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AXL is an Essential Factor and Therapeutic Target for Metastatic
Ovarian Cancer
Erinn B. Rankin1, Katherine C. Fuh1,2, Tiffany E. Taylor1, Adam J. Krieg1, Margaret
Musser3, Jenny Yuan4, Kevin Wei4, Calvin J. Kuo4, Teri A. Longacre5, and Amato J.
1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical
Sciences Research, Department of Radiation Oncology, University, Stanford, California
2Division of Gynecologic Oncology, Department of Radiation Oncology, University, Stanford,
California 94303-5152
4Division of Hematology, Department of Radiation Oncology, University, Stanford, California
5Department of Pathology Stanford University, Stanford, California 94303-5152;
3College of Veterinary Medicine, University of Illinois
The receptor tyrosine kinase AXL is thought to play a role in metastasis, but the therapeutic
efficacy of an AXL targeting agent remains largely untested in metastatic disease. In this study,
we defined AXL as a therapeutic target for metastatic ovarian cancer. AXL is primarily expressed
in metastases and advanced stage human ovarian tumors but not in normal ovarian epithelium.
Genetic inhibition of AXL in human metastatic ovarian tumor cells is sufficient to prevent the
initiation of metastatic disease in vivo. Mechanistically, inhibition of AXL signaling in animals
with metastatic disease results in decreased invasion and MMP activity. Most importantly, soluble
human AXL receptors that imposed a specific blockade of the GAS6/AXL pathway had a
profound inhibitory effect on progression of established metastatic ovarian cancer without normal
tissue toxicity. These results offer the first genetic validation of GAS6/AXL targeting as an
effective strategy for inhibition of metastatic tumor progression in vivo. Furthermore, this study
defines soluble AXL receptor therapy as a therapeutic candidate agent treating metastatic ovarian
cancer, where current therapies are ineffective.
matrix metalloproteinase; epithelial ovarian cancer; metastasis; growth arrest specific gene 6
Epithelial ovarian cancer (EOC) is a devastating disease that affects 1/72 women in the
United States. It is the 4th leading cause of cancer related deaths among women in the
United States and is the primary cause of all gynecologic cancer-related deaths worldwide.
Approximately 70% of patients diagnosed with EOC present with stage III or IV disease in
Correspondence should be addressed to Amato J. Giaccia (firstname.lastname@example.com) Tel: 650-723-7366 Fax: 650-723-7382.
Conflict of interest: None
NIH Public Access
Author Manuscript
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Published in final edited form as:
Cancer Res. 2010 October 1; 70(19): 7570–7579. doi:10.1158/0008-5472.CAN-10-1267.
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which the tumor has disseminated beyond the ovaries and pelvic organs to the peritoneum
and mesothelial lining of abdominal organs including the diaphragm, stomach, omentum,
liver, and intestines. Despite current surgical and cytotoxic therapies, 80% of patients
diagnosed with advanced EOC develop recurrent disease and only 30% of patients survive 5
years following diagnosis (1). These findings underscore that tumor metastasis remains a
major clinical challenge in the treatment of EOC. Thus, the identification of molecular
targets regulating ovarian metastasis is critical for the development of more effective
therapeutic agents for the treatment of EOC.
Ovarian tumor metastasis is a multistep process that is influenced by cell intrinsic factors,
the tissue microenvironment, and immune activity (2, 3). The demonstration of
premetastatic niches that can direct metastatic tumor cell behavior and the reseeding of
primary tumors by circulating tumor cells has reinforced the importance of the dynamic
relationship between the primary tumor and its metastatic derivatives (4). The interplay of
these factors has been proposed to explain why to date there has not been successful
targeting of metastatic disease. Intrinsic cellular activities associated with the metastatic
cascade include invasion/migration, changes in cellular adhesion, survival, and proliferation
(5). Invasion and migration are particularly important for metastatic ovarian tumor cells as
these processes are involved in both early and late stages of metastasis and are found to be
specifically upregulated in high-grade tumors and metastases (6, 7). Therefore, the
development of therapeutic agents targeting invasion/migration may be a useful strategy to
inhibit metastasis and may provide clinical benefits to patients with advanced ovarian
The receptor tyrosine kinase AXL has recently been identified as a critical factor driving
tumor cell invasion and migration. AXL is the founding member of the TAM family of
RTKs, which include Tyro3 (or SKY), AXL, and MER (8, 9). TAM receptors are
characterized by an extracellular domain containing two immunoglobulin-like (IG) domains
and two fibronectin type 3-like domains. The ligand GAS6 (growth arrest specific gene-6) is
the common ligand for all three receptors. GAS6 has highest affinity for AXL and is the
only known ligand for AXL (10). GAS6 binding to AXL results in AXL dimerization and
autophosphorylation of tyrosine residues 779, 821, and 866 which serve as docking sites for
a variety of intracellular signaling molecules (11). AXL signaling has been shown to
promote cellular adhesion, invasion, migration, proinflammatory cytokine production, anti-
apoptosis, proliferation, and survival (11).
In tumor cells, AXL plays an important role in regulating cellular invasion and migration.
Overexpression of AXL in tumor cells with low metastatic potential promotes migration and
invasion (12–14). In addition, blockade of AXL signaling in metastatic tumor cells is
sufficient to suppress tumor cell migration in vitro (12–17). In vivo, a role for AXL in
invasion and metastasis has recently been described in breast and glioma tumor models (15,
17–19). MMP-9 has recently been identified as an important effector of AXL-mediated
invasion. MMP-9 expression is affected by both overexpression and down regulation of
AXL in breast and pancreatic tumor cells (14, 16). These studies demonstrate that AXL is an
important factor for tumor cell invasion and metastasis, however the role of AXL in ovarian
cancer growth and progression remains unknown and importantly the efficacy of a
therapeutic agent specifically targeting AXL in metastatic disease remains largely untested.
In this study, we test the hypothesis that AXL is a critical factor for ovarian tumor metastasis
and that therapeutic blockade of AXL signaling may be an effective treatment for metastatic
ovarian cancer. We utilize both genetic and therapeutic approaches to directly assess the role
of AXL in the initiation and progression of metastatic ovarian cancer. This study
demonstrates that AXL is a therapeutic target for human ovarian cancer and shows that a
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specific therapeutic agent targeting AXL is sufficient to significantly inhibit metastatic
tumor progression without normal tissue toxicity.
Materials and Methods
Cell Lines
Ovarian SKOV3, SKOV3ip.1, and HEYA8 cells were obtained as a gift from Dr. Gordon
Mills (MD Anderson Cancer Center). Ovarian ES-2 and MESOV cells were a gift from Dr.
Branimir Sikic (Stanford University). OVCAR-3 cells were purchased from ATCC.
IGROV-1 and OVCAR-8 cells were purchased from the NCI-Frederick DCTD tumor cell
line repository. All cell lines were authenticated from the original source and were used
within 6 months of receipt. Additionally, cells were tested upon receipt for viability, cell
morphology, and the presence of mycoplasma and viruses including MPV, MVM, MHV,
Ectromelia, MAV-1, -2; Reo 1&3, LCMV, LDH, and TMEV (Charles River Laboratories).
Cells were cultured in the appropriate media supplemented with 10% heat inactivated fetal
bovine serum and 1% penicillin and streptomycin at 37°C in a 5% CO2 incubator.
shRNA Constructs
Oligos for AXL shRNA were synthesized as previously described (20) 5'-
GATTTGGAGAACACACTGA-3'. A scramble sequence was used as a non-targeting
shRNA 5'-AATTGTACTACACAAAAGTAC-3'. Oligos were cloned into the pSiren
RetroQ (BD Bioscience) vector. Infected cells were selected in puromycin (Sigma) and
polyclonal populations were tested for decreased AXL expression levels by western blot
The AXL ectodomain (amino acids 1–451) was amplified from the human AXL cDNA
(Open Biosystems) and cloned into the CMV-driven pADD2 adenoviral shuttle vector.
Transient transfections with control vector or AXL ectodomain were performed with
Lipofectamine 2000 (Invitrogen) into HCT116 cells. Conditioned media was collected 48–
72 hours following transfection.
Generation and Production of Adenovirus
The AXL ectodomain (aa 1–451) was cloned into the E1 region of E1−E3− Ad strain 5 by
homologous recombination followed by adenovirus production in 293 cells and CsCl
gradient purification as previously described (21). The production and purification of the
sAXL adenovirus and the negative control virus expressing murine IgG2α-Fc
immunoglobulin fragment was performed as previously described (21).
Growth of SKOV3ip.1 and OVCAR-8 Cells as Peritoneal and Subcutaneous Xenografts
All procedures involving animals and their care were approved by the Institutional Animal
Care and Usage Committee of Stanford University in accordance with institutional and NIH
For genetic studies, shSCRM and shAXL SKOV3ip.1 and OVCAR-8 cells were injected i.p.
with 1×06 and 5×106 cells respectively in 0.5 ml of PBS into female nude mice. After
sacrifice, the presence of ascites was identified, metastatic lesions were counted and all
visible lesions were dissected and removed to determine total tumor weight.
For therapeutic studies, SKOV3ip.1 and OVCAR-8 parental cells were injected i.p. with
1×106 and 5×106 cells respectively in 0.5 ml of PBS into female nude mice. Seven
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(SKOV3ip.1) or 14 (OVCAR-8) days following tumor cell injection, mice were injected
with sAXL or control 1.9×108 adenoviral pfu in 0.1ml PBS into the tail vein.
For subcutaneous tumors, 5 million cells in 0.1 ml of PBS were implanted subcutaneously
into the flanks nude (nu/nu) six-week-old female mice. Tumors were measured with calipers
over a 45-day time course. Volume was calculated using the following formula: width2 ×
length × 0.5.
Tissue Toxicity Studies
Blood was collected from tumor bearing Ad-Fc or Ad-sAXL treated mice. Comprehensive
metabolic panel and CBC analysis was performed by the Department of Comparative
Medicine at Stanford University. Tissue samples were collected from all major organs
including liver, kidney, brain, and spleen, fixed in 10% formalin, embedded in paraffin,
sectioned and counter stained with hematoxylin and eosin.
Statistical Analysis
Statistical analysis of AXL expression in human tissue samples was performed using the
Fisher's Exact test. All other statistical tests were performed using the Student's t test. Values
with a p value of < 0.05 were considered statistically significant.
AXL is a marker of Type II ovarian cancer and metastasis
We first compared AXL expression in normal ovarian tissue, primary tumor, and metastases.
AXL expression was first examined in specimens of normal ovarian surface epithelium
(OSE) taken from patients with benign ovarian disease since the majority of ovarian tumors
are thought to arise from OSE (22). AXL was expressed in 0% (0/10) of specimens with
normal OSE (Table I and Figure 1). In contrast, 73% (219/297) of all ovarian tumor samples
including both Type I and Type II tumors were positive for membranous AXL staining in
the epithelium demonstrating that AXL expression is significantly higher (P<0.0001) in
ovarian carcinomas than normal ovarian epithelium (Figure 1 and Table I). Additionally, we
found that the number of cases with positive AXL staining (score of 2 or 3) was
significantly higher in Type II (high-grade serous and high-grade endometrioid) than Type I
(low-grade serous and low-grade endometrioid) primary tumors (p < 0.0001, Table I). Type
I tumors usually present at low stage and are not aggressive whereas Type II tumors present
at advanced stage and are highly aggressive indicating that AXL expression correlates with
aggressive behavior in Type II ovarian tumors (23). Furthermore, metastatic tumor samples
collected from the omentum and peritoneum of serous ovarian cancer patients showed high
AXL expression in 75% (24/32) and 90% (27/30) of specimens respectively (Figure 1 and
Table I). These findings demonstrate that AXL expression is significantly induced in
aggressive ovarian tumors and its expression is maintained at high levels in ovarian tumor
AXL is a critical factor for ovarian tumor metastasis
To examine the functional role of AXL in metastasis, we utilized a genetic approach to
inhibit AXL in mouse models of ovarian metastasis. For this purpose, we screened a panel
of human ovarian cancer cell lines for AXL protein expression in order to identify metastatic
cell lines with high levels of AXL expression. Similar to our clinical findings, AXL was
highly expressed in the majority of metastatic ovarian (SKOV3, OVCAR-8, ES-2, MESOV,
HEYA8) cell lines, whereas AXL was expressed at undetectable or low levels in cell lines
with low metastatic potential (IGROV1 and OVCAR-3, Figure 2A). AXL deficient
metastatic ovarian (SKOV3ip.1 and OVCAR-8) cell lines were generated using previously
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described AXL shRNA targeting sequences (20). Western blot analysis confirmed that cells
expressing shAXL targeting sequences expressed less than 5% of AXL protein compared to
cells expressing the scramble control shRNA targeting sequence (shSCRM, Figure 2B).
We first examined if AXL plays a general role in the regulation of ovarian tumor cell
proliferation and growth. To address these questions, we performed in vitro proliferation
assays in which total cell numbers between AXL wild type (shSCRM) and AXL deficient
(shAXL) cells were counted over a 10–14 day period. We found no significant difference in
cellular growth curves between shSCRM and shAXL SKOV3ip.1 or OVCAR-8 cells in
vitro (Figure 2C). Similarly, no significant difference was observed in subcutaneous growth
of shSCRM and shAXL SKOV3ip.1 cells (Figure 2D). These findings indicate that AXL is
not required for ovarian tumor cell proliferation or subcutaneous growth.
To determine whether genetic inactivation of AXL affects the ability of ovarian cancer cells
to metastasize in vivo, we compared the ability of shSCRM and shAXL SKOV3ip.1 and
OVCAR-8 cells to form metastases using the peritoneal xenograft model of ovarian cancer.
This model recapitulates the peritoneal dissemination of human ovarian metastases in which
nude mice develop rapidly progressive disease consisting of ascites and more than 100 small
metastatic lesions attached to the mesentery, diaphragm, liver, and other peritoneal surfaces
following peritoneal injection of metastatic human ovarian tumor cells (24).
Immunohistochemical analysis of AXL expression in SKOV3ip.1 peritoneal metastases
revealed that similar to human ovarian metastases, AXL is highly expressed in SKOV3ip.1
metastatic lesions, confirming that this is a relevant model system to investigate the role of
AXL in ovarian metastasis (Figure 3A). Twenty-eight days following peritoneal injection of
shSCRM or shAXL cells, shSCRM mice displayed signs of severe ascites and morbidity
necessitating us to sacrifice the mice and investigate changes in tumor burden between the
shSCRM and shAXL injected mice. While mice injected with shSCRM cells developed
ascites and >100 peritoneal metastases, mice injected with shAXL cells developed very few
metastases (Figure 3B). The average number of peritoneal metastases greater than 5mm in
size was significantly reduced from 13.4+/− 4.3 in shSCRM injected mice to 0.8+/− 0.5 in
shAXL injected mice (Figure 3B). Similarly, the average weight of these tumors was
significantly reduced from 236 +/− 74 mg in shSCRM-injected mice to 39.2 +/−18 mg in
shAXL-injected mice (Figure 3B). In support of these findings, knockdown of AXL
expression in OVCAR-8 cells significantly inhibited total ovarian peritoneal tumor mass and
tumor number in mice injected with these cells (Figure 3C). Collectively, these findings
demonstrate that AXL is a critical factor for the establishment of ovarian tumor metastasis.
AXL regulates ovarian tumor cell invasion
To determine a mechanism for AXL-mediated metastasis, we took an unbiased approach
and directly compared the role of AXL in the critical cellular functions associated with the
metastatic cascade including proliferation, invasion, migration, adhesion, and survival (5).
We found that shAXL SKOV3ip.1 and OVCAR-8 cells were significantly impaired in the
ability to invade through type I collagen (Figure 4). We also observed a modest decrease in
cellular migration in shAXL cells, yet we were unable to find a difference in adhesion to
ECM proteins or survival following serum withdrawal indicating that AXL predominately
affects invasion in the metastatic cascade (Supplementary Figure 1).
Matrix metalloproteinases MMP-1, -2, and -9 are key contributors to ovarian tumor cell
invasion and progression (25). Therefore, we investigated whether AXL regulates the
expression and/or activity of these enzymes in human ovarian cancer cells. Using shSCRM
and shAXL OVCAR-8 and SKOV3ip.1 cells, we found that AXL regulates the expression
of all three MMPs in human ovarian cancer cells. Loss of AXL significantly reduced the
expression of MMP-1 and MMP-2 in SKOV3ip.1 cells (Figure5A). Similarly, in OVCAR-8
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text:
BOSTON - Cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone, according to new research from The University of Texas M. D. Anderson Cancer Center.
The findings of the phase III randomized trial were presented at today's 50th annual meeting of the American Society for Therapeutic Radiology and Oncology.
Led by Eric L. Chang, M.D., associate professor in the Department of Radiation Oncology at M. D. Anderson, the study offers greater context to the ongoing debate among oncologists about how best to manage the treatment of cancer patients with one to three brain metastases.
The American Cancer Society estimates approximately 170,000 cancer patients will experience metastases to the brain from common primary cancers such as breast, colorectal, kidney and lung in 2008. More than 80,000 of those patients will have between one and three brain metastases.
Over the last decade, SRS, which uses high-doses of targeted x-rays, has gained acceptance as an initial treatment for tumors that have spread to the brain. SRS is also commonly used in combination with WBRT, radiation of the entire brain, to treat tumors that are visible and those that may not be detected by diagnostic imaging.
"Determining how to optimize outcomes with the smallest cost to the quality of life is a treatment decision every radiation oncologist faces," said Chang. "While both approaches are in practice and both are equally acceptable, data from this trial suggest that oncologists should offer SRS alone as the upfront, initial therapy for patients with up to three brain metastases."
The seven year study observed 58 patients presenting with one to three newly diagnosed brain metastases who were randomized to receive SRS followed by WBRT or S
|Contact: Lindsay Anderson
University of Texas M. D. Anderson Cancer Center

subset: commoncrawl


text:
Given all the recent and turbulent attention on "innovation," as it relates to set-top boxes and IP gateways, I'd like to provide some industrial context. As a company involved in set-top and IP gateway innovation for almost half a century, we certainly have an informed viewpoint. After all, set-top boxes are a core part of our video DNA.
Let's briefly review the innovation chronology for the cable set-top box. The original function of a set-top box – back when they were called "converter boxes," in the early 1980s – was to convert an incoming channel so it could be watched on the TV.
Another big chapter was called addressability: The ability to remotely control a box's ability to descramble and tune premium channels. Then came the "advanced analog" box, so named because it contained enough memory and graphics resources to accept downloaded features, like an on-screen display, volume control, virtual text channels, a sleep timer, parental locks, reminder messages, multi-lingual displays.
In the mid 1990's the industry took the big leap to digital video compression, and the first digital set-tops. Initial benefit: More channels – Ten video streams could fit into the space of one analog TV channel. High Definition TV later followed with HD set-tops, which brought much higher video quality. Next came digital video recorders, which gave rise to the mass adoption of time-shifted television, with thousands of hours of on-demand content, in both standard and high definition. And let's not forget caller ID on TV, multi-room and whole home DVR, and EBIF-based interactivity, all in various stages of rollout by service providers today.


text:
- Mike Function coordinator w (63)
Welcome to our lovely home.
We are empty nesters who have our own respective businesses. Kim runs Swan Valley Wine Tours and is happy to offer a complimentary wine tour for our guests. Mike runs Elysium Functions which is a corporate and wedding events coordinating business. This gives us flexibility with our holidays but can only get away during our quiet season which is around May - Aug. We have 1 pet dog, a schnoodle (poodle/schnauzer) which we plan to leave with friends whilst away. We enjoy the theatre, eating out and a drink or two so this is a perfect location for all that. We enjoy meeting new people and are open to visiting any location. We are tidy and respectful of other people's places and leave them in the condition we find them.
We stayed one week in Kim and Mike house. It was non simultaneous swap so we had the opportunity to meet them. We were incredibly welcomed by our host. They picked us at the airport and they helped us during all our stay with our baby. More than host we met friends in Perth. The house is perfectly located from downtown, shops and public transport. The house is beautiful, very elegant and very well furnished. Thank you to Kim and Mike and see you soon in Maisons-Laffitte!
We fell so lucky to be able to stay at Elodie and Fabrice's apartment. It is on a quiet street and it is just a few mnutes walk to the train station. In 15 minutes we were in Paris. It is in a beautiful neighbourhood with 2 wine bars on the corner and fabulous gourmet shops along the main street. Elodie and Fabrice welcomed us and showed us around the neighbourhood before leaving us with some nibblies in the fridge and immaculate place to stay. Thanks for a great stay, guys.


text:
Octobre 2010
- Vicky.Stardoll
- Its not often we get to see super shy Janet Jackson on the red carpet! She is in a new movie "For Coloured Girls" and she appeared at a special screening for the movie week in one of her interesting outfits. Is it a pantsuit or a one piece? We can't really tell...do you love or hate it? Vote!
- Vicky.Stardoll
- Callie.Stardoll
- Celebrities such as Leona Lewis, Girls Aloud, Beth Ditto, Ronan Keating, Shayne Ward and Sean Kingston get together to beat bullying. Each celebrity has filmed a selection of special anti-bullying messages and you can view them all on this channel.
Join the campaing on Beatbullying!
- Callie.Stardoll
- Elle.Stardoll
How to justify that runway look
By Britt Aboutaleb | October 28, 2010 4:00 p.m.
Sometimes a runway look's just a runway look, but sometimes it's so much more, like the perfect Halloween costume. Whether you're trying to channel a human heart with a blood red Vivienne Westwood gown or impress your local dry cleaners with a Viktor & Rolf shirtdress, we've scoured the runways to equip you with the most high fashion costume.
When Ashish Gupta, the designer behind Ashish, sent this gingham gown down his spring runway he probably entertained thoughts of red carpet glory…
Photo: Imaxtree
- Elle.Stardoll
- Vicky.Stardoll
- Juliette Lewis was seen in this red lacey Dolce & Gabbana dress first at the New York City screening of her latest film "The Conviction", while new mommy Isla Fisher chose the same dress to wear to the London premiere of her movie "Burke and Hare", but she changed it up a bit, taking in the lace at the hem and adding a cropped jacket, black clutch, stockings and matching pumps, while Juliette just wore a sexy strappy sandal.
- Vicky.Stardoll
- Vicky.Stardoll
- Taylor Swift was at the Madame Tussauds Wax Museum in New York yesterday to show off her very own wax figure. Taylor and the doll were wearing the same beaded, sparkly silver dress and usually when that happens its difficult to tell the real star from the wax model, but in Taylor's case it was obvious, her figure is definitely not the best we have seen! Some are even saying it looks more like fellow country star and frenemy Carrie Underwood. What do you think?
- Vicky.Stardoll
- Callie.Stardoll
Beatbulling have launched a special campaign for Anti Bullying week called "The Big March" where thousands of young people across the world will be 'taking action together' against bullying by marching...
- Callie.Stardoll
- Vicky.Stardoll
- Its about time Olivia Palermo had some competition when it comes to red carpet style! Last night at the Whitney Musuem Gala party, even though Olivia was her usual chic self in a white retro-inspired shift, bright heels and a clutch, it was Chanel Iman who really caught our eye! She impressed us with her Boho-chic pattern blending really stood out from the crowd, don't you agree?
- Vicky.Stardoll
- Vicky.Stardoll
- Are you starting to feel the winter chill and layer up like Rumer Willis and Fearne Cotton or are you lucky enough to live in a warm all year place like Anna Kournikova and Pamela Anderson in California? These ladies were all rocking some pretty interesting looks this week, take a look and be inspired!
- Vicky.Stardoll
- Vicky.Stardoll
- Rocker and fashionista Gwen Stefani proved once again why we think she is the fiercest mom in Hollywood!
- Vicky.Stardoll
Rencontre nos Starbloggeuses
- 84MyOr57 Titre: "Selfie or no selfie "
- 79XxliiOxX
- 61AmelKassia17 Titre: "Colors Blocks"
- 43Alepatricia13
- 61kitty-chaanel17 Titre: "DIY Relookez vos tongs !"
- 71XxXcha-chaXxX
- 60crystaldeglace17 Titre: "Phénomène "Gangnam Style" "
- 60Clarounette-x3 Titre: "You, Me & Charlie"
- 68Sisine7
- 41Noemie.Stardoll Titre: "SONDAGE SUR LES "RARES""
- 79Callie.Stardoll
- 38lovemimi2442 Titre: "Tendance marron "
- 72gjystina
- 55missanissou16 Titre: "Maquillages Avengers"
- 55Jenaa.xx
- 81IrisSaphire17


text:
|Numéro de publication
|Type de publication
|Numéro de demande
|Date de publication
|1 sept. 2005
|Date de dépôt
|26 oct. 2004
|Date de priorité
|22 avr. 2002
|Numéro de publication
|Richard Kaplan
|Cessionnaire d'origine
|Kaplan Richard D.
|Exporter la citation
|BiBTeX, EndNote, RefMan
|Citations de brevets (4), Référencé par (120), Classifications (10)
|Liens externes: USPTO, Cession USPTO, Espacenet
This application is a continuation part application of my co-pending patent application Ser. No. 10/111,248, filed Apr. 22, 2002 and Ser. No. of 60/161646, filed Oct. 27, 1999.
The present invention relates to tour-guide systems.
Tour-guide systems are known. In the simplest form, a self-guided tour system may include signposts and marked walking paths. The user follows the marks that indicate the route to each exhibit and reads the signs or displays that provide information about the historical and cultural significance of each exhibit. Outdoor self guided tour systems may include walking paths formed by dots or lines of bricks imbedded in the sidewalks, or markers on trees and buildings, which lead users to points of interest. Exhibits, as used herein, can mean anything of interest to a user, ranging from a building, a machine, a work of art or an artifact, to a living thing, or just a site having historical, cultural, entertainment or educational significance.
Some exhibits, in addition to displays containing text and graphics, are known to include audio programming devices that provide speech, music and sound effects relating to the exhibit. In well-known museum systems, the user approaches the exhibit and initiates the audio programming by pressing a button. Other tour-guide systems include short-range radio transmitters that broadcast audio programming to specially adapted receivers carried by the user. In the latter wireless system, as the user approaches each exhibit, the radio receiver carried by the user (which typically includes an earphone or headset for privacy) begins to receive the broadcast related to that exhibit.
Self-guided tours with portable information devices are known. For example, art museum systems have been known to include a portable device that plays audio information about each exhibit. The user enters the number of the exhibit into the portable player, which responds by playing pre-recorded information regarding the exhibit. Such systems typically store the recorded information in a programmed memory chip.
Guided tours by audio tape recorder are also known. The user inserts the tape (or other recording medium) into the player, and follows the instructions given. The user receives information about each exhibit, and directions to find the next exhibit on the tour. The tour-guide tape may include sound effects and music in addition to spoken material to effectively recreate historical-context or information of interest relating to each exhibit.
More recently, self-guided tour systems using the Global Positioning Satellite (GPS) system have been proposed. U.S. Pat. No. 5,767,795 to Shaphorst shows an electronic tour-guide system using a GPS receiver and a local data storage device, such as a CD-ROM. The GPS receiver determines the instantaneous geographic location, and the CD ROM player provides audio or video information on the history, geography, and culture associated with the geographic region including comments about a specific point of interest.
The present invention is embodied in an interactive tour guide system downloaded from a tour-guide web site to a PDA (portable digital assistant) or tablet laptop computer. The user indicates his geographic location to the interactive tour-guide device. Intelligent agent software, responsive to a request from the user creates a customized tour program. The intelligent agent guides the user along the customized tour route by voice, video and/or graphics, and provides information about each exhibit on the tour. The interactive tour-guide system responds like a human tour-guide to the needs of the user.
The downloaded interactive tour guide system provides a dynamic city map with interactive guided tours, theme guided tours and a self-guided "wander mode" tour. The dynamic city map is also an interactive map that provides for a variety of overlaid information such as transit lines, restaurant locations, and hotel accommodations and the like.
The present invention is also embodied in a wireless virtual tour-guide device and system enabled to access a global communication network, such as the Internet. The tour-guide system is further embodied in a portable wireless device such as a cellular telephone or laptop computer with a cellular modem enabled to access a virtual tour-guide web site on the World Wide Web (WWW). The virtual tour-guide web site is designed as a portal for the global tourism community to access the Internet.
The geographic location of the wireless tour-guide device is reported to the virtual tour-guide web site. A customized tour program, such as a historical, cultural or entertainment tour is created and made available to the user by an intelligent agent software module that then guides the user along the selected tour route.
The present virtual tour-guide system may provide a directed tour and can personalize or customize the guided tour by taking the user's individual expressed preferences into account. An intelligent agent software module, using request/response software with voice recognition and text to speech conversion, makes the present invented tour-guide system a goal directed and interactive virtual tour-guide. The virtual tour-guide of the present invention is thus more like a human tour-guide than are any of the self-directed or fixed program tour-guide systems of the prior art.
A wireless virtual tour-guide system in combination with a cellular telephone system is shown in
The cellular central station 17 has the capability to determine the geographic location of the handset 10, as well as the identity of the user (by using caller ID features, for example). The raw data representing location of the handset may be determined using either relative time of arrival of the signal from handset 10 at the multiple communication towers 12, 14, 16, or by signal sensing directional receiving antennas, or any other means. The raw location data (time of arrival, direction and the like) is converted to useful form by location processing 22. The raw location data is converted to universal coordinates (latitude, longitude and altitude). If necessary, the location data is further converted to human recognizable form, such as names, street addresses and familiar landmarks. Cell phones also include cameras, clocks and secure credit information (for purchases) that can be useful for tourist.
The flow chart of
At the cellular central station (17 in
Based on determined location for the user's handset, the web search portal redirects 52 the intelligent agent software to connect to a web site (or to plural web sites) specific to the cellular phone location and/or user requests at step 54.
In particular, the specialized search portal (30 in
Intelligent Agent Tour-Guide
Using the web site specific to the location of the handset as an information source, the intelligent agent software downloads 54 selected local tour-guide information to the guide central computer. Tour-guide information may include names and locations of local exhibits, along with text, graphics and audio related to such local exhibits. The intelligent agent software assembles or constructs one or more suggested guided tours for the user at step 56. As an alternative to creating a tour from scratch (a fully customized tour), the intelligent agent software may select from an inventory of canned tours, or modify a canned tour to create a new semi-customized tour. The intelligent agent asks the user, for example, "What kinds of places would you like to visit?" Or "would you like me to guide you on a tour of historical sites in the city?"
In its simplest form, the suggested tour is a fixed itinerary. The intelligent agent 58, via the voice interface text to speech conversion 60, instructs the user by voice response 44 to proceed to the nearest exhibit on the fixed tour. When the location detector indicates that the user is near the first exhibit, prepared information about the first exhibit is played (or offered to be played). If the information is of a preliminary nature and there is more information available about the exhibit, the intelligent agent may ask 44, "Would you like to know more?" The user may respond 43 by speaking a voice response into the microphone on the handset. The voice recognition interface (18 in
Depending on the user's response, the intelligent agent provides more detailed information regarding the first exhibit. Then the intelligent agent directs the user to the next (typically nearest) exhibit on the tour. If the user responded "no" to the last request above, the intelligent agent might ask, "Would you like to continue to the next destination?" If "yes", the intelligent agent presents directions to the next exhibit on the fixed tour, and so forth. In the preferred embodiment, the intelligent agent uses speech to provide directions, however the intelligent agent may provide directions to an exhibit using text and/or graphics as well.
The user can cut short a description in progress of the current exhibit by an expression indicating no further interest in the current exhibit. In such case, the intelligent agent may suggest moving on to the exhibit on the tour. As indicated below in the discussion of revenue models and advertising, the intelligent agent may also direct the user to restaurants, lodging, stores, movies, shows, souvenir shops, beauty parlors, drug stores, gift shops and the like along the tour route. The intelligent agent may also provide topological information or describe other natural features along the tour route.
The user can customize the tour in progress (as well as the initial tour) by expressing special interests and indicating areas of interest and non-interest (examples of user preferences). The universe of requests and responses for users in a given locale is anticipated and programmed into the intelligent agent software. Collaborative filtering may be used to suggest other exhibits that previous users visited that might be of interest to the user. In such manner, the intelligent agent "learns" from the requests and responses of all visitors, so that the virtual tour-guide becomes more knowledgeable with experience. Furthermore, the intelligent agent "learns" from past experience with the preferences of a particular user as to which types of exhibits that most interest that particular user.
Tour-Guide Data Format: Exhibits
The data format for each exhibit in the downloaded local tour database is shown in
Exhibit location is recorded in universal coordinate form (latitude, longitude and altitude) 156, human readable form (address and street name) 158 or by other methods of indicating location. The data record 150 may also include exhibit location recorded in raw data form to simplify location processing elsewhere in the system. That is, if the exhibit location is available in raw data form, location processing (22 in
In addition to the point location of an exhibit, the exhibit location field 156 contains a region or area location in which the user may view the exhibit. For example, a mural on the outside of a building may only be viewed while the user is standing in a region outside the building near the mural. At the same site, a painting inside the same building may only be viewed while the user is standing in a region near the painting inside the building. For this reason, the exhibit location field 156 also includes the viewing region for each exhibit in addition to the center point location.
The data record for each exhibit further contains an approximate estimate of time spent (dwell time) at that exhibit by a typical user. The typical dwell time information is used together with the typical travel time between exhibits to calculate an estimated total tour time. The experience of prior users is collected in a collaborative filtering process to estimate such typical dwell times and travel times.
The exhibit data record 150 contains one or more descriptive texts with accompanying audio and graphics 160, 161 related to the exhibit. For a simple exhibit, there may be a single description 160. For a more complex exhibit, there may typically be an introductory description 160 that is followed by one or more additional detailed descriptions 161, which are linked together in a logical order and called up as needed based on requests from the user for further information.
Tour-Guide Data Format: Tour Format
A tour consists of an ordered list of exhibits. A tour can be a prearranged list of exhibits, i.e., a fixed itinerary referred to as a "canned tour." A tour can also be assembled by the intelligent agent tour-guide software, which creates the ordered list based on expressed preferences of the user. The downloaded database typically may include a collection of "canned" tours. For example, there may be a "one hour art museum tour", a "three hour battlefield tour", an "all day tour of the city landmarks," and the like.
An initial task of the intelligent agent virtual tour-guide is to match one of the canned tours 164, 166 to the preferences of the user. In addition, the intelligent agent virtual tour-guide selects a beginning point for the selected tour, typically at the exhibit closest to current location of the user.
If none of the canned tours 164, 166 is suitable to match the preferences of the user, the intelligent agent virtual tour-guide may construct an original tour from the exhibit records (150 in
As another example, if the user indicates that only a short amount of time is available for a tour, the intelligent agent software selects fewer exhibits, and/or selects exhibits that are closer together. One way to create a short tour is to remove exhibits from a longer canned tour so that the total time required for the modified canned tour matches the time available to the user. In the alternative, the intelligent agent software may ask the user to indicate preferences and priorities of each exhibit in a long tour, in order to allocate the available time for a short tour. The tour exhibits may also be reordered according to the priority of expressed user preferences rather than the shortest route.
Alternate Embodiments
A wireless virtual tour-guide system is embodied in combination with a wireless data system as shown in the alternate embodiment of
An alternative embodiment to either a GPS location module or antenna triangulation is to present a map to the user on the display and have the user request or indicate his location on the map. Such feature would permit the user to receive a tour in any locale without a GPS receiver or triangulation system, so long as the user provides periodic location updates to the intelligent agent. The self-location feature would also permit the user to take a web based virtual tour in any country or city by indicating a desired location on a corresponding map. Such trial virtual tour using a web enabled virtual tour-guide permits the traveler to explore the exhibits at a destination before actual arrival. Virtual tours are available from any user location by visiting the virtual tour-guide web site (84 in
There are two types of location information of significance in the present invented web enabled wireless tour-guide system. First, the user specifies a general first location for the tour. The tour guide web site then constructs a tour of exhibits in the vicinity of the supplied first location. Second, while on the tour, the user supplies second location information as to the user's location on the tour. The tour guide web site provides descriptions of the individual exhibit based on when the user is near an exhibit. For a virtual tour, the second location(s) are not real. For an actual tour, the second location(s) are the actual physical location(s) of the user. In either type of guided tour, the first location may be either virtual or actual. A user may request a tour either before or after arrival at the desired destination.
The wireless data system of
Elsewhere connected to the Internet is a virtual tour-guide web site 84. The virtual tour-guide web site 84 may include a voice over IP interface 86, a natural language processor 88, an intelligent agent tour-guide 90 and a database of historical, cultural and entertainment information 92.
The operation of the system of
The portable computer translates 102 voice commands using voice recognition or other software, into voice over IP format, and processes received text to speech 106 as well as VXML commands into audio. Also, the portable computer reports 101 its location over the TCP/IP connection 104.
At the virtual tour-guide web site 116, the user identity and location is received 108. Standard browser cookies are used to identify previous visitors to the virtual tour-guide web site 116, without requiring a specific user identity (e.g., without an actual name). If the user has previously visited the virtual tour-guide web site 116 (determined from the cookie), the user preferences are retrieved at step 110. If the user is a first time web site user (determined by the lack of a cookie), a preferences file for the new user is established at step 110. Alternatively, the new user may prefer to register at the virtual tour-guide web site 116 and communicate the user's personal preferences.
The virtual tour-guide web site 116 receives and processes user requests and responses at step 114, which requests/responses may be by voice input or by keyboard input. In response to user requests, a local tour is constructed or selected at step 112. A series of questions, instructions and responses are generated at step 113 in connection with the generated tour at step 112. The intelligent agent (software layer 90 in
Hybrid Approaches
A key difference between the embodiments of
A hybrid of the above two approaches provides a logical way to deploy a web enabled virtual tour-guide system, which also provides a migration path for continued growth. Beginning with a single web site provides the opportunity to establish uniform data format standards for exhibits and tours used by the intelligent agent virtual tour-guide software.
An initial database limited to the most popular exhibits and tours for a single city, for instance, is easily accommodated on a single web site. Later, additional web sites (28 in
Linking to plural web sites (28 in
Another difference between the embodiments of
Interactive Tour Guide
A third embodiment that does not require a continuous online connection to the Internet is shown in
To obtain the interactive tour-guide software, a PDA or portable tablet laptop computer 600 is coupled to a tour guide web site 614 via the Internet 612 and Internet service provider (ISP) 610. A tour guide web site 614 contains a library 620 of interactive guidebooks (software forming individual interactive tour guides for each given city or location). Each interactive guidebook (interactive tour-guide) contains an intelligent agent tour guide, a respective database of exhibits and a respective dynamic city map.
To obtain an interactive tour guide for a specific city, the user connects to the tour guide web site 614 and selects a desired city 616. In response, the tour guide web site 614 downloads 618 an interactive tour guide for the selected city to the PDA or portable tablet laptop computer 600. Although the Internet service provider is shown as a wireless ISP 610, the PDA 600 may receive its interactive tour guide software and dynamic city map by any alternative connection to the Internet or even by preloading such interactive tour guide software and dynamic city map from a CD ROM or other media.
In operation, the user launches the interactive tour guide program on the PDA 602. A dynamic city map appears on the screen (
That is, in order to function as an interactive tour guide, the user indicates his physical location on the dynamic city map to the intelligent agent tour guide software 630 so that the interactive tour guide can provide the rich set of instructions, interactive questions, suggestions, directions and exhibit information relevant to the tour being conducted by the interactive tour guide.
The user indicates his location information 626 to the intelligent agent tour guide software 630 through one of several methods. The tourist may indicate his position on the dynamic city map by first clicking on a LOCATE button 826 and then clicking on the dynamic city map. In response to entering location information, a moveable tourist "icon" such as a small stick
In the case where the PDA includes a GPS module, the stick
A compass rose (713 in
Similar to the operation of the virtual tour guide web site (116 in
The intelligent agent tour guide 630 receives and processes user requests and responses at step 628, which requests may be by voice via microphone 624 or by clicking on designated portions of the screen of the PDA 602. In response to user requests, a local tour is constructed or selected at step 634. A series of questions, instructions and responses are generated at step 636 in connection with the tour generated at step 634.
Exhibits are stored in a relational database 638. Construction and revision of a local tour at step 634 may be implemented in using relational database technology such as standard structured query language (SQL) technology. In a relational database for example, data related to buildings may be stored as a single entity "building" data table while data relating to an architect may be stored another entity "architect" data table. Many-to-many relationships may be established by using a "building/architect" association table. In such manner, a tour consisting of all the buildings designed by single architect may be easily constructed by a simple database query.
As another example, data related to historic sites may be stored as a single entity "historic site" data table while data relating to a historical figure may be stored another entity "historical figure" data table. Again, many-to-many relationships may be established by using a "historic site/historical figure" association table. In such manner, a tour consisting of all the historic sites related to a single historical figure is easily constructed by simple database query.
As before, the user can customize the tour in progress by expressing special interests and indicating areas of interest in non-interest. The intelligent agent tour guide 630 "learns" from the requests and response of the user so that the tour guide becomes more knowledgeable with experience. For example, the intelligent agent tour guide will remember that a user in New York City had a strong interest in art museums. Later, when running another interactive tour guide for Paris, the intelligent agent tour guide software will remember such preference and suggest a tour of local art museums.
Dynamic City Map
A dynamic city map provides a graphical interface and between the user and the interactive tour guide. For example,
A dynamic city map allows the entire city to fit into the limited space of the personal digital assistant. The opening screen shows an overall map of the city, with individual districts presented schematically, each shown in a different color and labeled by name. Tapping (i.e., clicking on) any of the individual districts opens a district map, in the same orientation as the overall map, and showing city blocks (in gray), streets and avenues (in white, and street/avenue labeled in black), parks and open spaces (in green, also labeled), and about thirty to forty "sites" (in blue), i.e., "exhibits" that are places of interest to a tourist.
The user indicates an area of interest by clicking on the map. Selecting the area for Greenwich Village 710 will bring up the display of
To aid in orientation, the district name appears in the lower navigation panel, (i.e. Greenwich Village) alongside "zoom in; and "zoom out; buttons 814, 816 which allow the user to survey a smaller or larger part the area. An additional button 812 labeled "Fit" reverts the "zoomed" size map to its "district" size.
Four arrow buttons on the top, bottom, left and right, corresponding to north (uptown) 818, east 820 and west 822, and south (downtown) 824, allow the user to navigate or "drag" the district map in any direction.
A neighborhood borderline indicates when a new district appears on the screen, and the district name in the lower navigation panel automatically changes accordingly if the curser moves into that district.
The dynamic city map contains various controls to provide an overview 810, a guided tour 910, a wander mode 1010, various scenes 1110 and information about transit lines 1510.
Various points of interest to tourists are indicated as "hot spots" (dynamic links or hyper links) on the dynamic city map. The clicking or tapping on any of the dynamic links will bring up information box about the exhibit. In addition to a textual description of the exhibit and its history, the information box may contain a photograph of each exhibit as it exists in the present day, as well as a photograph of the exhibit as it existed in the past. The past and present photographs may blend into each other in the manner of time-lapse photography, either going forward or backwards in time.
Hyperlinked City Descriptions
Unlike a printed guidebook, the exhibit descriptions in an interactive tour-guide are cross-linked (hyperlinked) to each another in a dynamic, interactive manner. Each district is described (by text, voice or video) through three or four related screens or panels. One screen provides an overall introduction to the district while the other screens describe notable aspects of the district's history, character, famous personalities, as well as many local services.
The texts of both the district overviews and the local exhibits contain certain terms, names, and phrases that are highlighted in blue; these are hyperlinked to other "screens". Further desired information can be "drilled down" by clicking on successive hyperlinks. Finally, a hyperlinked alphabetical index to all proper names of places, buildings, events, etc. allows users to search the interactive tour-guide for any specific and pertinent City information. The interactive tour-guide is the first handheld mobile wireless City encyclopedia.
The interactive tour-guide software offers pre-arranged (canned) tours through city districts. By tapping the "guided tour" button 910 at the upper navigation panel, one or more tour routes appear on the screen, each designated by a different color and letter. Tapping the "start" or "end" point of any of these tours brings up a panel describing that particular route, along with a prompt to the first exhibit on the tour. The text entry for the selected "site" concludes with instructions to the next exhibit, and so on.
In operation, clicking on the guided tour button 910 will bring up the display of
To begin a tour, the user indicates his location as being at a given first exhibit. The interactive tour guide then delivers either spoken, textual, graphic and/or video information about the first exhibit. The user may ask for more information (by spoken word or by data entry) about the present exhibit or indicate that he wants the tour to continue on to the next exhibit. If so, the interactive tour guide will give travel directions (again, by speech, text, graphics and/or video), explaining to the user how to go to the next exhibit on the tour. Video may include a talking avatar. After the user indicates (again, by spoken word or by clicking on the screen) that he has arrived (is located) at the new exhibit, the interactive tour guide will provide information about the new exhibit. A silent mode of output (i.e. text or images only) may be preferred in a quiet environment, unless headphones are available. A silent mode of input (i.e. data entry) may be preferred in a quiet environment where speech would disturb others.
If the user has not indicated any preferences, tours A, B and C will be canned tours. However, if the user has previously indicated preferences, the suggested tours will reflect those preferences. For example, if the tourist has indicated "no interest" in art museums, then the suggested tours will skip over art museums. A large variety of intelligent agent tour-guide responses (630 in
Continuing the above example, should the user indicate an interest by tapping on a specific art museum outside of the tour route, the intelligent agent tour guide might be programmed to ask, "Would you like to see this art museum?" If the answer was yes, directions are provided thus departing from the originally configured tour. Then, after departure from the art museum, the intelligent agent tour guide might be programmed to ask, "Would you like to see other art museums?" In such manner, the intelligent agent tour guide modifies the preferences of the tourist by learning what the tourist likes and dislikes.
Wander Mode
The interactive tour-guide system of the present invention offers users an opportunity to "wander" throughout the city, going "off" the selected tour route, selecting their own routes as they move through a district. At the lower left corner of most descriptive text "panels," there is a yellow icon ["w"], which, when tapped (selected) by the user, indicates adjacent "sites" of interest by flickering blue "site" buttons.
Clicking on the wander mode button 1010 will bring up the display of
The interactive tour guide then provides directions to the next exhibit. Upon arrival (when the tourist provides new location information), the interactive tour guide provides information about the selected exhibit. So long as the interactive tour guide remains in wander mode, a new selection of neighboring exhibits relative to the current exhibit, will flash on and off.
A specialized variety of prearranged (i.e. canned) guided tours are themed tours. Clicking on the themes button 1110 will bring up the display of
Historical (Archival) Photographs of Exhibits
A special visual feature of interactive tour guide software, which takes advantage of its multi-media capability, is a matched pair of images that may accompany the selection of each exhibit. The matched pair of images are a current photograph and a custom-created current (contemporary) photograph (or sketch) that precisely recreates a historic archival photograph of the exhibit from the same point of view.
The initial view of each selected exhibit opens with the contemporary photograph, which then, in a second or two, automatically dissolves into the archival view of the exhibit as it was in the past. A pair of control buttons below the image, which are labeled with the respective dates corresponding to the past and present images, allow the user to switch back and forth between the contemporary image and the archival image.
Overlaid Information
To facilitate traveling between exhibits, the dynamic city map includes overlays of available transit lines 1510. As shown in
Revenue Models
Revenue to support the interactive tour-guide system may be derived by levying tour fees, subscriber fees, advertising fees or licensing fees. The present system includes features that permit any revenue model or a combination of revenue models to be used. In the tour fee model, a fee may be charged to a credit card before the interactive tour-guide is downloaded. In the case of a wireless web enabled embodiment, a fee may be charged to a credit card before the guided tour is delivered. The fee may be either a flat fee per tour, a fee proportional to the length of the tour or the amount of data delivered during the tour. Charging by the amount of data delivered permits revenue sharing among various owners of copyrighted tour materials used in the tour.
Advertising may be included in the tour via the intelligent agent software. Users are given a list of nearby restaurants when the user asks, for example, "Where can we eat?" or says, "We're hungry." The intelligent agent can suggest a restaurant stop at certain points in a tour, for example. Other types of businesses of interest to users include lodging, travel and car rental agencies, clothing stores, movies, theatres, sporting events, souvenir shops, beauty parlors, drug stores, gift shops and the like. In each case, the intelligent agent is responsive to key words in a user's inquiry to look up in its advertiser database the closest business or businesses, which correspond to the user inquiry. The known geographic location of the user is taken into account in selecting the closest recommendations. Advertising revenue may be based on subscription, i.e., the amount of time a business is listed in the database such as a predetermined cost per month. In the alternative, advertising revenue may be based on the number of times a referral to such business is provided to the user, i.e., at a predetermined cost per play.
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|Vehicle roll control method using controllable friction force of MR dampers
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|System and method for displaying information using a compass
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|Adaptive pattern recognition based controller apparatus and method and human-interface therefore
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|Providing interactive services to enhance information presentation experiences using wireless technologies
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|Guide route generation methods and systems
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|Method for providing route guidance to a destination to which a vehicle is driven
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|31 mai 2005
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|Horozov Tzvetan T
|Location-based recommendation system
|31 mars 2006
|30 nov. 2006
|Gold Jonathan A
|Displaying images in a network or visual mapping system
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text:
This profile was last updated on 1/30/15 and contains information from public web pages and contributions from the ZoomInfo community.
Dr. Morris Vaagenes Sr.Wrong Dr. Morris Vaagenes Sr.?
Senior Pastor
Phone: (763) ***-**** HQ PhoneEmail: m***@***.net
Lutheran Church
1200 69 Th Avenue North
Brooklyn Center , Minnesota 55430
United States
Company Description: The library exists to help support the mission of LCM: to be a "life giving church, providing opportunity to personally know Jesus Christ and to make Him known... more
Pro2015_Iteration9_NoTests.148[04] SEIDXWK-42


text:
|SUMMARY: If you publish an email newsletter (either for marketing purposes or as a business in and of itself) this is an article worth checking out. We interviewed 5-year newsletter publisher Brent Winters (who has 470,000 opt-in readers) to bring you this exclusive story on why he finally went to HTML this month at long last, and what wisdom he has got to share with other newsletter publishers on format and HTML layout issues (plenty). Includes useful hotlinks to samples and more info.
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Mail-to-Order Marketing Takeaways: 5 lessons to be learned from subscription boxes
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text:
SIZE 2 oz
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All orders shipped complete, when all merchandise is in-stock; no partial orders shipped. You will not be charged until your order is shipped.
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According to ARCONA, pure is powerful. Known for their high quality, luxury formulations, ARCONA crafts seriously effective skincare. Their secret? All products are made from the finest active ingredients, cold-processed at very low temperatures in small batches. The result is state-of-the-art skincare that delivers unparalleled results.
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text:
Home >
Brands >
Bathroom >
Shower Products >
Handheld Accessories
Stainless steel
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Poor Uncle Owen and Aunt Beru... Oh Well!
View Single Post
February 5 2013, 09:48 AM
Location: Escaped from Delta Vega
Re: Poor Uncle Owen and Aunt Beru... Oh Well!
Kelthaz wrote:
TREK_GOD_1 wrote:
Set Harth wrote:
I don't think we should assume all Council members are at an equal level of ability.
Then what are they doing on the Council? Even Padawan Obi-Wan seemed to be stronger in various Force abilities than Mundi.
By that logic, Obama is the best hand-to-hand fighter in the world. After all, he is at the head of the most powerful military in the world.
Your point is illogical. Unlike the president, a Jedi Council member is an active user/participant, and is called on to use his various supernatural abilities, which they are all tested before becoming a knight, then master. The president has no such measuring stick, as each who ever held that title had no measured standard for power, skill or competency. Ultimately, their ability to get that job is based on the whim of voters, mass manipulation and a pile of money.
So again, the Jedi Coucil members should be expected to be more than cardboard cutouts for Sidious to cut down.
"...to be like God, you have the power to make the world anything you want it to be."
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Category:Alabama countiesEdit This Page
From FamilySearch Wiki
This category has the following 73 subcategories, out of 73 total.
Pages in category "Alabama counties"
The following 67 pages are in this category, out of 67 total.
- This page was last modified on 20 August 2012, at 22:29.
- This page has been accessed 1,041 times.
BROWSEby country by topic
Future Changes to the Wiki
Changes are coming to the FamilySearch Research Wiki in the near future. Find out more on the Wiki Community News page.Community News


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Please use this identifier to cite or link to this item:
|Academic staff recruitment and retention strategies at the University of Limpopo
|Ahwireng-Obeng, Frederick
Mokoditoa, Jocelyn Molly
|Employee retention
Employee recruitment
|Issue Date:
|University of Limpopo (Turfloop Campus)
|The paper examines the causes of the high turn-over rate and the non-retention of the academic staff at the University, and come up with possible solutions to curb the problem. The study addresses the factors that affect the academic staff recruitment and retention strategies. The paper further address identification of factors contributing to the high turnover rate of the academic staff at the University of Limpopo, analyze causes of the problems, work on the feedback obtained from interviewees, and make recommendations that will enable the University to come up with possible and implementable strategies for the recruitment and retention of the academic staff. This was evident by the results of the study through the literature review and the interviews held that academic staff recruitment and retention is a problem. It is therefore advisable for the University to take note of the results of this study, and that there should be a turn-around strategy that could be implemented and monitored. The Human Resource department should have a database that tracks the career path of all academic staff, and notify all appointees who are coming up for tenure. This notice could go out at the start of the last but one year before the appointees become eligible for appointment with tenure. The university must develop a culture of reasonable, clearly articulated, and enforced deadlines for processing applications for promotion. Human Resources department have a role to play in the promotion process as well. Access to information about the promotion process can be enhanced by revamping the websites for some of the institutions which are not really helpful in this respect. Relevant documents (e.g., conditions of service, appointment and promotion guidelines, benefits) can then be made accessible via institutional websites in a very organized manner than is currently the case in many universities
|Thesis (MPA)--University of Limpopo, 2011
|Appears in Collections:
|Theses and Dissertations (Public Administration)
Files in This Item:
|Mokoditoa, J. M..pdf
|519.26 kB
|Adobe PDF
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This slate-style hybrid has new Core M Skylake CPUs, plus a Surface-like kickstand and keyboard.
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Lenovo's Y-series gaming laptops get new CPUs, plus gamer-centric accessories.
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We don't know when it'll arrive or how much it'll cost, but the water-cooled Asus ROG GX700 sounds like a monster gaming PC.
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Regression 184.108.40.206 first take review promo dek one.
The Samsung Galaxy A7 is a svelte 4G smartphone, but doesn't include the latest Android software.
If you've ever wanted to connect a streaming and backup device to your TV that only works with Canon gear (and SD/CF cards), you're in luck.
This all-in-one adopts the same curved display as Samsung's big-screen 4K TVs.
The Wacom Creative Stylus 2 is a great, well-priced pressure-sensitive stylus for iPad artistes.
The Replay XD Prime X might not have the name recognition of others in the category, but thanks to its lightweight, ultracompact and waterproof body; solid 1080p video quality and pro-centric features, it deserves a spot on your short list.
Siemens adds iOS connectivity to a high-end oven, steam oven and dishwasher, with Android and more appliances to follow next year.
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text:
Benjamin Raich to miss rest of worlds
Updated: February 16, 2011, 9:10 AM ETAssociated Press
GARMISCH-PARTENKIRCHEN, Germany -- Benjamin Raich of Austria has been ruled out of the rest of the world championships after hurting his left knee in a crash during the team event.
The Austrian ski federation says the 2007 overall World Cup champion will have surgery after tearing ligaments and damaging cartilage and the meniscus during the first run of Wednesday's parallel slalom event.
The 32-year-old Raich, who has won seven medals at the worlds since 2001, will miss Friday's giant ...
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Angel Flight South Central
Rating: 5 stars 8 reviews
Issues: Health
Location: PO Box 763760 Dallas TX 75376 USA
Target demographics: people of all ages in need of medical care not available locally!
Direct beneficiaries per year: 2400 people
Geographic areas served: Texas, New Mexico, Oklahoma, Arkansas, Louisiana
Programs: free flights in small, 4-6 passenger planes.
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GreatNonprofits badges allow you to raise awareness of your favorite nonprofits on your own web sites!


text:
This book was written during the three last months of 1915 and the first month of this year in the form of letters from France, Greece, Serbia, and England. The writer visited ten of the twelve sectors of the French front, seeing most of them from the first trench, and was also on the French-British front in the Balkans. Outside of Paris the French cities visited were Verdun, Amiens, St. Die, Arras, Chalons, Nancy, and Rheims. What he saw served to strengthen his admiration for the French army and, as individuals and as a nation, for the French people, and to increase his confidence in the ultimate success of their arms.
burn down when the architect who designed the Place de la Concorde, in Paris, and the buildings facing it was still alive; and after his designs, or those of his pupils, Bordeaux was rebuilt. So wherever you look you see the best in what is old and the smartest in what is modern.
Certainly when to that city President Poincaré and his cabinet moved the government, they gave it a resting-place that was both dignified and charming. To walk the streets and wharfs is a continual delight. One is never bored. It is like reading a book in which there are no dull pages.
Everywhere are the splendid buildings of Louis XV, statues, parks, monuments, churches, great arches that once were the outer gates, and many miles of quays redolent, not of the sea, but of the wine to which the city gives her name.
But to-day to walk the streets of Bordeaux saddens as well as delights. There are so many wounded. There are so many women and children all in black. It is a relief when you learn that the wound
When the economic downturn ends Matty Cruzs co... Read more
Cara Devon has always suffered curiosity and im... Read more
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See it as donating a moment of your social media time, every little thing helps us improve and stay online.
The list of books below is based on the weekly downloads by our users regardless of eReader device or file format.
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text:
- 3Promote
Stationery Cards
Tropical Hibiscus in Red island art paintingby Surfer Art By Julia Watts Coleman
Set of folded stationery cards printed on bright white, smooth card stock to bring your personal artistic style to everyday correspondence. Each card is blank on the inside and includes a soft white, European fold envelope for mailing.
"Tropical Hibiscus in Red" island art painting
Colorful red hibiscus among green leaves tropical floral painting
Island & beach inspired art by Julia Watts Coleman


text:
Photo by Brian Leatart
Of all the aspects of Tuscan cuisine, not one stands out as much as its overwhelming variety of fresh vegetables. Zucchini is a favorite, of course, and so are the blossoms. The sweet, succulent flowers are prepared in countless ways, including fried, sautéed and, as in the following recipe, stuffed and baked. If you don't have zucchini in your garden, look for the blossoms in the supermarket or at a farmers' market. They are usually sold still attached to baby zucchini, which is how they are used in this recipe.
Leave a Review
This recipe is the best! We make it every year when our zucchini are flowering and everyone who has ever tried it raves about it.flag if inappropriate
The most inexperienced cook in our family made these and they were wonderful! He said he would double the fresh thyme next time, though, and we used a generous squeeze of lemon at the table. We voted them "company worthy" and wondered if a good variation would be to add some crab to the mix. yum.flag if inappropriate
I made this with just stuffing the blossoms unattached and then cut bigger zucchinis into strips. It was great but I would add more cheese and a little more seasonings in the bread stuff.flag if inappropriate
This was fabulous and so easy! The blooms I had were approx three inches long -- very easy to fill with the mixture. I used Dare's Cabaret Crackers (in the blue box) instead of bread crumbs and since I was only making four I used just the egg white. Didn't measure ingredients and had a shallot so used that. Squirted Pam (or some equivalent) in my glass baking dish rather than coating with oil and that worked. Even with my substitutions I didn't screw this up, but sounds like some people managed. Don't let them deter you. Try it!flag if inappropriate
I would use bigger zucchinis next time. The blossoms broke off when I served them. Also, not sure about the directions; Do you put the bread crumb mixture in the bottom of the pan?? I put a little on the bottom and it came out crusty--very good. Love this one too.flag if inappropriate
It was very good and unique. I had never eaten nor used zucchini blossoms. If I wanted to impress I would make this again. It doesn't save well.flag if inappropriate
Not a good recipe! The bread crumbs baked with egg were plump and moist almost like a heavy grain. The other flavors/textures were overstated too. How do these ingredients combine well as a stuffing for something as delicate as baby zucchini blossoms? I should have known.flag if inappropriate
I made this for close friends and they were not too impressed. I have to agree. It just seemed like more work than it was worth. BUT, big but, I will give it another try.flag if inappropriate
the bread crumb mixture was soggy, maybe i made it incorrectly. you need to let the readers know to inspect the inside of the blossom. if it is brown, do not use it and to check for little bugs. this recipe sounded great but i was not saitsfied with it however i do like your program.flag if inappropriate
I have made this recipe over and over and have shared it with many of my friends that have tasted this dish. If has been my signature 1st course many times. Delicious.flag if inappropriate


text:
The Son'a
View Single Post
October 7 2013, 04:44 PM
Fleet Captain
Location: CommishSleer
Re: The Son'a
Edit_XYZ wrote:
The federation is different from the klingons, romulans, etc because they don't go around conquering species, having an orwellian state complete with political police, etc etc.
That does NOT mean that 600 baku trespassing on an uninhabited federation planet can claim it as their own.
Much like cardassians, klingons or romulans trespassing on federation worlds can't claim them as their own. The federation might cede planets to them in certain conditions, rather than fight a war, though (which is about real-politik, not the laws in place).
In general:
Planets within federation space with indigenous conscious species are not federation planets.
Uninhabited planets - AKA with no indigenous conscious species - within federation space ARE federation planets. Much like uninhabited planets within romulan or klingon space are romulan/klingon planets. Trespassers don't change this fact - even when they've been around for a while, hiding.
So if say the Earth wasn't in the Federation and had established a Mars Colony or an Alpha Centauri colony then the Federation could say blow Mars up or order 'us' off it if they felt like it because the humans on it weren't native and Mars as well as Earth is in Federation territory
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A rare case of metastatic renal carcinoid
Department of Urology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan
BMC Urology 2010, 10:22 doi:10.1186/1471-2490-10-22Published: 14 December 2010
Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids.
Case presentation
We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract.
The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings.