text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 23, 1992
|Filing date
|Oct 24, 1989
|Priority date
|Oct 24, 1989
|Fee status
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|Publication number
|Lorraine M. Sordillo, Lorne A. Babiuk
|Original Assignee
|Ciba-Geigy Canada Ltd.
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|Patent Citations (2), Non-Patent Citations (38), Referenced by (7), Classifications (11), Legal Events (5)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention relates generally to the use of cytokines in the prevention of bacterial infections. More specifically, the instant invention pertains to the use of interferon-gamma in the prevention and treatment of bovine mastitis.
The mammary gland has a natural ability to prevent bacterial invasion, but various physiological events can inhibit this capability. For example, the ability of mammary gland neutrophils to phagocytize mastitis-causing pathogens and suppress bacterial multiplication is critical to, the outcome of intramammary infection (Paape et al., 1979). Although both neutrophils and macrophages predominate in mammary secretions and tissues (Sordillo et al., 1987; Sordillo and Nickerson, 1988), evidence suggests that the antibacterial activities of these cells are reduced in the presence of mammary secretions and compromised during physiological transitions of the gland (Paape et al., 1981; Nagahata et al., 1988; Sordillo and Nickerson, 1988). Consequently, the bovine mammary gland is highly susceptible to mastitis immediately following the cessation of lactation and during the periparturient period (Nickerson, 1989). Incidence of clinical mastitis is highest during early lactation often resulting from new intramammary infections obtained during the nonlactating period. Increased susceptibility during these times is most likely due to a combination of increased exposure of teat ends to mastitis-causing pathogens and diminished host defense mechanisms, as described above, during functional transitions of the mammary gland.
Mastitis during the periparturient and early lactating periods is caused by a multitude of bacteria. Common etiological agents include Escherichia coli and Staphylococcus sp. Coliform infection is rare in middle and late lactation, but is most severe during the first few weeks of lactation where it is a major cause of acute toxic mastitis. Disparities in establishment and severity of, coliform mastitis with respect to stage of lactation have been explained by the rate of growth of the organism within the gland, the elaboration and absorption of toxins, and the varying susceptibility of the host during these stages. A rapid and intense inflammatory response in lactating tissue has been observed following experimental challenge with E. coli (Hill, 1981). In most cases, the bacteria were eliminated rapidly without causing damage to secretory parenchymal tissue. In contrast, quarters infected with E. coli during the immediate postpartum period had minimal neutrophil influx, which probably allows the unrestricted growth of the organism. The delayed diapedesis of neutrophils and slow inflammatory response within the gland may be a result of decreased sensitivity of alveolar and ductular epithelium to endotoxins during functional transitions of the gland.
Interferons (IFN) are a family of closely related proteins of three major types (Lawman et al., 1989). Interferons-alpha and -beta are produced by a variety of cell types in response to several inducers including viral infections, bacterial products and tumor cells. Interferon-gamma is predominantly produced by antigen- or mitogen-stimulated T-lymphocytes. In addition to the antiviral and antiproliferative activities, all classes of IFN are known to exhibit many immunomodulatory properties (Lawman et al., 1989).
IFN-gamma has been shown to be a potent immunomodulator and appears to enhance natural killer cell activity, antibody-dependent cellular cytotoxicity, and cytotoxic T-lymphocyte activity (Lawman et al., 1989). Interferon-gamma also enhances macrophage-mediated cytotoxicity against tumor cells, induces membrane-bound Fc receptors for IgG on macrophages, and stimulates the synthesis and release of reactive oxygen metabolites from both macrophages and neutrophils (Bielefeldt Ohmann and Babiuk, 1986; Trinchieri and Perussia, 1985).
The efficacy of interferons in the treatment of mastitis has not heretofore been studied to applicants' knowledge.
The present invention is based on the surprising discovery that interferons can protect dairy cattle against coliform mastitis.
In one embodiment the present invention is directed to a method of treating or preventing mastitis in a mammal comprising administering to said mammal a therapeutically effective amount of interferon.
In another embodiment, the instant invention is directed to a method for treating or preventing coliform mastitis in a cow comprising administering to said cow a therapeutically effective amount of bovine interferon-gamma. The administration can be done either before or after infection.
These and other embodiments of the present invention will readily occur to those of ordinary skill in the art in view of the disclosure herein.
FIG. 1 depicts the effect of increasing IFN-gamma doses on bacterial phagocytosis of bovine mammary neutrophils pretreated with either periparturient mammary secretions (milk) or Hank's balanced saline solution (HBSS). Data are expressed as colony-forming units (CFU) of Staphylococcus aureus recovered from mammary neutrophils at t=0. Bars between IFN-gamma treatments with different letters (a,b) are significantly different (P<0.05).
FIG. 2 shows the effect of increasing IFN-gamma doses on bactericidal activity of bovine mammary neutrophils pretreated with either periparturient mammary secretions (milk) or Hank's balanced saline solution (HBSS). Bars between IFN-gamma treatments with different letters (a,b) are significantly different (P<0.05).
FIG. 3 demonstrates the effect of increasing IFN-gamma doses on the production or reactive oxygen species (ROS) by bovine mammary neutrophils pretreated with either periparturient mammary secretions (milk) or Hank's balanced saline solution (HBSS). Data are expressed as total area under the curve.
FIG. 4 shows the effect of recombinant bovine IFN-gamma on the rate and duration of experimental E. coli-induced bovine mastitis during the immediate portpartum period.
FIG. 5 depicts the effect of IFN-gamma treatment on the rate and duration of experimental E. coli-induced bovine mastitis during the prepartum period.
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of immunology, protein chemistry, biochemistry and molecular biology which are within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Handbook of Experimental Immunology, Vols. I-IV (D. M. Weir and C. C. Blackwell eds., 1986, Blackwell Scientific Publications), and the series Methods in Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.)
The present invention is directed to the treatment or prevention of mastitis in mammals by the administration of one or more interferons to the subject mammal. A preferred embodiment of the invention is the treatment or prevention of coliform mastitis in cattle using bovine interferon (BoIFN)-gamma.
The present invention contemplates employing any form of human or BoIFN, either alone or in combination. Thus, the present invention encompasses using native forms of the interferons. Particularly surprising, however, is that recombinant forms of the interferons have sufficient biological activity to provide for effective treatment or prevention of mastitis. Since the production of recombinant interferon has substantial advantages relative to the purification of native polypeptides, recombinant interferons are a preferred embodiment. It is also contemplated that synthetic forms of human or BoIFN, and muteins or fragments of BoIFN, exhibiting effective biological activity, are also within the scope of the invention. A mutein of human or BoIFN is a polypeptide substantially homologous to the native protein, and more homologous to the bovine or human form than to IFNs from other species. A fragment of human or BoIFN is a polypeptide that is homologous to a region of sufficient length in the protein such that the sequence is unique to human or BoIFN.
The production of recombinant animal interferons, including alpha (leukocyte) and gamma (immune), is known in the art. See, e.g., EPO Pub. No. 088,622, by D. Capon & D. Goeddel. Furthermore, recombinant BoIFN-gamma is available commercially from Ciba-Geigy, Ltd., Basel, Switzerland.
As indicated, the present invention is concerned with treating or preventing mastitis. By "treating" is meant curing or ameliorating an animal that has contracted mastitis. "Preventing" mastitis means preventing the occurrence of the infection, or tempering the severity of the infection if it is later contracted.
Typically, the interferons of the present invention are administered by intramammary injection; however, effective dosages may be administered via intramuscular, subcutaneous, or intravenous injection. When prepared as injectables, the interferons are generally administered using a pharmaceutically acceptable vehicle or excipient. Suitable vehicles are, for example, water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof. In addition, if desired, the vehicle may contain auxiliary substances such as wetting or emulsifying agents or pH buffering agents. The active ingredient will typically range from about 1% to about 95% (w/w) of the composition administered, or even higher or lower if appropriate.
A "therapeutically effective amount" of interferon is a dose sufficient to either prevent or treat mastitis in a subject to which the interferon is administered. The dosages of the interferons which can treat or prevent mastitis can be determined in view of this disclosure by one of ordinary skill in the art by running routine trials with appropriate controls. Comparison of the appropriate treatment groups to the controls will indicate whether a particular dosage is effective in preventing or treating a disease used in a controlled challenge. In general, effective dosage will vary depending on the mode of administration. It has been found that in the case of an intramammary injection using recombinant BoINF-gamma, administration of 105 U per quarter is sufficient to retard E. coli mastitis.
If administered intramuscularly, subcutaneously, or intravenously, effective dosages will depend on the weight of the animal and will typically run in the range of from about 0.1 ug/kg to about 40 ug/kg. More typically, the dosage will be at least about 1 ug/kg, but less than 10 ug/kg. On an absolute basis, single-dose formulations will contain from about 10 ug to about 1,000 ug. More typically, preferred single-dose formulations will be at least about 30 ug, 100 ug or even 200 ug, but usually no more than about 600 ug or 700 ug. Effective dosages are believed to fall within a relatively large range.
Beyond dosage, an effective administration of interferons according to the present invention will in part depend on the number and timing of the dosages. For example, multiple administrations of a dosage may be given to an animal, typically at least about 24 hours apart. In some circumstances it may be desirable to administer the interferon at least twice to the animal, or at least three times. It may even be desirable to administer even more dosages to the animal, such as six, seven, eight, or even nine over an equal number of days or longer. Again, it is believed that the precise combination of dosage and timing will be subject to a wide range of variation and that numerous combinations effective in treating or preventing a disease can be readily established by those of ordinary skill in the art in view of the present disclosure.
The interferons of the subject invention can be administered prior to infection, and thus serve as a prophylactic or can be given after the subject has shown signs of infection.
Described below are several examples illustrating the practice of the present invention. These examples are provided for illustrative purposes only, and are not intended to limit the scope of the appended claims.
Preliminary experiments were performed to determine the effect of recombinant BoIFN on mammary neutrophil activity during the periparturient period.
Neutrophils were isolated from the mammary gland of a heifer after intramammary injection of 5 ug of lipopolysaccharide (LPS) in 5 ml of HBSS. At 15 h after LPS administration, 30 ml of HBSS were injected into the LPS-treated quarter and mammary secretions were collected into a sterile polypropylene tube. Mammary neutrophils were purified by Ficoll-Hypaque density centrifugation. After 2 washings, the cells were resuspended in HBSS containing 5% fetal bovine serum (FBS) and filtered through a 30 um Nitex filter (Tetko Co., Elmsford, N.Y.). Separation of mammary leukocytes via this technique consistently resulted in a more than 96% neutrophil population. The percentage of viable cells was determined by hemacytometer count using trypan blue exclusion. Mammary neutrophils were cytocentrifuged onto poly-L-lysine-coated slides and stained with Wright,s stain for differential cell counts.
Mammary secretion samples from individual quarters (n=8) were collected from 2 cows at approximately 14 and 7 days prior (�2 days) to expected parturition (C-14 and C-7) and at parturition (C-0). Aseptic foremilk samples were collected in duplicate and used to determine infection status of each quarter. Bacteriologic evaluation of foremilk samples revealed that all quarters (n=8) were free of intramammary infection during the entire sampling period. Secretions were centrifuged for 30 min (3,000 g at 5� C.) to remove fat and cellular debris (skim milk).
Skim milk preparations (1 ml) from each sampling period were mixed with 1 ml of mammary neutrophils (8�106 cells) and allowed to incubate for 1 h at room temperature. Control cells were incubated in HBSS. The mixture was washed in HBSS and separated into four 1-ml volumes containing 2�106 cells each. For each sampling period, skim milk-treated neutrophils were subsequently incubated with 10 U, 100 U and 1000 U of recombinant BoIFN-gamma (Ciba-Geigy Ltd., Basel, Switzerland) or HBSS for 2 h at room temperature. The cells were washed and resuspended in HBSS with 5% FBS to a final concentration of 1�106 cells/ml.
Mammary neutrophil phagocytic and bactericidal capacities were evaluated using Staphylococcus aureus isolated from a clinical case of bovine mastitis. Bacteria in log phase growth were opsonized with bovine sera with an agglutination titer of 1/16 against S. aureus.
Opsonized S. aureus cells (1�106 colony-forming cells (CFU) in 1 ml) were mixed with 1 ml of treated neutrophils (1�106) and incubated (10 min, 37� C.) in a shaking water bath. After initial incubation, the mixtures were washed, resuspended in HBSS containing lysostaphin (Sigma Chemical Co., St. Louis, Mo.), and incubated for 30 min to remove extracellular bacteria. Cells were washed and divided into 3 aliquots: t=0 min, t=30 min, and t=60 min. Following the second incubation, PMN were washed, resuspended in 1 ml HBSS, and subjected to sonication.
The number of viable bacteria for each time period was estimated by a standard plate count method. The mean CFU of bacteria at t=0 was used as an index of phagocytosis. Bactericidal capacity (percent killing) was computed from: ##EQU1##
Luminol-enhanced chemiluminescence was measured with a Packard Picolite luminometer (Packard Instrument Co., Downers Grove, Ill.). Treated neutrophils (1�106 cells/100 ul) were added to vials containing 15 ul luminol, 200 ul of opsonized zymosan (10 mg/ml), and 1,685 ul HBSS. Vials were counted for 10 s at 7 min intervals for a total of 210 min. All assays were performed in duplicate. For each quarter, mammary secretion from all sampling periods and the appropriate controls were assayed on the same day.
Mixtures containing skim milk-treated neutrophils, recombinant BoIFN-gamma, and S. aureus from one quarter were fixed in 2.5% glutaraldehyde in 0.1M cacodylate buffer for 2 h and postfixed in 0.1M cacodylate-buffered osmium tetroxide for 1.5 h. Following dehydration in a graded series of ethanol washes, cell pellets were embedded in epoxy resins. Ultrathin sections (60 nm) for electron microscopy were stained with 5% uranyl acetate in 50% methanol for 20 min followed by 0.4% lead citrate for 10 min. Sections were examined using a Philips 300 transmission electron microscope (Philips Export, Eindhoven, Netherlands) operating at 60 kV.
Data were analyzed by least-squares analysis of variance using the general linear model procedure to determine effects of mammary secretion and increasing doses of recombinant BoIFN-gamma on mammary gland neutrophil function. Statistical analysis included effect of cow, mammary secretion, recombinant BoIFN-gamma, and interaction of mammary secretions with recombinant BoIFN-gamma. Preplanned comparisons of least square means from the overall model were made by pairwise t-test.
The effects of periparturient mammary secretion of neutrophil function are shown in Table 1. Mammary neutrophils treated with secretions obtained during the last 2 weeks of gestation had significantly lower phagocytic and bactericidal activity when compared with control cells incubated in HBSS. Cells incubated with skim milk preparations also had significantly less production of reactive oxygen species (ROS) when compared with control neutrophils incubated in HBSS. Secretions obtained at C-7 and C-0 tended to inhibit neutrophil function more than secretions obtained at C-14.
Ultrastructural examination of skim-milk-treated neutrophils frequently revealed phagocytic vacuoles containing casein-like micelles and debris in addition to ingested bacteria. In contrast, control neutrophils incubated in HBSS primarily had internalized bacteria with very little ingested debris.
Treatment with recombinant BoIFN-gamma significantly increased the phagocytic and bactericidal capacity of neutrophils for S. aureus (FIGS. 1 and 2) for both skim milk-treated and control cells. However, skim milk-treated neutrophils consistently showed lower phagocytic and bactericidal capabilities when compared with cells incubated in HBSS. There were no significant effects of recombinant BoIFN-gamma on production of ROS by mammary neutrophils although values tended to be slightly higher following recombinant BoIFN-gamma treatment (FIG. 3).
There were no apparent dose-dependent responses of skim milk-treated neutrophils to increasing recombinant BoIFN-gamma concentrations for bacterial phagocytosis, bactericidal activity, of ROS generation. In contrast, HBSS-treated neutrophils showed a trend of enhanced response with increasing doses of recombinant BoIFN-gamma for all parameters measured (FIGS. 1-3).
TABLE 1______________________________________Effects of periparturient mammary secretions onpolymorphonuclear leukocyte function in vitro Bacterial ROSSecretion Phagocytosis Activity Production2Sample (CFU/ml)-3 (% kill) (1 � 107)______________________________________HBSS 1.5a � 0.14 81.9a � 3.5 247.6a � 19.2C-01 1.0b � 0.10 61.6b,c � 2.5 172.1c � 13.6C-7 1.0b � 0.10 57.9c � 2.5 181.9b,c � 13.6C-14 1.3a,b � 0.10 69.1b � 2.5 217.3a,b � 13.6______________________________________ a,b,c Means within each parameter with different superscripts differ (p < 0.05). 1 Days preceding calving (C). 2 Data expressed as total area under the curve over a 203 min period
Thus, treatment of mammary neutrophils with recombinant BoIFN-gamma reversed the suppressive effects of mammary secretion, resulting in higher chemiluminescent activity and significantly more bacterial phagocytosis when compared with untreated controls. Results of this study suggested that recombinant BoIFN-gamma may have some immunomodulatory value for the prevention and treatment of bovine mastitis during the periparturient period.
To test this hypothesis, the following experiment was performed.
The influence of recombinant BoIFN-gamma on the establishment, severity, and duration of experimentally induced E. coli mastitis in dairy cattle was tested using the following method.
Eight Holstein-Frisian dairy cows were used in this study. These cows were purchased from local dairy producers. Animals arrived at the testing facility during their last trimester of pregnancy and were allowed to acclimate at least one month prior to experimental manipulation. Duplicate quarter foremilk samples were collected aseptically, immediately following arrival to determine infection status of each quarter. Bacteriologically positive quarters were treated with appropriate lactating intramammary antibiotic preparations based on sensitivity tests. The withdrawing time for antibiotic preparations was 72 hours. Animals were resampled approximately one week prior to experimental manipulation to ensure all quarters were free of intramammary infection. Only cows with healthy appearances and normal rectal temperatures, heart rates, and respiration were used in this trial.
Cows were randomly assigned to one of four treatment groups as outlined in the following table:
TABLE 2______________________________________Treatment groupsGroup # Lactation Stage Treatment*______________________________________1 4 days prepartum 105 U IFN/qtr at -24 hour2 4 days prepartum control, no IFN treatment3 ≦7 days postpartum 105 U IFN/qtr at -24 hour4 ≦7 days postpartum control, no IFN treatment______________________________________ *Treated cows were intramammarily infused into all four quarters (qtr) with 105 U recombinant BoIFNgamma at 24 hours prior to experimental challenge. All animals were challenged with approximately 50 CFU of E. coli into each quarter.
Mammary quarter secretion samples, sera, and rectal temperatures were collected from each group as outlined in the following table:
TABLE 3__________________________________________________________________________Sample schedule (hours)Group Time Post-infusion Time Post-challenge# 0 4 6 8 12 0 4 6 8 12 24 36 48 60__________________________________________________________________________1 x x x x x x x x x x2 x x x x x x x3 x x x x x x x x x x x x4 x x x x x x x x__________________________________________________________________________
In groups 1 and 2, all samples were collected again at calving and at 3, 7, and 14 days post-calving. In groups 3 and 4, all samples were collected again at 7 and 14 days post-challenge. During all sampling periods, clinical status of each quarter was recorded. Mammary secretion samples were used to determine infection status and to quantitate concentrations of lactose, fat, total protein, serum albumin, and lactoferrin. Total somatic cell counts, pH, and cytokine levels were also determined. Blood samples were used to determine total and differential cell counts and to quantitate concentrations of total protein, fibrinogen, zinc, iron, and copper.
Quarter milk production was recorded at each milking (8:30 a.m. and 8:30 p.m.). Mammary gland preparation for milking consisted of a prewash with a disinfectant iodine solution and drying with individual paper towels. Prior to each milking, a strip cup was used to observe clinical signs of mastitis in the first few streams of foremilk. Immediately following milking, teats were dipped with a 1% iodophor solution.
At 14 days post-challenge, the cows were slaughtered and approximately 1 cm3 of tissue was obtained from each quarter. Tissue specimens were prepared for both light and electron microscopy.
Mammary glands were washed with a disinfectant iodine solution and thoroughly dried with a single service paper towel. A few streams of foremilk were stripped from each quarter. Teat ends were scrubbed with swabs containing 70% isopropyl alcohol. Infusions of IFN-gamma were diluted in 10 ml of sterile saline to a final treatment concentration of 105 U recombinant BoIFN-gamma per quarter. A sterile 10 ml syringe fitted with an infusion canula was used to deliver the IFN-gamma solution into the streak canal of each quarter. The IFN-gamma infusion was massaged up into the gland cistern and teats were dipped with a disinfectant iodine solution.
E. coli was isolated from an acute case of bovine mastitis from the University of Saskatchewan Research Herd. The gram-negative isolates were typed using the API-2pE typing system. Stock cultures of E. coli-V374 were stored at -70� C. in skim milk until needed.
The bacterial challenge was prepared by streaking the stock culture of E. coli-V374 onto Esculin Blood Agar plates containing 5% whole blood. After 48 hours incubation at 37� C., a single colony was used to inoculate 100 ml of Ultra High Temperature (UHT) pasteurized milk and incubated for 12 hours at 37� C. The 12 hour culture was mixed well and a 100 ul aliquot removed to inoculate a second 100 ml of UHT milk. After a 6 hour incubation at 37� C., the culture was serially diluted in 10-fold increments using sterile saline. The colony-forming units (CFU)/ml of each dilution was determined by plate pouring 100 ul of the bacterial suspension onto McConkey agar plates. The dilution containing 50 CFU of E. coli/ml of saline was selected from each trial. Organisms were refrigerated during the time interval between inoculum preparation and actual infusion (approximately 24 hours). Inocula were plated post-challenge to confirm viability counts.
The actual bacterial counts used to challenge each experimental animal were as follows:
______________________________________ CFU/ IFN- CFU/CONTROLS QUARTER TREATED QUARTER______________________________________088 50 005 50.sup. 006a 75 .sup. 007a 75.sup. 033b 30 .sup. 013b 30048 50 040 50______________________________________
Animals between treatment groups with the same superscript (a,b) were challenged on the same day with the same bacterial suspension. The efficiency of establishing E. coli mastitis with this model system to mimic acute coliform mastitis as it occurs in the field is summarized in Table 4.
TABLE 4__________________________________________________________________________Rate of experimental intramammary infection in dairy cattle with an E.coli mastitis modelAverage CFU # Eligible Quarters1 # Infected Quarters % Success__________________________________________________________________________51 15 13 86__________________________________________________________________________ 1 Quarters which were not pretreated with recombinant BoIFNgamma prior to experimental challenge with E. coli Strain V374
The clinical status of all quarters was recorded immediately prior to experimental challenge and for 26 consecutive observations made at 12 hour intervals. The clinical scores were recorded on a scale from 1 to 5 where: 1 is normal milk with no quarter swelling; 2 is questionable milk but no quarter swelling; 3 is obvious abnormal milk but no quarter swelling; 4 is abnormal milk and swollen and/or tender quarter; and 5 is acute mastitis with systemic involvement.
The results of this study can be seen in Tables 5 and 6 and FIGS. 4 and 5.
TABLE 5______________________________________Effects of recombinant BoIFN-gamma on the severityof experimental E. coli mastitis Average AverageTreatment # % Days Clinical %Group Quarters Clinical1 Scores2 Mortality______________________________________PrepartumIFN 8 17.79 1.32 0CONTROL 8 90.39 3.09 50PostpartumIFN 8 15.39 1.33 0CONTROL 7 60.90 1.93 50TotalIFN 16 16.59 1.33 0CONTROL 15 75.64 2.51 50______________________________________ 1 Average % days that quarters showed clinical signs of mastitis (i.e., clinical score of 2 or above). 2 Average clinical score calculated from the 26 consecutive observations following challenge.
Those cows treated with interferon had significantly lower clinical scores, especially in the prepartum period. Furthermore, IFN-treated cows had a 0% mortality rate attributed to mastitis, whereas the control group had a 50% mortality rate (Table 5). IFN-gamma effectively reduced the percentage of infected quarters (Table 6 and FIG. 4), and reduced the rate and duration of experimental E. coli mastitis during the prepartum period (FIG. 5).
TABLE 6______________________________________Efficacy of recombinant BoIFN-gamma againstexperimental E. coli mastitis in dairy cattle Quarter: Quarter: Quarter: # at # infected % infectedTreatment beginning at end of at end of %Groups of trial trial trial Reduction______________________________________PrepartumIFN 8 2 25 71.4CONTROL 8 7 87.5PostpartumIFN 8 1 12.5 85.4CONTROL 7 6 85.7TotalIFN 16 3 23.1 73.4CONTROL 15 13 86.7______________________________________
Thus, an effective treatment for mastitis has been demonstrated. Although preferred embodiments of the subject invention have been described in some detail, it is understood that obvious variations can be made without departing from the spirit and the scope of the invention as defined by the appended claims.
Bielefeldt Ohmann, H., and I. A. Babiuk. 1986. Alteration of some leukocyte functions following in vivo and in vitro exposure to recombinant alpha and gamma interferon. J. Interferon Res., 6:123.
Hartmann, P. E. 1973. Changes in the composition and yield of mammary secretion of cows during the initiation of lactation. J. Endocrinol. 59:231.
Hill, A. W. 1981. Factors Influencing the Outcome of Escherichia coli Mastitis in the Dairy Cow. Res. Vet. Sci. 31:107.
Lappegard, K. T., H. B. Benestad, and H. Rollog. 1988. Interferons affect oxygen metabolism in human neutrophil granulocytes. J. Interferon Res. 8:665.
Lawman, M. J. P., M. Campos, H. Bielefeldt Ohmann, and L. A. Babiuk. 1989. Recombinant cytokines and their potential therapeutic value in veterinary medicine. In: Comprehensive Biotech. Pergamon Press, London. In press.
Miller, R. H., U. Emanuelson, and E. Perrson. 1983. Relationships of milk somatic cell counts to daily milk yield and composition. Acta Agric. Scand. 33:209.
Newbold, F. H. S., and F. K. Neave. 1965. The recovery of small numbers of Staphylococcus aureus infused into the bovine teat cistern. J. Dairy Res. 32:157.
Nagahata, H., S. Makino, H. Takahashi, and H. Noda. 1988. Assessment of neutrophil function in the dairy cow during the perinatal period. J. Vet. Med. 35:747-751.
Nickerson, S. C. 1989. Immunological aspects of mammary involution. J. Dairy Sci. In press.
Paape, M. J., and N. J. Carlett. 1984. Intensification of milk somatic cell response to intramammary device. Am. J. Vet. Res. 45:1572.
Paape, M. J., W. P. Wergin, A. J. Guidry, and W. D. Schultze. 1981. Phagocytic defense of the ruminant mammary gland. Adv. Exp. Med. Biol. 137:555.
Sordillo, L. M., S. C. Nickerson, and R. M. Akers. 1989. Pathology of Staphylococcus aureus mastitis during lactogenesis: relationship with bovine mammary structure and function. J. Dairy Sci. 72:228-240.
Sordillo, L. M., S. C. Nickerson, R. M. Akers, and S. P. Oliver. 1987. Secretion composition during bovine mammary involution and the relationship with mastitis. Int. J. Biochem. 19:1165.
Sordillo, L. M., and S. C. Nickerson. 1988. Morphological changes in the bovine mammary gland during involution and lactogenesis. Am. J. Vet. Res. 49:1112.
Trinchieri, G., and B. Perussia. 1985. Immune IFN: a pleiotropic lymphokine with multiple effect. Immunol. Today. 6:131.
Weber, K., E. Peterhans, and R. Wyler. 1983. The chemiluminescent response of bovine polymorphonuclear leukocytes isolated from milk and blood. Vet. Immunol. Immunopathol. 4:397.
|Cited Patent
|Filing date
|Publication date
|Mar 8, 1976
|Apr 11, 1978
|President Of The University Of Tokyo
|Therapeutical method for treating infection of mink hemorrhagic pneumonitis
|Apr 16, 1987
|Oct 21, 1987
|Cetus Oncology Corporation
|Lymphokines for use in the treatment of infections
|Billiau, J. Interferon Res., (1987), 7:559 567.
|Billiau, J. Interferon Res., (1987), 7:559-567.
|Frost et al., Australian Vet. J., (1986), 63(10):327 331.
|Frost et al., Australian Vet. J., (1986), 63(10):327-331.
|Hershman et al., "Modulation of Infection by Gamma Interferon Treatment Following Trauma", Infect. Immun., (1988), 56(9).
|Hershman et al., Clin. Exp. Immunol., (1988), 72:406 409.
|Hershman et al., Clin. Exp. Immunol., (1988), 72:406-409.
|Hershman et al., J. Interferon Res., (1988), 8:367 373.
|Hershman et al., J. Interferon Res., (1988), 8:367-373.
|Hershman et al., Modulation of Infection by Gamma Interferon Treatment Following Trauma , Infect. Immun., (1988), 56(9).
|Hill et al., Res. Vet. Sci., (1984), 37:179 187.
|Hill et al., Res. Vet. Sci., (1984), 37:179-187.
|Hill, Res. Vet. Sci., (1981), 31:71 112.
|Hill, Res. Vet. Sci., (1981), 31:71-112.
|Jensen et al., Cell. Immunol., (1988), 117:369 377.
|Jensen et al., Cell. Immunol., (1988), 117:369-377.
|Lawman et al., "Comprehensive Biotechnology", (1989), Permagon Press, London, Chapter 4, pp. 64-106.
|Lawman et al., Comprehensive Biotechnology , (1989), Permagon Press, London, Chapter 4, pp. 64 106.
|McDonald et al., Am. J. Vet. Res., (1981), 42(2):229 231.
|McDonald et al., Am. J. Vet. Res., (1981), 42(2):229-231.
|Nagahata et al., J. Vet. Med., (1988), 35:747 751.
|Nagahata et al., J. Vet. Med., (1988), 35:747-751.
|Nickerson et al., J. Diary Sci., (1989), 72(6):1665 1678.
|Nickerson et al., J. Diary Sci., (1989), 72(6):1665-1678.
|Ohmann et al., J. Interferon Res., (1986), 6:123 136.
|Ohmann et al., J. Interferon Res., (1986), 6:123-136.
|Paape et al., International Symposium on the Ruminant Immune System, Plymouth, N.H., (1980), J. E. Butler, ed., Plenum Press, New York, pp. 555 578.
|Paape et al., International Symposium on the Ruminant Immune System, Plymouth, N.H., (1980), J. E. Butler, ed., Plenum Press, New York, pp. 555-578.
|Shemer et al., Interferon and Nonviral Pathogens, (1988), G. I. Byrne et al., eds., Marcel Dekker, Inc., New York, pp. 73 94.
|Shemer et al., Interferon and Nonviral Pathogens, (1988), G. I. Byrne et al., eds., Marcel Dekker, Inc., New York, pp. 73-94.
|Sordillo et al., Am. J. Vet. Res., (1988), 49(7):1112 1120.
|Sordillo et al., Am. J. Vet. Res., (1988), 49(7):1112-1120.
|Sordillo et al., Int. J. Biochem., (1987), 19(12):1165 1172.
|Sordillo et al., Int. J. Biochem., (1987), 19(12):1165-1172.
|Trinchieri et al., Immunol. Today, (1985), 6(4):131 136.
|Trinchieri et al., Immunol. Today, (1985), 6(4):131-136.
|van Dissel et al., J. Immunol., (1987), 139(5):1673 1678.
|van Dissel et al., J. Immunol., (1987), 139(5):1673-1678.
|Citing Patent
|Filing date
|Publication date
|Jun 29, 1992
|Aug 9, 1994
|American Cyanamid Company
|Method of treating or preventing mastitis in animals with involuting mammary glands by administering recombinant cytokines
|Dec 20, 1991
|Aug 30, 1994
|American Cyanamid Company
|Compositions for the treatment of mammalian diseases
|Jun 7, 1995
|Jun 9, 1998
|Ambi Inc.
|Moist bacteriocin disinfectant wipes and methods of using the same
|Feb 28, 2002
|Apr 5, 2005
|University Of Vermont
|Treatment of Staphylococcus infections
|Oct 27, 2000
|Aug 15, 2006
|University Of Vermont
|Treatment of staphylococcus infections
|Feb 28, 2002
|Dec 19, 2002
|Bramley A. John
|Treatment of Staphylococcus infections
|Apr 23, 2003
|Dec 25, 2003
|Harrison Richard J.
|Mastitis prevention
|U.S. Classification
|424/85.5, 514/885, 424/85.4, 514/889
|International Classification
|Cooperative Classification
|European Classification
|Nov 30, 1989
Owner name: CIBA-GEIGY CANADA LTD., A CORP. OF CANADA, CANADA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:SORDILLO, LORRAINE M.;BABIUK, LORNE A.;REEL/FRAME:005198/0665
Effective date: 19891106
|Feb 20, 1991
Owner name: CIBA-GEIGY CORPORATION, 444 SAW MILL RIVER ROAD, A
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:CIBA-GEIGY CANADA LTD.;REEL/FRAME:005608/0315
Effective date: 19900914
|Jan 30, 1996
|Maintenance fee reminder mailed
|Jun 23, 1996
|Lapse for failure to pay maintenance fees
|Sep 3, 1996
|Expired due to failure to pay maintenance fee
Effective date: 19960626


text:
Jack and Jeans, MAASTRICHT
Jack and Jeans
- Address:
- Muntstraat 48
- Zip code:
- City:
- Country:
- Netherlands
- Phone:
- +31 (0)43 321 37 18
- Website:
- http://www.jacksandjeans.nl/
From tight to regular. Here are the Nudie Jeans fits. Spin them around and compare look and measurements. Visit Fit Guide
We take a great interest in where and how the Nudie Jeans collection is produced. See for yourself in the Production Guide
Your jeans go
where you go.
They live your lifestyle.
They get abrasions
and scars.
And they bleed.
Just like you.

subset: commoncrawl


text:
"Republicans more concerned about the headlines are going to say about them... than what their constituents are saying about them... they're making a really big mistake."
Excerpted, "Dana Loesch: Not afraid to fire away" Politico:
Excerpted, "Dana Loesch: Not afraid to fire away" Politico:
Loesch, 35, has never been one to shy away from controversy, whether it's battles with CNN's Piers Morgan over the Second Amendment or defending the U.S. Marines who were caught on video urinating on what appeared to be dead Taliban fighters. And now she's looking to expand both her program, "The Dana Show — the Conservative Alternative," which can currently be heard in St. Louis and Indianapolis or streamed online, and her reach. Loesch — who calls herself a "conservatarian" — is just as likely to go after Republicans as she is Democrats.
And right now, she's not liking what the right is doing in Washington, D.C. "I'm going to start bashing the GOP — I almost sound like the opposite of what I am," Loesch said in a recent interview.
"Fear is an epidemic right now in the Republican Party because Republicans are more concerned with what the headlines are going to say about them tomorrow than what their constituents are saying about them today," she added. "And that's where they're making a really big mistake."
Loesch has also kept busy debating the future of the Republican Party but says the names currently bandied about for 2016 just don't look like real, conservative winners to her. Florida Sen. Marco Rubio "damaged himself with immigration," while Kentucky Sen. Rand Paul, to whom she gives credit for "promoting a more libertarian element" with the party, may still be too much of a "newbie." And New Jersey Gov. Chris Christie may be "good for his state" and "great in terms of how he approaches education," but he's not someone who will attract the grass-roots conservative movement, she said.Read the full feature story at the link above.


text:
WiFi Hacker Prank (bgn)
by: Nugget Games | 401
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from 401 reviews
Free - V1.1 - 2M
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This app is no longer available.


text:
My First Weber
- Save Your Searches
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Welcome to my passion! Having over 10 years' experience as your Badger Real Estate Agent, my number one priority is helping you establish and accomplish your real estate goals in a prompt, fun, professional manner.
I use the latest technology and marketing initiatives in conjunction with personal networking to create a smooth, hassle-free real estate process.
As a former UW Alum and Badger Athlete, I have a love for the state of Wisconsin that runs deep and am proud to help my clients find their forever home, starter home, hunting land, business storefront, family cabin and so much more!
Listing Company: Keller Williams Realty
My goal is to provide superior real estate services through a smooth, streamlined process maintaining equal parts professionalism and care, tailored directly to your buying and selling needs. I strive for consistency through hard work to get you results in a stress-free, fun and relaxed manner.
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text:
MAC Frost Blush in Margin
235 reviews
85% would repurchase
Package Quality: 4.3
Price: $$$
Package Quality: 4.3
Price: $$$
Age: 44-55
Skin: Combination, Medium, Warm
Hair: Blond, Straight, Medium
Eyes: Blue
One of my favourite frost blushes by Mac! Great colour pay off and no need for highlighter /bronzer as this acts as all three! A very neutral shade in coral. Even though it's Frost don't be put off. It shows up as matte with a little frost. Best to swatch this though as it may show up differently.
Age: 25-29
Skin: Oily, Medium, Not Sure
Hair: Red, Other, Other
Eyes: Brown
I picked this boy up only yesterday and I love him sooooo much already I usually go for pink or coral blushes & I have over 50 blushes and this one is definitely one of my top 5 blushes it has such a beautiful sheen I swatched it on my hand and had to buy it. It's beyond beautiful it's like a bronzer highlighter blush in one I usually fake tan but I put it on this morning with no tan I'm roughly a mac nc20 and with a light hand it looked amazing made me look so healthy and glowing I think this blush would suite any skin tone ..this damn blush is such a player he'll suck you in and you'll never wanna leave him for another :)
Age: 18 & Under
Skin: Normal, Tan, Warm
Hair: Brunette, Straight, Medium
Eyes: Blue
Along with MAC Sweet as Cocoa, this is my fave blush ever!
I can't even describe how gorg this shade is! It's this kind of apricot, very slightly coral shade with gold shimmer through it, I mean, it's beautiful! Very flattering on medium-tan skin (think NC37-42) and it can actually be used for a day to school/office. I thought that it's only gonna be good for going out/clubbing because it's a frost, but with a light hand, it's totally perfect for anything, so if you're looking for this perfect summery, peachy-golden glow, then Margin is totally made for this!:)
Age: 19-24
Skin: Combination, Fair, Not Sure
Hair: Blond, Other, Other
Eyes: Grey
Coral blush with more of a bronze finish and some shimmer. I am pretty pale with really dark circles under the eye area and coral doesn't really look good on me on a daily basis. BUT in the summer that I tan I love wearing it, and I'd dare say it even looks good on me! Girls with a darker complexion than mine should definitely try/buy it.
As long as duration is considered, after a couple of hours you will definitely need to reapply it, like all blushes. The pigmentation though is something else; it is one of the highest pigmented blushes I've ever seen!
I wouldn't repurchase it only because I want to explore more of the fabulous colors MAC has!
Age: 25-29
Skin: Dry, Fair, Warm
Hair: Brunette, Curly, Fine
Eyes: Brown
I think this is a really special blush. It's unlike anything I own in my collection. I will say that I only wear it when I (sunless) tan as it makes me look really ill when I'm pale. When I'm tan it's like a bronzer/blush/highlighter in one that really compliments my tan and makes me glowy. Basically, it makes me feel like I'm radiating sexiness lol. I know that sounds ridiculous. Be careful not to over apply though because it is a frost blush. I apply with a big fluffy brush. Love it.
Age: 25-29
Skin: Combination, Medium, Warm
Hair: Brunette, Wavy, Other
Eyes: Blue
I've been using this blush since June and LOVE it! I don't have many of MACs frost blushes in my collection but this has been a welcome change from my usual sheertone shimmer blushes. I find this gives my cheeks a beautiful glow and just the right amount of color and shimmer that I don't need to use a bronzer or highlighter. It makes my cheeks pop like no other blush I own. I would definitely repurchase if I ran out. For reference, I'm an NW30.
Age: 30-35
Skin: Combination, Olive, Warm
Hair: Brunette, Wavy, Coarse
Eyes: Hazel
I love this blush so much, it has become my HG (and i have tons of blushes, I have 15 from Mac alone!) It is a lovely warm golden peachy bronze. It doesnt pull orange on my NC30 skin tone. It has shimmer which gives my skin a glow. It pairs really well with bronze smokey eyes and a neutral lip, but i think it would work with anything as it is a fairly natural looking blush. So happy I found this little gem! :)
Age: 19-24
Skin: Acne-prone, Fair-Medium, Warm
Hair: Brown, Straight, Medium
Eyes: Brown
LOVE :D! okay seriously this blush needs more love from the makeup world. I've been hunting for more of a skintone blusher...I mean MAC's blushbaby is lovely but it still leans dusty pink. Don't let the "frost" label cause you to turn this guy down! I was initially so skeptical about this blusher but I've never tried a skin tone blusher like this before so why not.
this is a 3-in-1 product for me! it adds the most awesome highlight sheen, a subtle color and gives my face depth in regards to contouring my cheekbones.
to all the warm tone girls out there - this blush does NOT pull orange at all! it's so awesome and it would be a shame if you didn't give this a chance. pigmentation is stellar and it's easily bendable. I have oily-acne prone skin and it lasts 7-8 hours on my cheeks and has not broken me out at all. I'm totally addicted to this blusher and I'm finding it hard to use any other ones when this is sitting on my vanity :D
Age: 19-24
Skin: Combination, Fair-Medium, Not Sure
Hair: Brown, Other, Other
Eyes: Brown
All mac products feels lux. This is another great product
Age: 25-29
Skin: Oily, Other, Not Sure
Hair: Brown, Other, Other
Eyes: Brown
My favorite go-to blush. It is a must have for everyone! It applies nicely, not too dark and leaves a healthy glow.
Popular Blush Products
365 Reviews
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text:
The hotel is in the centre of town, with markets and food outlets nearby. Rooms are a good size and well equipped. Clean and modern ensuite bathroom. The only complaint about the room is that the bed was as hard as rock but this is probably juts a local preference. TV programs were virtually 100% in Chinese. The onsite restaurant... More
Top-rated Attractions Nearby
Top-rated Restaurants Nearby


text:
Elegant 8-bedroom ocean view Jamaica villa
Enjoy our full staff and amenities galore, without the beachfront premium!
Presenting the newly updated
Mais Oui Tennis and Spa Villa
With 8 boutique-like bedrooms, this large but intimate, fully-staffed, Discovery Bay, Jamaica vacation rental, a mere 2-minute leisurely stroll to the beach, makes villa living a dream! Don't need such a large Jamaica villa retreat? No problem. We accept smaller groups. Mais Oui sleeps 6 - 17. Mais Oui . . . once experienced never forgotten.
The Jamaica villa of choice for family holidays and reunions, corporate retreats, spa vacations, small group getaways, destination weddings and anniversary celebrations. Rented exclusively to one group at a time . . . YOURS!
"Thank you for sharing your lovely island, beautiful home and exceptional staff with our family. We had a wonderful time, and our vacation was truly unforgettable, thanks to you!"M & MLS, Austin, TX July, 2014


text:
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text:
Royalty Free Music Unique To Your Project - Every Time
Royalty Free Music — Comical & Quirky
Browse Keywords:
(How To Use Search tutorial)
Track Search Results Switch to ALBUM VIEW
The following tracks match: Comical, Quirky
Carefree AfternoonClassic commercial music that could sell any product, this quirky little tune features piano & hand claps.https://www.smartsound.com/producer/images/PS69_200.jpgSingle12102-ST$ 39.9512102-EX$ 59.9512102-W$ 149.95Emotions: Cool, Carefree, Comical, Funny, Innocent, Refreshing, Quirky Genre: Specialty Production Types: Kids, Commercials, Indie Film, Comedy Instrument: Guitar (Acoustic), Piano, Instrumental, Guitar
Carefree Afternoon from the album The Lighter Side (PS69)
Cartoon CrittersAn upbeat quirky-yet-melodic themed tune, ideal for goofy characters or an opening theme song. Features a deep saxophone and hard-hitting drums.https://www.smartsound.com/producer/images/PS69_200.jpgSingle12103-ST$ 39.9512103-EX$ 59.9512103-W$ 149.95Emotions: Driving, Positive, Cool, Comical, Funny, Motivating, Wacky, Quirky, Fun Genre: Cartoon, Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Piano (Electric), Saxophone, Instrumental
Cartoon Critters from the album The Lighter Side (PS69)
Whistler's DreamThis soothing tune will make you feel like you're walking on a beach. Featuring a whistling melody and tuba.https://www.smartsound.com/strata/images/STRATGSS_200.jpgSingle69310-ST$ 39.9569310-EX$ 59.9569310-W$ 149.95Emotions: Tongue-in-cheek, Carefree, Comical, Goofy, Heartwarming, Refreshing, Whimsical, Quirky, Angelic Genre: Nostalgic, Whistling, Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Accordion, Mandolin, Piano (Electric), Tuba, Instrumental
Whistler's Dream from the album Goofy, Silly & Sweet
Strut Your StuffIdeal for commercials or goofy montage scenes, this playful and inviting tune features trombone and piano.https://www.smartsound.com/strata/images/STRATGSS_200.jpgSingle69308-ST$ 39.9569308-EX$ 59.9569308-W$ 149.95Emotions: Tongue-in-cheek, Cool, Cheerful, Comical, Goofy, Leisurely, Refreshing, Wacky, Whimsical, Quirky, Fun Genre: Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Brass Section, Piano, Trombone, Instrumental
Strut Your Stuff from the album Goofy, Silly & Sweet
Walk in the ParkUpbeat and goofy, this sweet track is ideal for couples spending time together. Featuring a bass clarinet melody.https://www.smartsound.com/strata/images/STRATGSS_200.jpgSingle69309-ST$ 39.9569309-EX$ 59.9569309-W$ 149.95Emotions: Tongue-in-cheek, Cool, Carefree, Comical, Goofy, Old-Fashioned, Refreshing, Tranquil, Wacky, Whimsical, Quirky, Fun Genre: Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Clarinet (Bass), Flute, Guitar (Acoustic), Vibraphone, Vocal, Guitar
Walk in the Park from the album Goofy, Silly & Sweet
Sneaky Affairhttps://www.smartsound.com/strata/images/STRATPWP_200.jpgSingle7100049-ST$ 39.957100049-EX$ 59.957100049-W$ 149.95Emotions: Driving, Energetic, Happy, Positive, Comical, Effervescent, Exuberant, Fresh, Funny, Incessant, Refreshing, Suspenseful, Wacky, Quirky, Sneaky, Investigative, Spy Genre: Funky, Cartoon, Corporate/Technology, Urban Production Types: TV/ Film Drama, Commercials, Corporate, Video Games, Comedy, Corporate Communications, Home Videos Instrument: Bass (Acoustic), Drums, Piano (Electric), Vibraphone, Violin, Instrumental
Sneaky Affair from the album Power Play
Mystery ShopperThis playfully mysterious track lends itself comedic detective situations. Featuring a pizzicato melody and tuba.https://www.smartsound.com/strata/images/STRATGSS_200.jpgSingle69306-ST$ 39.9569306-EX$ 59.9569306-W$ 149.95Emotions: Tongue-in-cheek, Secret Agent, Cool, Comical, Funny, Goofy, Wacky, Whimsical, Quirky, Sneaky, Fun Genre: Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Studio Orchestra, Strings, Tuba, Instrumental
Mystery Shopper from the album Goofy, Silly & Sweet
Quirky PlaygroundA very funky electric piano & drum-fuzed groove. Perfect for that quirky offbeat kind of scene, such as driving, chasing or goofy detecting.https://www.smartsound.com/producer/images/PS66_200.jpgSingle11806-ST$ 39.9511806-EX$ 59.9511806-W$ 149.95Emotions: Comical, Funny, Goofy, Leisurely, Wacky, Quirky, Sneaky, Fun Genre: Urban Production Types: Kids, TV/ Film Drama, Animation, Video Games, Comedy Instrument: Electronic, Piano (Electric), Instrumental
Quirky Playground from the album Indie Score (PS66)
Quirky MelodiesAn Upbeat tune ideal for any comedy situation. Features accordion and brass melodies.https://www.smartsound.com/strata/images/STRATGSS_200.jpgSingle69307-ST$ 39.9569307-EX$ 59.9569307-W$ 149.95Emotions: Tongue-in-cheek, Comical, Crazy, Funny, Goofy, Perky, Wacky, Quirky, Fun, Upbeat Genre: Specialty Production Types: Kids, Commercials, Comedy, Home Videos Instrument: Accordion, Saxophone, Instrumental
Quirky Melodies from the album Goofy, Silly & Sweet
Challenging PuzzleTrombone, honeyed strings and a rolling snare propel this hearty and confident track to a comical ending.https://www.smartsound.com/artist/images/ASFB04_200.jpgSingle7100193-ST$ 39.957100193-EX$ 59.957100193-W$ 149.95Emotions: Driving, Energetic, Exciting, Happy, Tongue-in-cheek, Positive, Cool, Uplifting, Comical, Competitive, Delicate, Effervescent, Expansive, Fierce, Fresh, Funny, Gentle, Goofy, Incessant, Inspiring, Majestic, Motivating, Powerful, Striving, Tense, Thrilling, Triumphant, Wacky, Whimsical, Quirky, Fun, Hopeful, Fantasy, Investigative, Magical, Military Genre: Orchestral Production Types: Kids, Animation, Video Games, Comedy Instrument: Orchestra, Studio Orchestra, Bass (Acoustic), Brass, Chimes, Clarinet, Clarinet (Bass), Flute, Harp, Oboe, Percussion, Piano, Strings, Instrumental
Challenging Puzzle from the album Orchestral Comedy
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text:
St. Stephen's Episcopal Church
Sunday, February 14, 2016
There's a place for you here.
Icon Writing Workshop
Icon Writing Workshop at St. Stephen's | August 2-7, 2015 | St. Stephen's Icon Guild
ONLINE REGISTRATION HAS CLOSED BECAUSE THE CLASS IS FULL. To be added to a waiting list, please send an email to Betsy Lee in the parish office.
We are thrilled to offer the popular icon writing workshop for the fifth year in a row.
Painting an icon can be a compelling experience. Using techniques developed at the end of the Iconoclast period (before the year 1000 A.D.), the painter sees a face gradually emerge from the darkness, a face glowing with an internal light.
The process has less to do with your ability to paint than with your willingness to let go and trust. All are invited to experience this joy, with no art experience required. The language of icons is the language of prayer. God's love and God's presence are revealed on a deeper, non-verbal level. "The process of writing an icon", according to Suzanne Schleck, the iconographer who will lead this retreat, "is not about finding something new but about returning to your true being."
Icons will be made using the traditional materials of egg tempera and gold leaf on gessoed panels. Participants may write the icon of the Three Marys or the Deesis icon (Mary, Jesus and John the Baptist). Beginners may write the icon of the Holy Face.
About the workshop: Days begin at 8:10 with Morning Prayer and Eucharist in the Holy Spirit Chapel followed by an anointing of hands in the studio. Each day ends around 5:00 p.m.
About the Instructor: Suzanne Schleck of Whiting, N.J., is a recently retired public school art teacher. She has studied for more than 20 years with the Rev. John Walsted, master iconographer and expert on 14th to 16th century Russian icons, and has taken additional workshops with Robert Lentz and the Prosopon School of Iconography. Her work has been published in Episcopal Life and in several online exhibits with Episcopal Church and the Visual Arts, as well as at the 2006 General Convention and Princeton Theological Seminary. This will be Suzanne's fifth annual workshop at St. Stephen's. Participants--who have come from the parish and beyond--have found it a deeply enriching experience.
Registration cost and waiting list
The Workshop is full as of April 15, but you may ask to have your name added to a waiting list. Workshop tuition (including all supplies) is $375. A deposit of $100 is required to hold your place, and should be paid by July 10. You may register Some scholarship assistance is available; please contact Gene LeCouteur in the parish office about assistance.
A group of women and men who have taken part in the icon workshop at St. Stephen's enjoyed this practice so much that they are continuing it. They have formed an icon guild which gathers on Friday mornings in one of the Sunday school rooms at St. Stephen's to write icons together. All are welcome. To learn more about this group, send an email to Donny Dunn.


text:
Rainfurrest 2011 T-Shirt by TaniDaRealWatch
©2011-2016 TaniDaReal
T-Shirt design I made for Rainfurrest 2011 (a convention in Seattle), featuring the convention's cougar mascot. The con theme is "Furry Camping".
I'm very much looking forward to see the shirt printed. ^^
You can buy the t-shirt at the convention. Sorry, I am NOT selling those shirts myself, it's the official con t-shirt and so handled by the con.
I'm very much looking forward to see the shirt printed. ^^
You can buy the t-shirt at the convention. Sorry, I am NOT selling those shirts myself, it's the official con t-shirt and so handled by the con.
Can I buy this?? and will you be making another one for this year?
Looks reeeeeaaaallly amazing lol I just payed for my way into Rainfurrest and really hope to find and buy this shirt x3
That's neat.
You are like so incredible haha. ^^
Tani how do you make your T-shirts?
I don't do them myself, I just submitted the artwork (file). The convention staff will take care about the printing (I don't know where they do it). ^^
I'd like 1 8D
Need BIGGER tent
And i love this one!
And i love this one!
It looks great! I'm sure people will love it!
are you going to this convention?
Omg. Thats an awesome shirt.
I cant wait to get it!
I cant wait to get it!
Ahhh this is absolutely well done! I love the expessions, and I just laughed at the back of the shit X3
Any way to get one of the shirts without going to the Con? I unfortunately can't aford to goto the convention, but I'd love to own one of the shirts.
AW! This is super cute! I really love the back! And the little Racoon, such a rascal! LOL!
Hmm...I live less than an hour away from Seattle
This is so cute!~ I really love the back xD
This is so cute!~ I really love the back xD
in seattle you say? i must look in to this convention
Very nice
Love it
i bet they will sell lods! your art is always amazing no wonder they hired you!
That looks great. Well done.
Awesome shirt
haaah - i always love the paws when You draw such type of pics..
aww...I love it ^^
I wish I could be in Seattle at this convention... *_*
I wish I could be in Seattle at this convention... *_*
cool cute too i wood like 1 but im from nz hehe
Cant wait! Finally get to debut my suit at a con! I love the racoon and his little diet card, hehe
lol nice
Wow! The conventioneers must have paid you at least $1000 to design this!
daaaaaaaamn I want it soooo much :<
OMG i aint much of a fan when it comes to furry but i love ur work and i totally want one of these!!!!
Haha I was actually invited to this by some friends! I so have to go hehe
Heh. that's a cute shirt.
Awesome awesome
Thats adorable!
Those are so cute / funny, you did a wonderful job on them and I am sure you're honored to have them be printed up as actually tee-shirts I'd love one and understand you yourself are not selling them so maybe I'll swing by the con to pick one up
Awwww!I wish I could go to get one of those shirts! I'd die to have a t-shirt with your art on it!
Too cute. Love the design. Wish there were more shirts like this available where I am, would so buy it.
man.i sooo want this shirt.but i haz no idea where the con is,and i dont think i'd have enough money to buy this.xD
The Con. itself is up in Seattle, WA at the Hilton Seattle Airport & Conference Center and its going on Sept. 22-25
Too bad that is a whole country away, that shirt is awesome!
I love cougars/pumas/mountain lions! I think my icon is a giveaway XD
Aww I really wanted to order this shirt. It looks amazing


text:
Ben Camey Wallace (Big Ben)
Position: Center and Power Forward ▪ Shoots: Right
Height: 6-9 ▪ Weight: 240 lbs.
Born: September 10, 1974 in White Hall, Alabama
High School: Central in Hayneville, Alabama
College: Virginia Union University
NBA Debut: November 1, 1996
Sponsor this page for $105 and help Basketball-Reference.com provide this service. Your message will replace this ad.


text:
My other Clown by Ironwi11Watch
©2009-2016 Ironwi11
Daily DeviationGiven 2009-04-29
The suggester says, "My other Clown by ~Ironwi11 is so very different from all the blood and gore, and it sends shivers up my spine looking at it - it's only ONE eye staring at me, but what is it thinking...oh, how I hate clowns!" ( Suggested by pullingcandy and Featured by RockstarVanity )
O_____________O ..... That's okay, I didn't feel like sleeping tonight anyway
oh the poor clown eye looks hurt *hugs the clown*
scary but great one
thats twisted! in a good way
Just a quick message to inform you that your piece has been featured in the A, B, C's of Horror under the letter "C". C is for clowns, after all.
i am absolutely TERRIFIED of clowns, and i cringed when i saw this.
but after looking at it for a minute. i love it!
but after looking at it for a minute. i love it!
Oh shit. That was pretty scary, but pretty awesome too
It's perfect! Good job.
I love clowns! xD I even have an evil clown bobble-head on my dresser! <3 Amazing!
nice photo...
wow.. stunning photo!
and i have a slight fear of clowns too..
and i have a slight fear of clowns too..
I love this. And everything about it xD I love how the make up is done and the expression. Wonderful job :3 ♥
that clown has a beautiful eye


text:
Entries in 'beta' (59)
GAME hosts Destiny early access tour
UK GAME stores will give those awaiting Destiny the chance to play Bungie's online multiplayer shooter early.
Braben admits Elite Dangerous pricing 'looks terribly capitalist'
You can play Elite: Dangerous RIGHT NOW. Providing you're willing to pay £100.
Activision details Destiny beta runs on PlayStation and Xbox consoles
Destiny's beta will take place later this month as two four-day runs on PlayStation hardware and one four-day run on Xbox consoles, Activision has announced.
Transformers Universe beta opens
The open beta for Jagex's MOBA Transformers Universe will be launching shortly.
Destiny beta on Xbox One and 360 kicks off in late July
The Xbox One and Xbox 360 Destiny beta will launch sometime late next month, Bungie has revealed.
PlayStation Now beta hitting Sony TVs next week
Some Sony TVs will next week begin offering direct access to the PlayStation Now beta.
PlayStation Now beta prices are a tad steep
Sony has added some prices to its ongoing PlayStation Now streaming beta in North America.
VIDEO: Doom reveal set for QuakeCon next month
Bethesda has promised to reveal its new Doom title at QuakeCon 2014.
Battlefield Hardline PS4 and PC multiplayer beta open now
A closed multiplayer beta for Battlefield Hardline is now online for PlayStation 4 and PC.
EA: Battlefield: Hardline PS4 Beta starts right now
EA's new Battlefield game was properly shown off during the firm's pre-E3 press conference today.
The Witcher board game coming to PC
The Witcher Adventure Game is headed to PC and Mac later this year, developer CD Projekt announced at an event last night.
£100 Elite Dangerous Premium Beta begins as Star Citizen stalls
Frontier's Elite: Dangerous has exited alpha and officially entered premium beta.
PlayStation Now US private beta hits PS4 this week
The private beta for game-streaming service PlayStation Now will launch for PS4 in the US on May 20th, Sony has announced.
Destiny beta scheduled for July
The beta release of Bungie's Destiny is now set for July, Activision Blizzard revealed during its quarterly financial report.
Elite: Dangerous Premium beta goes live today
Those who have purchased to £100 Elite: Dangerous Premium Beta can get stuck in from today.
Hearthstone officially released
Blizzard's popular digital card game Hearthsone: Heroes of Warcraft has exited beta.
Project Spark beta arrives on Xbox One
Microsoft's beta for the ambitious Project Spark is now available on Xbox One.
VIDEO: Minecraft introduces mini-games
Mojang is currently testing mini-games in Minecraft.
Respawn dev dignifies Titanfall bribery trolls with response
The press has reacted really positively to the now-ended Titanfall beta – and that seems to have caused upset.
Titanfall beta extended for one day as PC opens to all
The much-hyped Titanfall beta will remain open for 24 hours longer than previously planned.
UPDATED: GAME no longer offering Titanfall beta codes with pre-orders
UPDATE: GAME has also informed MCV that customers who pre-order Titanfall from the retailer will no longer receive beta codes.
Hearthstone open beta is live in Europe
Blizzard's card battler Hearthstone has entered live beta in Europe.
DayZ unlikely to enter Beta until the end of 2014
The developers behind digital smash-hit DayZ have warned that the game is unlikely to exit its Alpha phase before the end of the year.
Valve to ship beta Steam Machines this week, SteamOS also available
300 beta testers will get their hands on the Valve-produced Steam Box and its new touch-based controller.
VIDEO: Destiny beta to launch first on PlayStation consoles
PS3 and PS4 owners will get first crack at beta testing Bungie's Destiny, the studio has revealed.


text:
E-tutorial on the Post-2015 Framework for Disaster Risk Reduction
Duration of event:
Programme area:
Event focal point email:
Other events details:
The registration is closed
Deadline for registration: 30 March 2015
The new DRR Framework for Action to be adopted in March 2015 will be the outcome of a process unfolding over two years including a variety of stakeholders and several on-line, regional and thematic consultations. These consultations help build consensus but also bring to the fore new issues that have to be discussed and agreed during the Preparatory Committee Meetings and ultimately at the Sendai World Conference on Disaster Risk Reduction.
The challenge for diplomats and experts acting as delegates is to maintain a fair appraisal of the key issues being discussed while remaining up-to-date on the current process and the forthcoming deadlines and events. This online tutorial aims to contribute to establishing a levelled playing field for all actors involved, thus facilitating in a transparent and impartial way the discussion and adoption of the new Framework.
This initiative is undertaken in consultation with the SRSG for Disaster Reduction and in collaboration with the United Nations Office for Disaster Reduction (UNISDR).
Event Objectives
This initiative has the goal of creating a level playing field for all actors involved, ensuring a minimum standard of understanding of the main issues by all concerned and a common starting point for the negotiation of the outcome document to be adopted in Sendai. This is done with the intention of supporting the process leading to the World Conference in Sendai and facilitating the adoption of the new DRR framework for action.
By the end of this tutorial, participants will be able to:
- Define disaster risk reduction and its essential components;
- Outline the main features of past DRR international agreements and HFA;
- Understand the structure of HFA and its implementation and review process;
- Understand the process leading to the Third UN WCDRR and the variety of stakeholders involved;
- Assess the relation between the new framework for DRR, the Post-2015 Development Agenda, and climate change.
Content and Structure
The tutorial is structured in 4 modules that require a total learning time of 3 hours in one or various sessions:
1. Disaster Risk Reduction and its essential components.
2. Evolution of the DRR agenda and the Hyogo Framework for Action.
3. Coherence between DRR, development and climate change.
4. A delegates' guide to the Third UN World Conference on Disaster Risk Reduction.
The tutorial will be updated with special modules on emerging areas of interest for the new framework, such as:
- Science and climate prediction for reducing risks;
- DRR and agriculture;
- DRR and health;
- Women's leadership in DRR;
- Private sector involvement and business;
- Responsibility and accountability in the new framework.
Targeted Audience
The E-tutorial is designed for delegates and experts participating in the preparatory process of the Third UN World Conference on Disaster Risk Reduction (WCDRR, Japan, March 2015) and in the Conference itself. The tutorial is also open to government officers in ministries involved in the process towards the World Conference.
Additional Information
The approximate time to complete the tutorial is about 3 hours.
The modules can be accessed as many times as needed, and will be available until 31 March 2015.
A certificate of participation will be issued to participants who complete modules 1 to 4. Because this tutorial does not include assessment tests, to obtain the certificate participants have to access and go through all slides of modules 1 to 4 and complete a short feedback questionnaire available on the tutorial main page (the average time for completing the questionnaire is about 3 minutes).
- Upcoming Events
- Closing soon
- Current Events
- Past Events
- Core Diplomatic Training
- Location
- E-Learning
- Programme Area
- Special event
- Environment
- Governance
- Peace Security and Diplomacy
- Satellite Imagery and Analysis
- Other
- About UNITAR Events
Registration Mode
- Public - by registration
- Public - by application
- Private - by invitation
- Open to register/apply
Mode of Delivery
- Face-to-Face
- E-learning
- Blended
- Other
- Arabic
- Chinese
- English
- French
- Japanese
- Portuguese
- Russian
- Spanish
- Other


text:
Visit our other Wisconsin Historical Society websites!
Refine or narrow your results by clicking any term in the gray boxes below.
Expand your results by removing any breadcrumb in a gray outlined box above. Click on the blue "X" to remove the term.
Narrow your results by entering a keyword into the search box above. Then click the "Search Within" checkbox, then click on the orange "Search" button.
If you did not find what you are looking for or you did not get any results, try changing your search term(s). See our Search Help page for more tips.
Date: 1860
Description: View of St. John's Catherdral with the original tower.
Date: 1858 ca.
Description: Hölzlhuber's first extensive excursion in Wisconsin was a walking tour from Madison to Prairie du Sac along the Wisconsin River. He lost his way along Lake...
Description: Hölzlhuber located this farm at about three German miles from Stevens Point. The region's soil was quite fertile. A wooden dwelling house stood in the mids...
Date: 1875 ca.
Description: Seifert's watercolor is fairly large, measuring 27" wide by 21" high, and provides a detailed depiction of a nineteenth century Wisconsin farm. The small s...
Date: 1862-04-24
Description: Watercolor view of Manhattan, Kansas, from the bluff westward. The watercolor portrays the 12th Wisconsin Volunteers on their way to Fort Riley, on April...
Date: 1938 ca.
Description: Home of Newell Dodge (1845-1934) Madison alderman from 5th ward, attorney and fuel dealer, 1127 West Johnson Street.
Date: 1862-04
Description: Watercolor of the 12th Wisconsin Volunteers marching through on their way to Fort Riley, April 1862. Created by John Gaddis of Company E.
Date: 1856
Description: "Three views in a short space show the peaceful appearance of what is now a busy paper mills center. The first, a double lock around which the village of C...
Date: date unknown
Description: Ink and watercolor of prehistoric mounds near the mouth of Haigs Creek and the Scioto River.
Date: 1840 ca.
Description: A view of the Roman Catholic community of St. Nazianz.
Date: 1881
Description: Watercolor painting of farm and farmhouse, residence of Mr. Daniel Lewis.
Description: "....The third view was twelve miles farther up the river [from De Pere], at Rapid Croche, on the border of the present Brown and Outagamie counties. It is...
Date: 1862-07-28
Description: The alarm at Humboldt, Tennessee, July 28th, 1862. A watercolor by John Gaddis of the 12th Wisconsin Volunteers Company E.
Date: 1842 ca.
Description: American Fur Company with both Mission churches. Sketch purportedly by a Native American youth. Probably an overpainted photographic copy enlargement. Pape...
Date: 1834
Description: View of Rodolf farm.
Date: 1937
Description: Boyhood home of Hamlin Garland.
Date: 1950 ca.
Description: The home of Moses Strong, a prominent attorney, politician, speculator and land agent who moved to Wisconsin Territory and settled in Mineral Point in 1836...
Date: 1860 ca.
Description: In April of 1860 Hölzlhuber took the railway from Milwaukee to Lake Horicon to visit the small town that was developing on its shore. Since the settlers we...
Date: 1862-03
Description: Ossawattamie, Kansas, as it appeared at the time the 12th Wisconsin Volunteer's passed through on their march from Leavenworth to Fort Scott in March of 18...
Description: Neighbors work together in the final process of sawing firewood, as they saw poles into blocks. The man with the plaid shirt and suspenders is the owner of...
If you didn't find the material you searched for, our Library Reference Staff can help.
Call our reference desk at 608-264-6535 or email us at:
© 1996-2016 Wisconsin Historical Society, 816 State Street, Madison, WI 53706


text:
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Section 2257


text:
Not @Propercase, But @Scottishcase!
This Article Covers
Domino Resources - Part 7
the product descriptions are all in uppercase. I have created an application
which takes the product description and creates a letter document which
contains a computed field with the product description in proper case.
However, moaned my user, we don't want it to say Mcdougalls, we want it to say
This small formula does the job for any string which may contain mcdougalls as
it's first word. Variations of this could be used for any of those annoying
scottish names...
Note that Prodname needs to be replaced with the field you are converting...
@If(@UpperCase(@Left(ProdName;10))="MCDOUGALLS" ; "McDougalls " +
@ProperCase(@Right(Prodname; " ")) ; @ProperCase(Prodname) )


text:
Book your room at Mercure Caen Centre Port de Plaisance
Standard Room, 1 Double BedMax Occupancy: 2 guests
Standard Room, 2 Single BedsMax Occupancy: 2 guests
Privilege, Room, 1 King BedMax Occupancy: 2 guests
Get an overview of this hotelBoardwalk Caen hotel in Caen City Centre with marina
Located in Caen City Centre, this hotel is within a 10-minute walk of Eglise de la Sainte Trinite, Church of St. Pierre, and Musee des Beaux-Arts de Caen. Caen Castle and Universite de Caen are also within 15 minutes.
Hotel Features
This smoke-free hotel features a marina, a casino, and a restaurant. WiFi in public areas is free. Additionally, a nightclub, a bar/lounge, and a coffee shop/café are onsite.
Room Amenities
All 126 rooms offer free WiFi, minibars, and flat-screen TVs with digital channels. Guests will also find room service, rainfall showerheads, and coffee makers.Information missing or incorrect? Tell us!Opens in a new window
Hotel Amenities
Hotel Amenities
Mercure Caen Centre Port de Plaisance features a marina. The hotel offers a restaurant and a coffee shop/café. A bar/lounge is on site where guests can unwind with a drink. A computer station is located on site and high-speed wireless Internet access is complimentary.
Business-related amenities at this 4-star property consist of a business center and meeting rooms. Event facilities measuring 10764 square feet (1000 square meters) include conference space. This business-friendly hotel also offers a casino, a nightclub, and a library. Onsite parking is available (surcharge).
Mercure Caen Centre Port de Plaisance is a smoke-free property.
- Airport transportation - pickup (surcharge)
- 24-hour front desk
- Express check-out
- Total number of rooms - 126
- Number of floors - 3
- Hair salon
- Restaurant
- Bar/lounge
- Breakfast available (surcharge)
- Business center
- Casino
- Coffee shop or café
- Free newspapers in lobby
- Conference space
- Dry cleaning/laundry service
- Elevator/lift
- Express check-in
- Fireplace in lobby
- Computer station
- Library
- Marina on site
- Meeting rooms 17
- Multilingual staff
- Nightclub
- Garden
- Terrace
- Porter/bellhop
- Luggage storage
- Safe-deposit box at front desk
- Self parking (surcharge)
- Conference space size (meters) - 1000
- Number of meeting rooms - 17
- Year Built 1986
- Conference space size (feet) - 10764
- Smoke-free property
- Number of buildings/towers - 1
- Free WiFi
Family Friendly Amenities
- Family Hotel
- Free Wi-Fi
- Cribs/infant beds (complimentary)
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Self parking (surcharge)
Room Amenities
- Premium TV channels
- Climate control
- Air conditioning
- Phone
- Free bottled water
- Minibar
- Coffee/tea maker
- Daily housekeeping
- Private bathroom
- Hair dryer
- Shower/tub combination
- Rainfall showerhead
- Desk
- Iron/ironing board (on request)
- Digital TV service
- Flat-panel TV
- Blackout drapes/curtains
- Room service (limited hours)
- Connecting/adjoining rooms available
- Free cribs/infant beds
- Separate bedroom
- Pillow menu
- Free WiFi
Where to Eat
Buffet breakfasts are available for a surcharge and are served each morning between 6:30 AM and 10 AM.
Courtepaille - This steakhouse specializes in international cuisine and serves lunch and dinner. Open daily.
Room service (during limited hours) is available.
Nearby Activities
The recreational activities listed below are available either on site or nearby; fees may apply.
- Bicycle rentals nearby
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible bathroom
- In-room accessibility
- Roll-in shower
Hotel Policies
Check-out time is Noon
Payment types
Pets allowed
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
24-hour check-in
No rollaway/extra beds available
- A tax is imposed by the city: EUR 1 per person, per night. This tax does not apply to children under 16 years of age.
Optional extras
- Fee for buffet breakfast: EUR 16 per person (approximately)
- Airport shuttle fee: EUR 20 per vehicle
- Self parking fee: EUR 10 per night
- Pet fee: EUR 10 per pet, per night
- Rollaway bed fee: EUR 0 per day
Hotel Name
- Mercure Caen Centre Port
- Mercure Caen Centre Port Plaisance
- Mercure Plaisance
- Mercure Plaisance Hotel
- Mercure Plaisance Hotel Caen Centre Port
- Mercure Caen Centre Port Plaisance Hotel
- Mercure Caen Centre Port De Plaisance Hotel Caen
We should mention
The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.
National Rating
This hotel has received its official star rating from the French Tourism Development Agency, ATOUT France.


text:
Baked Cranberry Relish Recipe
5 1
"Orange marmalade and walnuts make this chilled cranberry sauce a delightful change from the ordinary," assures Anita Curtis of Camarillo, California. With just five ingredients, it's a simple dish that adds festive color to the table.
- 4-1/2 cups cranberries
- 1-1/2 cups sugar
- 1 cup chopped walnuts, toasted
- 1 cup orange marmalade
- 2 tablespoons lemon juice
- Toss cranberries and sugar; place in a lightly greased 2-qt. baking dish. Cover and bake at 350° for 1 hour. Stir in walnuts, marmalade and lemon juice. Refrigerate. Yield: 6-8 servings.
Originally published as Baked Cranberry Relish in Quick Cooking November/December 1999, p57
Reviews for Baked Cranberry Relish
Please Log In or Join to add a rating and review.
Click stars to rate
Any changes to your rating or review will appear where you originally posted your review


text:
STARmeterSEE RANK
Up 53,168 this week
Bruce Baum
Bruce Baum is an actor and writer, known for Shakes the Clown (1991), Kandyland (1987) and The Garry Shandling Show: 25th Anniversary Special (1986). See full bio »
More at IMDbPro » Contact Info: View manager, publicist and company
Represent Bruce Baum? Add or change photos
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text:
This blog post originally appeared on RealMoney Silver on July 9 at 8:05 a.m. EDT.Since I have been out for a few days of meaningful and persistent downside pressure, let's frame the market expectations that have led up to my current outlook for stocks over the balance of the summer and into the fall.
- More tangible signs of economic traction are necessary before the markets move higher.
- The trajectory of economic growth will be shallow and will likely disappoint the equity markets during the second half of 2009.
- Massive cost cutting has resulted in better-than-expected first-quarter 2009 profits, but it holds a downside as significant employee layoffs (and a still-weakened consumer) threaten the seeds of domestic economic growth over the intermediate term.
- Savings rates will remain high, and personal consumption expenditures will remain low for an extended period of time.
- The specter of rising taxes and higher interest rates in late 2009/early 2010 will likely impact an already fragile recovery in the economy and in the markets -- a double-dip is due then.
- Near term the market looked increasingly exposed and the upside was certainly capped.


text:
Database Applications
Pipeline Compliance System optimizes traceability.January 28, 2016
With change logging capability, PCS Axis v1.10 enables pipeline operators to track database changes to prove traceability, pinpoint and resolve cathodic protection data errors so they don't come up during audit, identify malicious or unintended changes, and view change history for specific measurement. Program automatically embeds photos in users' PCS databases rather than external drive. It also offers bridge importer and form creation and editing features. Read More
Model Libraries aid MCU application testing and programming.November 2, 2015
VarioTAP® model libraries, used for universal processor emulation, are available for Infineon XMC MCUs based on ARM® Cortex™-M cores. As part of IP library, VarioTAP model contains all relevant access information for respective target processor. This lets users select processor corresponding to their design and test/validate connected hardware unit as well as program Flash memories. Processor is reconfigured to provide design-integrated test and programming instruments via native debug port. Read More
Software Suite improves survey, CAD, and GIS workflows.September 21, 2015
Promoting efficacy when working with GIS databases, Trimble Business Center v3.60 provides editing and QC options for surveyors and GIS professionals. CAD and drafting tools let CAD professionals create final project deliverables within Trimble Business Center. In addition to tools for generating precise and accurate data, software enables surveyors to post process individual GNSS constellations. In addition CAD package compatibility, software enables production of client deliverables. Read More
Design Management Software fosters customer collaboration.August 27, 2015
Pilot-ICE enables design firms, architectural studios, project offices, and design departments of industrial firms to store, track, and analyze project data. Functionality also promotes collaboration between companies and their customers and sub-contractors. Software uses virtual cache drive on virtual file system (Pilot-Storage), which becomes visible to all connected computers, and all virtual cache drive content is synchronized automatically with server. Read More
Information Management Software helps qualify composites.March 26, 2015
With tools for capturing, processing, and reporting on composite data, GRANTA MI:Composites supports rigorous, auditable composite qualification process, particularly where data traceability is important for regulatory purposes. Engineering enterprises can manage all valuable but complex data associated with composite materials, including layup, cure cycle, and directional properties. Composites Qualification Service configures GRANTA MI:Composites software for organization's specific needs. Read More
Forestry Software manages load data.March 26, 2015
Offering mobile ticketing solution, 4Loads™ simplifies creation, access, and sharing of harvested timber data for loggers, foresters, and haulers. Application eliminates manual tracking, provides instant access to data online, and minimizes time to summarize load financial information. Harvest operators enter load data on iOS or Android mobile devices in field, which automatically synchronizes with Trimble mobile cloud service for access via Trimble Forestry Mobile Website. Read More
Database Management Software offers maximum scalability.March 3, 2015
Using Caché® 2015.1, data is simultaneously available via NoSQL, SQL, and object paradigms. Just-in-time analytics capabilities, on both structured and unstructured data, give developers means to deliver insight at point of action. Caché also provides technology for rapidly developing mobile and web applications. With maximum scalability, software targets organizations pursuing large-scale medical informatics programs as well as aggressive growth strategies in healthcare. Read More
Research Analysis Module incorporates citation and usage data.March 3, 2015
SciVal Trends module is used within SciVal and builds upon its flexibility to define and analyze user-created research areas — by key words or discipline at journal, institution, or country level — based on citation and publication data from Scopus. Used to analyze and benchmark research, module includes research analyses based on usage data drawn from Scopus and ScienceDirect. Solution combines citation, publication and usage data to provide full set of research-strategic, analytical markers. Read More
Materials Management Software integrates with CAD/CAE/PLM systems.February 11, 2015
Appearing as pop-up window inside host system, GRANTA MI:Materials Gateway 3.0™ lets engineering enterprises manage diverse information on materials specified in their products within CAD, CAE, and PLM systems. Approved and traceable data is made available directly within engineers' design, simulation, or PLM environments, which reduces time spent looking for information while promoting accuracy and consistency. Solution fully utilizes functionality of GRANTA MI v8. Read More
Quality Data Management Software simplifies reporting.February 4, 2015
Tailored for SMBs, extended version of PiWeb sbs makes it possible to connect all gauging and inspection devices into one common reporting system, allowing customers to standardize reporting requirements across metrology inspection devices and personalize reports. Program combines and reports inspection data into graphical part stories, SPC charts, and quality documents. Users can also create graphical interfaces to assist inspectors in collecting data from manual gauges. Read More
Mobile HVAC Industry App offers drive management module.January 28, 2015
Toolbox Technician®, compatible with IOS 8+ and Android, features HVAC Drive Kit Management module, which recognizes OEM content for blower drives of North American manufacturers. By scanning QR code on drive or inputting data from Browning drive kit label, user gains immediate access to product information. Registered users can save/email data, set push notifications, and add data on related components. Other features include bearing section, V-belt ID wizard, and efficiency calculator. Read More
Data Management Software enables real-time collaboration.January 27, 2015
Available in Component, Workgroup, and Enterprise editions for design teams of varying sizes, Altium Vault® v2.1 software provides enterprise ECAD design data management and collaboration platform. Centralization, management, and formalization of component libraries, design data, and team collaboration promotes productivity and reduces potential errors for design teams. Specifically, solution manages product versions and releases, design reuse, and design library management.
Read More
Construction Specification Software offers online updating.January 14, 2015
Designed to produce construction specifications, BSD SpecLink-E delivers continuous, online data updates that provide architects and engineers with up-to-the-minute information that merges automatically with data already included in developing project specification without altering current output. Any product sections in template that are not currently in use are automatically updated, and any section already in use is updated selectively, to avoid making changes without user's knowledge. Read More
Clinical Research Management Tools support cross-study reporting.December 29, 2014
DATATRAK ONE® Unified Experience™ simplifies clinical research management by providing enterprise-wide eClinical® tools. Cross-Study Managers fulfill information needs of each research professional, whether reporting at individual or cross-study level, with instant access to real-time, enterprise-wide data. Solution also offers flexible reporting capabilities across 100+ fields, online data management tools, role- and time-specific Scheduler, cloud-based collaboration, and File Versioning. Read More
Clinical Trial Software manages results reporting.December 17, 2014
Stock Plan SaaS increases control via interactive reporting.December 11, 2014
Offering filtering capabilities, one-click sorting, and drag and drop columns, Equity Administration Solutions, Inc (EASi) Interactive Reporting increases control over data organization and presentation. Architecture optimizes report customization within EASi application, application of conditional formatting aids data analysis, and ability to save customized report definitions promotes productivity. Users also gain control over column size, order, and visibility. Read More
Data Management Software aids healthcare application performance.December 11, 2014
VPSX/EI (Epic Interface) is used to manage output from Epic® healthcare applications. Run as single executable, GUI-based administration interface replaces multiple modules of first-generation Epic interface to optimize I/O performance. Graphical configuration screens streamline process of installation and configuration, and plug-ins foster custom processing. Memory management minimizes RAM utilization during ROI preview job to improve throughput and lower server RAM requirements. Read More
DCMSYS Interface enhances medical facility data flow.December 8, 2014
Accommodating medical facilities of any size, WebBridge allows any native or Web-based, third-party application to upload any non-standard data to DCMSYS Enterprise Imaging Suite and Vendor Neutral Archive. Users can connect to DCMSYS product suite to access patient data, search studies, link data to appropriate study, as well as store, modify, share, and connect to any repository. Data may be retrieved in presentation-ready format, as specified by requester, or in native DICOM format. Read More
Materials Information Software helps mitigate risk.December 1, 2014
With GRANTA MI: Restricted Substances Software, materials professionals can manage, analyze, certify, and maintain materials data, making it available for use across enterprise in secure and controlled manner. Program helps avoid lost data and duplicated work, ensure traceability, and guarantee accuracy. In addition, software enables users to make better informed materials decisions and mitigate problems associated with restricted substances and supply chain disruption. Read More
Database connects technicians, customers, and internal staff.November 14, 2014
Featuring 21 CFR compliance, GenCal II™ connects field service technicians, customers, and internal support staff with immediate access to electronic calibration data. Included iPhone app, which lets mobilized workforce access work orders and customer information, also features customer digital sign out function. Calibration software suite integrates seamlessly to Certificate Management System™ (CMS), which allows 365/24/7 password-protected access to electronic calibration records. Read More


text:
Bubbly Personality by AnaduKuneWatch
©2012-2016 AnaduKune
Another fun pic I have had in my backlog for a while. I was playing with this idea with a couple of other characters as well.
Derpy is my absolute favorite pony. There are more funny ones and there are more cute ones, but Derpy (at least in the fandom) has just the right amount of both. She made me a Brony long before I ever saw the show and was featured on the first MLP shirt I've ever purchased. She looks so adorable right here, good work.
Derpy rocks!
Simply adorable! XD
Fantastically adorable.
Derpy and bubbles make me happy.
Derpy being adorable, nice.
She is so cute! <3
Aww, the bubbles.
Up next is Pinkie Pie floating on her balloons.
Did you actually read my mind? Its not my next pic but I do have one.
D'aww!!! SO CUTE!
Congrats on the Equestria Daily Drawfiend feature. This looks positively adorable. Love it.


text:
The Missouri Review
Volume 36, Number 3, 2013
pp. 27-33 | 10.1353/mis.2013.0063
How History Would Have It by Rose McLarney.
Redemption by Rose McLarney.
Arcadia by Rose McLarney.
Watershed by Rose McLarney.
Rose McLarney "A couple of years ago, thinking about the cautionary-feeling but often rather irrational and amoral Appalachian lore that haunted the area where I grew up, I set out to write contemporary folk tales and ghost stories. But I'm not actually all that interested in the otherworldly or transcendent, and I am keenly concerned with the earthly and idiosyncratic. So the project turned into an examination of the many versions of any story that almost always exist. I looked at how, due to the subjectivity of first-person accounts and the shape-shifting quality of memory, the telling makes the meaning, whether we are taking folk tales across oceans and through centuries or forming our recollections of the events of our own lives. And I began permitting my poetic voices, which had once aspired to be authoritative, to speak like human voices, to ask questions, to pause, to waver if need be. Even more, I wanted to let them be generous and inclusive, allowing for the multiple versions of the story (and the reader's speculation and input). There are signs of the poems' restlessness and their dissatisfaction with the moral that history is supposed to teach in the early poem 'Arcadia.' Then, the later poems can be seen constructing themselves and heard correcting themselves. Rather than the absolute of writing what I know or continuing the traditions of a kind of regional writing in which I could claim expertise, I began to try to evoke another effect. It's the feeling of the inquiry 'Don't I know you from somewhere?' a traveler gets when she walks into a new place and still, somehow, recognizes a quality in a face or can hum a refrain in an otherwise strange song."
Rose McLarney's collection of poems, The Always Broken Plates of Mountains, was published by Four Way Books. She has received a number of awards and fellowships for her work, which has appeared in theKenyon Review, Orion, Slate, New England Review, Painted Bride Quarterly and dozens of other journals. Rose earned her MFA from Warren Wilson's MFA Program for Writers and currently is assistant professor of poetry at Oklahoma State University.
T1 - How History Would Have It, and: Redemption, and: Arcadia, and: Watershed
A1 - Rose McLarney
JF - The Missouri Review
PB - University of Missouri
UR - http://muse.jhu.edu/journals/missouri_review/v036/36.3.mclarney.html
N1 - Volume 36, Number 3, 2013
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