text:
Frozen and lyophilized compositions for a metalloproteinase fibrinolytic agent (fibrolase or NAT), a method for preparing the lyophilized composition, and a kit and method for reconstituting the lyophilized composition are described herein.
1. A method for preparing a pharmaceutical composition comprising:
(a) providing an aqueous composition comprising a therapeutically effective amount of a fibrinolytic metalloproteinase, a zinc stabilizer and, optionally, a bulking agent, in a pharmaceutically acceptable buffer comprising citric acid or a water soluble citric acid salt;
(b) lyophilizing said aqueous composition; and
(c) reconstituing said lyophilized composition.
2. The method of
3. The method of
4. The method of
This application is a divisional application of U.S. Ser. No. 10/226,408, filed Aug. 23, 2002, now U.S. Pat. No. 7,138,114, which is a divisional application of U.S. Ser. No. 09/411,335, filed Oct. 1, 1999, now U.S. Pat. No. 6,440,414, from which applications priority is claimed pursuant to 35 U.S.C. �120, and which applications are incorporated herein by reference in their entireties.
The present invention relates to novel pharmaceutical compositions of a fibrinolytic agent. More specifically, the present invention relates to frozen liquid and lyophilized compositions of fibrolase and, separately, of "novel acting thrombolytic" (NAT) (SEQ ID NO:1), as well as methods for the production and use thereof.
In general, polypeptides are marginally stable in the aqueous state and undergo chemical and physical degradation resulting in a loss of biological activity during processing and storage. Another problem encountered in aqueous solution in particular is hydrolysis, such as deamidation and peptide bond cleavage. These effects represent a serious problem for therapeutically active polypeptides which are intended to be administered to humans within a defined dosage range based on biological activity.
To reduce the degradation of polypeptides, water-based pharmaceutical compositions are generally kept refrigerated or frozen until ready for use. As an alternative, the process of freeze-drying is often employed to stabilize polypeptides for long-term storage, particularly when the polypeptide is relatively unstable in liquid compositions. A lyophilization cycle is usually composed of three steps: freezing, primary drying, and secondary drying; Williams and Polli, Journal of Parenteral Science and Technology, Volume 38, Number 2, pages 48-59 (1984).
In the freezing step, the solution is cooled until it is adequately frozen. Bulk water in the solution forms ice at this stage. The ice sublimes in the primary drying stage, which is conducted by reducing chamber pressure below the vapor pressure of the ice, using a vacuum. Finally, sorbed or bound water is removed at the secondary drying stage under reduced chamber pressure and an elevated shelf temperature. The process produces a material known as a lyophilized cake. Thereafter the cake can be reconstituted prior to use.
The standard reconstitution practice for lyophilized material is to add back a volume of pure water (typically equivalent to the volume removed during lyophilization), although dilute solutions of antibacterial agents are sometimes used in the production of pharmaceuticals for parenteral administration; Chen, Drug Development and Industrial Pharmacy, Volume 18, Numbers 11 and 12, pages 1311-1354 (1992).
Lyophilization is considered one of the best ways to remove excess water from polypeptide solutions. The freeze-drying process may yield products that are stable and amenable to handling for long-term storage. Lyophilized products can be stored at room temperature and are therefore easier to handle and distribute to a wider geographic market, such as foreign markets where refrigeration may not be available.
Excipients have been noted in some cases to act as stabilizers for freeze-dried products; Carpenter et al., Developments in Biological Standardization, Volume 74, pages 225-239 (1991). For example, known excipients include polyols (including mannitol, sorbitol and glycerol); sugars (including glucose and sucrose); and amino acids (including alanine, glycine and glutamic acid).
In addition, polyols and sugars are also often used to protect polypeptides from freezing and drying-induced damage and to enhance the stability during storage in the dried state. In general, sugars, in particular disaccharides, are effective in both the freeze-drying process and during storage. Other classes of molecules, including mono- and di-saccharides and polymers such as PVP, have also been reported as stabilizers of lyophilized products.
The present invention relates to stable pharmaceutical compositions of fibrolase and "novel acting thrombolytic" (NAT) (SEQ ID NO:1), some of which are liquid compositions suitable for storage in the frozen state, and others of which are suitable for lyophilization.
Because of the fibrinolytic properties of fibrolase and NAT (SEQ ID NO:1), the compositions of this invention are useful to lyse blood clots in vivo and may be administered therapeutically for such a purpose.
For purposes of this invention, the term "NAT" refers to the metalloproteinase having fibrinolytic activity which is characterized by SEQ ID NO: 1. The NAT polypeptide is encoded by the cDNA molecule of SEQ ID NO: 2, although any DNA molecule of variant sequence encoding the same polypeptide may be used for expression and manufacture in accordance with methods which are referred to hereinbelow.
Fibrolase is a known metalloproteinase which has been described in the scientific and patent literature; see Randolph et al., Protein Science, Cambridge University Press (1992), pages 590-600, and European patent Application No. 0 323 722 (Valenzuela et al.), published Jul. 12, 1989. Typically, the fibrolase employed in the compositions of this invention will be of SEQ ID NO: 3, which is encoded by the cDNA molecule of SEQ ID NO: 4 (or variants thereof encoding the same amino acid sequence).
Fibrolase and NAT (SEQ ID NO:1) are to be distinguished from other therapeutic agents for the treatment of blood clots in vivo, such as urokinase, streptokinase and tPA which are plasminogen activators. Unlike these other agents, fibrolase and NAT (SEQ ID NO:1) act directly on the clot to degrade both fibrin and fibrinogen.
The pharmaceutical compositions of this invention will contain, in addition to a therapeutically effective amount of fibrolase or NAT (SEQ ID NO:1), a zinc stabilizer and, optionally, a bulking agent with or without other excipients in a pharmaceutically-acceptable buffer which, in combination, provide a stable, frozen or lyophilized product that can be stored for an extended period of time.
In one of its aspects, the present invention provides a freezable liquid medicinal composition comprising fibrolase or NAT (SEQ ID NO:1), a water soluble zinc salt, a citric acid buffer, optionally an additional stabilizer selected from the group consisting of water soluble calcium salts, and optionally a bulking agent (for example, mannitol). A surfactant, such as Tween 80 (BASF, Gurnee, Ill.), may also be added to increase freeze-thaw stability. Tris buffer (Sigma, St. Louis, Mo.) or another buffer with a buffer capacity above pH 7.0 may be added to stabilize the pH at or above pH 7.4.
In another aspect of the present invention, the pharmaceutical composition can be a lyophilizable or lyophilized pharmaceutical composition comprising fibrolase or NAT (SEQ ID NO:1), a zinc stabilizer (e.g., water soluble zinc salt), and a citric acid buffer, with or without other excipients (e.g., bulking agent such as mannitol, glycine, or the like). The lyophilized composition may also contain a disaccharide sugar, such as sucrose or trehalose, as a lyoprotectant. A surfactant, such as Tween 80, may be added to protect against lyophilization stresses on the metalloproteinase (fibrolase or NAT (SEQ ID NO:1)). The pH will ideally be maintained at pH 8.0�0.5, using a suitable buffer with a pKa in this range (for example, Tris).
The invention also comprises a method for preparing a lyophilized composition, comprising the steps of (i) mixing fibrolase or NAT (SEQ ID NO:1) with a buffer and a water soluble zinc salt, as well as any desired optional ingredients, and (ii) lyophilizing this mixture.
In addition, the invention provides a kit for preparing an aqueous pharmaceutical composition, comprising a first container having the aforementioned lyophilized composition and a second container having a physiologically acceptable solvent therefor.
Still another aspect of this invention comprises a method comprising the steps of reconstituting the lyophilized composition and administering the reconstituted composition to a patient in need of blood clot lysis.
A variety of host-vector systems may be utilized to express the coding sequence for fibrolase or NAT polypeptide in accordance with standard methods for recombinant expression which are well known to those skilled in the art, and thereby obtain the fibrinolytically active polypeptide for the compositions. Such systems include, but are not limited to, eukaryotic cell systems such as mammalian cell systems infected with virus (for example, vaccinia virus, adenovirus, etc.); insect cell systems infected with virus (for example, baculovirus); microorganisms such as yeast containing yeast vectors; or prokaryotic cell systems such as bacteria (e.g., E. coli) transformed with bacteriophage DNA, plasmid DNA, or cosmid DNA. The expression elements of these vectors vary in their strengths and specificities. Depending on the host-vector system utilized, any one of a number of suitable transcription and translation elements may be used.
Preferably, a yeast expression system (e.g., Pichia pastoris) is employed for recombinant expression because of its greater efficiency. A detailed description of such a system may be found in U.S. Pat. No. 4,855,231 (Stroman et al.), U.S. Pat. No. 4,812,405 (Lair et al.), U.S. Pat. No. 4,818,700 (Cregg et al.), U.S. Pat. No. 4,885,242 (Cregg), and U.S. Pat. No. 4,837,148 (Cregg), the disclosures of which are hereby incorporated by reference. Expression of fibrolase in such a system will typically involve a DNA molecule of SEQ ID NO: 5, which encodes "prepro" sequence (nucleotides 1-783) in addition to the "mature" polypeptide (nucleotides 784-1392). Expression of NAT in such a system will typically involve a DNA molecule of SEQ ID NO: 6, which encodes "prepro" sequence (nucleotides 1-783) in addition to the "mature" polypeptide (nucleotides 784-1386).
Further details regarding NAT (SEQ ID NO:1) and methods for its preparation may be found in commonly assigned copending patent application Ser. No. 09/411,329, now U.S. Pat. No. 6,261,820, filed concurrently herewith, which is hereby incorporated by reference.
Once the polypeptide (fibrolase or NAT (SEQ ID NO:1)) has been prepared, purified, and then assayed for activity (using procedures for fibrinolytic agents known to those skilled in the art), it may be formulated into pharmaceutical compositions in accordance with this invention.
In the present compositions (whether frozen or lyophilized), a stabilizer (which can also be referred to as a "glass-forming additive") is added to prevent or reduce precipitation and chemical degradation of fibrolase or NAT (SEQ ID NO:1), whichever the case may be. A hazy or turbid solution at room temperature indicates that the polypeptide has precipitated. The term "stabilizer" means an excipient capable of preventing aggregation or other physical degradation, as well as chemical degradation (for example, autolysis, deamidation, oxidation, etc.) of fibrolase or NAT (SEQ ID NO:1) in an aqueous medium.
It has been found that the incorporation of a zinc stabilizer, and more specifically a water soluble zinc salt, increases the stability of the metalloproteinase (fibrolase or NAT (SEQ ID NO:1)) in each type of composition, as compared to formulations in which inorganic or other types of organic compounds are used to prevent aggregation and/or polypeptide decomposition. Specifically, zinc concentrations above 0.01 millimolar (mM) will stabilize the metalloproteinase, with the proviso that zinc concentrations above 1 mM significantly limit the solubility of fibrolase or NAT (SEQ ID NO:1). Thus, a range from about 0.01 mM to about 1 mM is advised. Examples of suitable zinc salts are zinc acetate, zinc sulfate and zinc chloride.
Frozen liquid compositions in accordance with this invention, in particular, may optionally (but not necessarily) also include a water soluble calcium salt as an additional stabilizer. Examples are calcium acetate, calcium sulfate or calcium chloride, which are preferably present in a concentration from about 0.001 to about 0.02 mM, and more preferably at a concentration of about 0.01�0.002 mM.
If desired, other stabilizers that are conventionally employed in pharmaceutical compositions, such sucrose, trehalose or glycine, may be used in addition to the above mentioned. Typically, such stabilizers will be added in minor amounts ranging from, for example, about 0.1% to about 0.5% (w/v). Surfactant stabilizers, such as Tween 20 or Tween 80 (BASF), may also be added in conventional amounts.
If desired, the frozen liquid and lyophilized compositions can also include a bulking/osmolarity regulating agent. Preferably, mannitol is incorporated in a concentration of about 2% to about 8% weight by volume (w/v), and usually at a concentration of about 5% (w/v).
The choice of a pharmaceutically-acceptable buffer and pH has also been found to affect the stability of the present compositions. Fibrolase or NAT (SEQ ID NO:1) is most stable above a neutral pH (7.0). Significant precipitation of either metalloproteinase occurs at a pH below 7.0 when the frozen composition is thawed or the lyophilized composition is reconstituted. The buffer system present in the compositions is selected to be physiologically compatible and to maintain a desired pH in the reconstituted solution as well as in the solution before lyophilization. Preferably, the buffers have a pH buffering capacity in the range of from about pH 7.0 to about pH 8.5.
Specifically, citric acid buffers (i.e., citric acid or a citric acid salt) are preferably incorporated in a concentration of about 20 mM to about 110 mM, and most preferably at about 100 mM in the frozen liquid composition and about 20 mM in the lyophilized composition. Citric acid salts are used as both buffering agents and stabilizing agents in the compositions of this invention. Whether an acid form itself or a salt thereof is used, the citric acid buffer will be chosen to adjust the pH of the composition to a value within the desired range as indicated above (in the case of the lyophilized composition, after reconstitution). Additional buffering agents, such as Tris, may be added in suitably effective amounts to maintain an adequate buffering capacity above pH 7.0.
A preferred liquid composition to be frozen will contain, in addition to solubilized fibrolase or NAT, zinc acetate in a concentration of about 0.08 mM to about 0.12 mM, calcium acetate in a concentration of about 0.008 mM to about 0.012 mM, and citric acid (or sodium citrate) in a concentration of about 95 mM to about 105 mM, at about pH 7.4. Another preferred liquid composition will contain fibrolase or NAT, zinc acetate in a concentration of about 0.08 mM to about 0.12 mM, citric acid (or sodium citrate) in a concentration of about 18 mM to about 22 mM, Tris in a concentration of about 0.02 mM to about 0.06 mM, mannitol in a concentration of about 3% to about 6% (w/v), and Tween 80 in a concentration of about 0.008% to about 0.012% (w/v), at a pH of about 8.0.
A preferred lyophilizable composition will contain, in addition to fibrolase or NAT, zinc sulfate in a concentration of about 0.08 mM to about 0.12 mM, citric acid (or sodium citrate) in a concentration of about 18 mM to about 22 mM, Tris in a concentration of about 3 mM to about 6 mM, mannitol in a concentration of about 3% to about 6% (w/v), and Tween 80 in a concentration of about 0.008% to about 0.012% (w/v), at a pH of about 8.0.
For all compositions in accordance with this invention, fibrolase or NAT is present in a concentration of about 0.1 mg/ml to about 50 mg/ml, preferably, with a concentration of about 5 mg/ml to about 40 mg/ml being more preferred, and a concentration of about 10 mg/ml to about 15 mg/ml being the most preferred.
The relative proportions of the excipients in these compositions will depend on several factors. For example, the amount of the metalloproteinase and bulking agent (e.g., mannitol) has an effect on the amount of zinc (and calcium, if present) needed to stabilize the composition. The amount of stabilizer used in the compositions will depend on the amount needed to maintain the structural integrity of fibrolase or NAT (SEQ ID NO:1) during lyophilization or other processing or upon storage.
Still other excipients known in the art can also be included in the composition, provided they are physiologically compatible and are in no way detrimental to fibrolase or NAT (SEQ ID NO:1). For example, the composition may contain minor amounts of additives, such as preservatives, tonicity-adjusting agents, anti-oxidants, or other polymers (for example, viscosity adjusting agents or extenders). Those skilled in the art can readily determine appropriate reagents that would be pharmaceutically useful, based on knowledge of and experience with other pharmaceutical compositions. See, for example, Remington's Pharmaceutical Sciences (latest edition), Mack Publishing Company, Easton, Pa.
The compositions are expected to be stable for at least two years at −30� C. for the frozen composition, and two years at 2� C. to 8� C. for the lyophilized composition. This long-term stability is beneficial for extending the shelf life of the pharmaceutical product and for long distance shipments.
In another aspect, the present invention also provides a method for preparing a lyophilized composition comprising the steps of:
(a) adjusting the pH of a mixture containing the composition ingredients without fibrolase or NAT to between pH 7.6 and pH 8.2,
(b) buffer exchanging a fibrolase or NAT containing solution into the composition solution of step (a) and then adding an effective amount of surfactant, and
(c) lyophilizing the mixture of step (b).
Fibrolase or NAT (SEQ ID NO:1) and effective amounts of the excipients are admixed under conditions effective to reduce aggregation of the dried fibrolase or NAT (SEQ ID NO:1) polypeptide upon reconstitution with the reconstitution medium, e.g., a solvent which is compatible with the selected administration route and does not negatively interfere with the metalloproteinase, such as sterile water, physiological saline solution, glucose solution or other aqueous solvents (e.g., alcohols such as ethyl, n-propyl or isopropyl, butyl alcohol or mixtures thereof) and, optionally, other components such as antibacterial agents.
The excipients may be admixed with the metalloproteinase at a suitable time before lyophilization. The time taken to mix the excipients and metalloproteinase should be for a sufficient period to prepare a suitable admixture; preferably, mixing will be carried out from about one to about thirty minutes.
Thereafter, the formulated metalloproteinase may be lyophilized, stored and reconstituted using standard methods; see Pikal, supra. The specific conditions under which fibrolase or NAT (SEQ ID NO:1) is freeze-dried and reconstituted are not particularly critical, provided that the conditions selected do not degrade the metalloproteinase and not be deleterious to the stabilizer. A preferred lyophilization cycle comprises freezing the composition at −40� C., annealing the frozen sample at −12� C., and conducting the primary drying at −30� C. to −35� C. for twenty to fifty hours and secondary drying at 20� C. for twenty to forty hours. Generally, the reconstituted composition will be used soon after reconstitution.
Both NAT (SEQ ID NO:1) and fibrolase are best delivered locally to the site of the clot for most effective treatment. Like fibrolase, NAT (SEQ ID NO:1) is covalently bound by α2 macroglobulin in the general circulation. While complexed with a2 macroglobulin, neither fibrolase nor NAT (SEQ ID NO:1) can access the target substrate (i.e., fibrin or fibrinogen) and are largely ineffective unless and until the maximum innate levels of α2 macroglobulin are exceeded. Thus, it is preferred that the compositions of this invention be administered directly to the blood clot via intraarterial or intravenous catheterization.
The following examples further illustrate of the present invention.
The recombinant NAT (SEQ ID NO: 1) used in Examples 1-3 was produced by expression in P. pastoris Details regarding a suitable expression system and method may be found in the Stroman et al., Lair et al., Cregg et al. and Cregg patents referred to above. All chemicals were either analytical or USP grade.
An aqueous solution containing 100 mM of citric acid, 0.01 mM of calcium acetate and 0.1 mM of zinc sulfate is prepared by admixture of the ingredients, with the pH adjusted to 7.4. An NAT-containing solution is buffer exchanged into the solution by dialysis (alternatively, ultrafiltration can be used). The resulting NAT solution is concentrated to 10 mg/ml and stored frozen at a temperature of −30� C. until ready for use.
Preparation of Lyophilizable Composition.
An aqueous solution containing 5 mM of Tris, 20 mM of citric acid, 5% (w/v) of mannitol, 0.5% (w/v) of sucrose and 0.1 mM of zinc sulfate was prepared by admixture of the ingredients, with the pH adjusted to 8.0. A NAT containing solution was buffer exchanged into the composition solution by dialysis (ultrafiltration can be used instead). The resulting NAT solution was concentrated to 10 to 12 mg/ml. Tween 80 was added to a final concentration of 0.01% (w/v). The solution was stored at a temperature of 2-8� C. until ready for lyophilization.
Freeze-drying Cycle for Lyophilized Product.
The above-prepared composition was first frozen at a temperature of −40� C. in the lyophilizer. The annealing temperature was set at −12� C.; the primary drying temperature was set at −30� C.; and the secondary drying temperature was set at 20� C. The resulting freeze-dried cake showed good morphology and contained less than 3% water, as detected by the Karl Fischer titration method; see Fischer, Angew Chemie, Volume 48, page 394 (1935). After the freeze-drying process was finished, the lyophilized cake was put into vials and rubber stoppers were sealed completely under vacuum by pressing down the upper metal shelves in the lyophilizer. The vials were then crimped with 13-mm flip-off aluminum seals and placed in incubators set at different temperatures.
Sample Time Points Analysis.
Sample vials were withdrawn from incubators at predetermined time intervals for the time points analysis. The lyophilized sample cake was first reconstituted by 0.9 ml of sterile water, i.e., "water-for-injection" (McGaw Inc., Irvine, Calif.). Clarity of the reconstituted sample solutions was visually examined. The filtered solution was analyzed by HPLC, UV-Vis spectroscopy and enzyme activity in order to quantify the remaining soluble NAT in these lyophilized samples.
Based on the above analyses, greater than 90% of NAT was recovered after reconstitution of the lyophilized product.
UV/Vis Absorbence.
150-200 μl of NAT solution was loaded into a quartz glass suprasil 1-cm path length ultra-microcell. UV/Vis absorbence was measured on an HP 8452A diode-array spectrophotometer (Hewlett-Packard Co., Wilmington, Del.). NAT concentrations were determined using A0.1%=1.05 at 280 nm, based on calculation from the amino acid composition; for reference, see Edelhoch, Biochemistry, Volume 6, pages 1948-1954 (1967). After rehydration of the lyophilized product, no detectable turbidity was observed when measuring the absorbence at 350 nanometers (nm).
High Performance Liquid Chromatography.
HPLC analyses of NAT samples were performed using an HP 1050 liquid chromatography system equipped with an HP 3D Chemstation for data acquisition (Hewlett-Packard Co.). NAT species were detected by absorbence at 280 nm and 214 nm using an HP diode-array detector.
For reversed-phase HPLC (RP-HPLC), samples were injected onto a
Zorbax 300SB -C8 column (4.6 X 250 mm) (Hewlett-Packard Co.) in a mobile phase consisting of 51.5% buffer A (2% isopropanol, 0.1% TFA) and 48.5% buffer B (90% acetonitrile, 2% isopropanol, 0.1% TFA) at a flow rate of 0.6 ml/mm. Buffer B was held for six minutes and then ramped up to 51% over twenty minutes. This concentration was held for one minute, followed by an eight-minute ramp and five-minute hold at 90%. Finally, buffer B was ramped back to 48.5% over a period of three minutes. Recovery of NAT (SEQ ID NO:1) after lyophilization as detected by this method was greater than 92%.
For ion-exchange HPLC (IEX-HPLC), samples were injected onto a Tosohaas DEAE-5PW column (7.5 X 75 mm) (Tosohaas, Montgomeryville, Ala.) in a mobile phase consisting of 90% buffer A (20 mM Tris, pH 8.5) and 10% buffer B (20 mM Tris, 250 mM NaCl, pH 8.5) at a flow rate of 0.5 ml/min. Then a gradient was applied, increasing from 10% buffer B to 75% buffer B in 20 minutes, then from 75% B to 90% buffer B in one minute. Buffer B was then held for five minutes, followed by a ramp to 10% buffer B in four minutes. Recovery of NAT (SEQ ID NO:1) after lyophilization as detected by this method was greater than 90%.
For size-exclusion HPLC (SEC-HPLC), samples were loaded into a Tosohaas G-2000SWXLcolumn (300�7.8 mm). Isocratic elution was applied at a flow rate of 0.8 ml/mm using a buffer containing 15 mM sodium phosphate, pH 7.0, and 0.140 M sodium chloride. Recovery of NAT (SEQ ID NO:1) after lyophilization as detected by this method was greater than 95%.
Samples were screened for activity against fibrin clots. Small aliquots of a serial dilution of NAT ranging from 0.01 to 1.0 mg/ml were loaded onto preformed fibrin clots in 96-well plates. The samples were incubated for eighteen hours, and clot lysis was quantitated by absorbence at 500 nm. A plot of absorbence vs. NAT concentration for various formulations were compared to a prepared NAT standard for relative activity. There was no measurable difference in the fibrinolytic activity of the NAT after lyophilization, relative to the control (non-lyophilized) sample.
Similar test results are obtained with the frozen liquid composition as well, after the latter is thawed at 4� C. and tested using these same protocols.
The foregoing invention has been described in some detail for purposes of clarity and understanding. It will also be obvious that various other combinations in form and detail can be made without departing from the scope of the invention as defined in the appended claims.
The procedures of Examples 1 and 2 are repeated with recombinant fibrolase in place of NAT to produce similar frozen liquid and lyohilized pharmaceutical compositions.
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You Can't Beat Price for These Horrors
By ERIC FEBER
By Eric Feber
The Virginian-Pilot
On Friday horror fans will again pay the Price.
As a tonic against last month's Steven Seagal gorge, the Central Library's monthly Fantasmo Cult Cinema Explosion film series will offer cult film freaks two deliciously campy horror flicks from one of the genre's best loved, and classiest stars, Vincent Price.
"Episode 39: The Price is Right, Vol. 3″ will feature two Price- less 1970s horror flicks: "Theatre of Blood (1973)" and "Madhouse (1974)." The screenings are part of the series' homage to one of horrordom's finest.
During January 2007′s Episode 22, the series showcased Price's memorable screen baddie, Dr. Anton Phibes, the frightful fried- freak who sought revenge on those who were responsible for his wife's death.
"Of all the Fantasmos we've done over the years, none have been more popular than those celebrating the genius of horror icon Vincent Price," says Jim Blanton, the Central Library's head of reference services, in his Fantasmo blog.
Blanton, one half of Team Fantasmo that plans and organizes the monthly screenings, said Friday's films "are terrific representations of the outrageous cinematic trends of their era."
Episode 39 will have Price as Paul Toombes in "Madhouse" – scheduled for 8
p.m. The movie also features classy horror honchos Robert "Count Yorga" Quarry and Peter Cushing. Here Price portrays a horror movie actor, popularly known as Dr. Death, who suffers a nervous breakdown on the eve of heading over to England to work on a television series. During this TV show's production, cast and crew members begin to die in the same manner that Dr. Death's victim did in Toombes' old movies.
The evening will round out, beginning at 9:45 p.m. with the wonderfully campy black comedy "Theatre of Blood," featuring Price as the egotistical, hammy Shakespearean actor Edward Lionheart. It seems ol' Ed has it in for his critics. Played by a veritable who's who in English screen and stage, including Robert Morely, Jack Hawkins, Ian Hendry and Milo O'Shea, these critics have never given him any praise or respect.
To affect his revenge, Lionheart and his daughter, played by screen legend Diana Rigg (Mrs. Peel of "The Avengers"), begin offing the offending critics through deaths inspired by the Shakespeare plays he made famous. This classic film is a must for horror and Price fans and even those enamored with the Bard of Avon.
"Two fantastic '70s era Vincent Price films on our 'Pricerific' big screen, the way they were meant to be seen," Blanton added.
And it's all for free, can't beat that Price.
Eric Feber, 222-5203, firstname.lastname@example.com
What The Fantasmo Cult Cinema Explosion's "Episode 39: The Price is Right, Vol. 3″ featuring the films "Madhouse (PG)" and "Theatre of Blood (R)."
Where Central Library, 298 Cedar Road
When Friday . "Madhouse" will be screened at 8 p.m., and "Theatre of Blood" will be shown at 9:45 p.m.
Free The comments? Hilarious. The ambience? Fun. The films? Price- less. Call 410-7135 for more demonic details.
Originally published by BY ERIC FEBER.
(c) 2008 Virginian – Pilot. Provided by ProQuest Information and Learning. All rights Reserved.

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this book has halped us take care of pretty bird. all birds are different and what works for one may not for another. pigeons have different dietary needs than other birds and different cage requirements.the book also helps the pigeon owner to be able to understand the mentality of this bird which allows better communication.i recommend this book to those people who have pigeons.
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Pyle PT-652T Digital AM/FM TunerItem#: YYPT-PYLPT652T | Model#: PT652T
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Winter!: Prepare for holiday gaming!
Also one of the first pc games i ever played, and boy did i do abunch of walking around... a lot of walking around but it doesnt mean it didnt open my eyes a bit, even if i didnt know what i was doing
Game Traits applied to Myst: 10th Anniversary DVD Edition (PC-MAC) by Grimsonofgray
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Our partnership with the Steamship Authority Fast Ferry, Iyanough, is continuing through the 2015 Season at even more attractive rates. Sherburne Inn guests who book two or more nights at the Inn are eligible for a 25% discount on Adult round-trip tickets from Hyannis if we make your ferry reservation! Please let us know you are interested in this promotion when you book your stay. Looking forward to seeing you soon!
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The Incumbent Challenge
You can't lead an insurgency from the top
You can't lead an insurgency from the top
What 2013 box office movies can you legally stream in 2014?
The battle over cable acquisition is about the next big internet providers
Google killing Google Reader may be the best thing to have happened to the RSS ecosystem in a long time.
Fake followers: Big brands are doing it too.
A New York startup is building the future of TV broadcast.


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Your InspiredCorp is one of my favourites too. It's a solid template and I'm sure it'll do better over time.
Sales have been slow for me as well but I'm putting that up to the fact that I have chosen not to go exclusive so I am no longer featured in the "Recent Items" lists haha. Perhaps that isn't it though if others are experiencing the same… who knows!
I'm really hoping that someday TF will provide visits/unique visits stats and other useful metrics for each of our template pages. That way I can work out hits vs. download ratio for when I provide a live preview and when I don't. That sorta thing would really rock! Anyway, tangent!
Really liking the look of your upcoming WP theme too btw. Good work =)
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text: Fiori - "Andiamo" by Tigers on a Leash published on 2013/01/15 14:01:36 +0000 Fiori is the newest addition to the TOAL roster, and we're super psyched to have them. Their first single, "Andiamo", includes the original and remixes by Populette, Mirror People, Pink Stallone & Lou Teti. I won't bore you with the fluff, just listen, you're going to like it. The multi-talented duo created both the music and the art for this album (and the art of the last two TOAL releases too). You'll be hearing a lot more from them soon, including a remix coming soon and a full EP coming this spring. Also, you can download a bunch of TOAL tracks for free and stay up to date on what we're doing by liking our Facebook Page.


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Looking for a way to enjoy this weekend's beautiful weather? Roseland Water Park in Canandaigua opens this Saturday.
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CY joined Cerro Gordo 4-H'ers for the North Iowa Band Fest parade May 26 in Mason City. It's one of the many activities on the busy Iowa State mascot's summer schedule. CY is booked for a number of county parades, fairs and other activities as well as some ISU Extension Sesquicentennial service projects.
"CY can't make it to every ISU Extension event but hopes you'll check the ISU Extension calendar and our service project Web site for fun summer activities," said Elaine Edwards, ISU Extension communications manager. "To celebrate Iowa State's sesquicentennial, counties are creating gardens, planting trees, building playgrounds, setting up historical displays, hanging barn quilts and much more. There are plenty of opportunities for service to Iowa communities."
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"This is good news. Cardia 7 can help in the fight against cardiovascular disease, such as those who have been diagnosed with cardiac risk factors, diabetes, and even weight management. No other natural product can say it has this much punch when it comes to fighting a variety of diseases," said Mausser.
Cardia 7 is only one of a select few who sell the purified form of Omega 7. Since introducing Omega 7's extraordinary health benefits, many consumers are wanting to try this incredible fatty acid. It makes sense that clinics, holistic and wellness centers begin to carry the product as well," said Mausser.
About Cardia 7
Cardia 7 is a brand new product distributed online or at the Cleveland Clinic Wellness Center. It is one of the few products on the market that uses a patent-pending 7-step purification process to express high levels of the monosaturated fatty acid, palmitoleic acid (C16:1n7) or Omega 7, from fish oil while also removing the saturated fatty acid, palmitic acid reducing it to below 1% making it (Palmitic Free).
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Discounts & Deals: Gifts for Teachers
Use the codes here to score bargains on these thoughtful teachers' gifts, chosen by Real Simple editors. (Before selecting, check to see if your child's school has a spending limit.)
Built Laptop Sleeve
In addition to enjoying the cheerful red-and-pink print by textile designer Alexander Girard, she can sling the convenient strap over her shoulder when her hands are full of papers.
RS reader price: $40, builtny.com. Enter the code REAL20 at checkout. (Discount available on all laptop sleeves.)
* These discounts will be available from August 1, 2010, to September 30, 2010, or while supplies last.


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During the Mongol invasion of Russia, the youngest of Vsevolod III's sons, Ivan, made Starodub his seat (1238). His descendants ruled the tiniest of Russian principalities for more than a century, desperately trying to fend off attacks by two powerful neighbours—Muscovy and Nizhny Novgorod. Their ephemeral power came to an end in the 1370s, when the town was eventually annexed by Dmitry Donskoy. Thereupon numerous scions of Starodub dynasty moved to Moscow, where they formed the families of Princes Gagarin, Khilkoff, Romodanovsky, Pozharsky, and many others.
During the Time of Troubles, the town was completely burnt to the ground by the Polish warlord Alexander Jozef Lisowski, who ravaged the area in March of 1609. Some historians believe that Prince Dmitry Pozharsky, who helped Russia to survive those turbulent times, lies buried in Starodub, the demesne of his forefathers.


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zoom Time Xpresso 12 Titan Pedals
Time Xpresso 12 Titan Pedals
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Time synonymous with speed and precision and the Time Xspresso 12 Titan road pedal, with its ergonomically rider friendly design, is not exception.
Top Features of the Time Xpresso 12 Titan Pedals
- Bioposition Concept — minimal distance sole to pedal axle
- Angular float (+/-5°) and lateral float (2.5 mm)
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- Weight: 155 g/pair
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The Time Xpresso 12 Titan has Time patented pre-opening engagement technology, the ability to make a wide range of adjustments to assist you in getting the perfect feel when riding. The Time Xpresso 12 Titan is constructed with a hollow titanium axle, and a carbon Pedal body to ensure maximum weight to strength ratio.
About the Time brand
Since 1987 TIME has been writing one of the brightest pages in the history of modern cycling. For this heir to unique know-how and technological methods ever more widely affirmed, each new product quickly becomes a standard, a true benchmark in the particularly demanding world of the bike. The highly sophisticated Time technology has led to a world beating VXRS frameset used by the Cofidis pro team which is producing some of the world's best racing achievements. Time pedals are claimed by road racing and MTB cyclists to have more advantages both anatomic and technical, than any other make. Total compatibility with other systems, self cleaning, faster step-in, no unwanted pre-release – these are just some of the latest generation of special features. New ranges of Time shoes are now available to suit. Since Time was created, their mission statement has been to innovate in order to deliver high-end, technical products. An intimate involvement in professional racing, combined with a strategy of product innovation, has made TIME into a prestigious brand, internationally known and respected.
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Now that photo-ops are done, many working with the transgender (TG) community are testing waters on how the Supreme Court ruling will actually translate into making a difference.
Equal rights activist Bindumadhav Khire of the Pune-based Samapathik Trust, which works with the community statewide, has written to the president of the Indian Psychiatric Society (IPS) Dr T V Asokan to remove 'Gender Identity Disorder'/'Gender Dysphoria' tag given to TGs in the International Classification of Disease (ICD ) and Diagnostic and Statistical Manual of Mental Disorders (DSM).
Often referred to as the 'Psychiatrist's Bible', both the ICD and DSM offer a common language and standard criteria for the classification of mental disorders
Referring to SC order, the letter quotes from the ruling to say, "They are to be provided a healthy environment in which they can flourish as any other citizen with various rights. They are to be respected and accepted in the mainstream so that they can live a life free of stigma and discrimination," and adds, "We at Samapathik Trust feel as long as the tag of 'Gender Identity Disorder' or 'Gender Dysphoria' is retained in ICD or DSMs the TG community will continue to be treated as 'sick' people by doctors and society. To remove this stigma, we feel it is important that this mention (of dysphoria or disorder) be removed from the disorder diagnosis list."
The letter has also been forwarded to president of the World Psychiatric Association, Prof Pedro Ruiz. "We want them to know that they will have to change nomenclatures to suit the times we live in," said Khire.
When dna contacted Dr Asokan, he tried to downplay the issue, "This can wait. We are in middle of looking how to make mental health accessible to all. Unless you want to talk about the work we are doing on that front you'll have to excuse me," he told dna.
Mumbai-based psychiatrist Dr Rajendra Barve felt some individuals who are having trouble adjusting to their new gender may need help. "This can vary from case to case. So the nomenclature in the classification needs to reflect that."
Others like counselling psychologist Deepak Kashyap echo Barve. "If someone is an introvert, s/he may need help if it is hindering their functioning in day-to-day life. But that doesn't make their condition pathological by any stretch of imagination. The same thing applies to a TG person too. If they need support or help while undergoing the gender-reassignment procedure then it should be accessible without them being labelled as diseased."


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Installed sources sort before all other sources
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Additional file 3.
Proteins identified by MS in salivary gland extracts of four Anophelesspecies. All MS/MS spectra resulting to every protein bands from each species (An. gambiae, An. arabiensis, An. stephensi and An. albimanus) were gathered and searched on sequence databases of the four Anopheles species together. A list of all unique proteins identified in salivary gland extracts in both replicates is presented for each Anopheles species. Salivary gland proteins were sorted according to their signal peptide prediction (SignalP Neural Network) [63,65] to discriminate secreted proteins from housekeeping ones.
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Fontaine et al. BMC Genomics 2012 13:614 doi:10.1186/1471-2164-13-614


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Post-Gaming: Steam Now Selling Useful Things Too
Not entirely sure whether this is relevant to our readership, but I guess it's important to keep documenting the eternal war between Valve and Microsoft. While MS does all sorts of strange things to Windows in the divisive upcoming 8, Valve have elected to move Steam beyond games. You can now buy several software packages on there, including 3DMark, 3DCoat, ArtRage and, most interestingly (or at least relevantly), GameMaker Studio. 'These are just the first. Many more to come' is the claim.
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EAST CARBON - Brent K. Jackson, age 58, passed away unexpectedly on May 12, 2015 at his home with his beloved wife and soul mate by his side. He was born on May 28, 1956 in Provo. ...
Max Russell Tolman
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ST. GEORGE - Our beloved husband, father and grandfather passed away on May 19, 2015 at the age of 66 after a long illness. He was born on June 6, 1948 to James Russell and Harriet LaRue Barney, the second of seven children in Logan. He married Karen...
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WebInspect 10.1: How to determine state from URL[ Edited ]
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01-10-2014 01:13 AM - edited 01-10-2014 01:15 AM
I am trying to scan some APEX based apps with WebInspect. The URL in the apps are mostly like:
The string like 15570571751825 is used as the session state by the inner APEX logic.
So it's crucial for WebInspect to capture this state, otherwise it will keep log in and out all the time.
I try several ways but don't work fine.
1. In HTTP Parsing, I put [\d]{14,} in 'HTTP Parameters Used For State', checking Query, Post and Custom
2. I also try to put p_instance in 'HTTP Parameters Used For State', checking Post, since I notice p_instance parameter in the post date(see below)
3. I also try to put [\d]{14,} in 'Determine State From URL Path'
Can anyone give me some advice here?
Thanks in advance.
A tipical get request looks like:
GET /console/f?p=7700:LOGIN:1758023415424 HTTP/1.1
Host: 10.10.0.10
User-Agent: Mozilla/5.0 (Windows; U; Windows NT 6.1; en-US; rv:188.8.131.52pre) Gecko/20110614 Firefox/3.6.3
Accept: text/html,application/xhtml+xml,application/xml;q=
Accept-Language: en-us,en;q=0.5
Accept-Encoding: gzip,deflate
Accept-Charset: ISO-8859-1,utf-8;q=0.7,*;q=0.7
Keep-Alive: 115
Connection: keep-alive
Pragma: no-cache
Cookie: ORA_WWV_APP_7700=ORA_WWV-W0URD5LtSRUwWU1N/bPKTLVu
X-WIPP: AscVersion=10.1.275.0
X-Scan-Memo: Category="Crawl.EventMacro.Startup"; SID="B975F8F8D3B49E1DE8E6C52B78CB98F1"; SessionType="StartMacro"; CrawlType="None";
X-RequestManager-Memo: Category="EventMacro.Login"; MacroName="av_auditor_login";
X-Request-Memo: ID="69fe75db-0fd3-45d2-b896-75e4aa6692ca"; ThreadId="37";
And the post looks like:
POST /console/wwv_flow.accept HTTP/1.1
Host: 10.10.0.10
User-Agent: Mozilla/5.0 (Windows; U; Windows NT 6.1; en-US; rv:220.127.116.11pre) Gecko/20110614 Firefox/3.6.3
Accept: text/html,application/xhtml+xml,application/xml;q=
Accept-Language: en-us,en;q=0.5
Accept-Encoding: gzip,deflate
Accept-Charset: ISO-8859-1,utf-8;q=0.7,*;q=0.7
Keep-Alive: 115
Connection: keep-alive
Referer: https://10.10.0.10/console/f?p=7700:LOGIN:17580234
Pragma: no-cache
Cookie: ORA_WWV_APP_7700=ORA_WWV-W0URD5LtSRUwWU1N/bPKTLVu
Content-Type: application/x-www-form-urlencoded
Content-Length: 476
X-WIPP: AscVersion=10.1.275.0
X-Scan-Memo: Category="Crawl.EventMacro.Startup"; SID="B9BF4E43D12264C9776F5F2A384FFD21"; SessionType="StartMacro"; CrawlType="None";
X-RequestManager-Memo: Category="EventMacro.Login"; MacroName="av_auditor_login";
X-Request-Memo: ID="bd09567a-276c-4f3b-9286-1eaa24feb893"; ThreadId="40";
Re: WebInspect 10.1: How to determine state from URL
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When there is a part of the URI that determines state, that is generally not handled by the Custom State-Keeping setting. For that situation, you would instead look to the HTTP Parsing panel of the scan settings, at the center field for "Determine State From URL Path". There are some ancient, sample signatures already defined there, such as for ASP.NET 1.1. This field generally requires a regex to help identify the portion of the URI that is state-keeping. The Regular Expression Editor tool can be helpful in formulating the necessary regex.
However, with your particular Request/Response data, this field would not necessarily be appropriate for you.
Since there is a clearly named parameter holding the state-keeping value, you would normally proceed with using the field at the top of the HTTP PArsing panel, for "HTTP Parameters Used For State". Simply put in the parameter's name, such as "p" (no quotes), and WebInspect will honor and utilize whatever value the target server assigns for it, even if the server reassigns it to a new value mid-scan. Note that you may also need to mark this same custom state-keeping parameter within your Login Macro so that it Plays fine, i.e. the macro dynamically updates the value rather than replaying the originally recorded value.
If you were unsure if you had a custom or standard state-keeping parameter, you could go down to the scan settings panel for Attack Exclusions. Here you will find all of the standard state-keeping parameters we have identified in the wild and declared them to WebInspect as being off-limits to auditing. It is possible you will want to add your custom state-keeping parameter's name here as well. The reason being, items declared on the HTTP Parsing panel are managed intelligently by WebInspect, but may still be audited "lightly". If any amount of auditing will cause you scan state issues, then adding the same parameter name to the Attack Exclusions prevents any and all fuzzing for that item.
Now, let's review the parameter you have in the Request/Response data. The first thing that worried me was that the value of the parameter "p" has colons in it. I am unsure if WebInspect will identify those characters as separators and as separate parameters (bad), or if the entire value will be accepted for "p" (good). You may need to contact Fortify Support to verify this. However, after you add the "p" parameter to HTTP Parsing, you could simply review the Traffic Monitor capture within a test/short scan to see if the value is used intact or not. So for this parameter, I would simply Add the name, "p" (no quote marks), to the HTTP Parsing field for state-keeping parameters. Since I am lazy, I would enable this entry for both POST and Query data so it will cover all the bases possible during the scan.
Unfortunately, I see in the HTTP Response that a portion of the value of "p=7700:LOGIN:1758023415424" may be reused for other parameters. Examples of this include "p_instance=1758023415424", and possibly "p_request=LOGIN" and "p_flow_id=7700". It is possible that these are additional state-keeping parameters which collect their value from the value assigned to "p". If so, simply adding "p" to HTTP Parsing may not manage those other parameters.
For starters, you could try adding "p_instance" and "p_flow_id" to the HTTP Parsing scan setting just as you had added "p". The application might push or suggest the field value to WebInspect, and then WebInspect would carry it forward in subsequent HTTP Requests. If entering these into HTTP Parsing does not manage it, you may need to build a Custom Parameter scan setting for these. I was recently involved in a Support case where the value from one parameter had to be assigned to a second parameter simultaneously, and the Developer on duty was able to make that happen with some script used in the Custom Parameter scan setting.
If you have investigated these items and are still at an impasse, you may need to contact Fortify Support (support.fortify.com) to dig into it further.
-- Habeas Data


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http://www.SarcasticSam.com Twitter's Smarmy Wiseacre... Makes no apologies for anything, unless you're hot! and have poptarts... probably not even then
Sunday, April 13, 2014
Happiness is a Decision
We have to Make a Decision to Be Happy... People search mountains, travel the Earth, look their entire lives for happiness. Only to determine that it is a decision ~ often which we must keep on making.
Posted by Samuel_Clemons at 10:16 PM
3 comments:
Wisdom and also as ever you are infallibly correct in your conclusions.~~wiggle~~ReplyDelete
I thought so too, for a while. But unhappiness has more purpose, don't you think? Misery breeds all kinds of insight.ReplyDelete
I'm with you, Icy Highs. Appreciation of "the good stuff," however we define implies you've paid your tolls along the way. To be "happy," must one not also have an appreciation of its antithesis?ReplyDelete
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Craftsy Member since November 2012
I'm enrolled in these Craftsy classes:
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Mastering Zipper Techniques
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2015 Craftsy Block of the Month
Machine Quilting Beautiful Borders
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Easy Piecing, Amazing Design
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Culture Department
In the field of culture, ASEF promotes various forms of cultural co-operation between Asia and Europe, including artistic collaborations, bi-regional networks and policy dialogue. In addition to fostering sustainable partnerships between Asian and European arts organisations, ASEF also facilitates dialogue between the arts sector and government agencies responsible for culture.
Our key projects are:
ASEF Cultural Policy Dialogue Series, which stimulates analysis and exchange of ideas on issues of mutual interest for practitioners and policymakers in Asia and Europe
culture360.asef.org, an information platform for artists, cultural professionals and policy makers in 53 countries across Asia and Europe
ASEF Creative Networks, which facilitates dialogue and co-operation among cultural networks in both continents (through a competitive annual open call for proposals)
Asia-Europe Museum Network (ASEMUS), which promotes knowledge exchange and joint activities among 100+ museum members across Asia and Europe
Creative Encounters: Cultural Partnerships between Asia and Europe, which supports artistic co-creation in contemporary art forms (such as dance, music, film, literature etc.) through a competitive annual open call for proposals
Team Members
- Ms Anupama SEKHARDirector
- Ms Valentina RICCARDIProject Manager
- Ms Sasiwimon WONGJARINProject Executive
- Ms Preeti GAONKARProject Executive
- Mr Hatta MOKTARAdmin / Project Officer
- Ms Mashyitah Binti MUSTAFFAIntern
Ms Anupama SEKHARDirector
Anupama SEKHAR, an Indian national, joined ASEF in January 2009. She is currently the Director of the Culture Department and is actively engaged in facilitating cultural exchange and collaboration among artists and arts organisations in 53 countries in Asia and Europe.
Anupama is in charge of the department's day-to-day operations as well as its overall programme portfolio, which comprises of artistic collaborations, support to networks, policy dialogues and information platforms.
In particular, she designs and manages the Department's work in the field of cultural policy with the aim of stimulating analysis and engagement reflective of current debates in the arts in Asia and Europe, as well as channeling policy ideas to the Culture Ministers' Meeting of the Asia-Europe Meeting (ASEM).
She is the co-editor of the upcoming Managing Heritage Cities: The Role of Public Private Partnerships – Good Practices from Asia and Europe (Singapore, ASEF, 2015) and Mapping Cultural Diversity: Good Practices from Around the Globe (Bonn/Singapore, German Commission for UNESCO and ASEF, 2010).
Anupama is a member of the U40 group of young cultural policy experts, launched by the German Commission for UNESCO and supported by the International Federation of Coalitions for Cultural Diversity.
She holds degrees in English Literature and International Studies. She is also a trained dancer in the Indian classical style of Bharatnatyam. Prior to joining ASEF, Anupama worked with the United Nations and in the arts sector in India.
Ms Valentina RICCARDIProject Manager
Valentina RICCARDI, an Italian national, joined ASEF in January 2009. She is currently Project Manager in the Culture Department, where she oversees ASEF's initiatives related to the development of information platforms, artistic exchanges and cultural networks.
She focuses specifically on ASEF's arts and culture portal culture360.asef.org, an online platform that provides information and stimulates cultural dialogue between Asia and Europe. The portal has been identified in 2014 by the European Union as 'an excellent model of information exchange for Asia-Europe cultural co-operation' in its Report on the Preparatory Action on the Role of Culture in EU External Relations.
She was responsible for the conceptualisation and launch of film.culture360.asef.org, a website dedicated to independent cinema, and the redesigned website of the Asia-Europe Museum Network (ASEMUS). She currently oversees the communication activities of the department, with specific focus on culture360.asef.org, the ASEMUS network, the Creative Encounters: Cultural Partnerships between Asia and Europe and ASEF Creative Networks.
Previously, Valentina worked in Rome with Monti & Taft, an organisation focusing on cultural management and heritage-related projects. Prior to entering the cultural sector, she worked in fashion and marketing in Rome and New York. She was also a contributor to the Asian contemporary art publication Asian Art Now (Chiu M. and Genocchio B., Thames and Hudson 2011).
Valentina holds a Bachelor of Arts degree in Political Sciences from the University of Rome – La Sapienza. She obtained her Master's degree in Art Business from Sotheby's Institute of Art Singapore – University of Manchester and completed a thesis on the validation system of Indian contemporary art.
Ms Sasiwimon WONGJARINProject Executive
Sasiwimon Wongjarin, a Thai national, joined ASEF in January 2009. She is currently a Project Executive in the Culture Department and works on the Asia-Europe Museum Network (ASEMUS), Creative Encounters: the Asia-Europe Cultural Partnerships Initiative and ASEF Creative Networks.
In the framework of Asia-Europe Museum Network or ASEMUS, Sasiwimon works closely with the Network's Secretariat and supports the promotion of the Network in Asia and Europe.
Sasiwimon is presently in charge of the Creative Encounters programme, which promotes artistic collaborations between Asia and Europe. She also manages the ASEF Creative Networks programme, which aims to strengthen cultural networks in Asia and Europe.
Prior to ASEF, Sasiwimon was based in Chiang Mai, Thailand. She worked as a Manager for The Land Foundation and as Museum Co-ordinator at the Chiang Mai University Contemporary Art Museum. Sasiwimon received her Bachelor's degree in Fine Art in Education from the School of the Arts and her Master's in Museology from the Reinwardt Academy, both based in Amsterdam, the Netherlands.
Ms Preeti GAONKARProject Executive
Preeti Gaonkar, an Indian national, joined ASEF in January 2013. She is responsible for the creation and development of projects that support research and dialogue on cultural policy issues of common relevance for Asia and Europe. The main programme aligned to this area of work at ASEF is the ASEF Cultural Policy Dialogue Series, which facilitates dialogue between government officials and civil experts on relevant issues of mutual interest for Asia and Europe inspired by ASEM's cultural agenda through a series of Experts' Meetings and Public Forums, the most recent of which was held in Amsterdam, Netherlands (October 2014). This programme also supports research on arts and culture in ASEM countries through the WorldCP-International Database of Cultural Policies initiative.
Prior to joining ASEF, she worked with the British Council and in the arts sector in India.
She holds a Master's degree in Management Studies and a Bachelor's degree in Economics from Mumbai University in India.
Mr Hatta MOKTARAdmin / Project Officer
Hatta MOKTAR, a Singaporean national, joined ASEF in August 2010. He currently works as an Admin/Project Officer in the Culture Department.
Although from a marketing background, Hatta has always had a passion for the arts. This blossomed during a three-year stint as a Marketing Executive with the independent Singapore arts centre, The Substation, where he supported local artists in signature events like SeptFest and the Asian Film Symposium.
Hatta holds a Bachelor of Science degree in Information Technology from the National University of Singapore. He enjoys travelling, eating and running.
Ms Mashyitah Binti MUSTAFFAIntern
Mashyitah MUSTAFFA, a Singapore national, joined ASEF's Culture Department in May 2015 as an intern. She is primarily providing support to the culture360.asef.org online project.
She is pursuing a Bachelor of Arts (History) degree at the Nanyang Technological University (NTU), Singapore. Despite having been more inclined towards English Literature during her pre-university years, Mashyitah is keen in exploring diverse themes and research areas in the field of history. Her current research interests include European history and battlefield/military archaeology. Prior to NTU, she held temporary positions in Sphere Exhibits (a subsidiary of Singapore Press Holdings Ltd) and the Employment and Employability Institute (renamed Devan Nair Institute of Employment and Employability).
Mashyitah enjoys reading, running, and sketching during her free time.


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- 中文
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Beijing Chi Fan for Charity & wine tasting at Temple Restaurant
On 7 November, 2011 By Shanti Christensen (湘緹)
A grey autumn day didn't keep me indoors this past Saturday.
Wine seminar at Temple Restaurant
A wine seminar held at Temple Restaurant Beijing woke up my senses with Chardonnays and Pinot Noirs from Burgundy, taught by Marco Caschera, directeur of export for Continue Reading →
Chinese market sights: Donglianxing market
On 2 November, 2011 By Shanti Christensen (湘緹)
Beijing, China — Always something new, same place, same time. Another walk to the market brings in new experiences…
I ordered a kilo of lamb leg meat and asked for him to cube the pieces for me. The […]Continue Reading →
Pomelo Honey Tea
On 28 October, 2011 By Juling He (何菊玲)
About the author: Wén Xiāng Mógu (闻香蘑菇) is a girl who lives in the lower reaches of Changjiang river in China. She loves writing, photography, eating, and embraces a joyful sense of life! Read her blog at blog.sina.com.cn/u/2012228677 or follow her on Weibo weibo.com/2012228677.
Not long […]Continue Reading →
Bursting Pomelo
On 27 October, 2011 By Shanti Christensen (湘緹)
It's officially autumn, but here in Beijing the nights have been falling to 0°C — it's freezing already. Change of climate means pack on the Vitamin C. I bought a beautiful pomelo to do just that. In Chinese, the fruit is known as yòuzi (柚子) which is synonymous to the […]Continue Reading →
Hóngshāo ròu (红烧肉, red-cooked pork belly)
On 21 October, 2011 By Shanti Christensen (湘緹)
Hóngshāo ròu (红烧肉, red-cooked pork belly) is one of my favorite classic Chinese dishes. After learning a few variations of this timeless recipe from a few families in China, I created my own and was invited by my friend Bee to guest blog it on her amazing Website, RasaMalaysia.com.
[…]Continue Reading →
Shanghai Hóngshāo Ròu (红烧肉, red-braised pork); Chen Chen's family recipe
On 19 October, 2011 By Shanti Christensen (湘緹)
There has never been a more simple hóngshāo ròu (红烧肉, red-braised pork belly) known to me until the day I visited Chen Chen's family in Shanghai. Deliciousness is the result after braising pork belly in soy sauce, sugar, ginger, and star anise. This recipe is for a hóngshāo ròu of a sweeter flavor. For my friend's […]Continue Reading →
Beijing, China — After catching glimpses of popup cafes in California and New York via Twitter or blogs, I felt inspired to participate in one, but wondered how. Beijing Design Week offered that opportunity. Continue Reading →
ShowShanti cooking at Sky Light pop up café
On 29 September, 2011 By Shanti Christensen (湘緹)
Beijing, China — Last Saturday, I 'popped' into Kupa Studio's Sky Light Pop Up Café during Beijing Design week. Co-founder, Rania Ho, invited me to cook what I please. I felt inspired! Come share the inspiration this weekend as I share one of […]Continue Reading →


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Earlier this week I spoke at a seminar in London on 'Perspectives on Evidence in Youth and Community Work' organised by The Professional Association of Lecturers in Youth and Community Work and the Centre for Youth Impact.
Youth work and evidence-based practice: worlds apart?
"Some things I can't do, but some things I can"
We are in the process of editing a book on young people facing severe and multiple disadvantage, the results on an Inquiry led by young people and supported by Dartington and the LankellyChase Foundation. There are lots of words spilling on to the cutting room floor, some of them very good words, including this poem prepared by Sean Mahoney.
The bad behaviour of good people
People are neither bad nor good, they are both. So goes the argument of Amelia Kohm – a collaborator and former student of the SRU – in the first of a new series of ibooks by the SRU.
How to copy and get away with it
A consortium led by Catch-22 in partnership with the Social Research Unit at Dartington, the Young Foundation and Substance have been working on a major project funded by the Big Lottery Fund called Realising Ambition for a few years now. We have allocated £25 million to enable 23 voluntary organisations – large and small – […]
How does social work, work?
At the end of September I led a seminar at the LankellyChase Foundation on behalf of Frontline, an organisation testing innovations in social work training. The seminar brought together a group of experts, in social work, in children and families, and in research. Our idea is to start a conversation about how social work works, […]
Focusing on what works, not just what is new
This is the approach taken by Realising Ambition – a £25 million programme replicating interventions aimed at preventing children and young people from entering the criminal justice system. This blog is the first of a series looking at features that support organisations to replicate effectively. Here Tim Hobbs and Cassandra Ohlson explore the importance of having a tightly defined intervention with a clear focus on outcomes.
Standards, standards, everywhere
In the children's services field we are seeing the emergence of a number of sets of standards – specifically, standards of evidence. This is on the back of a renewed commitment to evidence informing policy and practice. In this blog Nick Axford gives an overview and provides some suggested 'rules', or principles, that might help those of us involved in developing and applying standards of evidence.
Growing frogs
A common objection to evidence-based programmes is that they are squeezing out innovation. Here we argue the opposite: that these programmes are products of innovation, and therefore that more – and, critically, better – innovation is needed. This is why we have recently published 'Design & Refine: Developing effective interventions for children and young people'. We have written it to help people working in children's services to design an intervention and plan for its implementation.
New solutions for early years care
Our co-director, Louise Morpeth, blogs for the Big Lottery Fund on why it is so important for communities to join professionals and policymakers in generating solutions that enhance the delivery of early years care.
Tim Hobbs presents on the 'Innovation to Proven Impact Pipeline'
Senior Researcher Tim Hobbs presented on the 'Innovation to Proven Impact Pipeline' at the Wales Third Sector Funding Conference 2013.
Tim drew on our work on the BIG Lottery Fund's Realising Ambition programme to illustrate the features of an effective service and some of the routes from innovation to proven impact. He also shared a number of tools to help funders and commissioners identify best practice and for service delivery organisations to become best practice.


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NEW YORK ( TheStreet) -- Penny stocks have gotten punished as investors sold the riskiest shares since the April sell-off. The following 13 companies received notice in December that they failed to trade above $1 a share for a certain period, a Nasdaq requirement, and now they face delisting after a six-month grace period. Their possible fate: languishing on the thinly traded Pink Sheets.
Altair Nanotechnologies (ALTI)
Closing Price: 30.4 cents (June 29)
Six-Month Stock Performance: -68%Received Nasdaq Notice: Dec. 22 Management's Expected Action: The lithium-battery maker was granted an additional 180 days to regain compliance with the minimum bid price rule. Altair now has until Dec. 20 to get its stock price to close above $1 for 10 consecutive trading days. The solution may end up being a reverse stock split. Altair said its board of directors has authorized a reverse split in the range of 3-to-1 to 10-to-1, although that plan has been put aside due to the grace period extension. For now, Altair said it "shall continue to seek compliance with the minimum bid price rule through revenue growth and other positive operational achievements."


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Australian Gymnastics Championships, the Women's and Men's Apparatus finals.
A selection of photographs from around the world by Age Picture Editor Nicky Catley.
Melbourne Zoo's female gorilla Julia died overnight from complications which developed from injuries inflicted by the young Silverback male ...
Australia's hopes of winning the 60th annual Eurovision Song Contest have been dashed at the last, with Sweden storming to the top of the ...
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Pittsburgh Pirates (48-37) at Milwaukee Brewers (40-45), 8:10 p.m.
Probable Starting Pitchers: Pittsburgh - James McDonald (9-3, 2.37) Milwaukee - Zack Greinke (9-3, 3.32)
(Sports Network) - The Pittsburgh Pirates look to continue their surprising season when they take on the NL Central-rival Milwaukee Brewers this evening in the opener of a three-game series at Miller Park.
The Pirates are first in the Central standings -- one game ahead of Cincinnati and 2 1/2 games in front of St. Louis -- and took two of three matchups with the San Francisco Giants before the All-Star break. The Pirates exploded for a 13-2 victory on Sunday and A.J. Burnett benefited from the run support to improve to 10-2 on the season. Burnett allowed two runs in 6 1/3 innings.
Andrew McCutchen homered twice and knocked in four runs, while Neil Walker had five hits, including a home run, two RBI and four runs scored for Pittsburgh, winners in 10 of their last 12 games. Walker has a 12-game hitting streak.
"I feel like it's pretty good for us to end how we did in the first half of the season," said McCutchen. "Hopefully we can continue that momentum going into the second half."
Casey McGehee added three hits and a pair of RBI before leaving the game in the sixth inning with a left groin strain. He is questionable for Friday.
Pittsburgh, which hasn't had a winning season since 1992, will also visit Colorado on its road trip.
James McDonald has been a big part of the Pirates' success this season and will take the mound tonight in Brew City. McDonald has won four straight starts and last toed the rubber on July 7 in a 3-1 win over the Giants. He allowed just one run and struck out 10 batters in seven innings, pushing his record to 9-3 in 17 starts with a 2.37 earned run average.
McDonald, a right-hander, defeated the Brewers on June 3 and is 1-2 with a 4.84 ERA in seven career games (3 starts) against them.
Milwaukee entered the All-Star break in impressive fashion, winning six of nine games, and will begin the second half of the 2012 campaign with six games at home versus the Pirates and Cardinals.
The Brewers won two of three meetings in Houston and squeezed out a 5-3 win in 10 innings on Sunday. Corey Hart and Rickie Weeks delivered RBI singles in the top of the 10th inning and John Axford closed the door in the bottom half for his 15th save of the season. Weeks ended 3-for-5 with a homer and two RBI.
Brewers starter Zack Greinke, who was ejected after throwing just four pitches for spiking a ball following a close play at first on Saturday, made his second straight start. He surrendered three runs on five hits and two walks in three innings.
"Zack struggled a little bit there in the first inning and that kept him from going deeper in the game," Brewers manager Ron Roenicke said. "He was fatigued after that."
Manny Parra picked up the win following a 1-2-3 ninth.
Oddly enough, Greinke gets the nod again tonight versus the Pirates and will become the first pitcher to start three straight games since Red Faber of the White Sox back in 1917. Greinke is 0-1 in his last three outings, but owns a strong 9-3 mark in 19 starts with a 3.32 ERA. The right-hander is 4-0 in seven home starts and is riding a 15-game home winning streak -- the longest in franchise history. He is 15-0 with a 2.68 ERA in 23 games (22 starts) at Miller Park.
Greinke was 11-0 at home a year ago and is 4-1 with a 5.17 ERA in five career starts against the Pirates.
Milwaukee lost two of three to the Pirates at home from June 1-3 this season, but went 12-3 in this series a year ago.


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LOS ANGELES, Oct. 23 /PRNewswire/ --
Have a Grab 'n Go Bag for each person in the house in the event you need to evacuate due to wildfires. If you need to evacuate, grab your bag and go.
-- Flashlight, batteries, or light sticks
-- Portable radio and batteries
-- Keys (house and car)
-- Money (coins and bills)
-- Cell phone (and charger)
-- Dust masks or rag for smoke
-- Glasses, contacts lenses and solutions
-- Medications (at least one-week supply)
-- Comfortable shoes, two pairs of socks
-- Comfortable clothing (sweats, extra underwear)
-- Jacket or sweatshirt
-- Whistle (call for help if trapped)
-- Emergency phone list, out-of-state contact #
-- Lists of people to notify if you are injured
-- Copies of important documents: insurance, identification, social
security, medical records, etc.
-- Good book, cards, crossword puzzles
-- Blanket
-- Photos, keepsakes and sentimental items
-- Road map for alternate routes
-- Drinking Water
-- Snacks (granola bars, trail mix, peanut butter)
Seniors, Disabled or Special Needs
-- Food for special diet needs
-- Batteries for hearing aids, wheelchair, etc.
-- List of style and serial # of medical devices
-- Special supplies: oxygen, catheters, etc.
-- Prescriptions for eyeglasses (not older than one year)
-- Personal sanitary items (Depends, disposable bags, ties, wipes)
Infant and Toddler
-- Formula, disposable bottles, nipples
-- Diapers and wipes
-- Instant baby cereal
-- Bowl and spoon
-- Sunscreen
-- At least two changes of clothes and a Light jacket
-- Tylenol, Triaminic and other medications
-- Firm soled slippers or shoes
-- Toys, books, stuffed animals
Pet Grab 'n Go Bag
-- Food
-- Water and Bowls (non-spillable)
-- Collar, leash and
|SOURCE Team SAFE-T
Copyright©2007 PR Newswire.
All rights reserved


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Crescent Zucchini Pie Recipe
A tender, flaky crust makes this egg- and zucchini-based pie a special treat. The cheese, herbs and seasonings add delectable flavor. —Zelda DeHoedt, Cedar Rapids, Iowa
- 1 tube (8 ounces) refrigerated crescent rolls
- 2 teaspoons Dijon mustard
- 4 cups sliced zucchini
- 1 cup chopped onion
- 6 tablespoons butter, cubed
- 2 eggs, lightly beaten
- 1 cup (4 ounces) shredded part-skim mozzarella cheese
- 1 cup (4 ounces) shredded Colby-Monterey Jack cheese
- 2 tablespoons dried parsley flakes
- 1/2 teaspoon salt
- 1/2 teaspoon pepper
- 1/4 teaspoon dried basil
- 1/4 teaspoon dried oregano
- 1. Separate crescent dough into eight triangles and place in a greased 9-in. deep-dish pie plate with points toward the center. Press dough onto the bottom and up the sides of plate to form a crust; seal seams. Spread with mustard.
- 2. In a large skillet, saute zucchini and onion in butter until tender. In a large bowl, combine the eggs, cheeses, seasonings and zucchini mixture. Pour into crust.
- 3. Bake at 375° for 20-25 minutes or until a knife inserted near the center comes out clean. Cover edges loosely with foil if crust browns too quickly. Yield: 6 servings.
Nutritional Facts
1 piece equals 413 calories, 30 g fat (16 g saturated fat), 128 mg cholesterol, 849 mg sodium, 22 g carbohydrate, 1 g fiber, 15 g protein.
Wine Pairings
Sparkling Wine
Enjoy this recipe with a sparkling wine.
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