quality MINI UV Flatbed printer LED UV Printer for Ghana Factories
Product Detail
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Good Quality MINI UV Flatbed printer LED UV Printer for Ghana Factories Detail:
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- Model Number: CO-UV4590
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Shokhan Hidayat Hamarashid
I'm a Lecturer with a MS.c degree in Food Science (Food Science Department), teaching in theFaculty of Agricultural Sciences at University of Sulaimani in Kurdistan Region, F.R. IraqRecently I am member of the TQA at UOS.
I teach several topics at my faculty, i.e. My research interests focus on1. Food Processing 1. Food Processing2. Principle if Food Processing 2. Cereals3. Field Crops Processing


text:
One Global Prescription
Client's Challenge: A Global Pharmaceutical Makes Security a Priority
Three years ago, a U.S.-based, multi-billion dollar, NYSE-traded diversified healthcare provider embarked on an aggressive campaign to accelerate growth through the acquisition of international assets.
As the company's global footprint expanded, so did the complexity in managing its operational risks – particularly with respect to security, emergency preparedness and business continuity. Keen on establishing a much more strategic approach to security worldwide, the CEO acted on a reference from a peer in his senior executive network – and called Hillard Heintze CEO Arnette Heintze.
Our Solution: Rationalizing Security's Role and Position Within the Enterprise
At the time, the company's security function was buried several layers down on the organizational chart under Facility Management. Security practices were inconsistent across global regions, facilities and lines of business. And critical capabilities – from a centralized security command center to a common global set of security policies – were non-existent.
Serving initially as the company's interim Chief Security Officer (CSO) and reporting directly to the President, Hillard Heintze immediately undertook high-level risk, threat and vulnerability assessments of the entity's most critical facilities. At the same time, it helped the enterprise establish its first formal CSO position, interview a select list of exceptional candidates, and engage a new full-time CSO. Hillard Heintze also put into place the building blocks of a best practice-based Global Security function, including a high-level global security strategy blueprint that helped define the program's mission, goals, priorities, milestones and metrics applicable in annual stages through 2015.
Impact on the Client: Stronger Security. And an Excellent Structural Baseline for the New CSO.
With Hillard Heintze's ongoing support, the new CSO is executing the first-year objectives for this strategy. And through a risk-driven approach to security-related decision making, the company is making savvy, cost-effective choices about where ongoing security investments will create the most business value.
Unplugged: The Project Manager's Post-Engagement Perspective
"This is a well-known company with an exceptional reputation for quality in their products – and in how they address the critical business processes crucial to building steady, sustainable longterm growth in shareholder value.
So how did it find itself in 'catchup' mode with respect to security? The company grew overnight. Yes, with respect to revenue. But also on so many other levels. When you suddenly acquire a rush of new assets to expand your leadership position in core markets – and attractive adjacent ones – you don't get to reap the rewards of this new portfolio until you've integrated this new war chest.
And that's exactly what we are helping this company do – across its global operations in 75 different countries."