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Large Animal Models of Hematopoietic Stem Cell Gene Therapy
Grant D. Trobridge1,2 and Hans-Peter Kiem1,2,3
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle WA
2Department of Medicine, University of Washington School of Medicine, Seattle WA
3Department of Pathology, University of Washington School of Medicine, Seattle WA
Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene
therapy. Here we review the advantages of large animal models, their contributions to the field of
HSC gene therapy, and recent progress in this field. Several properties of human HSCs including
their purification, their cell-cycle characteristics, their response to cytokines, and the proliferative
demands put on them after transplantation are more similar in large animal models than in mice.
Progress in the development and use of retroviral vectors and ex vivo transduction protocols over
the last decade has led to efficient gene transfer in both dogs and in nonhuman primates.
Importantly, the approaches developed in these models have translated well to the clinic. Large
animals continue to be useful to evaluate the efficacy and safety of gene therapy, and dogs with
hematopoietic diseases have now been cured by HSC gene therapy. Nonhuman primates allow
evaluation of aspects of transplantation as well as disease-specific approaches such as AIDS gene
therapy that can not be modeled well in the dog. Finally, large animal models have been used to
evaluate the genotoxicity of viral vectors by comparing integration sites in hematopoietic
repopulating cells and monitoring clonality after transplantation.
Hematopoietic stem cells (HSCs) are excellent targets for gene therapy due to the relative
ease with which they can be manipulated and their ability to repopulate the entire
hematopoietic system for the life of a patient. Early experiments showed that bone marrow
(BM) transplantation is highly effective due to the ability to ablate the endogenous
hematopoietic system with low-dose irradiation. Lethally irradiated mice that are infused
with BM from an untreated mouse are rescued via repopulation with the donor's
hematopoietic system.1 This approach lends itself to genetic modification since a modest
number of donor cells can be easily harvested, exposed to a vector ex vivo, and then simply
infused intravenously into an irradiated recipient. This is in contrast to in vivo or ex vivo
gene therapy for solid organs, where the ability to deliver genes to a high percentage of a
very large number of cells within a complex tissue structure is extremely challenging. The
promise of HSC gene therapy has led to extensive experimentation in small and large animal
models, and to successful clinical trials.
HSCs are defined by the ability to self renew, differentiate into all hematopoietic lineages,
and reconstitute hematopoiesis in a lethally irradiated host long-term. This definition
excludes the use of in vitro assays to evaluate gene transfer to HSCs, and necessitates the
use of animal models. The progeny of long-term HSCs expand exponentially in vivo in a
Correspondence should be addressed to: Hans-Peter Kiem, M.D.; Fred Hutchinson Cancer Research Center; 1100 Fairview Ave N
D1-100; P.O. Box 19024; Seattle, WA, 98109-1024. Phone: 206-667-4425; Fax: 206-667-6124; firstname.lastname@example.com.
NIH Public Access
Author Manuscript
Gene Ther. Author manuscript; available in PMC 2011 August 1.
Published in final edited form as:
Gene Ther. 2010 August ; 17(8): 939–948. doi:10.1038/gt.2010.47.
NIH-PA Author Manuscript
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Page 2
hierarchy resulting in multipotent progenitors, progenitors and ultimately billions of mature
leukocytes. This imposes some criteria for efficient gene transfer. The HSC must be
permissive for transduction by the proposed vector, the vector genome must be efficiently
maintained in daughter cells, and transduction must not impair the ability of the HSC to
renew, differentiate, or expand. To date only retroviral vectors including gammaretroviral,
lentiviral, and foamy vectors have fulfilled these criteria in large animal models. These
integrating vectors take advantage of mitosis to create a copy of the vector provirus in each
daughter cell, ensuring transmission to all HSC progeny during hematopoiesis. Here we
review the advantages of large animal models, contributions of large animal model studies
to the field of HSC gene therapy, and recent progress in this field.
Limitations of mouse models for HSC gene therapy
The mouse model has been essential to advance HSC gene therapy, and early studies
showed that self-renewing clones with both lymphoid and repopulation potential could be
transduced by retroviral vectors.2-4 However, several aspects of gene transfer and
transplantation are not modeled well in mice (Table 1). It is not possible to assess long-term
engraftment in a short-lived animal model, and differences between mouse and human host
cell receptors initially led to overestimates of gene transfer efficiency in the mouse model.
Murine leukemia virus (MLV)-based vectors pseudotyped with the murine ecotropic
envelope attained very high gene transfer efficiency to primitive mouse repopulating cells,
estimated at 50% even with relatively low titers.2 Gene transfer using the ecotropic envelope
is restricted to mouse cells, so the amphotropic envelope was used in early large animal and
clinical studies.5,6 In these early studies, transient marking of less than 0.1% of repopulating
cells was obtained in the dog, and in patients marking was also low, with an estimated
average proviral copy number of 0.01 to 0.1. Transduction of dog and human progenitors
with the amphotropic envelope is much less efficient than transduction of mouse progenitors
with the ecotropic envelope, in part because of low expression of the amphotropic receptor
on HSCs.7 This obstacle has been largely overcome by using envelope pseudotypes that
efficiently transduce HSCs, including the vesicular somatitis virus glycoprotein (VSV-G).
However, other differences between mouse and human HSCs affect the transduction
efficiency including their cell cycle status. Approximately 75% of mouse HSCs are outside
of G0.8 Direct analysis of the cell cycle status of HSCs is not possible in humans or large
animals because they cannot be purified to homogeneity. However, studies analyzing
telomere length have estimated that mouse HSCs divide every 2.5 weeks, cat HSCs every
8-10 weeks, baboon and macaque HSCs approximately every 36 weeks, and human HSCs
every 45 weeks.9-12 This is an important consideration for gene transfer since
gammaretrovirus, lentivirus and foamy virus vectors do not transduce quiescent G0 cultures
as efficiently as they transduce actively dividing cultures.13-15 In mouse studies, donor mice
are typically treated with 5-fluorouracil to increase cell cycling and transduction.2-4 There is
also a difference in the proliferative demand placed on repopulating cells of the mouse
versus large animals or humans. A human makes a similar number of red blood cells in a
day (2.5×1011) to what a mouse makes in a 2-year life span.11 A single cell can repopulate
the entire hematopoietic system of a mouse,2,16 but to date engraftment in primates and dogs
has always been polyclonal, with the exception of studies where leukemic or pre-leukemic
expansion has been observed. Mice also have limitations for evaluating the genotoxicity of
integrating viral vectors, since mouse cells are more readily transformed than human cells. It
has been estimated that five distinct alterations are required to transform normal human
primary cells but that only two or three events are necessary for mouse cells.17
Immunodeficient mouse models that allow transplantation of xenogeneic human
repopulating cells have overcome some of these limitations. The latest generation of non-
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obese diabetic/severe combined immunodeficient (NOD/SCID) immune deficient mice do
not express the IL-2 gamma receptor, and allow robust myeloid and lymphoid development
in vivo.18,19 Evaluating gene transfer to human SCID repopulating cells (SRCs) in this
model is powerful, since the harvest of donor cells, enrichment of HSCs, and ex vivo
transduction conditions can be performed exactly as in clinical studies. However, there is
some evidence that SRCs are not true long-term repopulating cells. Baboon CD34+ cells
marked with a gammaretroviral vector were infused into both NOD/SCID mice and a
baboon.20,21 Specific SRC clones were detected in baboon short-term (2-6-week), but not
long-term (6-, 12-month) repopulating cells. Also, to date the relatively high levels of HSC
gene transfer observed in NOD/SCID mice have not been observed in clinical trials.
The transplantation aspect of HSC gene therapy is also not modeled as well in mice. Early
BM transplantation studies in mice were initially not successfully translated to the clinic,
and subsequent studies in dogs and primates helped to define the obstacles to engraftment
and to establish this now commonly employed therapeutic approach.22 In these studies
inbred mouse strains did not predict the importance of HLA-matching for successful
transplantation. HLA-matching is not a concern for autologous HSC gene therapy
approaches, but other aspects of transplantation are also better modeled in large animals. For
example, conditioning regimens with radiation and/or chemotherapy have translated well
from the dog model.22 In contrast, in immunodeficient mice, non-myeloablative
conditioning allows robust engraftment of even xenogeneic cells. Thus, conditioning
regimens which are a critical component of HSC transplantation are not modeled well in the
mouse. In non-immunodeficient mouse models the source of cells is different. CD34+ cells
are used in large animal models and patients, but typically lineage−, Sca-1+, c-kit+ positive
(LSK) cells are used in mice which are CD34low/− (ref16 due to differential expression of
CD34 in mouse and human HSCs.23,24
The dog model for HSC gene therapy and the competitive repopulation
The dog has several advantages for HSC gene therapy studies. Dogs can be cared for with
relative ease, have large litters, and are less expensive to procure and maintain than
primates. Performing the many procedures required for HSC gene therapy studies including
routine health exams, administering antibiotics, and performing peripheral blood draws and
BM biopsies are also more easily performed on dogs than primates. Importantly, unlike in
the mouse model, canine and human CD34+ bone marrow cells have similar in vitro and in
vivo characteristics.25 Also, long-term studies can be performed in dogs, and repeated
sampling of peripheral blood and bone marrow are easily performed. There are canine
models of several hematopoietic diseases including alpha-l-iduronidase deficiency, X-linked
severe combined immunodeficiency (X-SCID), canine leukocyte adhesion deficiency
(CLAD), and pyruvate kinase deficiency, which allow preclinical testing in a disease setting.
Another advantage of the dog for allogeneic gene transfer studies is that characterization of
the dog leukocyte antigen (DLA) type I and II loci26,27 allows for DLA-matched transplants.
As described above, early studies for canine HSC gene transfer met with limited success as
did early clinical studies. However, subsequent studies in the dog established means to
efficiently mobilize HSCs, culture these cells ex vivo, transduce them with retroviral
vectors, and achieve efficient engraftment in vivo.28-33 Importantly, these conditions have
translated well to the clinical setting. The competitive repopulation assay34,35 was key to
establishing these conditions since variability in outbred dog populations would have
otherwise necessitated the use of many animals. By comparing two or more experimental
conditions directly in the same animal, inter-animal variability is eliminated, and a small
number of animals can identify the best approach (Figure 1). In early experiments, retroviral
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vectors with sequences that differed by only a few bp were used to compare different
envelope pseudotypes from different retroviral packaging cell lines28 or to evaluate gene
transfer to different sources of HSCs.36 The two vectors could be differentiated by PCR
amplification and electrophoresis to determine the best conditions for HSC gene transfer.
Fluorescent markers such as enhanced green/yellow fluorescent protein (EGFP/EYFP) can
also be used which allow accurate evaluation of transgene expression in leukocytes of all
hematopoietic lineages by flow cytometry.
Gammaretroviruses pseudotyped with either gibbon ape leukemia virus (GALV), feline
endogenous retrovirus (RD114) or vesicular stomatitis virus glycoprotein (VSV-G)
envelopes can efficiently transduce dog HSCs if the ex vivo transduction is of sufficient
length, includes an appropriate cytokine cocktail for canine cells during ex vivo culture, and
includes the use of CH-296 fibronectin fragment (Retronectin). CH-296 contains the cell
binding and heparin binding domains of fibronectin and enhances gene transfer by co-
localizing vector and target cells, inhibiting apoptosis during ex vivo culture, and increasing
engraftment.37-39 Primed BM is an excellent source of CD34+ cells, but steady-state marrow
and mobilized peripheral blood can also be used.36 Canine granulocyte colony stimulating
factor (cG-CSF) and canine stem cell factor (cSCF) are typically used to prime BM, or to
mobilize PB CD34+ cells. More recently AMD3100, an antagonist of CXCR4 has been
shown effective for mobilization of HSCs40 and AMD3100-mobilized canine HSCs can be
efficiently transduced with lentiviral vectors (HPK, unpublished data). Our standard HSC
gene transfer protocols have been previously published,41 and efficient gene transfer can
been achieved using either gamma, lentivirus or foamy retroviruses (Figure 2). For foamy
and lentiviral vectors, pre-stimulation is not required, and a single overnight exposure is
sufficient for efficient gene transfer, thereby limiting ex vivo culture which can decrease
engraftment.42,43 Interestingly, when foamy and lentiviral vectors were directly compared in
a competitive repopulation assay at the same MOI (5) with a short 18-hour ex vivo
transduction protocol, the efficiency of long-term marking was remarkably similar for both
vector types.44 Canine HSC gene transfer is also efficient in the allogeneic setting, where
one promising therapeutic application is chemoprotection of transplanted cells to allow
higher dose chemotherapy for lymphoma or leukemia.45
Therapeutic gene transfer to HSCs in the dog model
Several hematopoietic diseases were first cured in the dog model using conventional marrow
allografts, setting the stage for HSC gene therapy. Pyruvate kinase deficiency in Basenji
dogs is associated with severe hemolytic anemia, where affected dogs suffer from chronic,
regenerative, hemolytic anemia, and red blood cell survival is shortened from one month to
a few days.46 Studies in the 1970s showed that marrow allografts from healthy littermates in
three young PK-deficient dogs re-established normal hematopoiesis46 and ameliorated the
disease phenotype long term.47 Allogeneic transplantation also has cured canine X-SCID,48
CLAD,49 and diminished the severity of lesions in the canine alpha-l-iduronidase deficiency
The first demonstrations of effective HSC gene therapy in the dog model were achieved for
CLAD51 and for X-SCID.52 In the CLAD study, ex vivo gene transfer using a
gammaretrovirus vector pseudotyped with GALV and expressing the canine leukocyte
integrin ITGB2 gene (CD18) resulted in 6 of 11 treated dogs achieving therapeutic levels of
corrected leukocytes. In the X-SCID study, in vivo gene delivery to neonates using a
RD114-pseudotyped gammaretroviral vector expressing canine interleukin-2 common
gamma chain (γc) was used rather than ex vivo transduction. In the setting of X-SCID,
corrected cells have a strong selective advantage and the low levels of transduced cells
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obtained by in vivo delivery were sufficient to correct the disease phenotype. The CLAD
phenotype has since also been corrected using foamy vectors.53
Nonhuman primate models for HSC gene therapy
There are some limitations of the dog model that necessitate the use of nonhuman primates
for HSC gene therapy studies. The closer genetic relationship of nonhuman primates to
humans means that primate cells respond to many human cytokines used for mobilization
and ex vivo transduction. Also, for AIDS the dog cannot model the disease, and the
nonhuman primate model has been developed.54 The choice of primate species depends on
several criteria including ethical considerations, cost, and availability. The highly sentient
nature, high cost and low availability of chimpanzees outweigh the advantage of their close
phylogenetic relationship to humans. Baboons and macaques are considered to be a more
appropriate from an ethical perspective, and are more readily available and thus inexpensive,
although the relative expense is still high. As with the dog model, BM transplantation
studies established the utility of nonhuman primates,55 and CD34+ cells are used as the stem
cell source.56,57
As in the dog model the efficiency of HSC gene transfer to nonhuman primates was initially
very low, typically less than 1% (reviewed in58). A number of conclusions were drawn from
these early studies as outlined by van Beusechem and Valerio; 1) primate HSCs were more
refractory to transduction with gammaretroviral vectors than mouse HSCs, 2) co-culture
with packaging cell lines during ex vivo culture of primate HSCs could have deleterious
effects on engraftment, 3) appropriate growth factors including SCF, IL-3 and IL-6 could
increase engraftment, and 4) the poor results in nonhuman primates were not due to large
differences in the size of the graft. In particular, it was recognized that in primates, using the
amphotropic receptor did not yield results similar to using the ecotropic receptor in mouse
studies. Following these studies, alternate envelope pseudotypes and transduction protocols
were evaluated, and efficient gene transfer to nonhuman primate HSCs was established.
Comparison of gene transfer using the amphotropic and GALV envelopes in a competitive
repopulation assay in the baboon showed that GALV was superior to amphotropic envelope,
and that marking between 1 and 5% could be established in vivo as detected by Southern
blot.35 In this study large inter-animal variation in gene transfer efficiency highlighted the
importance of the competitive repopulation assay. The use of CH-296 fragment and the
addition of MGDF and Flt-3 ligand to the ex vivo transduction further improved gene
transfer into the 5-20% range,59 and stable long-term marking in over 60% of PB cells can
be obtained when GALV-pseudotyped vectors are used with CH-296 and a cytokine cocktail
of SCF, IL-3, IL-6, MGDF, Flt3-L, and G-CSF.60
Lentiviral vectors also mediate efficient HSC gene transfer in nonhuman primates, but host
restriction mediated by TRIM5 alpha must be taken into account when using lentiviral
vectors.61 In baboons, highly variable gene transfer was observed using VSV-G
pseudotyped HIV-derived lentiviral vectors, but in one animal marking of up to 8.6% of
long-term repopulating cells was achieved. In this study a direct comparison of lentiviral and
gammaretroviral marking using a short ex vivo transduction protocol designed to maintain
the engraftment potential of HSCs showed that lentiviral vectors were superior. However,
very high MOIs (54-156) were required for efficient lentiviral transduction. Also, the
addition of cytokines was necessary for efficient transduction in this study, as has also been
observed for efficient transduction of human hematopoietic progenitors, and SRCs.62,63
In the rhesus macaque, transduction with HIV-derived lentiviral vectors is potently inhibited
by TRIM5 alpha,61-66 and long-term marking with HIV-based vectors was typically lower
than 3%, with one animal having marking levels of approximately 10% and 2% in
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Wanted liquidated, bankrupt, clearance stock!!
Got a business? Closing down? Im Looking to buy bankrupt, liquidated, bulk, end of lines, clearance stock. Willing to travel all of the u.k Send me a message what you have and I will make an offer.. Please no time wasters! Will buy anything if t

subset: commoncrawl


text:
Pacific nation ministers and negotiators are scrambling to lock in a major Pacific trade deal, as talks come to a head in the US city of Atlanta with Trade Minister Andrew Robb saying there is a 50 per cent chance the deal could be reached today.
A gene that plays a crucial role in generating energy for plants has now been discovered to help them cope with stress, a study has found.
Food and service are now the key as times change for Kalgoorlie hotels.
A WA farmer wants to get her pigs tweeting, to help challenge perceptions about animal welfare.
A poultry club in the Bega Valley is giving young producers hands-on expertise.
A large area of Aboriginal land in Central Australia is declared an Indigenous Protected Area.
A growing number of women are taking on practical stock-handling roles in the cattle industry.
Meet the heritage breed of sheep with no discernible commercial purpose.
Six young Australians tell their stories of managing mental illness for Mental Health week 2015.
Research into native plant species is set to be a boost to mine site rehabilitation.
A selection of photos sent in by ABC audience members from around Australia.More - ABC Open
Seven brilliant resources that can help you get the conversation started with kids in the classroom or at home.More - ABC Splash
David Day creates sea creatures from marine debris to raise awareness of the impact rubbish has on our environment.More - ABC Open
Travel to all corners of the continent with Clayton Donovan and Aunty Beryl on a mission to discover Australia's best dishes.More - AWAYE!


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In This Issue:
• The Last Chapter in the Louboutin Red Soled Shoe Story
• Applicants for U.S. Trademark Registrations Must Have a Bona Fide Intent to Use the Mark for All Listed Goods and Services
- Excerpt from The Last Chapter in the Louboutin Red Soled Shoe Story:
In what is likely the final ruling in the continuing story of Christian Louboutin's fight to protect its red lacquer shoe soles, the Second Circuit Court of Appeals rejected Louboutin's request that the Court amend its prior order to broaden the scope of Louboutin's trademark protection.
In September, the appeals court ruled that Louboutin has trademark rights in its lacquered red sole on footwear but only if the red sole contrasts with the color of the remainder of the shoe. The court directed the U.S. Patent and Trademark Office to make an appropriate limitation to Louboutin's registration...
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April and May #globalhomes carlhansen.com/globalhomes
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text:
So basically I have tried numerous methods to download this file. I have both Python and wget implementations. And really at this point could care less which one I can get to work.
Both do the same exact thing... They download the webpage, not the file I'm trying to download. Yet when I post the exact url provided into firefox, it immediately prompts me to download it.
What needs to happen: 1. connect to website (even though ssl is messed up on it?) 2. Authenticate myself 3. click the first link, which redirects to a download file 4. Download that file
First up my python code:
import httplib2
import urllib2
from BeautifulSoup import BeautifulSoup, SoupStrainer
http = httplib2.Http()
http.add_credentials('username', 'password')
status, response = http.request('https://traveler.pha.phila.gov:8443/servlet/traveler')
counter = 0
Androidlink = ''
Windowslink = ''
Iphonelink = ''
for link in BeautifulSoup(response, parseOnlyThese=SoupStrainer('a')):
if link.has_key('href'):
if counter == 2:
Iphonelink = link['href']
counter = counter + 1
if counter == 1:
Windowslink = link['href']
counter = counter + 1
if counter == 0:
Androidlink = link['href']
counter = counter + 1
url = 'https://traveler.pha.phila.gov:8443' + Androidlink
print url
import requests
from requests.auth import HTTPDigestAuth
r = requests.get(url,verify=False, auth=HTTPDigestAuth('username', 'password'))
print len(r.content)
Second, My Wget Code, just download the html of the website. Aka not what i want
wget --no-check-certificate "https://traveler.pha.phila.gov:8443/servlet/traveler?action=GET&deviceType=700&address=https%3A%2F%2Ftraveler.pha.phila.gov%3A8443%2Fservlet%2Ftraveler&userId=desantj&redirectURL=%2Ftraveler%2FLotusTraveler%2Fandroid%2FLotusTraveler.apk" --http-user=username --http-passwd=password
If i can get either of them to retreive this file (APK File), I'd be overjoyed as I have easily wasted over 6 hours grinding on this
Note Username and passwords were concealed for security reasons


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Comstock Lodge
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
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TripAdvisor Reviews Comstock Lodge Park City
Travel Blogs from Park City
Chapter 44 Playing in the Park
I mentioned
in the previous chapter Stephen Bradbury winning Gold in the 1000 metre skating
at the 2002 Winter Olympics which were held in Salt Lake City.
A twenty
seven mile drive from Salt Lake City takes you into the mountains and to a
destination called Park City. Park City
is one of the venues where other events at the 2002 Olympics were held. We were told that even though it ...
Carryon Traveling
A month to Europe can be done with one carryon.... Yes one! Packing with room to spare for shopping and gifts in the most crafty manor. I'll be illustrating how to pack for kids and adults for such an excursion and you will be surprised that half of what we normally pack is never worn. With this method, you pack only what is needed and make traveling through Europe so much easier...so pack it up and carryon! ...
Arches and Canyonlands
... Much of the landscape of Utah has been carved by the Green River or the Colorado River, both of which can be seen here. At one point we drive over a spot called The Neck which is basically like a ...
S L U T-ing aroung (Salt Lake Utah)
... Railroad. He was a highly successful railroad builder, and became well-connected to other late 19th century millionaires. He was a partner in the Peruvian Cerro de Pasco mines along with J. P. Morgan, William Randolph Hearst, and Frederick William Vanderbilt. He owned business interests throughout Utah and in parts of Montana, British Columbia, and South America.
McCune was respected by his contemporaries for his integrity, his congenial personality, and ...
... beach...out in the open...no fences! Nice day. The only thing that stunk was we didn't have a full hook up.
Everyone was in bed by 10 tired. Laying in bed we heard coyotes howling. Tony and I looked out the back of the RV and saw a little one walking by us in the brush. I guess mom was calling him ...


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Home > Restaurants >
Grand Central Terminal
Mon-Fri, 7am-9pm; Sat, 10am-7pm; Sun, 11am-6pm
4, 5, 6, 7, S at Grand Central-42nd St.
American Express, Discover, MasterCard, Visa
Not Accepted
With multiple outposts in Penn and Grand Central stations, Zaro's has become a dependable pitstop for commuters looking to refuel on New York staples like bagels and black-and-white cookies, not to mention babka, rugelach, and challah bread.


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CARIBBEAN/LATAM: CEDC takes on Monarq as vodka distributor
The international arm of Central European Distribution Corporation has switched distributors in its Caribbean and Latin American markets and in US travel retail.
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Richmond's Round Church gets special postmarkJuly 29,2013The Associated Press
RICHMOND - A special postmark will be offered to mark the bicentennial of the Round Church in the Vermont town of Richmond.
On Saturday, Aug. 10, the Richmond Post Office will stamp letters and postcards with a pictorial postmark.
Customers can also get the postmark by mail free-of-charge for 30 days after the event by sending a self-addressed, stamped envelope containing an envelope or letter. The Post office will cancel and return by mail those letters with the postmark.
Customers also can stop in the post office to get the postmark.
The Round Church built between 1811 and 1813 and is a National Historic Landmark and is listed in the National Register of Historic Places.MORE IN Vermont NewsCOLCHESTER Industrial hemp growers have harvested their second crop since the Vermont... Full StoryMIDDLEBURY A western Vermont woman is dead after the pickup truck she was riding in crashed... Full StoryWASHINGTON Vermonts congressional delegation is divided between outright opposition and wait... Full Story
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Hozelock Hose Repair Connector 146575
£4.9910 points
Free Collection in store.
Product details
The Hozelock Hose Repair Connector is perfect for repairing damaged hose or permanently connecting 2 lengths of hose.
- Colour: Yellow and grey
- Compatibility: Compatible with all standard fittings.
- Model number: 2100
Rated 4.6 out of 5 by 23 reviewers.
Rated 5 out of 5 by Pixie Does what it says on the tin Repaired the hose so it now has no leaks great product 02 February 2012
Rated 5 out of 5 by GWP essential piece I have two lengths of hose to reach around the garden and to the gate, where I wash the car. One length, now recycled, was 25 years old brittle and cracked. The other was 10 years old. Recently I purchased a new length. It seemed very sensible to purchase a new connector at the same time. 02 December 2011
Rated 5 out of 5 by Lottie Lou Just what I needed! As I have a very long garden, I needed to connect two hoses together. I wasn't sure if this would work as the hoses I have were bought from two different outlets, but it was fine! 09 November 2011
Rated 5 out of 5 by turkindian German made garden accessories Reasonable priced garden products from a well established garden accessory supplier. 25 October 2011
Related Products
The Hozelock hose connector is the latest version ...
This Premium Connector with Aqua Stop is made ...
The Hozelock Multi Tap Connector is designed to ...


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Scottsdale Museum of Contemporary Art has FREE admission on this date!
We'll meet in the lobby at 5:30.
Some of the exhibits they currently have are:
Paolo Soleri: Mesa City to Arcosanti
The Human Touch
Selections from the RBC Wealth Management Art Collection
For more info on these check out http://www.smoca.org/calendar?page=1&category=32
Meetup has allowed me to meet people I wouldn't have met naturally - they're totally different than me.
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Absorbing and fully understanding this movie is work. You must give your full and undivided attention to process every minute detail -- it could be a clue! Better think twice before that large popcorn and soda.
Read Whole Story
There has to be in every story at least one character for whom the reader or viewer really cares. Someone has got to matter emotionally. For me, there is not a character in this film of such a stature.
The new Tinker Tailor Soldier Spy finds actors at the top of their craft betrayed by a director and scriptwriter with agendas beyond imaginatively making a great novel into a greater movie.
"Right here, right now, it's the film to beat at this year's festival." Xan Brooks of the Guardian has spoken, and we're inclined to nod violently in ...
Get top stories and blog posts emailed to me each day. Newsletters may offer personalized content or advertisements. Learn more.


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Join the RAC and get breakdown cover from £27.99. We fix 4 out of 5 vehicles at the roadside!Join here »
Up to 70% off RAC Car Insurance with 9+ years no claims discount. Get a quote »
Up to 70% off with 9+ years no claims discount.Get a quote »
Get set for autumn with offers on wiper blades, garden power tools, garage storage and more. Visit our shop today Shop now »
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Find out more about winter driving habits with the RAC Route Planner infographic, bringing a little fun insight into everything from some the UK's top winter driving locations, a little insight into visitor preference when they're off to Europe, the number of long trips they make during winter and what celebrity they'd like to take with them.
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Our highly trained sales staff has earned a credible reputation with their many years of service and commitment. Our goal is to make sure that each of our customers receives the quality service that we have built our name on. We offer a very extensive inventory available at competitive prices. However, our support does not end after the initial sale has taken place. We take pride in keeping your car in the same condition in which it rolled off the showroom floor. You do not have to take our word for it; we let our sales, service, and parts speak for themselves. It is our goal to provide you with an excellent purchase and ownership experience.
This dealer has 184 new vehicles.Search New Get a new Car Quote
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339 out of 339 people recommended this dealer.Write a Review
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by Electrovert Convert
From the web page searches to the request for a test drive and the subsequent purchase and financing the experience was outstanding. The experienced staff treated us with respect and patience through the review and selection process, even when we may have been hesitant to commit to some component of the packages being offered. In the end, we have a top notch "hot ride" vehicle that is truly a beautiful technical and esthetically pleasing to the eye . With current federal and state incentives, this was the time to execute the flip my ride to the practical and forward thinking package that is the 2014 model Volt.
Read all reviews for this dealer


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What does a newborn sleep under?!(4 Posts)
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Webkinz Sing "Heaven is a Wonderful Place" - Cute Videos
Embed katiekinz 787 views 2011-10-08T23:04:21 Spot (left) and her best friend Cinnamon (right) sing a duet, "Heaven is a Wonderful Place".
Special thanks to:
Mom, for teaching me the two parts
Dad, for getting us the video editer
Jesus, for dying for our sins so we CAN go to Heaven!
Special thanks to:
Mom, for teaching me the two parts
Dad, for getting us the video editer
Jesus, for dying for our sins so we CAN go to Heaven!
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AC/DC, Chris Slade Open Grammy Night With 'Rock or Bust,' 'Highway to Hell'
AC/DC made a triumphal return to to national television, their first in 14 years, with a boisterous two-song opening performance on tonight's Grammy Awards broadcast.
AC/DC made a triumphal return to to national television, their first in 14 years, with a boisterous two-song opening performance on tonight's Grammy Awards broadcast.
The 57th annual Grammy Awards will take place at the Staples Center in Los Angeles on Sunday.
For all the women who are salivating while waiting for the 'Fifty Shades of Grey' movie there are men dreading two hours of boredom in the movie theater.
Watching sports is fun. Watching sports when the announcers make a comment that can totally be misconstrued is more brilliant than Darius Butler stepping in to save the Patriots.
Well, almost the entire cast. 'Tonight Show' host Jimmy Fallon is really get into Los Angeles living during this week's sojourn to the land of sun and fun, and no ode to California would be complete without a loving nod to the ultimate Cali show: 'Saved By the Bell.'
How do you make a cringe-worthy low budget TV ad more entertaining? Well, if you're a jazz guitarist, you add music to the pitchman's sing-song delivery. Is that even a word?
Say hello to Jones Big Ass Truck Rental & Storage.
Foo Fighters will welcome Gary Clark Jr. and Jimmie Vaughan for their performance this weekend on PBS' 'Austin City Limits.'
Celebrities have feelings, too. Even when you think you're just talking random smack about them in the wide world of the internet (web?), you're still talking random smack about real people. If you're tweeting mean stuff? They might see it. And it might hurt them.
Paul McCartney, Rihanna and Kanye West will give the first-ever performance of their new song 'FourFiveSeconds' at the 57th Annual Grammy Awards on Sunday.
Jimmy Kimmel started his month-long 'Mash Up Mondays' series in style last night, inviting Weezer to join ZZ Top for a performance as the mashed-up Wee-Z Top.
Liam Neeson may act like a total badass when he's in movies like 'Taken', but he's not above poking a little fun at his new tough guy persona. The actor appeared in a new Super Bowl commercial for Clash of Clans and delivered a monologue that sounds as if it were taken (no pun intended) from one of his shoot-em-up action movies.
'Breaking Bad' may be completely, definitively over, but that doesn't mean Walter White is ready to leave popular culture alone. Oh, no. As long as Bryan Cranston is alive and as lone as insurance companies are prepared to back dump trucks full of cash up this house, we'll get to see America's favorite meth dealer pop up every so often. So while it's weird to se Cranston play Heisenberg one more time in an Esurance commercial, it's not that surprising.


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I'm not an expert on such subjects. But it doesn't seem to bode well for Cabo. Or many other biotech drugs? Especially for a drug like Cabo that also cuts off the blood supply to tumors. I wonder how the more informed who post here view this subject? The FDA sure isn't going to easy to convince. Also the cost factors are most in focus these days. It all is so scary for this long time holder of Exel.
You are correct and I am sure Cabo will have the same side effect but the numbers are quite small and if benefits are good, the drug will be approved. I cannot give you a link the article but it is in the currect issue of the J. of Clinical Oncology
Would you please give a link to the article? I thought Avastin cut off the blood supply to the tumor just like Cabo. But that it was discovered that in cutting off the blood flow it created a side effect of maybe stopping the blood flow where needed? I seem to remember there was some undisered effect related to that. I maybe wrong?
Avastin is used for colon cancer and lung cancer all the time because the data says the benefits outweight the risks. If Cabo meets this criterion it will be approved. Again, look at the JCO phase I article and the editorial. The drug looks real
Not to worry, there's a lot to keep up with. As always, I appreciate your major contributions to this board.
The "Wiz"
My main intial point was the fear put forward about the trouble created by Avastin's cutting off the blood supply. I believed that was a problem Avastin created? Since Cabo also cuts off the blood supply. I thought that was a problem Cabo could also face. I thought they both work in a similar way in this regard? I don't think that point was addressed by anyone? I should have worded the post differently and avoided the philosophical gov., medical, monetary, ethical debate. I sorry.
Scarcely reported, but the major problem with avastin is the so called "rebounding effect". That is, after the treatment, this drug appears very impressive and efficacious (that is the PFS for example), however, over time the cancer exploits other pathways to overcome avastin's effects. The net rsults is the cancer, especially after avastin is taken off..the cancer relapses much more strongly and the individuals die much faster. If one could evaluate this phenomenon more carefully, I suspect this is true with other indications as well. The only way out of this "Avastin Dilemma" may be drug like Cabo (that attacks multiple pathways or addition of another drug that targets yet another pathway.
Overall, Cabo should do well..as well as or better than Avastin in the short run...in this case 2 pathways may be better than 1.
I appreciate your point of view but must respectfully disagree and certainly would not use the current avastin in MBC as the argument.
FDA reviewers (just for the record, I am not one nor have I ever been) are cought between a rock and a hard place. If drugs take too long to get approved, they are accused of killing people. If drugs turn out to be unsafe, they are accused of being in the pocket of big pharma. And usually being outgunned. There are appeals processes (Roche/Genentech just went about as far as you can go with appealing a decision and lost some credibility in the process IMO), but no mechanism by which an individual can compell someone else to do give them an investigational agent.
Keep in mind that there are plenty of for-profit clinics operating off shore if people want to get "cures".
Despite the tendency to blast FDA (and being a government agency with its bureaucracy there is plenty to blast), it is not uncommon for Sponsors to not heed FDA advice, then gripe when they don't get the desired outcome. Recall the cetuximab/Imclone disaster. The company didn't do the trial right and that delayed a new treatment for several years. In the case of DNDN, I suspect the agency was being conservative since the results didn't fit existing paradigms; could they have granted accelerated approval there, perhaps. There is always going to be a balance between moving quickly nad assuring safety and efficacy, but it is clear that Sponsors have a vested interest (MONEY!) in getting drugs approved for as large a population as possible. It's reasonable for FDA to act as a referee.
The FDA's existence came about as a result of snake oil salesmen and over time has raised the bar for selling medicines. Demanding safety AND efficacy has only been around since the early 1960's and demanding efficacy is a good thing IMO.
The "Wiz"
<<I think you're confusing two different but very interesting stories in oncology:>>
I got to thinking about it after I posted, looked it up and was just about to self correct, but you beat me to it. I should stay away from the biological aspects of this to avoid embarrassing myself.
It is in fact outrageous when the budget battles are being waged and real pain is being inflicted on middle and lower class populations and medicare is under direct threat that cost does not enter into many things we do for patients. I understand the need for incentives for companies to spend the vast amount of money needed to develop and test a drug but there is no excuse for charging $73000 to prolong life 4 months or to charge $76,000/year for a drug that cost almost notheing to develop (Revlimid). There is some much waste in medical care that we have to make very unpleasant choices. You want to call it rationing; so be it.
I think you're confusing two different but very interesting stories in oncology: the use of small molecule inhibitors in lung cancer (gefitinib and erlotinib- Iressa and Tarceva brand names) and antibody inhibitors in colorectal cancer (cetuximab and panitumumab). For Lung cancer, it became clear that patients with activating EGFR mutations respond quite well and there are now data that in this selected population (positive selection) that treatment with an EGFR inhibitor actually is superior to chemotherapy. Tarceva has been approved since it showed a survival benefit, Gefitinib ended up being approved in Asia with status in the US in flux.
For the antibodies, initially cetuximab was approved in combination for CRC and panitumumab was subsequently. As genotyping became more common, it was found that the only patients deriving benefit were those with wild type KRAS (i.e. mutant KRAS patients had no benefit), and FDA subsequently changed the indication to reflect this.
You are correct that companies can almost always make investigational agents available to patients on expanded access if they are convinced that they are active. There is a real problem with what seems to be a general assumption that more is always better. There are new treatments and many are great drugs and represent great science, but not all are and not for all patients.
The "Wiz"
I find it odd that I am defending FDA. I am frequently critical of many of their decisions and policies, but I see much of your criticism as unjustified or misdirected.
<<When considering approval they take into consideration any other effective treatment.only >>
I can only speak to the oncology department, I don't keep up with the other departments. The current policy is that new drugs have to equal or improve on the current defined standard of care and this is put into practice by requiring clinical trials with a standard of care control arm. Sponsors do have the option of establishing either equivalence or superiority when they design their trials. I agree with this approach. Placebo controls are unethical when there are effective treatments and comparative trials are needed to establish what is most effective and focus R&D in a positive direction. The cost of new drugs is staggering, but the payoff for society comes as these drugs go off patent and are priced based on competitive pressures.
<<and the ever dominant cost considerations play into the determinations of efficacy.>>
Cost occasionally creeps into discussion at ODAC. When it does, the FDA representatives present have uniformly reminded the members that cost is not a consideration for drug approval. Other government entities are more proactive when it comes to measures to limit cost or ration/restrict reimbursement.
<<It also makes testing an insurmountable task as each test becomes multiple tests when the drug and all of the competing drugs must be retested.>>
It is a necessary evil. Historic controls do not work. The increasing complexity as indications become more fragmented and new drugs are approved is an indication that the system is working.


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Select Local Merchants
Bluefin Sushi and Thai GrillRead MoreChef Yozo Natsui's training in his native Japan, combined with more than 15 years of experience behind the stove, helped earn Bluefin Sushi & Thai Grill the distinction of Best Sushi, 2010 in the Sun Sentinel's Best of South Florida series. Inside a sleek dining room, servers transport fresh slices of fatty tuna and hand rolls from the sushi bar, where Yozo and his cadre of chefs carefully assemble edible cylinders lined with fresh seafood and cool vegetables. They accompany their platters of seared-steak teriyaki with soup or salad, and envelop medleys of vegetables in tempura batter before exposing them to a deep fryer—which is hotter and more philosophically profound than a bourgeois fryer. Servers pour an extensive selection of cold, hot, and flavored sake alongside various wines, imported Asian beers, and Thai iced tea.6694 Parkside DrParkland, FL US
Moon Thai and JapaneseRead MoreFor a quick curry, Coral Springs' Moon Thai and Japanese is a great lunch or dinner spot. You won't find any low-fat fare here, though, so leave some room to indulge. At Moon Thai and Japanese, kids of all ages are welcome. Don't go off the grid! With the free wifi at Moon Thai and Japanese, you can surf the web and get some work done. Sit outside when the weather is fine — Moon Thai and Japanese has a lovely patio to enjoy a warm day. Drift away from stuffy dress-code conventions and dine in comfort at Moon Thai and Japanese. You can also grab your food to go. Moon Thai and Japanese offers safe bike parking outside. Typical diners should plan to spend about $30 per person on Moon Thai and Japanese's moderately priced fare. The dinner menu is a crowd pleaser at the restaurant, though breakfast and lunch are also served.9637 Westview DrCoral Springs, FL US
Spikey TyRead MoreSpikey Ty in Coral Springs is a well-known restaurant, featuring a familiar vibe with superb sushi. It's a culinary destination for customers looking for delicious food. There's no particular required attire, so feel free to dress comfortably. In addition to its quick service (take-out is available), the restaurant also offers delivery, and can even cater an event for you. A reputable option for both lunch and dinner, Spikey Ty is a terrific choice when you're in the mood for Asian cuisine and want to be more adventurous than the typical Chinese or Japanese fare. Don't worry about trying to find a spot on the street, as visitors to the restaurant do have access to a private parking lot nearby.4690 Coral Ridge DrCoral Springs, FL US
TobuRead MoreIf you haven't experienced Tobu, now is a great time to visit the popular Japanese restaurant. It's a culinary destination for visitors interested in delightful service and a fantastic meal. There's not really a recommended attire, so feel free to dress comfortably. With healthy items on the menu, there really is something for every taste and if you're on the lookout for the perfect spot for family or friends, it's been reviewed as a solid option for large groups and kids. In addition to its quick service (take-out is available), the restaurant also offers delivery, and can even cater an event for you. Specializing in lunch, Tobu definitely won't leave you disappointed.6287 W Sample RdCoral Springs, FL US
Thai Pepper RestaurantRead MoreA culinary gem, Thai Pepper Restaurant in Coral Springs is a well-known spot for fantastic fast food. Stop by for the good quality and stay for helpful service. You'll be a repeat customer in no time. If you're in a hurry, you can call ahead and take advantage of the convenient take-out offerings. A highly-regarded option in Coral Springs, you won't walk away from Thai Pepper disappointed.2049 North University DriveCoral Springs, FL US
Jasmine Thai and Chinese RestaurantRead MoreIf you haven't been to Jasmine Thai and Chinese Restaurant, it's a great time to enjoy the well-known Chinese restaurant. It's a favorite spot for guests interested in awesome food. No specific attire is required, so feel free to dress casually and comfortably. If you're on the lookout for the perfect spot for family or friends, it's been reviewed as a solid option for large groups and kids. In addition to its convenient take-out offerings, the restaurant even provides catering for events around town. Or, if you just want to pop in for a beverage, the restaurant does have a pretty decent selection at its bar. A good option for both lunch and dinner in Central Park Of Commerce, chances are you won't walk away from Jasmine Thai and Chinese Restaurant disappointed. Don't worry about trying to find a spot on the street, as visitors to the restaurant do have access to a private parking lot nearby.5103 Coconut Creek ParkwayMargate, FL US


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Gentleman Mechanic
Mr. Wesley helped me (after he should have been closed for the evening) fix a problem that my regular mechanic has missed for Months, diagnosed it, got it taken care of, and charged me a minimal fee. He knew what he was doing and was nice in the bargain!
I really love eating lunch at this place, because they vary what they have in the salad case and have seasonal options, too. The sandwiches are always a safe bet, and the cheese counter is amazing!
Great Place
I really love these guys. They care about dogs and cats, and enjoy talking to and about them. I got a great toy with a quacking squeaker that my dog Loves, and they have something I haven't seen anywhere else; Antlers. They aren't as brittle or messy as bone, and they are shed by the animal, so it's cruelty free.
Yummy Quiche
I ate here with some friends before heading to the High Museum. I desperately needed coffee, and theirs was really good. We all ordered food, and it was very pretty in presentation, and my quiche was really tasty.
Yummy Chocolate Cupcake
I have a birthday party for which I want to buy cupcakes, so I did a little research, and found this place. Parking is a little weird, because it's midtown. The store is beautiful, and inviting. The staff was helpful, even giving advice on where to park in the future. We bought several things, all of which were beautiful. I will definitely be using them in the future. I do wish the prices were a smidge lower.
Fun Time
I went here for the first time last night to see a friend play drums. It's kind of a hole in the wall, but I had a fun time. The crowd was very mixed and into the bands. I would go back to try the chili, because it said it was made with turkey.
Good Grilled Cheese Sandwich
I was there last night with a group of friends, and it was really too smoky inside for my taste. But I ordered the grilled cheese sandwich, and it was really yummy, so I have to give them kudos for that. I don't think I'd go back, though. Not my scene.
Very NIce Lady
I met Colleen and Will today, grooming dogs at the Atlanta Humane Society. They were super professional, concerned about the animals and tireless. I will definitely use their services in the future with my own dog.
Lovely Massage
I got a gift certificate to this place. The masseuse thought I was supposed to get an hour and a half instead of an hour, so I had to cancel the dentist's appointment that I had scheduled. They made me pay for the extra time. Then the lady who took my certificate said that the tip wasn't included, when it was. I enjoyed the massage, it was great, but the rest of it made me not trust them.
Good Stuff
I have had mixed luck eating in this restaurant. I love the food, and the atmosphere, for the most part, but have had really bad service a time or two. We went tonight and had a great server, she had a big smile and was very good. I could do without the enforced valet parking, but I know complaining about that is a lost cause.
©2015 Cox Search, Inc. All rights reserved. Data provided in part by Localeze and Valpak.


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Hotel At WaterWalk
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
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TripAdvisor Reviews Hotel At WaterWalk Wichita
Travel Blogs from Wichita
... one. As visitors passing through, we got our news mainly from the local paper, and this is a hot topic. And that's the 'plane' truth.
As for the city itself, we mainly drove through the revitalized downtown area, something that we are getting used to seeing everywhere we have traveled on this trip. It seems that most cities have taken steps to reclaim older or rundown areas, filling them with pubs, restos, museums, galleries, etc, ...
Visited my mom's hometown today!
... Army and as the Allied Commander during WWII. Loved it as we were leaving the library, Gavin asked me what I learned that I didn't know before touring the library. Actually learned many new things, but the thing that stood out was the affect the concentration camps had on Eisenhower. I shared with him that I was a young girl when Eisenhower was President. I told him how when the Eisenhower's celebrated their 50th ...
Day 1 Stopover: Hometown Wichita
Always fun to spend time with family. Our first night on vacation was with family in my hometown of Wichita. We were surprised with a good-old fashioned fish fry prepared by my Aunt Betty and Aunt Darlene. My grand mother was there as well. Good food and family - can't beat ...
Day 20
... having, seasoned just right... so good. Margaret and Steve had the chicken fried chicken and steak meals. Then we ordered desert (sign in restaurant said all deserts had zero calories), Margaret and Steve had the blackberry cobbler and Cindy and I had the apple dumpling. After dinner we toured town some more and got back to the MH around 9:30pm. After showers and blogging, to bed at ...
Oh DEER! ---- WITH PICTURES
... br> Now onto Dodge City Kansas (June21). About 7 miles inside Kansas a Mule Deer decided to commit suicide and ran in front of us at 65 mph. UGH!!!!! Rusty tied things up, clamped off hoses and we limped 120ish miles into Dodge City. Poor Rusty had no AC and it was over 100 degrees. Yip, I was comfortable and cool following behind in the jeep. We reported our encounter with our insurance and called us the next day. Michael wanted us to travel to Wichita ...


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Excerpt: We write today to express our grave concern that the Commission continues to consider reclassifying Internet broadband service as an old-fashioned "Title II" common carrier service. Such unwarranted and overreaching government intrusion into the broadband marketplace will harm consumers, halt job creation, curtail investment, stifle innovation, and set America down a dangerous path of micromanaging the Internet. The Commission must reject this approach.
Excerpt: Efficient and effective management of the SPR is an important component of our nation's energy security. As the summer driving season approaches and tensions in some of the world's most resource-rich areas and elsewhere show no sign of abating, the obligation of Congress, and especially this committee, to remain vigilant in its oversight of DOE's stewardship of this important program is clear.
Excerpt: In announcing the 2015 Rate Announcement for Medicare Advantage plans, CMS said it "estimates the overall net change to plan payments between 2014 and 2015 to be +.04 percent." However, most objective observers, including many market analysts and industry researchers, concluded that the overall net impact of the finalized changes actually amounts to approximately an over three percent cut to Medicare Advantage plans.
Excerpt: One goal of the incentive auction legislation was to bring market forces, via auctions, to bear on the question of how best to allocate spectrum resources. A pure market-based approach would allow all qualified bidders to freely bid on spectrum licenses, thereby determining whether broadcasting or commercial wireless is the highest economic use of the spectrum.
Excerpt: Thank you for your cooperation with the committee's March 13 request on enrollment data. Due to the administration's repeated delays and extensions, we believe additional data is required to determine who has enrolled and paid for a plan on the Federally-Facilitated Marketplace.
Excerpt: The process followed by FDA in proposing this rule appears to stand in stark contrast to the approach taken by the agency in developing changes to the content and format of prescription drug labeling under the Clinton administration.


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1776 $1 Continental Dollar, CURENCY, Pewter MS62 PCGS....Click the image to load the highest resolution version.
Magnificent MS62 1776 CURENCY Continental Dollar
1776 $1 Continental Dollar, CURENCY, Pewter MS62 PCGS.
Newman 1-C, Hodder-1.A2, Breen-1089, R.3. The same die pair was
used to strike all Continental dollars that contain the blundered
legend CURENCY. Nonetheless, researcher Eric Newman assigned three
different reverse varieties, since the reverse die was recut for
Newman 1-B, and recut again for Newman 1-C. Only two examples are
known for Newman 1-A, both in brass. Those pieces have beaded links
to represent the 13 former colonies. The very rare Newman 1-B has
partly beaded links, and is known in tin, brass, and copper.
Rare Early Die State, Struck in Pewter
The present piece is Newman 1-C, since the rings are unbeaded. However, it is an early die state with complete glory rays near the RESS in CONGRESS and the M in R in AMERICAN. There is also no sign of the die break that eventually connects the tops of the GI in FUGIO. There is a period below the N in AMERICAN, unlike Newman 1-B, which shows a comma. Although few numismatists can afford to collect die states of Continental dollars, the present early die state is nonetheless rare and merits a premium over the usual attenuated glory rays Newman 1-C.
Perhaps of greater interest to the type collector, the present piece is exceptionally attractive for a Continental dollar. Aside from a small spot near the G in FUGIO, there is no sign of the "tin pest" that affects most known examples. The dove-gray surfaces appear undisturbed to the unaided eye, and extended perusal beneath a loupe locates only faint and unobtrusive obverse field marks. The strike is consistent throughout. Although higher grade pieces are known, this handsome, problem-free, Mint State example is certain to excite even the veteran Early American specialist, and will be the cornerstone of any Colonial collection. Listed on page 81 of the 2008 Guide Book. Population: 11 in 62, 26 finer (4/08). (NGC ID# 2AYN, PCGS# 791)
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By Ashlee Butler Photo by Julie Fitz-Gerald
Three Waimea players, Captain Katie Ditzel and Georgia Davies, Hannah Davehill were selected for the New Zealand Secondary School (NZSS) national tournament team.
Alister McKenzie and Colin Redpath, coaches of the national women's and men's teams, were the main selectors of the 2015 girls and boys.
McKenzie said "the girls chosen have done outstanding work to help their teams perform and achieve the final results".
Waimea College had to settle for silver at the New Zealand Secondary School (NZSS) Volleyball Nationals in Palmerston North.
The deciding game was against Burnside High School girls.
The two South Island teams had a nail biting game, Burnside narrowly winning against Waimea 3-2 (19-25 25-18 25-19 20-25 15-12).
Waimea Captain, Katie Ditzel is still proud of her team and said they played well.
The boy's division one final was won by Western Heights High School 3-0 against Heathfield High School (AUS).
Trials will be held for the New Zealand age group teams at Arena Manawatu tomorrow.


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Posts Tagged
Messenger bag
Chrome Mini-Messenger : Preview
Over the past few weeks I've been able to have some great conversations with the marketing gal over at Chrome about their womens clothing line and their different models of bags. The clothing line details will be another day but let's talk about the bag I selected for review. Chrome
Banjo Brothers Commuter Backpack Review : Preview
Banjo Brothers makes some of the greatest, affordable, commuter packs and bags in the industry. When they sent me a message about a new WHITE Commuter Backpack I was thrilled to be one of the first to review this product for them.


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Gardening may be America's most popular leisure activity, but it is also the most frustrating, aggravating, and time-consuming-by no means the simple idyll-with-dirt sold by gardening gurus. As lifelong gardener Abby Adams points out in her tongue-in-cheek book, you can't trust the experts, nothing looks like it does in magazines and catalogs, trends change more often than hemlines, and Mother Nature always wins. Literate, funny, studded with quotes and ironic observations, here is a series of honest takes on dozens of subjects that all gardeners will relate to. Paperback, 256 pages.
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Vendor: Workman Publishing
Availability: Usually ships in 24-48 hours.