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A network for anyone with an interest in adult education and mental health
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The team were really pleased that 50 learners from the project attended the annual ACL adult learners' celebration (2/3 of participants!). 39 completed our next steps booklet and 4 received an award in recognition of their progress!
Invisible Illness
We are a writing group who have come together because we are involved in a government- funded
Another positive testistment to the project in St Helens, in the learners own words
Positive feedback from one of the learners in St Helens who has successfully found employment, and has taken the time to email our project today...
I'd highly recommend the courses to anyone as I've really enjoyed them and they've helped me in ways I didn't realise I needed x
Hi All
We have been catching up with learners from year 1.....
Here's our latest overview for our group B project. Thoughts/ comments/ suggestions welcome.
We have lots of activity planned to keep promoting and hopefully raise the number of volunteers here...
Learn to Grow
Learn to Grow project December Update
Here's a quick update on where we are upto here in St Helens.
Questions, comments or support welcome! Please contact Andrea on firstname.lastname@example.com or call 01744 677596


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No man is an island, entire of itself
Every man is a piece of the continent, a part of the main . . .
Thus starts the famous meditation by poet John Donne. The point Donne is making is that all of us are interrelated, connected and dependent upon each other.
Connectedness and Collaboration are the Catalysts of Economic Growth
This need to be connected pervades 21st century society. It has in fact become the foundation of new business models, entirely new value chains, and much higher expectations from customers as a result. From social networks that operate on a 24/7 basis to enterprise-wide order management and supply chain systems that manage millions of transactions a day, collaboration is the new economic accelerator of growth.
Studies from AMR Research, Gartner Group, Forrester and others all show that collaboration, not just short-term cross-functional teams, lead to challenging goals being attained. The tighter the collaboration, the greater the ability to reach levels of company-wide performance not possible before. Scale that out to global supply chain and manufacturing networks, and business models not possible before suddenly become achievable and profitable.
No One Makes It Alone Anymore
People working together toward a common goal are far more effective over the long run than the "lone wolf" or "cowboys" of the world. Combining intelligence and effort through collaboration and shared data, the most complex and challenging goals of any company are being achieved. While the "lone wolf" and "cowboys" of the world are often celebrated, they often do more harm than good when it comes to a company attaining its most difficult goals. Lack of collaboration often leads to short-term gains at the price of long-term pain. Examples of this include the following:
• We got the sale! But, the discount exceeded our built in margin.
• We save 10% more using this new supplier! But, we lost our discount for the other products our old supplier still sells to us.
• We've doubled our production of widgets! But, we only need half the widgets we make.
• We've slashed our headcount by 40%! But, we can't meet our production goals due to staffing shortages.
Organizations that collaborate don't make these mistakes. However, collaboration has to be more than people sharing information and trying to work together. Collaboration needs to extend beyond the human component.
Collaboration must extend into three high level areas.
1. People
- Roles – What functions they fulfill
- Responsibilities – What deliverables do they guarantee?
- Tasks – What are their daily activities?
2. Processes
- Finance – AR, AP, Ledger, standards compliance, SEC compliance
- Engineering – Product design, configuration, product performance
- Sales – Moving product into the user community
- Manufacturing – Inventory management, production processes
- IT – Maintaining data, information and hardware infrastructure and systems
- Human Resources – Assuring human assets are available
- Marketing – Crafting and delivering messaging to prospects and users
3. Systems
- ERP – Back office systems
- CRM – Customer care and front office apps
- SCM – Maintenance of relationship with suppliers
- PLM – Maintenance of the product lifecycle
- HR – Support human resources activities
- Other – Apps and systems deployed throughout the enterprise
When we look at the "interconnectedness" of these elements, a couple of things become apparent.
First, the single solution or platform approach to managing the enterprise is going to be greatly challenged. When we look at the big system vendors, Oracle and SAP, recent moves by their management suggest some recognition of this reality. Executives in these companies are realizing that one size does not fit all in the ERP, supply chain, CRM, analytics, performance management, and role-based data management arenas. This is why Oracle specifically has been on an acquisition binge, seeking to capture the depth of functionality they lack in key application areas.
A recent AMR commentary on enterprise application strategies made the point that SAP's Management changes had more to do with the difficulties SAP faced with keeping Net Weaver ahead of the curve as far as it's place in the overall strategy within B2B architectures. Oracle's acquisition of AmberPoint fits into this theory as well. Oracle has been on a bit of a tear in terms of acquiring technology and the need is there to facilitate better management between these functional units.
The second point is the fact that "infrastructure" is really where things are at. Making all of these applications operate like a single system, rather than a collection of tools, is where the true payoffs are. Again the AMR piece cites a couple of things which bear this out. The need for analytical capabilities that extend from data collection into job execution are manifested by facilities that deliver real time information to decision makers is a case in point. This is done in a way that drives effective and timely decision-making.
The need for more sophisticated user interfaces (UIs) that support and exploit these complexities also present an opportunity. Timely data, relevant to a pending action and the tools to execute that action must be coincidentally presented to the user.
Making Collaboration Strategic
To facilitate this type of integration, Cincom Systems has developed Environ. Environ, coupled with Microsoft's SharePoint solution, provides a series of Web Services that enable real-time integration, role-based activity monitoring and event-driven execution of applications.
Environ is made up of four basic components which are briefly described below:
Environ Portal Framework Services (PFS)
PFS is a SharePoint based solution that provides web-based access between entities within and outside the four walls of an enterprise. PFS is used for managing supply chain, distribution and external partner integration at the process level. PFS also manages the UI of each portal, from suppliers, distribution, channel partners and management teams within an organization.
PFS drives the user experience and serves as the administrator over role based access to information, processes or other users.
Environ Workflow Services (WFS)
The function of WFS is to bring the people and process elements together.
Workflow processes, linking people, systems and data can be designed with cut and paste, drag and drop simplicity through the Business Oriented Designer. Internet, Intranet and Extranet accessibility parameters can be defined and built into each process. Templates are available to users that can serve as either a finished process or basic design for modification to spec for the enterprise.
This ease of use makes it possible for line-of-business users to define their own wor5kflows without having to rely on IT.
Environ Integration & Automation Services (IAS)
When people execute processes within complex organizations or enterprises, those processes usually access data and invoke systems from multiple sources. Apps from assorted ISVs, internally developed legacy apps, systems and data located within supplier or customer datacenters outside of the enterprise all must communicate with each other.
Built on BizTalk Server, IAS serves as a clearinghouse for all of the data that passes back and forth between these many systems. To the end user, it all appears like magic on the screen. Behind the scenes, IAS is very busy indeed facilitating the communication of all these disparate systems with each other. IAS maintains meta-data on all systems within the environment, this makes it possible to take data from one system and pass it to another system transparently.
IAS is in some ways analogous to the translator booth at the United Nations. A delegate from France addresses the body in French. Delegates from other countries hear that address in their native language as translators re-articulate the French message into Swahili, English, Mandarin, Arabic or any other language used by those in attendance.
Business Intelligence and Data Services (BIDS)
Maintaining huge amounts of data does no good for any enterprise if that data cannot be brought to the person requiring it to make good decisions related to the business. Decision-making requires information, which is the distilled product of data.
BIDS matches information to role and presents it to the user via dashboards. The dashboard is designed around the specific needs of the role using the data. Each role will have different KPIs and require access to different scorecards in order to be fully empowered as a decision-making entity within the enterprise.
BIDS is able to handle structured as well as unstructured data, which is critical since the vast majority of data in the world is in an unstructured format. Harnessing the power of SQL Server with the analytical and reporting services delivered via SSRS and SSAS functionality, BIDS is a powerhouse for handling data and turning it into actionable information.
Environ is really the backbone of the Control 2010 solution set. Collaboration always sounds like a wonderful goal, but without the Environ solution, Collaboration is likely to be no more than a goal, Cincom makes collaboration a reality.

subset: commoncrawl


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Free meals, buy one get one free deals, gigantic steaks and free beer are just some of the restaurant deals for 2017 Father's Day. Here is our roundup.
Tag Archives | Spaghetti Warehouse
Spaghetti Warehouse coupons and specials.
Daily Deals: Saturday
Our roundup of Saturday restaurant deals includes a $14 prime rib dinner and free kids meals.
Warehouse Happy Hour
Spaghetti Warehouse has a new happy hour with appetizers and drinks starting at $3.
Mother's Day Restaurant Deals
Here are the best deals for Mother's Day from the nation's top restaurant chains. Get a free meal and other deals.
Super Bowl Takeout Specials
Here's our roundup of Super Bowl takeout deals announced by the major chains. Get discounts on pizza, wings, Mexican and Italian foods, burgers and more.
Restaurant Gift Card Deals
Cheesecake Factory, Chipotle, Chili's, Olive Garden, Red Lobster and more restaurant chains have gift card deals for the holidays. Most of these deals end on December 31, 2016 and won't be back until Mother's Day.
EXPIRED Cyber Monday Restaurant Deals
EXPIRED Cheesecake Factory, Carrabba's, Starbucks and more chains have specials for Cyber Monday.
EXPIRED Free Meals on Veterans Day
EXPIRED Veterans Day is Friday, November 11, 2016, today and many restaurant chains including Applebee's, Bob Evans, Chili's, Hooters, and IHOP have free meals to honor the nation's veterans.
EXPIRED Kids Free Spaghetti
EXPIRED Spaghetti Warehouse has an online coupon for free kids meals with an entree purchase, good weekdays through Friday, August 26, 2016.
EXPIRED Lasagna Day Deals July 29
EXPIRED Many Italian restaurants are celebrating National Lasagna Day today, Friday, July 29, 2016, with half off Lasagna, Lasagna BOGOs and other specials.
EXPIRED AYCE Spaghetti 4/28
Spaghetti Warehouse has all-you-can-eat spaghetti with a coupon good only on Thursday, April 28, 2016.
EXPIRED Super Bowl 2016 Specials
Fox & Hound, Dave & Buster's, Hooters, Outback, Papa John's, Papa Murphy's, Sonic and more restaurant and bar chains have takeout specials today for Super Bowl Sunday.
EXPIRED 2016 Valentine Dinner Specials
Here's our annual roundup of Valentine's Day dinner deals. Get dinner for two for $25 to $200 at fast food, casual and fine dining places.
EXPIRED New Year's Eve Dinner Deals
Here are your dinner specials for New Year's Eve at many chain restaurants.
EXPIRED Restaurant Gift Cards Deals for 2015 Holidays
The Holidays are the best time of the year to buy restaurant gift cards. Most specials end on December 31, 2015.
EXPIRED Best Cyber Monday Deals
Get $25 off an online order at Starbucks and Teavana, get free slices of cheesecake with a gift card purchase at The Cheesecake Factory, and more deals in these online specials for Cyber Monday.
EXPIRED Free Meals on Veterans Day 2015
Restaurant chains across America have free entrees and other deals on Veterans Day, Wednesday, November 11, 2015.
EXPIRED National Lasagne Day Roundup
National Lasagne Day is Wednesday, July 29, and Italian restaurants like Carrabba's and Spaghetti Warehouse are celebrating with lasagne deals and specials.


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Our food
We serve a range of dishes at The Royal Naval Reserve - if you're looking for a light bite, you can order a sandwich, but if you're looking for something more filling, we have a great selection of pub grub. Being so close to the harbour, we also have some fantastic fresh fish and seafood dishes.
On Sundays, we serve a traditional Sunday roast and it is very popular, so we suggest you make a reservation today to be sure of getting a table!
Our drinks
We serve an excellent selection of lagers and ales from Shepherd Neame, Britain's oldest brewer.
We also have a great selection of wines, spirits and soft drinks.
Sample fish dishes
We serve great-tasting fish and chips, all freshly cooked to order...
- Home battered cod
- Plaice
- Rock
- Skate
...as well as other delicious fish and seafood dishes, including:
- Grilled rainbow trout
- Salmon in wine
- Breaded fishermans platter
- Scampi
- Mussels in wine


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As an official Pix4D Reseller, Field of View is your one stop shop for any and all Pix4D software sales and support. The team at Field of View has extensive experience with the software solution and can work hand-in-hand with clients to meet their goals
After placing an order, you will receive the license key via email from Field of View within one business day
*For orders outside of the US or Canada, please contact Field of View directly at firstname.lastname@example.com
- Rent for 1 Year or 30 Days
- Unlimited processing*
- Desktop + Cloud
- Support & Upgrade included
- Perpetual Desktop software
- Unlimited processing*
- Desktop + Cloud
- Support, Upgrade & Cloud included for 1 Year (optional as of 2nd year)
- Pix4Dmapper EDU will not be used for any commercial purposes
- Pix4Dmapper EDU will only be used for Educational/Teaching purposes and/or scientific research
- Pix4D and Pix4Dmapper EDU will be cited in all publications and papers
- You or your institution will keep Pix4D updated about the usage of Pix4Dmapper EDU upon request
- If possible, you or your institution will facilitate the exchange and sharing of datasets, case studies, teaching material and/or publications with Pix4D, to be used for research and marketing purposes
The densified point cloud gives users their first form of 3D visualization with minimal processing time required. Survey grade accuracy can be obtained throughout the point cloud.
3D Textured Mesh
Fully textured 3D models can help the user share ideas and provide the perfect form of visualization for potential clients.
High resolution aerial maps that are geo-located, allowing the user to manipulate and analyze their spatial data with high confidence.
Digital Surface Model
An accurate depiction of the ground to help the user in further analysis of data.
These maps are created by measuring reflectance with multispectral cameras. The results provide crucial information to plant health and allow farmers to better monitor their crops and increase their yields.
Precise and easy to calculate, the volume tool allows users to efficiently measure stock pile volumes with only a few clicks
Environmental Monitoring
The orthomosaic aides in environmental research, such as invasive species classification.
Infrastructure Inspection
The point cloud gives the ability to inspect and measure all aspects of the feature being studied.
Contour Lines
A form of visual elevation change throughout the mapped area.
Google Tiles
The orthomosaic can be exported in formats which can be directly integrated into both Google Earth and Google Maps.
Global Mapper is an affordable and easy-to-use GIS data processing application that is suitable as a standalone spatial data management tool and as an integral component of an enterprise-wide GIS.
Pix4Dmapper Pro Demo
Pix4D Support
Detailed Feature List


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Adventure Time
Adventure Time, Cartoon Network's original animated series introduces viewers to unlikely heroes Finn & Jake, buddies who traverse the mystical Land of Ooo and encounter its colorful inhabitants. The best of friends, our heroes always find themselves in the middle of heart-pounding escapades. Finn, a silly kid with an awesome hat and Jake, a brassy dog with a big kind heart, depend on each other through thick and thin.
This group does not currently have a forum.


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PhD scholarship, ARC funded Discovery: Fit for the future: Photosynthetic traits as "key performance indicators" of coral health
The Centre for Systems Genomics is holding a 1-day symposium on metagenomics and microbiome research, Tuesday November 17 at Bio21.
Interested in presenting? Register now! and complete the abstract section.
This free event will feature talks on a range of microbiome-related topics including new computational and lab methods, covering a range of application areas including the human microbiome in health and disease, environmental metagenomics, ecology, agriculture and ancient DNA.
Microverse Books now have three kids bookson sale detailing a day in the life of some familiar bacteria. Order online at Micronovo Books . Books are delivered free to your address. Great presents for your children, nieces, nephews, grandchildren, neighbours children, children sick in hospital, children playing too much ipad etc. If you don't have a spare $7.95 then you can just like us on Facebook . Children deserve to know the truth about who runs the planet!
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JAMS will be presenting a seminar series at the Westmead Millennium Institute, held 3-7pm Thrusday October 8th.
Registration is free, please RVSP.
Afternoon tea and dinner with drinks will be provided.
Seminar Speakers:
Dr Cameron Webb – Plenary
Mosquito‐borne disease in Australia: emerging threats and novel solutions
Prof Shari Forbes
Profiling breath samples for detection of volatile bacterial 'fingerprints' in lung infections
Dr Carola Venturini
Gut microbial ecology: the side‐effects of antibiotic treatment
Dr Gurjeet Kohli
Hunt for toxin biosynthesis genes in dinoflagellates
Dr Matthew O'Sullivan
Managing healthcare workers with suspected Ebola in Sierra Leone
Connie Ha
The guts of lifestyle disease management: targeting host‐microbiome interactions for optimal intervention
Dear Australian colleagues,
Please see attached advert for the 4th New Zealand Microbial Ecology Consortium (NZMEC) meeting, to be held at the University of Auckland on 18-19thFebruary 2016. Registration for this meeting is free, and we think you'll agree that there is a very strong line-up of speakers.
Rm 564, Building G08, The University of Sydney
Hi all
Please be aware of the following courses being advertised to run at HIE in the next few months. These are a good opportunity to hone your skills in essential and commonly-used science technologies.
1) 'Data Analysis And Visualization With R' Course - Monday 13th April to Friday 17th April 2015
The R statistical computing environment has become a standard for scientific data analysis, visualization and reproducible research. At the HIE, we offer an introductory course to help you climb the steep learning curve. This five-day course is aimed at postgraduate students and staff, and is for newcomers to R.
UWS staff and students can enrol at no charge.
Information at www.uws.edu.au/rcourse
Registration is now available!
The 4th Annual JAMS Symposium will be held on Wednesday the 25th of February 2015 at the Australian Museum followed by an evening meal amongst the dinosaurs. We have a fantastic guest speaker line up for the symposium including Colin Murrell, Stefan Wuertz, Lisa Moore and Kat Holt. We promise no less than a night to remember.
Attention students! There is a student poster session with a prize of $500 for the winner.
The symposium and dinner will be preceded by a two day workshop (23rd - 24th February) also at the museum. The main purpose being to introduce postgrads and early career postdocs to current approaches used in scruitinising microbial community and genomic datasets.
This year's workshop is hands-on and will require a 64bit laptop with a minimum of 2GB of memory. Attendees will also need to install VirtualBox. Workshop registration cost is $290.
Registration and payment for both events is being provided through EventBrite. Please follow the links provided below.
Register for the 4th Annual Symposium and Dinner.
Register for the 2014 TOAST Workshop
A commemorative t-shirt is available on registration for either event, the design can be seen in the attachment below and at registration time.


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The ISD 318 School Board convened for its annual organizational meeting on Monday, Jan. 9 at the Administration building. The first item on the agenda was the election of officers. Tom Peltier was unanimously elected as board chair. Harvey Hietala was unanimously elected to the clerk position, and Ben Hawkins was unanimously elected treasurer.
Following the vote, Peltier took over as board chair. He noted that he and Pat Medure had won their bids for re-election in November, while Molly Miskovich was the only new face on the board. Miskovich replaces Sue Zeige and begins a four-year term.
The board moved onto to appoint Pat Goggin as its Chief Financial Officer for the coming year. Goggin is the District's business manager.
The Board made the Herald-Review the official newspaper of the district and designated KOZY/KMFY as its official radio station. The official posting site of the district will be the Administrative Offices.
In other business, the board:
• Hired five replacement ESPs, one coaching position, and one replacement secretary.
• Approved a change order for electrical and plumbing work to accommodate the district's newly acquired STEM equipment.
• Approved the cooperative agreement with Greenway for girls and boys tennis, lacrosse, and girls hockey.


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S.Res.336 - A resolution to condemn the harmful, destructive, and anti-Semitic statements of Mahmoud Ahmadinejad, the President of Iran, and to demand an apology for those statements of hate and animosity towards all Jewish people of the world.109th Congress (2005-2006)
ResolutionHide Overview icon-hide
|Sen. Santorum, Rick [R-PA] (Introduced 12/16/2005)
|Senate - Foreign Relations
|Latest Action:
|12/16/2005 Referred to the Committee on Foreign Relations. (All Actions)
This bill has the status Introduced
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Summary: S.Res.336 — 109th Congress (2005-2006)All Information (Except Text)
There is one summary for S.Res.336. Bill summaries are authored by CRS.
Shown Here:
Introduced in Senate (12/16/2005)
Condemns recent statements by President Ahmadinejad of Iran that denied the occurrence of the Holocaust and supported moving the State of Israel to Europe, and demands an official apology for these anti-Semitic statements that ignore history, human suffering, and the loss of life during the Holocaust.
Supports efforts by the people of Iran to exercise self-determination over the form of their country's government.
Reaffirms the need for Iran to: (1) end its support for international terrorism; and (2) join other Middle Eastern countries in seeking a successful outcome of the Middle East peace process.


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16 x 20″ or 24 x 30″ signed and numbered limited edition print from the museum exhibition "The Socratic Dialogues." Limited edition series of 50.
This product is currently out of stock and unavailable.
Giclee on watercolor 230 gsm smooth paper, aqueous pigmented inks rated at 200 years.
Size based on total surface area. (images are printed with a 2″ border for signing, matting and framing)


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Upfront resistance to chemotherapy and relapse following remission are critical problems in leukemia that are generally attributed to subpopulations of chemoresistant tumor cells. There are, however, limited means for prospectively identifying these subpopulations, which hinders an understanding of therapeutic resistance. BH3 profiling is a functional single-cell analysis using synthetic BCL-2 BH3 domain–like peptides that measures mitochondrial apoptotic sensitivity or "priming." Here, we observed that the extent of apoptotic priming is heterogeneous within multiple cancer cell lines and is not the result of experimental noise. Apoptotic priming was also heterogeneous in treatment-naive primary human acute myeloid leukemia (AML) myeloblasts, and this heterogeneity decreased in chemotherapy-treated AML patients. The priming of the most apoptosis-resistant tumor cells, rather than the median priming of the population, best predicted patient response to induction chemotherapy. For several patients, these poorly primed subpopulations of AML tumor cells were enriched for antiapoptotic proteins. Developing techniques to identify and understand these apoptosis-insensitive subpopulations of tumor cells may yield insights into clinical chemoresistance and potentially improve therapeutic outcomes in AML.
Patrick D. Bhola, Brenton G. Mar, R. Coleman Lindsley, Jeremy A. Ryan, Leah J. Hogdal, Thanh Trang Vo, Daniel J. DeAngelo, Ilene Galinsky, Benjamin L. Ebert, Anthony Letai
Reducing expression of the fetal hemoglobin (HbF) repressor BCL11A leads to a simultaneous increase in γ-globin expression and reduction in β-globin expression. Thus, there is interest in targeting BCL11A as a treatment for β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia. Here, we found that using optimized shRNAs embedded within an miRNA (shRNAmiR) architecture to achieve ubiquitous knockdown of BCL11A profoundly impaired long-term engraftment of both human and mouse hematopoietic stem cells (HSCs) despite a reduction in nonspecific cellular toxicities. BCL11A knockdown was associated with a substantial increase in S/G2-phase human HSCs after engraftment into immunodeficient (NSG) mice, a phenotype that is associated with HSC exhaustion. Lineage-specific, shRNAmiR-mediated suppression of BCL11A in erythroid cells led to stable long-term engraftment of gene-modified cells. Transduced primary normal or SCD human HSCs expressing the lineage-specific BCL11A shRNAmiR gave rise to erythroid cells with up to 90% reduction of BCL11A protein. These erythrocytes demonstrated 60%–70% γ-chain expression (vs. < 10% for negative control) and a corresponding increase in HbF. Transplantation of gene-modified murine HSCs from Berkeley sickle cell mice led to a substantial improvement of sickle-associated hemolytic anemia and reticulocytosis, key pathophysiological biomarkers of SCD. These data form the basis for a clinical trial application for treating sickle cell disease.
Christian Brendel, Swaroopa Guda, Raffaele Renella, Daniel E. Bauer, Matthew C. Canver, Young-Jo Kim, Matthew M. Heeney, Denise Klatt, Jonathan Fogel, Michael D. Milsom, Stuart H. Orkin, Richard I. Gregory, David A. Williams
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration. Using intravital imaging in an antigen-loss CD19-negative relapse xenograft model, we determined that CART123, but not CART19, recognized leukemic blasts, established protracted synapses, and eradicated CD19-negative leukemia, leading to prolonged survival. Furthermore, combining CART19 and CART123 prevented antigen-loss relapses in xenograft models. Finally, we devised a dual CAR-expressing construct that combined CD19- and CD123-mediated T cell activation and demonstrated that it provides superior in vivo activity against B-ALL compared with single-expressing CART or pooled combination CART. In conclusion, these findings indicate that targeting CD19 and CD123 on leukemic blasts represents an effective strategy for treating and preventing antigen-loss relapses occurring after CD19-directed therapies
Marco Ruella, David M. Barrett, Saad S. Kenderian, Olga Shestova, Ted J. Hofmann, Jessica Perazzelli, Michael Klichinsky, Vania Aikawa, Farzana Nazimuddin, Miroslaw Kozlowski, John Scholler, Simon F. Lacey, Jan J. Melenhorst, Jennifer J.D. Morrissette, David A. Christian, Christopher A. Hunter, Michael Kalos, David L. Porter, Carl H. June, Stephan A. Grupp, Saar Gill
Pain is a life-long symptom in sickle cell disease (SCD) and a predictor of disease progression and mortality, but little is known about its molecular mechanisms. Here, we characterized pain in a targeted knockin mouse model of SCD (TOW mouse) that exclusively expresses human alleles encoding normal α- and sickle β-globin. TOW mice exhibited ongoing spontaneous pain behavior and increased sensitivity to evoked pain compared with littermate control mice expressing normal human hemoglobins. PKCδ activation was elevated in the superficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory neurons. Functional inhibition and neuron-specific silencing of PKCδ attenuated spontaneous pain, mechanical allodynia, and heat hyperalgesia in TOW mice. Furthermore, we took a hematopoietic stem cell transplantation approach to generating a SCD model in PKCδ-deficient mice. Neither spontaneous pain nor evoked pain was detected in the mice lacking PKCδ despite full establishment of SCD phenotypes. These findings support a critical role of spinal PKCδ in the development of chronic pain in SCD, which may become a potential target for pharmacological interventions.
Ying He, Diana J. Wilkie, Jonathan Nazari, Rui Wang, Robert O. Messing, Joseph DeSimone, Robert E. Molokie, Zaijie Jim Wang
Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E–binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplanted with MLL-AF9–positive leukemic stem cells by modulating AKT and 4E-BP1 phosphorylation. Taken together, these results suggest that S6K1 acts through multiple targets of the mTOR pathway to promote self-renewal and leukemia progression. Given the recent interest in S6K1 as a potential therapeutic target in cancer, our results further support targeting this molecule as a potential strategy for treatment of myeloid malignancies.
Joydeep Ghosh, Michihiro Kobayashi, Baskar Ramdas, Anindya Chatterjee, Peilin Ma, Raghuveer Singh Mali, Nadia Carlesso, Yan Liu, David R. Plas, Rebecca J. Chan, Reuben Kapur
BACKGROUND. Clinical laboratory tests are now being prescribed and made directly available to consumers through retail outlets in the USA. Concerns with these test have been raised regarding the uncertainty of testing methods used in these venues and a lack of open, scientific validation of the technical accuracy and clinical equivalency of results obtained through these services.
METHODS. We conducted a cohort study of 60 healthy adults to compare the uncertainty and accuracy in 22 common clinical lab tests between one company offering blood tests obtained from finger prick (Theranos) and 2 major clinical testing services that require standard venipuncture draws (Quest and LabCorp). Samples were collected in Phoenix, Arizona, at an ambulatory clinic and at retail outlets with point-of-care services.
RESULTS. Theranos flagged tests outside their normal range 1.6× more often than other testing services (
CONCLUSION. While laboratory practice standards exist to control this variability, the disparities between testing services we observed could potentially alter clinical interpretation and health care utilization. Greater transparency and evaluation of testing technologies would increase their utility in personalized health management.
FUNDING. This work was supported by the Icahn Institute for Genomics and Multiscale Biology, a gift from the Harris Family Charitable Foundation (to J.T. Dudley), and grants from the NIH (R01 DK098242 and U54 CA189201, to J.T. Dudley, and R01 AG046170 and U01 AI111598, to E.E. Schadt).
Brian A. Kidd, Gabriel Hoffman, Noah Zimmerman, Li Li, Joseph W. Morgan, Patricia K. Glowe, Gregory J. Botwin, Samir Parekh, Nikolina Babic, Matthew W. Doust, Gregory B. Stock, Eric E. Schadt, Joel T. Dudley
Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia–rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes
Jayanth Kumar Palanichamy, Tiffany M. Tran, Jonathan M. Howard, Jorge R. Contreras, Thilini R. Fernando, Timothy Sterne-Weiler, Sol Katzman, Masoud Toloue, Weihong Yan, Giuseppe Basso, Martina Pigazzi, Jeremy R. Sanford, Dinesh S. Rao
The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of
Jaclyn Andricovich, Yan Kai, Weiqun Peng, Adlen Foudi, Alexandros Tzatsos
The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule–delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi.
Rudy E. Fuentes, Sergei Zaitsev, Hyun Sook Ahn, Vincent Hayes, M. Anna Kowalska, Michele P. Lambert, Yuhuan Wang, Donald L. Siegel, Daniel W. Bougie, Richard H. Aster, Daniel D. Myers, Victoria Stepanova, Douglas B. Cines, Vladimir R. Muzykantov, Mortimer Poncz
Iron homeostasis is tightly regulated by the membrane iron exporter ferroportin and its regulatory peptide hormone hepcidin. The hepcidin/ferroportin axis is considered a promising therapeutic target for the treatment of diseases of iron overload or deficiency. Here, we conducted a chemical screen in zebrafish to identify small molecules that decrease ferroportin protein levels. The chemical screen led to the identification of 3 steroid molecules, epitiostanol, progesterone, and mifepristone, which decrease ferroportin levels by increasing the biosynthesis of hepcidin. These hepcidin-inducing steroids (HISs) did not activate known hepcidin-inducing pathways, including the BMP and JAK/STAT3 pathways. Progesterone receptor membrane component-1 (PGRMC1) was required for HIS-dependent increases in hepcidin biosynthesis, as PGRMC1 depletion in cultured hepatoma cells and zebrafish blocked the ability of HISs to increase hepcidin mRNA levels. Neutralizing antibodies directed against PGRMC1 attenuated the ability of HISs to induce hepcidin gene expression. Inhibiting the kinases of the SRC family, which are downstream of PGRMC1, blocked the ability of HISs to increase hepcidin mRNA levels. Furthermore, HIS treatment increased hepcidin biosynthesis in mice and humans. Together, these data indicate that PGRMC1 regulates hepcidin gene expression through an evolutionarily conserved mechanism. These studies have identified drug candidates and potential therapeutic targets for the treatment of diseases of abnormal iron metabolism.
Xiang Li, David K. Rhee, Rajeev Malhotra, Claire Mayeur, Liam A. Hurst, Emily Ager, Georgia Shelton, Yael Kramer, David McCulloh, David Keefe, Kenneth D. Bloch, Donald B. Bloch, Randall T. Peterson
Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic
Jessica R. Hitchcock, Charlotte N. Cook, Saeeda Bobat, Ewan A. Ross, Adriana Flores-Langarica, Kate L. Lowe, Mahmood Khan, C. Coral Dominguez-Medina, Sian Lax, Manuela Carvalho-Gaspar, Stefan Hubscher, G. Ed Rainger, Mark Cobbold, Christopher D. Buckley, Tim J. Mitchell, Andrea Mitchell, Nick D. Jones, N. Van Rooijen, Daniel Kirchhofer, Ian R. Henderson, David H. Adams, Steve P. Watson, Adam F. Cunningham
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.
Sebastian Vogel, Rebecca Bodenstein, Qiwei Chen, Susanne Feil, Robert Feil, Johannes Rheinlaender, Tilman E. Schäffer, Erwin Bohn, Julia-Stefanie Frick, Oliver Borst, Patrick Münzer, Britta Walker, Justin Markel, Gabor Csanyi, Patrick J. Pagano, Patricia Loughran, Morgan E. Jessup, Simon C. Watkins, Grant C. Bullock, Jason L. Sperry, Brian S. Zuckerbraun, Timothy R. Billiar, Michael T. Lotze, Meinrad Gawaz, Matthew D. Neal
Erythropoiesis requires rapid and extensive hemoglobin production. Heme activates globin transcription and translation; therefore, heme synthesis must precede globin synthesis. As free heme is a potent inducer of oxidative damage, its levels within cellular compartments require stringent regulation. Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear. Here, we determined that erythropoiesis failure occurs in these animals at the CFU-E/proerythroblast stage, a point at which the transferrin receptor (CD71) is upregulated, iron is imported, and heme is synthesized — before ample globin is produced. From the CFU-E/proerythroblast (CD71+ Ter119– cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119– erythroid cells when studying erythroid marrow failure in murine models.
Raymond T. Doty, Susan R. Phelps, Christina Shadle, Marilyn Sanchez-Bonilla, Siobán B. Keel, Janis L. Abkowitz
Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (
Junsong Zhou, Yi Wu, Lu Wang, Lubica Rauova, Vincent M. Hayes, Mortimer Poncz, David W. Essex
The development of inhibitory antibodies to factor VIII (FVIII) is a major obstacle in using this clotting factor to treat individuals with hemophilia A. Patients with a congenital absence of FVIII do not develop central tolerance to FVIII, and therefore, any control of their FVIII-reactive lymphocytes relies upon peripheral tolerance mechanisms. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulatory enzyme that supports Treg function and peripheral tolerance in adult life. Here, we investigated the association between IDO1 competence and inhibitor status by evaluating hemophilia A patients harboring F8-null mutations that were either inhibitor negative (
Davide Matino, Marco Gargaro, Elena Santagostino, Matteo N.D. Di Minno, Giancarlo Castaman, Massimo Morfini, Angiola Rocino, Maria E. Mancuso, Giovanni Di Minno, Antonio Coppola, Vincenzo N. Talesa, Claudia Volpi, Carmine Vacca, Ciriana Orabona, Rossana Iannitti, Maria G. Mazzucconi, Cristina Santoro, Antonella Tosti, Sara Chiappalupi, Guglielmo Sorci, Giuseppe Tagariello, Donata Belvini, Paolo Radossi, Raffaele Landolfi, Dietmar Fuchs, Louis Boon, Matteo Pirro, Emanuela Marchesini, Ursula Grohmann, Paolo Puccetti, Alfonso Iorio, Francesca Fallarino
Inherited thrombocytopenias are a group of disorders that are characterized by a low platelet count and are sometimes associated with excessive bleeding that ranges from mild to severe. We evaluated 36 unrelated patients and 17 family members displaying thrombocytopenia that were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study. All patients had a history of excessive bleeding of unknown etiology. We performed platelet phenotyping and whole-exome sequencing (WES) on all patients and identified mutations in schlafen 14 (
Sarah J. Fletcher, Ben Johnson, Gillian C. Lowe, Danai Bem, Sian Drake, Marie Lordkipanidzé, Isabel Sánchez Guiú, Ban Dawood, José Rivera, Michael A. Simpson, Martina E. Daly, Jayashree Motwani, Peter W. Collins, Steve P. Watson, Neil V. Morgan, on behalf of the UK Genotyping and Phenotyping of Platelets study group
Epigenetic regulators play critical roles in normal hematopoiesis, and the activity of these enzymes is frequently altered in hematopoietic cancers. The major type II protein arginine methyltransferase PRMT5 catalyzes the formation of symmetric dimethyl arginine and has been implicated in various cellular processes, including pluripotency and tumorigenesis. Here, we generated
Fan Liu, Guoyan Cheng, Pierre-Jacques Hamard, Sarah Greenblatt, Lan Wang, Na Man, Fabiana Perna, Haiming Xu, Madhavi Tadi, Luisa Luciani, Stephen D. Nimer
Severe congenital
neutropenia (SCN) is often associated with inherited heterozygous point
mutations in
Ramesh C. Nayak, Lisa R. Trump, Bruce J. Aronow, Kasiani Myers, Parinda Mehta, Theodosia Kalfa, Ashley M. Wellendorf, C. Alexander Valencia, Patrick J. Paddison, Marshall S. Horwitz, H. Leighton Grimes, Carolyn Lutzko, Jose A. Cancelas
Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34+ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.
Lukas F. Mager, Carsten Riether, Christian M. Schürch, Yara Banz, Marie-Hélène Wasmer, Regula Stuber, Alexandre P. Theocharides, Xiaohong Li, Yu Xia, Hirohisa Saito, Susumu Nakae, Gabriela M. Baerlocher, Markus G. Manz, Kathy D. McCoy, Andrew J. Macpherson, Adrian F. Ochsenbein, Bruce Beutler, Philippe Krebs
Transfusion of donor-derived platelets is commonly used for thrombocytopenia, which results from a variety of clinical conditions and relies on a constant donor supply due to the limited shelf life of these cells. Embryonic stem (ES) and induced pluripotent stem (iPS) cells represent a potential source of megakaryocytes and platelets for transfusion therapies; however, the majority of current ES/iPS cell differentiation protocols are limited by low yields of hematopoietic progeny. In both mice and humans, mutations in the gene-encoding transcription factor GATA1 cause an accumulation of proliferating, developmentally arrested megakaryocytes, suggesting that GATA1 suppression in ES and iPS cell–derived hematopoietic progenitors may enhance megakaryocyte production. Here, we engineered ES cells from WT mice to express a doxycycline-regulated (dox-regulated) shRNA that targets
Ji-Yoon Noh, Shilpa Gandre-Babbe, Yuhuan Wang, Vincent Hayes, Yu Yao, Paul Gadue, Spencer K. Sullivan, Stella T. Chou, Kellie R. Machlus, Joseph E. Italiano Jr., Michael Kyba, David Finkelstein, Jacob C. Ulirsch, Vijay G. Sankaran, Deborah L. French, Mortimer Poncz, Mitchell J. Weiss


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|Myrna van Lunteren <m.v.lunte...@gmail.com>
|Re: [jira] Commented: (DERBY-4073) Creation/configuration of ClientXDataSource fails because of two setSsl methods
|Thu, 19 Mar 2009 16:08:30 GMT
On Thu, Mar 19, 2009 at 2:45 AM, Kristian Waagan (JIRA) <email@example.com> wrote: > > [ https://issues.apache.org/jira/browse/DERBY-4073?page=com.atlassian.jira.plugin.system.issuetabpanels:comment-tabpanel&focusedCommentId=12683392#action_12683392 ] > > Kristian Waagan commented on DERBY-4073: > ---------------------------------------- > > Replacing {@code string} with string is a simple solution. > However, I'm slightly confused. When I grep the 10.3 source files, I find at least 72 occurrences of @code. Why aren't those a problem? > Second, if I run 'ant derbydocs' with JAVA_HOME pointing to Java 1.4.2, it fails when processing the files containing Java 5.0 features (in my case I see it fail when processing ConcurrentLockSet). > > Is my ant.properties file wrong? > I don't know if your ant.properties is wrong - if it is, so is mine. I too saw other errors. I've only the one ant.properties in my $HOME and stupidly didn't save the 10.3 settings from before, and have modified them for trunk(/10.5) since Rick's latest set of changes. So I'm not sure anymore what's happening and what's the right settings, or rather, what settings I had when everything worked. Unfortunately I don't have time to look into this at the moment. But this is one case where a file changed recently and it seemed there ought to be a way to fix this at least... Then we can figure out what's up with the rest of those issues later. Myrna
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Dr. Stephen Schurlknight MD Patient Reviews
- Anesthesiology Rockledge, FL
Overall Rating
1 Patient Reviews
- Wait Time 10 minutes
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Showing 1 - 1 review
5.0 of 5
August 8th, 2010
This doctor is very courteous and kind. He spent a good deal of his time comforting us and alleviating our fears after my father had a very complicated surgery. Truly a top notch professional!
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I will be interviewing the creators of the Wingmakers Material tomorrow - Any questions you would like asked?
|Anonymous Coward
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I will be interviewing the creators of the Wingmakers Material tomorrow - Any questions you would like asked?
I look forward to asking them about the following...
The interviews contained in this section of the WingMakers' website are transcripts taken from a series of interviews between Dr. Neruda (the defected ACIO scientist) and Sarah the journalist he contacted shortly after his defection. These interviews provide provocative insights into the Advance Contact Intelligence Organization (ACIO) - the secret government organization responsible for reverse-engineering acquired extraterrestrial technologies.
The Neruda Interviews also provide remarkable insight into a wide variety of topics, including the human genome, secret societies, new physics, cosmology, extraterrestrial influence on earth, and the spiritual nature and purpose of humankind. The interviews are recorded and then transcribed by Sarah exactly as they occurred. These are the original files. It is recommended to read them in the order they were recorded.
[link to wingmakers.com]
The ACIO and Labyrinth Group
I know because of very real "Behind the scenes" folks have contacted me, The ACIO and Labyrinth Group are very real.
Within the ACIO, there are 14 distinct levels of security clearance. Those who are at level 12 and above are aware of the Corteum Technology Transfer Program (TTP), and they, according to Dr. Neruda, are about 120 in number, and are primarily in India, Belgium, and the United States. There are only 7 who have level 14 clearance, and they are the Directors of Intelligence, Security, Research, Special Projects, Operations, Information Systems, and Communications.
These Directors report to the Executive Director, who is known simply as "Fifteen", which is the unique classification that is reserved for the head of the ACIO. Fifteen, in the eyes of Dr. Neruda, is the most powerful human on the planet, and what I think he meant by "powerful" is that Fifteen is able to deploy technologies that are well in advance to any that our world's governments have access to. However, Dr. Neruda portrayed Fifteen and his seven Directors as a benevolent force, not a hostile or controlling force.
The eight people who comprise this inner sanctum of the ACIO are in possession of radical technologies that have been part of the Corteum TTP. However, there were also other extraterrestrial technologies that had been derived from recoveries of spacecraft or other alien artifacts, including various discoveries contained in ancient texts that had never been revealed before. All of this information and technology has been collected and developed within the ACIO scientific core – all of whom possess clearances of level 12 or higher.
This scientific core is called the Labyrinth Group, and consists of both men and women who have utilized the Corteum intelligence accelerator technologies to their advantage, and have created a secret organization within the ACIO. When Dr. Neruda was explaining this to me, it got so complicated that I asked him if he could draw me a visual diagram of how all of these organizations worked. (Click here to see a rendering of this diagram.)
The Labyrinth Group consists of all the personnel within the ACIO that qualify for levels 12, 13, and 14 clearance. Fifteen is the leader of this most secret organization. It was split from the ACIO to enable secrecy from the NSA and lower ranking members of the ACIO, which would facilitate the Labyrinth Group's agenda to create its own applications of the Corteum TTP. The Labyrinth Group is in possession of the pure technologies derived from the Corteum TTP. It takes these technologies and dilutes them to the point where the ACIO or Special Projects Laboratory will sell them to private industry and government agencies, (which includes the military).
This secret organization is the most powerful organization on earth in Dr. Neruda's opinion, but they do not choose to exercise their power in a way that makes them visible. Thus, their power is only discernible to their members. For about 40 years they have accumulated considerable wealth apart from the NSA's oversight. They have managed to build their own security technologies that prevent detection from intelligence agencies like the CIA or MI5. They are, for all practical purposes, in total control of their agenda – perhaps this is what makes them a unique organization.
Dr. Neruda had a clearance of level 12 and was still kept from vital information that only the Director level was aware. And it was assumed that even Fifteen kept vital information from his Directors, though this was never a certainty. The symbol used by the Labyrinth Group is four concentric circles. Each circle representing a clearance level (12, 13, 14, 15), and each circle had a unique insight into the agenda of the Labyrinth Group, and its coordination with the Corteum.
Fifteen was an enigma to everyone within the Labyrinth Group. He had been a physicist before he became the Executive Director of the ACIO. He was a renegade because he never interacted with the protocols and the political environment of academia. He operated outside of the institutions and was selected to be part of the ACIO because of his combination of brainpower, independence, and relative obscurity within scientific circles. He was one of the first to make contact with the Corteum and establish communication with them. The Corteum essentially appointed Fifteen as their liaison to the ACIO, and Fifteen became the first to utilize the intelligence accelerator technologies that the Corteum initially offered.
These technologies not only enhance cognitive abilities, memory, and higher order thinking skills, but also enhance the consciousness of the individual so that they can utilize the newly gained intelligence in a non-invasive manner. Meaning, they don't exploit their intelligence for personal gain at the expense of others. This apparent increase in both Fifteen's IQ and ethical consciousness caused him to create the Labyrinth Group in order to retain the pure-state technologies of the Corteum TTP from the NSA.
What technologies are released to the NSA are diluted forms of the pure-state technology, which are significantly less potent in their military and surveillance applications. What I expected to hear from Dr. Neruda was a secret organization of intelligent, evil elitists – individuals intent on exploitation and control. Why else would they want to hide beneath the cloak of such incredible secrecy?
The answer, according to Dr. Neruda, was surprising. The Labyrinth Group view themselves as the only group with sufficient intellect and technology to develop a specific form of time travel technology. They are essentially focused on this agenda because they desire to prevent future hostilities that they believe will occur unless this technology is developed. The Corteum is assisting, but despite their considerable intellects, they have been unable to develop this technology.
What I'm about to tell you will seem impossible to believe, but again, I'm only reporting what my notes say based on my initial conversations with Dr. Neruda. He explained to me that there are as many as 12 different extraterrestrial races currently involved in the past, present, and future of earth and its destiny. The ACIO, because of its mission with the NSA, is the most knowledgeable group about the various agendas of these 12 alien races.
Source - Wingmakers.com
Look into the DR. Neruda interview at the Wingmakers site.
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|I will be interviewing the creators of the Wingmakers Material Tonight - Any questions you would like asked?
|Wingmakers/Dr. Neruda Interview Material validated by former executive director of the American Association of Remote Viewers
|JAMES (creator/translator) of Wingmaker's Website give an INTERVIEW
|The Wingmakers Material is real!
|A Letter from James of Wingmakers regarding statements made by A'shayana Deane in her interview
|The Neruda Interviews - The WingMakers
|Read the Dr. Neruda interviews at the Wingmakers site for the best knowledge of what is truly happening.
|NEW AUDIO INTERVIEW SESSIONS OF JAMES of The WINGMAKERS
|3 part Mp3 Interview with James of the Wingmakers - human destiny, individual purpose, 2012, heart/mind integration, and a variety of other topics and
|New interview with James / Wingmakers 10/28/09 by Conscious Media Network


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*Treatment results may vary
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This sweet mother of two did all she could to get her tummy back. She almost made it but had some fat that would not go away. She had liposuction of the abdomen (tummy) and lower flanks (love handles) by Dr. Severinac with Power Assisted Lipoplasty and SAFElipo.


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Ka mahi te ringaringa aroarohaki taua
The hand which quivers in the face of the enemy is to be admired
Marae are a key feature of Māori society. The marae is a place where the Māori language can be spoken, where customs can be explored and debated, and where important ceremonies can be performed.
Te Reo Māori
Te Reo Māori is the indigenous language of Aotearoa, New Zealand. It is one of three official languages of the nation.
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The Māori Housing Network has been set up to support the energy, enthusiasm and entrepreneurship in the Māori housing sector with information, advice and practical support to build capability.
Matika – Moving the Māori Nation
Moving the Māori Nation is a contestable fund to promote Whānau Ora through whakapakari tinana and is aimed at improving the wellbeing of whānau Māori.
Rangatahi Suicide Prevention
Māori suicide rates are high in Aotearoa. Te Puni Kōkiri is working with other government agencies, expert groups and community organisations to reduce Māori suicide.
Whānau Ora
Whānau Ora is about increasing the wellbeing of individuals and whānau to lead full lives and uses the power of whānau to improve the wellbeing of individuals and whānau.
Effective Governance
This effective governance information is designed to help trustees and directors of Māori organisations with their responsibilities and role as guardians and leaders.
IT and Innovation
Te Puni Kōkiri works in partnership with other government agencies and the private sector to develop policies and opportunities that support the growth and development of Māori within the Information Technology sector.
New Zealand Honours
Our honours system is a way for New Zealand to say thanks and well done to those who have served and those who have achieved.
Māori Land Service Updates
Creating a new Māori Land Service focused on what land owners need is essential. Upcoming wānanga will ensure their voice directly informs the proposed new services.


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text:
I could barely catch my breath. I had made the mistake of agreeing to go jogging with Brad, a guy I've had a huge crush on ever since I met him a few months ago. My idea of jogging is half a mile in six minutes, Brad's idea of jogging is two miles in ten minutes. By the time we reached the one mile mark I felt like my heart was about to explode. The only thing that kept me going was the sight of Brad's body glistening in the sun as sweat trickled down his bare torso.
Brad: "I thought you worked out everyday"
Mason: "I do but I don't run everyday."
Brad: "Aren't you planning on running a marathon in six months?"
Mason: "Yeah and I have six months to train."
Brad: "Well today is a great day to start. Keep up!"
I wish I had his energy. I'm more of a wake up at 10AM, go to bed at 2AM kind of guy, Brad on the other hand felt it was perfectly within reason to bang on my door at 4:30AM, clearly stating that I had agreed to go jogging with him in the "morning." Admittedly I did tell him just to come over and wake me up when he wanted to go jogging, but I didn't think it'd be that early. Note to self, be more specific in the future. Oh well, I finally got to watch the sunrise, something I haven't done in quite sometime.
After the jog Brad came over to play soul caliber, I honestly just wanted to pass out on the sofa, but we were both drenched in sweat and my urge to get clean over powered my desire to fall asleep. I set a towel out in the guest bathroom for Brad and headed into my own bathroom to unwind in a long refreshing shower.
Mason: "I set a towel out for you in the guest bathroom. Feel free to take a shower. I'm going to do the same myself."
Brad: "Thanks. I could definitely use a shower."
A few minutes later…
Knock Knock – My bathroom door opens
Brad: "Hey man do you have shampoo, there wasn't any in there"
Brad was completely naked. If I hadn't of been so tired I probably would of gotten an instant erection. All I could muster up for him was a semi but it was enough to give him a hint. A hint that he either totally missed or intentionally ignored. Or so I thought.
Mason: "Oh yeah. Sorry about that, here you can take this bottle in there."
Brad: "Wow. You're shower is awesome. You have like six shower heads in here."
Mason: "Seven. Theres the rain shower above me."
Brad: "Oh cool! Move over I'm getting in there."
What the hell… not that I was complaining. I just didn't know what he was thinking. Did he really just want the ultimate shower experience, like I did when I had seven shower heads installed, or was he teasing me. This boy had the sexiest Double Mint smile that he knew would drive anyone wild, otherwise he wouldn't of smiled so much plus had the body of an Adonis that could only be sculpted by a life in gymnastics. His manhood was nothing to scoff at either. I mean it was huge! And I've seen a lot of cock in my day.
No matter how hard I tried, I couldn't read him. Every time I looked into his piercing blue eyes trying to decipher his inner most thoughts all I could think was "HOT!" and then I immediately think about Oprah Winfrey naked in an attempt to stop my dick from giving him a full salute.
I know you must be wondering why a kid with my job experience is all worried about what someone else is thinking. But I'm human. I love playing the guessing game just as much as the next person but my arousal caused me to grow impatient, I just had to ask.
Mason: "What are you doing?"
Brad: "What do you mean?"
Mason: "Why are you in my shower?"
Brad: "Ha. Didn't your mother teach you to share?"
Mason: "You know what I mean."
Brad: "…. Guess what he said and how this story ends. Seriously write your guess as a comment. I want to know what you think happened.


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Beth has said more than once that she wants to be a dentist when she grows up. This unprompted drawing has it all- Crest toothpaste, a toothbrush, and a dentist's chair.
6. {Nash Baylor Poe}
4 months ago
Her drawings are getting so much more detailed. She's growing up. Boo!
Such detail in her drawings now.
Why a dentist? That's great.


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Services Included
- En Suite
- Free WiFi
- Freezer
- Games
- Hot Tub (£90)
- Parking
- Pets Allowed
- Television
Name: House Martins
Accommodation: 2 x Double, 1 x Twin, 1 x Sofa Bed
House Martins – luxury timber clad semi-detached cottage with garden and hot tub available.
Spacious lounge with double sofa bed, Freeview TV, CD/DVD player, DVDs and board games. Entrance lobby with water closet.
Open plan kitchen/dining area with dishwasher, fridge freezer and utility room with washer/dryer.
First floor double bedroom with ensuite shower room. Second double bedroom and twin bedroom. Shared family bathroom with jacuzzi bath.
Private garden with seating. Designated parking spaces.
House Martins has a maximum occupancy of 8 guests.
Additional images are available in the gallery »


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Get found with SEO
A website is only successful if it can be found. So, when people search online for the product or services you offer, we'll make sure your found. Optimizing your website for search engines is what we do.
Search Engine Optimization Service
The Internet has evolved into a driving force
It shouldn't be too much of a surprise that the Internet has evolved into a force strong enough to reflect the greatest hopes and fears of those who use it. After all, it was designed to withstand nuclear war. We will discuss in more detail what we offer for SEO services. Without some sort of Search Engine Marketing, including SEO, a website will surely fail to attract and retain visitors. Feel free to contact us to discuss the process of Search Engine optimization (SE0) in more detail. Phone: (203) 303-4WEB (4932), Email: firstname.lastname@example.com.
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It's About Being an Authority In Your SpacePeople use search engines to find websites that have the information, products or services they are looking for. It's very important to search engine companies like Google and Bing to provide accurate search results. So how do search engines determine which websites to list for each search query? And how will you get your website to rank better for a particular search result?
Providing Value for VisitorsThe answer is Search Engine Optimization (SEO), a method of getting your website to rank higher in search engines such as Google, Bing and Yahoo. SEO helps to guide web developers to make websites more valuable in a particular space, and websites that provide value will rank higher in search results.
Get Found When People SearchWe at WebNet take pride in helping people achieve online success. We know what search engines are looking for. We know how to determine and then increase the quality and value of a website. We'll help you get found when people search.
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We Know Search EnginesAt WebNet we have years of experience working in the online marketing space. We believe that research, education and hard work are needed to get the job done. If you are looking for a new website or need to bring more traffic to your current website please feel free to contact us. We can be reached at 203-303-4WEB (4932) or email: firstname.lastname@example.com.
The semantic web and Schema.org
The Semantic Web provides a common framework that allows data to be shared and reused across application, enterprise, and community boundaries. It is a collaborative effort led by W3C with participation from a large number of researchers and industrial partners. For success a website must be involved with the Semantic Web community that helps set guidelines for search engine optimization, including, Structured Data and Schema.org. Industry leaders such as Google, Bing, Yahoo, Facebook and Ask.com have embraced Schema.org and so have we.


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Apartment Features
- Air Conditioning
- Balcony
- Cable Ready
- Ceiling Fan(s)
- Dishwasher
- Oversized Closets
- View
- Washer & Dryer Connections
- Garbage Disposal
- Patio
- Refrigerator
Special Features
- Pets
Community Features
- Accepts Credit Card Payments
- Accepts Electronic Payments
- Clubhouse
- Emergency Maintenance
- Extra Storage
- Green Community
- High Speed Internet Access
- Public Transportation
- Swimming Pool
- Conference Room
- Carport
- On Site Maintenance
- On Site Management
- Pet Friendly
Additional Features
- Assigned or covered parking*
- We Love Military
- Enlcosed Patios and Balconies
- Full Size Pantry
- Mature Oaks
- Kiddie Pool
- Weight restriction: 40Deposit: 300$150 Non Refundable Fee Breed Restriction
Floor Plans & Pricing
Prices and availability subject to change without notice.
Move-in Specials!
Call For Specials!
Take advantage of this fantastic offer today!
Property Details
Summit Oaks
PERFECTLY PLACED, PERFECTLY PRICED! Welcome home to Summit Oaks. Our staff of expert and caring professionals enables our residents to enjoy the very best of service and carefree living. Our excellent location is convenient to three major shopping malls, dining, Sea World, Six Flags (Fiesta Texas), Medical Center, Kelly and Lackland AFBs and quick access to all highways to Eagle Ford and Permian Basin. When you're looking for a place to call home...come to Summit Oaks!
Lease Terms
6-Month, 12-Month
Office Hours
Open Today
Summit Oaks is the ideal environment to relax with spacious with updated style apartment home living in a well manicured community with quick access to all that San Antonio has to offer.
Ratings & Reviews
General Directions
From Loop 410 East, exit Bandera & stay on access road. Cross Evers Road and SUMMIT OAKS on your right.
From Loop 410 West, exit Evers Road, take the turn around. SUMMIT OAKS on right.
MEDICAL DISTRICT - 3.5 miles
DOWNTOWN/RIVERWALK - 10.2 miles
AIRPORT (SAN ANTONIO INT) - 9 miles
LACKLAND AFB BASE - 10.4 miles
RANDOLPH AFB - 22 miles
GOVERNMENT CANYON STATE PARK - 18.2 miles (Run, Mountain Bike, Hike, unspoiled outdoors)
CANYON LAKE - 41 miles, clear blue water - up to ten feet visibility.
TEXAS COAST - 155 miles get your fish on!
$99 Move-in on 12 month leases. Will consider 6, 9, 12 month leases.
Military ...we do back flips to accommodate TDY, Orders, etc. and Military get their first full month 1/2 off!
OIL FIELD WORKERS love our location with quick access to I-37 South towards Pleasanton, and I-35 South toward Pearsall, Cotulla, Catarina, I-10 East to Eagle Ford wet production or heading to Houston or back home to Louisiana, and I-10 West toward the Permian Basin.
Helpful Information
Fax: 2106846479


text:
1300 36 33 32
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Dr Lee is the co-principal investigator of the CLOT study (Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer), a landmark study that established low-molecular-weight heparin as the treatment of choice for preventing recurrent venous thromboembolism in cancer patients. Her current research activities include studies in catheter-related thromobosis, diagnosis of deep vein thrombosis and pulmonary embolism in pregnant women, and thromboprophylaxis in patients undergoing major orthpaedic surgery. She is also involved in translational research exploring the role of coagulation in cancer biology. She is a co-chair of the subcommittee on Hemostasis and Malignancy of the International Society of Thrombosis and Haemostasis and has chaired various educational sessions at annual meetings at the American Society of Hematology and the American Society of Clinical Oncology.
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CMMC Recommends:
Learn more about Marconi and the events in his life at
See a synopsis of radio history at
The History Of Radio
Explore the 1914 Marconi Station at Camp Evans in Wall NJ at
Read the intriguing history of the 1901 Marconi Station in South Wellfleet at
Learn - and practice - Morse International Code at
Morse Code Practice
Take a practice exam for the FCC Amateur Radio License at
Amateur Radio Exam Practice
FOR KIDS: Try the Crypto Challenge Puzzle of the Week at
the NSA's Facebook page
Learn more about shark tagging - and track your favorite shark - at
OCEARCH Global Shark Tracker
Historic Marine Radio and Wireless:
Antique Wireless Association, Apalachin,NY
British Vintage Wireless Society, UK
Marine Radio Historical Society, Point Reyes Station, CA
National Capital Radio and Television Museum, Bowie, MD
New England Wireless and Steam Museum, E. Greenwich, RI
Radio Officers Association -- Marine, Aeronautical and Coast Station Radio Officers
Radio Technology Museum at Infoage, Wall Twp, NJ
RadioTelegraphy.net: History, Keys, Operations, Technology
Vintage Radio & Communications Museum of Connecticut
Amateur Radio:
ARRL -- The National Association for Amateur Radio
Barnstable Amateur Radio Club
Falmouth Amateur Radio Association
W1AA - Marconi Radio Club, Cape Cod, MA
Pilgrim Amateur Radio Club
Poldhu Amateur Radio Club & Poldhu Marconi Centre; Poldhu, Mullion, UK
QSL.NET -- Connecting Hams Around the World
TAPR -- Tuscon Amateur Packet Radio
BAMLOG -- Bruce's AM Log for DX'ers
CARS -- Chelmsford Amateur Radio Society - UK
Ham Radio Resource Guide
Ham Radio in the 21st Century (from EDN Magazine)
Video of Princess Elettra Marconi talking about her Father.
Marconi Corporation plc archives at Oxford University
Cape Cod National Seashore --- History
Marconi Corporation of America Archives --- at former Marconi Belmar station, at Camp Evans, Wall NJ
Description of the Marconi 1899 Wireless Demonstration and related information
Lizard Marconi Wireless Station; The Lizard, Cornwall, England
Ericsson Acquisition of Marconi, Oct. 2005
Fessenden and Marconi: Their Differing Technologies
, by John S. Melrose, 1995
The Marconi Society awards the Marconi Prize annually
Brief list of Marconi's accomplishments with photos
Brief History of Telecommunications
Codebreaking & Enigma:
Bletchley Park, UK
National Cryptologic Museum -- NSA; Ft. Meade, MD
Look Inside NSA's Code Breaking Museum; from
The Atlantic
, Oct 10, 2010
Solving the Enigma: History of the Cryptanalytic Bombe, by Jeniffer Wilcox, NSA, 2006
All Things Enigma, The Enigma Museum , Hancock VT
Dr. Tom Perara, Enigma expert, Hancock VT
Enigma Code Machine, Crypto Museum, The Netherlands
U-505 Submarine Exhibit, including Enigma, Museum of Science & Industry, Chicago
Enigma Code Machine (has virtual tour); Museum of World War II , Boston MA
Build Your Own Enigma Cypher Machine, by Stephen Cass,
IEEE Spectrum
, Dec. 10, 2014
Enigma Machine; Wikipedia
The Marconi Wireless Installation in R.M.S. Titanic
RMS Titanic Radio Page
Titanic Radio Room
S.S. Titanic "MGY"
Titanic Historical Society
Titanic Photographs
STEM - Science, Technology, Engineering and Math:
Carnegie Mellon Robotics Academy
Goldieblox - get girls building
Junior Tech, Osterville MA
Museum of Science, Boston MA
Motorola Solutions Foundation
Verizon Foundation
STEM Standards, MA
STEM Standards, National Academy of Sciences
Local Museums & Businesses:
Cape Cod Museum Trail: highlights of many Cape Cod museums
Atwood House Museum, Chatham MA
Brewster Historical Society, Brewster MA
Harwich Historical Society & Brooks Academy Museum, Harwich MA
Cape & Islands Historical Association: Museums, Historical Societies and Libraries
Cape Cod Maritime Museum, Hyannis MA
Cape Cod Museum of Natural History, Brewster MA
Chatham Railroad Museum, Chatham MA
Coast Guard Heritage Museum, Barnstable MA
French Cable Station Museum, Orleans MA
Eastham Historical Society & Schoolhouse Museum, Eastham MA
Eldredge Public Library, Chatham MA
Godfrey Windmill, Chatham MA
Historic Chatham: town museums and educational institutions, Chatham MA
Mass Audubon Wellfleet Bay Wildlife Sanctuary, Wellfleet MA
Monomoy National Wildlife Refuge, Chatham MA
Nickerson Family Association, North Chatham MA
Orleans Historical Society & Meeting House Museum, Orleans MA
Pilgrim Monument & Provincetown Museum, Provincetown MA
Truro Historical Society & Highland House Museum, Truro MA
Wellfleet Historical Society Museum, Wellfleet MA
eTourChatham, a smartphone tour of Chatham
Cape Cod Chamber of Commerce, Cape Cod, MA
Chatham Chamber of Commerce, Chatham MA
Great Island Software, Chatham MA
Mooncusser Films, Chatham MA
Pleasant Bay Community Boating, Chatham MA (Program Partner)
Where the Sidewalk Ends Bookstore, Chatham MA
The Guidebook: Cape Cod