text:
|Publication number
|Publication type
|Application number
|Publication date
|Dec 10, 1996
|Filing date
|May 12, 1995
|Priority date
|May 12, 1995
|Fee status
|Also published as
|Publication number
|Masao Yafuso, Robert J. Linhardt
|Original Assignee
|Minnesota Mining And Manufacturing Company
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (71), Non-Patent Citations (10), Referenced by (34), Classifications (13), Legal Events (6)
|External Links: USPTO, USPTO Assignment, Espacenet
This application generally relates to processes to activate sulfated polysaccharides and particularly relates to a high-yield chemical process to efficiently activate biologically useful sulfated mucopolysaccharides where the activated mucopolysaccharide may then be attached to suitable polymeric, composite or metallic surfaces in order to provide biocompatible materials which may directly contact tissues, blood or blood products.
Surfaces of medical devices that are in direct contact with biological materials, such as tissues, blood and blood products, have been treated with surface modifying agents in order to make the contacting surfaces compatible with these types of sensitive biological materials. Sulfated polysaccharides have been used in a variety of applications to make biocompatible medical surfaces. For example, the blood contacting surfaces of devices such as blood oxygenators, blood pumps, catheters, or connection tubes and tubing may be treated with biologically active polysaccharides, particularly heparin or heparin derivatives, to make the surfaces of such devices nonthrombogenic and thus prevent clotting or clot formation related to surface contact with blood or blood products.
Several methods for specifically attaching or binding heparin or heparin derivatives to substrate surfaces have been reported. U.S. Pat. Nos. 4,613,665 and 4,810,784 report a process to attach heparin to different types of substrates. The reported process degrades a polysaccharide antithrombogenic agent, such as heparin, with nitrous acid to give fragments which react with primary amino groups on the substrate's surface to form intermediate Schiffs base conjugates. Reduction of the intermediate conjugates then covalently binds the fragments to the support.
In addition, U.S. Pat. No. 4,565,740 reports a substrate modified to include degraded heparin fragments where the substrate is initially treated with a polyamine and a dialdehyde crosslinker, then treated with dextran sulfate, further treated with a polyamine and finally treated with degraded heparin and sodium cyanoborohydride to chemically bind the heparin fragments to the polyamine. Similarly, U.S. Pat. No. 5,049,403 reports a substrate modified to include degraded heparin fragments where the substrate is initially treated with a polyamine that is crosslinked with crotonaldehyde.
Further, U.S. Pat. No. 4,326,532 reports a layered substrate coated with chitosan that reacts with an antithrombotic agent such as heparin. Specifically, heparin is condensed with a layer of chitosan that is initially applied to an acid oxidized or plasma etched hydrophobic substrate and, if needed, the condensed heparin is then reduced using sodium cyanoborohydride.
Alternative methods of modifying surfaces with activated heparin have also been reported. For example, U.S. Pat. Nos. 4,720,512 and 4,786,556 report activating heparin with sodium periodate, reacting the periodate-activated heparin with an amine-containing material to form a conjugate and then reducing the conjugate using sodium cyanoborohydride.
Besides various heparin activation and chemical bonding methods, other processes have been used to fix or attach heparin to substrates without actually chemically bonding heparin to the substrate. For example, U.S. Pat. No. 4,871,357 reports an ionic binding of heparin to surfaces using quaternary ammonium salts. Subsequent irradiation of ionically bound heparin using quaternary ammonium salts has been reported to covalently bond heparin to the surface. See, e.g., International Application No. PCT/US92/07661 published Apr. 1, 1993.
In spite of the many approaches to modify surfaces with biologically useful agents, a need exists for an efficient, effective process to prepare such modified surfaces which uses reagents which are easy to handle and are not toxic or hazardous to use. Polysaccharides are particularly difficult to work with because these polymers are generally not soluble in organic solvents and thus are not readily used with many common reaction methodologies. Thus, a preferred process would be carried out in an aqueous system.
Furthermore, the biological activity of active polysaccharides may be very sensitive to processing conditions. A desirable process would allow binding biologically active polysaccharides, such as heparin, to surfaces without degrading or otherwise altering the biological activity of the active polysaccharide when it is used to modify the surface of a substrate. A need exists for a process which may be adapted for use with many different types of active polysaccharides and substrates and which does not result in degradation or alteration of the biological activity of the active polysaccharide.
The present invention is directed to a novel, high-yield, efficient process to prepare an activated sulfated polysaccharide which may then be used in subsequent reactions or processes to bind the activated polysaccharide with a nucleophilic agent or an aminated surface. A preferred activation process comprises the steps of i) forming a polysaccharide tetraalkylammonium salt by contacting an aqueous mixture of a sulfated polysaccharide salt with an acid source such as a cation exchange resin to give a polysaccharide free acid followed by contacting the polysaccharide free acid with a tetraalkylammonium hydroxide to give the polysaccharide tetraalkylammonium salt, and then ii) forming an activated sulfated polysaccharide e.g. by contacting the polysaccharide tetraalkylammonium salt of step i) with a coupling reagent in an aprotic organic solvent at ambient temperatures for a period of time sufficient to form the activated sulfated polysaccharide. The activated sulfated polysaccharide of this invention may be used in further processing steps in commonly used organic reactions using aqueous mixtures or common organic solvents and conventional reaction conditions.
A variety of different sulfated polysaccharides may be activated using this invention. Those of ordinary skill in the art will recognize that sulfated polysaccharides or derivatives thereof are complex polymeric moieties as well as mixtures of such polymers. For example, heparin principally includes both one major and one minor polymeric moiety which are schematically represented by Formula A, the major structure, and Formula B, the minor structure. ##STR1## In Formulas A and B, the variables are defined as follows: n is an integer, R5 is a moiety --SO3 Na or --H and R6 is a moiety --COCH3, --SO3 Na or --H. Typically, the ratio of the major polymeric structure of heparin to the minor polymeric structure of heparin is about 85:15.
Suitable sulfated polysaccharides or polysaccharide derivatives which may be used in the present process include known biologically active polysaccharides such as heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, dextran sulfate, fucoidin sulfate, and keratan sulfate.
A preferred acid source for use in the first step of this process is an acidic cation exchange resin or membrane. Such resins or membranes are advantageous because they are available in solid form, may be used in ion exchange columns, and do not exude toxic and/or volatile fumes.
Suitable tetraalkylammonium hydroxides for use in the invention include ammonium hydroxides either with symmetrical tetraalkylammonium groups, e.g., tetrabutylammonium hydroxide, or with unsymmetrical ammonium groups, e.g., tributylethylammonium hydroxide. The alkyl groups are generally straight or branched chain alkyl groups of one to six carbon atoms. The preferred cyanating reactions may be carried out under conventional reaction conditions for cyanogen halides at temperatures of about -10� to 30� C.
Preferred coupling reagents include cyanating reagents such as cyanogen halides, p-nitrophenyl cyanate, N-cyanotriethylammonium tetrafluoroborate and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate as well as other known coupling reagents such as disuccinimydyl carbonates, toluenesulfonyl chloride, tresyl chloride, carbonyl diimidazoles, 2-fluoro-1-methylpyridiniumtoluene-4-sulfonate and derivatives thereof. Typically, the preferred cyanating agents are used in the presence of an inorganic base such as sodium hydroxide or sodium carbonate or an organic base such as an amine. A particularly preferred cyanating reagent is a mixture of a cyanogen halide and an excess, e.g., about a 10% molar excess, of a trialkylamine in an aprotic organic solvent.
In another embodiment, this invention provides a process to bind or couple a sulfated polysaccharide to a nucleophilic agent. This process comprising the steps of i) forming a polysaccharide tetraalkylammonium salt by contacting an aqueous mixture of a sulfated polysaccharide salt with an acid source such as a cation exchange resin to give a polysaccharide free acid followed by contacting the polysaccharide free acid with a tetraalkylammonium hydroxide to give the polysaccharide tetraalkylammonium salt, and then ii) forming an activated polysaccharide by contacting the polysaccharide tetraalkylammonium salt of step i) with a coupling reagent in an aprotic organic solvent at ambient temperatures for a period of time sufficient to form the activated sulfated polysaccharide, and iii) contacting the activated polysaccharide with a nucleophile for a period of time sufficient to bind or couple the nucleophile to the activated polysaccharide. The nucleophile typically is used as a solution or mixture in a suitable solvent such as water or commonly used organic solvents. Suitable nucleophilic agents for use in this process include primary and secondary amines, including aminated polymers, or thiols.
Similarly, this invention provides a process to couple a biologically active, sulfated polysaccharide or derivative thereof to at least one exposed surface of a suitable support such as a polymeric of metal substrate or support. The steps of this embodiment comprise i) contacting at least one exposed surface of a support such as a polymeric support with a water-soluble aminated polymer at ambient temperatures for a period of time sufficient to give a primed surface, and ii) contacting the primed surface with a reactive biologically active polysaccharide in which the reactive biologically active polysaccharide is prepared by the polysaccharide activation process described above.
Preferred aminated polymers or primers include polyalkylene amines such as polyethyleneimine or polyethyleneimine crosslinked with suitable difunctional agents such as dialdehydes, acroleins, diepoxides or divinylsulfones. Suitable polyalkylene amines will have a molecular weight between 1,000 and 100,000. Suitable polymeric substrates for use in this embodiment include polyamides, polyurethanes, polyvinyl alcohols, polysulfones, nylons, polyvinyl chlorides, polyalkylenes such as polyethylenes and polypropylenes, celluloses, poly(meth)acrylates, polycarbonates, fluoropolymers such as poly(tetrafluoroethylene), silicones or polyesters such as polyethylene terephthalate, as well as other materials which have been used in known medical devices such as glass, stainless steel and titanium.
Polymeric, metallic or composite materials having utility in the present invention include solid organic polymers, glass and metals in the form of shaped articles, powders, granules, pellets, films, fibers or foams. Preferably, such polymeric, metallic or composite materials are biomaterials in the form of medical devices used for in vivo, ex-vivo, and in vitro diagnostic and therapeutic procedures. Examples of these devices include blood contacting medical devices such as vascular grafts, catheters, cannulas, stents, indwelling blood monitoring devices, artificial kidneys, artificial heart-lungs, extracorporeal circuits for auxiliary circulating devices, A-V shunts, artificial heart valves, temporary blood by-pass tubes, and dialysis membranes.
An alternative embodiment of this invention is related to the process using an aminated polymer to prime a surface. In this embodiment, however, the surface of a polymeric support is mechanically primed to provide a surface containing nucleophilic groups using known etching processes such as chemical or plasma etching as described, for example, in U.S. Pat. No. 4,326,532. After the surface of the polymeric support has been etched or primed, an activated polysaccharide prepared by the present process is contacted with the mechanically primed surface.
FIG. 1 is a schematic representation of the steps used to activate dextran sulfate with a coupling reagent.
FIG. 2 is a schematic representation of the steps used to activate heparin represented by Formulas 1 and 2 with a coupling reagent.
FIG. 3 is a schematic representative of the steps used to couple a sulfated polysaccharide such as activated heparin represented by Formulas 7 and 8 to a primed surface.
FIGS. 4a-4c are structural representations of polysaccharide derivatives of Formulas 1-11.
The present invention provides a high-yield, efficient process to activate polysaccharides and then use the activated polysaccharide to bind to nucleophilic agents or to the surfaces of materials used to make medical devices which contact tissues, blood or blood products. The present activation process is readily described as occurring in two separate steps although it is not necessary to perform an isolation or purification process between the two steps. In the first step, an aqueous mixture of a sulfated polysaccharide is contacted with an acid source such as a cation exchange resin or membrane to form a polysaccharide free acid which is an intermediate acidified derivative of the polysaccharide. A readily used resin is a macroporous cationic ion exchange resin such as AMBERLITE IR 120 resin (commercially available from Aldrich Chemical Co., Milwaukee, Wis.). When a cationic ion exchange resin is used, the aqueous polysaccharide mixture may be simply passed through a short column of the resin, and the resin then rinsed with deionized water.
The intermediate acidified polysaccharide is then immediately quenched with an alcoholic mixture such as a methanolic mixture of a tetraalkylammonium hydroxide at ambient temperatures to give a polysaccharide tetraalkylammonium salt. The quenching process may be readily monitored using a pH electrode in the mixture as the tetraalkylammonium hydroxide is added to the acidified polysaccharide. The resulting polysaccharide tetraalkylammonium salt at neutral pH values, preferably at a pH value of about 7, is soluble in polar organic solvents and may be isolated, if desired, by evaporative removal of the solvent such as methanol and then freeze drying the remaining aqueous mixture.
In a second step, the polysaccharide ammonium salt is converted into an activated agent using a suitable coupling agent, preferably a cyanating agent, in an aprotic polar organic solvent such as acetonitrile, N,N-dimethylformamide, dimethylsulfoxide or N,N-dimethylacetamide. Suitable cyanating reagents include cyanogen halides, preferably cyanogen chloride or cyanogen bromide, in combination with trialkylamines such as triethylamine. When used in a preferred embodiment of the present process, a mixture of cyanogen bromide and acetonitrile is added to a mixture of the polysaccharide ammonium salt in acetonitrile followed by the addition of a mixture of triethylamine in acetonitrile. When the mixture of triethylamine is initially added to the polysaccharide ammonium salt and cyanogen bromide, a precipitate briefly forms which then redissolves within a few minutes after the addition to provide a homogeneous mixture of the activated polysaccharide. Initial stability studies have demonstrated that the activated polysaccharide may be stored for several weeks at -4� C.
In the present invention the activated polysaccharide will readily couple with, i.e., react or coat onto, a suitable substrate or solid support by reaction of the activated polysaccharide site with a nucleophilic group, which is either attached to, associated with, or is actually a component of the substrate. This nucleophilic group will generally be an amino or thiol group which is part of a suitable polymer. Preferred polymers are aminated polymers such as polyethyleneimine which may be further crosslinked on the substrate using known processes, if desired. Suitable polyethyleneimine based polymers for use in this invention are well known and are described, e.g., in U.S. Pat. No. 4,565,745 or are commercially available, such as Polymin SN and Polymin P available from BASF, Nalco 7134 available from Nalco Chemical Company, or polyethyleneimine available from Aldrich Chemical Company.
The following examples are provided to further illustrate the practice of the present invention. The examples are not intended to limit the invention which is defined in the appended claims.
In the examples, the surface-bound concentration of heparin may be measured by a thrombin inhibition assay. The inhibition assay exploits the observation that thrombin enzymatically cleaves a commercially available synthetic substrate (S-2238) to yield a product whose concentration is proportional to its absorbance at 405 nm, and the rate of formation of product is therefore proportional to a thrombin concentration. Decreased amounts of product reflect inhibition of thrombin by heparin in the presence of excess amounts of antithrombin-III. Briefly, the assay is performed by adding, in the following sequence, the listed materials to test tubes: 0.05 ml of an unknown sample and 0.05 ml of buffer (where the sample has an unknown concentration of heparin on the surface), or 0.05 ml of a standard heparin solution, 1.0 ml of 0.3 mM S-2238, 0.1 ml of antithrombin-III (5 units/ml), and 0.1 ml of thrombin (0.1 units/ml). The standard heparin solutions (50 microliters) contain, for example, 0.08, 0.04, 0.02, 0.01 and 0.0 micrograms of heparin. The assay is carried out at 37� C. with overnight incubation in a water bath, with continuous mixing. Measurements are made on 0.20 ml aliquots taken from the unknown and standard solutions using microtiter plates and optical density at 405 nm is recorded. The optical density values are related to heparin concentration using the heparin standard solutions.
More specifically, the assay procedure is a modification of Chandler et al., J. Biomed. Mater. Res. 22:497-508 (1988) which uses the following reagents.
______________________________________Reagent Manufacturer Concentration______________________________________Antithrombin-III Sigma 5 units/mlS-2238 Kabi 0.3 mMThrombin Sigma 5 units/mlHanks' Buffer Sigma 0.1 units/mlHeparin Sigma 10 units/ml______________________________________
Antithrombin-III is reconstituted to 5 units/ml with 10 ml deionized distilled water and refrigerated at 4� C. S-2238 is reconstituted to 0.3 mM using 133 ml of buffer stock solution of PBS (phosphate buffered saline) with 1 mg/ml BSA (bovine serum albumin, Cat. No. A7838, Sigma Chemical Company, St. Louis, Mo.) and 1 mg/ml polyethylene glycol (8000MW, Cat. No. P2139, Sigma Chemical Company, St. Louis, Mo.) and stored at 4� C. Thrombin is reconstituted to 10 units/ml with 10 ml Hanks' phosphate buffered saline and stored at -20� C. in 1 ml aliquots. A 1:100 dilution of thrombin is used in the assay.
Standard heparin solutions are prepared from the 10 units/ml stock solution by serial dilution. Each new batch of thrombin and/or heparin must be tested to insure maximum sensitivity. Representative values of standard heparin solutions are listed in the following table.
______________________________________Standard Concentration______________________________________1 .08 μg/50 μl2 .04 μg/50 μl3 .02 μg/50 μl4 .01 μg/50 μl5 0 μg______________________________________
To measure absorbance, 0.05 ml of appropriate standards as well as an unknown sample having a measured surface area together with PBS/BSA buffer (0.05 ml) are dispensed into tubes. The following reagents are added to each of the tubes, 0.1 ml antithrombin-III, 1.0 ml S-2238 and 0.1 ml thrombin, all tubes are vortexed and then incubated overnight at 37� C. After incubation, 0.2 ml from each tube is added to a well of a microtiter plate in duplicate for each tube and optical density readings are taken at 405 nM. (All standards and samples are run in duplicate, with duplicate optical density readings at 405 nM.)
Step 1. Preparation of tetrabutyl ammonium salt of heparin:
Ten grams of heparin, sodium salt was dissolved in 100 g of deionized water. This solution was passed through 35 g of AMBERLITE IR 120 cation exchange resin in the acid form in a 2.8 cm diameter column. The column was rinsed through with an additional 150 g of deionized water. The effluent was collected in the beaker with a magnetic bar and pH electrode, and the effluent was neutralized to a pH value of about 7 with a 25% solution of tetrabutyl ammonium hydroxide solution in methanol as it was being collected. 38 g of the tetrabutyl ammonium hydroxide solution was used. The methanol was stripped under a water aspirator vacuum with a rotary evaporator, and the solution freeze dried to yield 20.5 g of tetrabutyl ammonium heparin as a white solid.
Step 1a. Preparation of tetrabutyl ammonium dextran sulfate:
Four grams of dextran sulfate was dissolved in 40 cc of deionized water. This solution was passed through 50 ml of AMBERLITE IR 120 cation exchange resin in a 3.5 cm diameter column. The effluent was neutralized to a pH value of about 7 with 16.5 g of 25% tetrabutyl ammonium hydroxide in methanol. The methanol was stripped off with a rotary evaporator and the residue was freeze-dried to yield 9.5 g of tetrabutyl ammonium dextran sulfate.
Step 2. Activation of tetrabutyl ammonium heparin:
Tetrabutyl ammonium heparin was dissolved in acetonitrile to make a 100 mg/ml solution. To 5.0 ml of this solution in an ice bath was added 5.0 ml of a 100 mg/ml solution of cyanogen bromide in acetonitrile. To this solution was added 6.0 ml of a 100 mg/ml solution of triethylamine in acetonitrile. The reaction mixture became immediately cloudy with the last addition of base which then clarified within a few minutes. This solution has remained active after two weeks of storage at -4� C.
Step 2a. Activation of tetrabutyl ammonium dextran sulfate:
To 1.3 ml of a 100 mg/ml solution of tetrabutyl ammonium dextran solution in methanol cooled with an ice bath was added 0.26 ml of a 5M solution of cyanogen bromide in acetonitrile. To this solution was added 1.3 ml of a 100 mg/ml solution of triethylamine in acetonitrile. The reaction mixture became cloudy immediately with the last addition which clarified within a few minutes.
Step 3. Attachment of activated heparin to a substrate:
Plastic polycarbonate strips were dipped in a 5 mg/ml solution of poly(ethylenimine) solution in deionized water, then rinsed in deionized water. These primed strips were immersed in a solution of a 1:10 dilution of the activated tetrabutyl ammonium heparin solution from Step 2. in pH 3.5, 0.1M sodium phosphate solution at room temperature for about one hour. The coated polycarbonate strip was rinsed for 10 minutes in 25% saline to remove ionically bound heparin, then subjected to thrombin inhibition assay. The results showed heparin activity of about 0.1 μg/cm2 after 20 minutes and about 0.16 μg/cm2 after one hour.
Step 3a. Attachment of activated dextran sulfate to a substrate:
Plastic polycarbonate strips were dipped in a 5 mg/ml solution of poly(ethylenimine) solution in deionized water, then rinsed in deionized water. These primed strips were immersed in a solution of a 1:10 dilution of the activated tetrabutyl ammonium dextran sulfate solution from Example 2a. in pH 7 phosphate buffered saline at 50� C. for 20 min. The coated polycarbonate strip was rinsed for 10 minutes in 25% saline to remove ionically bound dextran sulfate. This strip gave a violet color when stained with a toluidine blue solution to verify the presence of the negatively charged sulfate groups of tetrabutyl ammonium dextran sulfate.
External surfaces of polycarbonate (sold under the tradename HYZOD by Sheffield Plastics Inc., Sheffield, Mass.) sheets cut into strips as well as external surfaces of extracorporeal centrifugal pumps (made of polycarbonate and poly(methyl methacrylate), Model 7850, Sarns/3M, Ann Arbor, Mich.), were immersed in a 0.1 wt. % polyethyleneimine (PEI) solution (0.40 g PEI in 400 ml distilled water, PEI having an average molecular weight of 50,000 commercially available from Aldrich Chemical Company, Milwaukee, Wis.) at room temperature for fifteen minutes. The polycarbonate strips and pumps were then removed from the PEI solution and rinsed thoroughly with distilled water. The polycarbonate strips and pumps were next immersed in a 0.03 wt. % dextran sulfate (DS) solution (0.15 g DS in 500 ml pH 3.9 citrate buffer prepared by mixing 11.0 g citric acid monohydrate and 9.0 g sodium chloride in one liter distilled water and adjusting the pH to 3.9 with 5N sodium hydroxide, DS having an average molecular weight of 500,000 commercially available from Sigma Chemical Company, St. Louis, Mo.) at room temperature for five minutes. Again, the polycarbonate strips and pumps were rinsed thoroughly with water and then re-immersed in a 0.1 wt. % polyethyleneimine solution at room temperature for fifteen minutes.
The now primed polycarbonate strips and pumps were then exposed to an activated heparin solution heated to a temperature of 50� C. for ten minutes. The activated heparin solution was prepared by mixing 0.5 g heparin tetrabutyl ammonium salt prepared according to the process of Example 1, 50 ml acetonitrile, 10 ml 5M cyanogen bromide in acetonitrile (commercially available from Aldrich Chemical Company, Milwaukee, Wis.) and 55 ml 10 wt. % triethylamine in acetonitrile. This mixture was stirred at room temperature for about two hours to yield a homogeneous solution. After exposure to the activated heparin solution, the polycarbonate strips and pumps were rinsed thoroughly with distilled water, immersed in a 25 wt. % sodium chloride solution at room temperature for five minutes and finally rinsed again with distilled water.
After the surfaces of the polycarbonate strips and pumps were primed and coated with heparin the heparin activity of the coated surfaces was assayed using the thrombin inhibition assay described above. This assay demonstrated that the heparin activity on the heparin coated articles was about about 0.09 μg/cm2.
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Owner name: MINNESOTA MINING AND MANUFACTURING COMPANY, MINNES
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:YAFUSO, MASAO;LINHARDT, ROBERT J.;REEL/FRAME:007487/0837
Effective date: 19950512
|Jul 9, 1999
Owner name: TERUMO CARDIOVASCULAR SYSTEMS CORPORATION, NEW JER
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MINNESOTA MINING & MANUFACTURING COMPANY;REEL/FRAME:010043/0831
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Effective date: 20041210


text:
Thursday, September 9, 2010
As for putting the pressure on and getting an answer from them now I have cooled down. Might as well play their game since I have my own set of cards to deal. Plus I know they are busy with squaring the old and new teacher. Finally, I want to secure a good recommendation from this school which I have been working hard on creating.
A little birdie told me that it is dangerous to bring up the topic of "living together with your boyfriend" when negotiating a contract. Since the Principal could be conservative and think that living together before marriage is a sin and therefore see you as a bad seed. Certainly I felt some of this at my previous public school from the Principal, but just for dating a Korean man.
It reminded me that for my next job hunt I should be more sensitive with this issue if it comes up.
Anyways I feel more on my path this morning than I did yesterday. :)
3 comments:
No need to apologize. Your blog is about and for your thoughts, and anxieties. Saying that, I'm glad you've cooled down:). I would also so be cautious about laying out your cards and telling them you want to live with your bf. Win them over first, whether this place or a new school, and then drop the "bomb" or maybe they don't need to know that at all.ReplyDelete
My question is though is whether your school would even help you find a place for your bf and you. I mean, to them since you aren't married they have no obligation to get you a bigger place, but I guess if you ge the allowance then you can do whatever you want.
Hopefully it all works out, and yay for you and JH:)!!!
Yea ... the cards i have to play are just that I am not going to stay at the school and take a break from Korea. Then comes the rest they don't need to know about.ReplyDelete
As for house hunting I think JH and I will be taking care of that.
:) Thanks!!
House hunting together! So exciting. I'd definitely say that is a new more exciting chapter opening in your life. I'd keep it a bit under wraps as well just in case your current or future principal is a bit conservative about these things.ReplyDelete
G'Luck *^^*

subset: commoncrawl


text:
Weekly Health Update Week of: Monday, May 7th, 2012 Courtesy of: Health and Wellness Chiropractic (701) 483-NECK(6325)
"Simple diet is best; for many dishes bring many diseases; and rich sauces are worse than heaping several meats upon each other." ~Pliny
Mental Attitude: Berry Good News. Men who regularly consume foods rich in flavonoids (such as berries, apples, certain vegetables, tea and red wine) may significantly reduce their risk for developing Parkinson's disease. Flavonoids are naturally occurring, bioactive compounds present in many plant-based foods and drinks. Neurology, April 2012 Health Alert: Stressed? The risk for coronary heart disease and stroke increases by 30% in a person whose partner has cancer. The cause is probably the negative stress to which the cancer patient's partner is exposed. Previous studies show that stress can affect the nervous system, blood pressure, and inflammation, increasing the risk of developing coronary heart disease and stroke. Centre for Primary Healthcare Research in Malmö, April 2012 Diet: Pain Relief. The supplement Methylsulfonylmethane gave osteoarthritis patients relief from symptoms of pain and physical dysfunction. Osteoarthritis Cartilage, 2008 Exercise: Being Fit. Improving or maintaining physical fitness appears to help obese and overweight children reach a healthy weight. During a four-year study, obese and overweight girls and boys who achieved fitness were 2.5 to 5 times more likely to reach a healthy weight than those who stayed underfit. Obesity, April 2012 Chiropractic: Slowing Degeneration? Morphologic changes in the endplate that occur with advancing age or degeneration can interfere with normal disk nutrition and further the spinal degenerative process. Degeneration decreases the ability of the spine to move through a full range of motion, which alters the integrity of the proteoglycans and water concentration, reducing the number of viable cells with decreased movement of solutes in and out of the disk. Pain, 2004 Wellness/Prevention: Unhealthy Snacks, Sodas and Watching TV. In a study of obesity among European children, Dr. Yannis Manios, Assistant Professor at Harokopio University in Athens, writes, "We found that many countries are lacking clear guidelines on healthy eating and active play. However, there is good evidence linking sedentary behavior (like TV watching) with subsequent obesity. Therefore, TV-watching in kindergartens should be replaced by more active, non-competitive, fun activities which will promote the participation of the whole class and help children to achieve optimal growth, health and well-being. Similarly at home, TVs in the bedroom and unhealthy snacks in the kitchen cupboard are a bad idea. Parents should also remember that their role is not only to provide healthy food and drink options but to act as a role model themselves, since kids are copying their behaviors." Obesity Reviews, March 2012
Weekly Health Updates
Weekly Health Update Week of: Monday, April 30th, 2012 Courtesy of: Health and Wellness Chiropractic (701) 483-6325
"Anything is possible. You can be told that you have a 90% chance or a 50% chance or a 1% chance, but you have to believe, and you have to fight." ~ Lance Armstrong
Mental Attitude: Meditation. Adults with memory impairment and memory loss may benefit from mantra-based meditation (12 minutes of meditation per day for 8 weeks). Mantra-based meditation has demonstrated a positive effect on patients' emotional responses to stress, fatigue and anxiety. Findings revealed a substantial increase in cerebral blood flow in the patients' prefrontal, superior frontal, and superior parietal cortices, and also better cognitive function. Journal of Alternative and Complementary Medicine, March 2012 Health Alert: Diabetics And Stroke. 26 million Americans have diabetes, and more than half are younger than 65. The longer you have diabetes, the higher your risk for stroke. Compared to people without diabetes (after considering other factors such as age, smoking history, physical activity, history of heart disease, blood pressure and cholesterol), the risk of stroke increased 70% in people with diabetes for less than 5 years, 80% in people with diabetes for 5-10 years and three-fold in people with diabetes for 10 years or more. American Heart Association, March 2012 Diet: Seeing Things? Hungry people see food-related words more clearly than people who've just eaten. This change in vision happens at the earliest perceptual stages, before higher parts of the brain have a chance to change the messages coming from the eyes. Psychological Science, March 2012 Exercise: Good Reasons. Exercise helps to alleviate low-back pain, helps to reduce the amount of insulin required to control blood sugar levels in Type I (insulin-dependent) diabetics and improves mental alertness. Surgeon General's Report on Physical Activity and Health, 1996 Chiropractic: Hold Your Head Up! "Head in forward posture can add up to thirty pounds of abnormal leverage on the cervical spine. This can pull the entire spine out of alignment. Forward head posture (FHP) may result in the loss of 30% of vital lung capacity. These breath-related effects are primarily due to the loss of the cervical lordosis, which blocks the action of the hyoid muscles, especially the inferior hyoid responsible for helping lift the first rib during inhalation." ~ Rene Cailliet M.D., famous medical author and former Director of the Department of Physical Medicine and Rehabilitation at the University of Southern California Wellness/Prevention: Avoid Absenteeism. The US is losing $226 billion per year due to employee absenteeism. A worker is less likely to take sick leave if their supervisor offers support (lightened work load or stress management training) when an employee is experiencing psychosomatic stress symptoms. The worker feels inclined to reciprocate the supportive treatment by keeping their work effort high. European Journal of Work and Organizational Psychology, January 2012
Weekly Health Update Week of: Monday, April 23rd, 2012 Courtesy of: Health and Wellness Chiropractic (701) 483-6325
"Common sense is the collection of prejudices acquired by age eighteen." ~ Albert Einstein
Mental Attitude: Get Your Sleep! Older adults with poor sleep habits have an altered immune system response to stress that may increase their risk for mental and physical health problems. Stress leads to significantly larger increases in a marker of inflammation in poor sleepers compared to good sleepers; a marker associated with poor health outcomes and death. Poor sleepers report more depressive symptoms, more loneliness and more global perceived stress relative to good sleepers. As people age, a gradual decline in the immune system occurs, along with an increase in inflammation. Heightened inflammation increases the risk for cardiovascular disease, diabetes and other illnesses, as well as psychiatric problems. American Journal of Geriatric Psychiatry, March 2012 Health Alert: Slow Down -- You Move Too Fast? People who are considered ambitious, attend the best colleges and universities, have prestigious careers and earn high salaries don't necessarily lead more successful lives. Ambition has its positive effects (in terms of career success, it certainly does) but ambitious people are only slightly happier than their less- ambitious counterparts and they actually live somewhat shorter lives. Journal of Applied Psychology, March 2012 Diet: Fish Oil. Six weeks of supplementation with fish oil significantly increased lean mass and decreased fat mass in test subjects. International Journal of Sport Nutrition and Exercise Metabolism, October 2010 Exercise: Good Reasons. Exercise helps you maintain proper muscle balance, reduces the rate and severity of medical complications associated with hypertension, helps alleviate menstrual symptoms and lowers your heart rate response to submaximal physical exertion. Surgeon General's Report on Physical Activity and Health, 1996 Chiropractic: Adjustment or Microdiskectomy for Sciatica? 60% of patients with sciatica (symptoms of unilateral lumbar radiculopathy secondary to lumbar disk herniation at L3-4, L4-5, or L5-S1) who had failed other medical management (patients must have failed at least 3 months of nonoperative management including treatment with analgesics, lifestyle modification, physiotherapy, massage therapy, and/or acupuncture) benefited from spinal manipulation to the same degree as if they underwent surgical intervention. JMPT, October 2010 Wellness/Prevention: Dark Chocolate Good For The Heart. A flavonoid called epicatechin, found in dark chocolate, enhances mitochondria structure in people with advanced heart failure and type 2 diabetes. Mitochondria are cellular structures that provide the energy a cell requires in order to move, divide, and contract. Both heart failure and type 2 diabetes impair these cells, resulting in abnormalities in skeletal muscle. In individuals with diabetes and heart failure, these abnormalities in the heart and skeletal muscle cause decreased functional capacity, resulting in difficulty walking even short distances, shortness of breath, and a lack of energy. Clinical and Translational Science, March 2012
Weekly Health Update Week of: Monday, April 16th, 2012 Courtesy of: Health and Wellness Chiropractic (701) 483-6325
"The main goal of the future is to stop violence. The world is addicted to it." ~ Bill Cosby
Mental Attitude: Music and Emotions. Music can evoke positive emotions, which in turn can lower stress levels. In a survey study, positive emotions were experienced more often and more intensively in connection with music listening. The more the participants liked the music, the less stress they experienced. To get the positive effects of music, you have to listen to music you like. University of Gothenburg, March 2012 Health Alert: Slow Brain Growth In Babies Linked To Depression During Pregnancy! Many women experience a roller coaster of emotions during pregnancy: stress, confusion, fear, sadness and depression. Babies whose mothers are depressed during pregnancy have a greater chance of growing slower, resulting in the head and body showing retarded growth. Also, antidepressants increase the risk of slow growth in the development of babies' brains. Archives of General Psychiatry, March 2012 Diet: High-Fat Diets Increase Colon Cancer Risk. Eating too much fat and sugar puts a person at greater risk for colon cancer and obesity. In normal tissue from patients with colon cancer, they found that epigenetic marks on genes involved in breaking down carbohydrates, lipids and amino acids (abundant in the fatty Western diet) appeared to have been retrained. Epigenetic marks are chemical modifications that serve as on/off switches for many genes. These foods are changing the methylation patterns on a person's insulin genes so that they express differently, pumping out more insulin than the body requires. Cancer Prevention Research, March 2012 Exercise: Exercise Linked To Change In DNA. Exercise almost immediately alters DNA in healthy but inactive men and women. Although the genetic makeup is not altered, DNA molecules change structurally and chemically when a person exercises. One researcher noted, "Our muscles are really plastic. We often say 'You are what you eat.' Well, muscle adapts to what you do. If you don't use it, you lost it and this is one of the mechanisms that allow that to happen." Cell Metabolism, March 2012 Chiropractic: Is Chiropractic Safe? YES. Chiropractic's non-surgical, drug-free approach to health places it among the safest of all health care practices. Remember, chiropractic takes nothing out of the body and puts nothing in. As a result, chiropractors enjoy one of the lowest malpractice rates of all health care professionals. Massachusetts Chiropractic Association Wellness/Prevention: How Much Selenium? While too much selenium may result in the development of type 2 diabetes, high selenium intake has been shown to protect against certain cancers, such as lung, colorectal, bladder, and prostate cancer. It also increases male fertility and has positive effects on antiviral function. Low selenium intake has been linked to memory and brain decline, low immune system quality, and a greater risk of death. The Lancet, March 2012
Week of:
Monday, April 2nd, 2012
Mental Attitude: Memory and Stress.
Anyone who has ever experienced chronic stress knows it can take a toll on both your emotions and your ability to think clearly. Researchers have discovered a neural mechanism that directly links repeated stress with impaired memory. This study also provides critical insight into why stress responses can act as a trigger for mental illnesses. Neuron, March 2012
Health Alert: Sleeping Pill Dangers!
Sleeping pill sales increased by 23% from 2006-2010 and generated about $2 billion in annual sales. Sleeping pills (including Ambien and Restoril) are linked to a 4.6 times higher risk of death and a significant increase in cancer. Among patients who were prescribed just 1-18 sleeping pills per year, the risk of death was 3.6 times higher. Rates of new cancers were 35% higher among patients who were prescribed at least 132 doses a year, compared with those who did not receive prescriptions. BMJ Open, March 2012
Diet: Rosemary Essential Oil On My Mind?
Blood levels of a rosemary oil component correlate with improved cognitive performance. Results indicate, for the first time in human subjects, that concentration of 1,8-cineole in the blood is related to an individual's cognitive performance, with higher concentrations resulting in improved performance. Both speed and accuracy were improved, suggesting that the relationship is not describing a speed-accuracy trade off.
Therapeutic Advances in Psychopharmacology, March 2012
Exercise: Yoga And Stress.
Yoga may be effective for stress-related psychological and medical conditions such as depression, anxiety, high blood pressure and cardiac disease. The theory could be used to develop specific mind-body practices for the prevention and treatment of these conditions in conjunction with standard treatments.
Medical Hypotheses, March 2012
Chiropractic: Safety of Adjusting.
No one pays closer attention to injury statistics than Malpractice Insurance carriers. Scott Haldeman, M.D., D.C. reviewed malpractice claims records for a 10-year period between 1988 and 1997. In reviewing 134.5 million chiropractic adjustments, there were 23 cases of stroke or vertebral artery dissection. 10 of these had complicating factors such as high blood pressure, use of oral contraceptives, or a history of smoking, all associated with vascular disease. The incidence of stroke or vertebral artery dissection following neck adjustments was one per 5.85 million. On average, a chiropractor would have to work for 1430 years (48 full chiropractic careers) for this to happen once! Driving to the office is probably more dangerous. Canadian Medical Association Journal, 2001
Wellness/Prevention: Irregular Heartbeat?
An irregular heartbeat, atrial fibrillation, is a strong predictor of cognitive decline and the loss of independence in daily activities in older people at risk of cardiovascular disease. This is just another good reason to maintain your heart health and get checked to prevent heart problems.
Canadian Medical Association Journal, March 2012
"The more serious the illness, the more important it is for you to fight back, mobilizing all your resources - spiritual, emotional, intellectual, and physical." ~ Norman Cousins
Page 4 of 5
Feb 2012 Newsletter
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text:
Why we like the Azimuth Meridian International Health Insurance Plan for non-profit workers and workers with charitable groups, esp. those looking to start, or grow, their family:
- May have the best international maternity coverage for young couples and families working overseas, of any international career health insurance plan:
- On Meridian Essential – No waiting period if you select the maternity rider. Your maternity/pregnancy health benefits start right away. The maternity benefit = $10,000 per birth and a $50,000 for the lifetime of the policy.
- On Meridian Enhanced – After 12 months maternity coverage starts full benefits. Maternity is packaged in with your medical insurance automatically. Coverage for maternity has a maternity deductible of $5,000 for each birth. There is a $100,000 maternity benefit for life of policy.
- More maternity details here
- Thanks to their "First Two Free" feature, you enjoy the benefit of having your first two children under age 10 covered at no extra charge if both parents are insured on the plan
- We like that at the moment they have some of the most flexible underwriting guidelines for those living/working/volunteering overseas for more than a year
- They get back to you quickly – Usually within 2-3 business days. And you have full 7 days no-risk to cancel for full-return
- Can choose to "Exclude USA and Canada"– Choose treatment anywhere else in the world to get a lower premium
- We like that they are backed by Lloyd's of London
- For these reasons, we always recommend Azimuth insurance for young families and new families moving overseas and/or seeking affordable insurance
- Medical coverage – $5,000,000 Maximum Limit
- Deductibles choices – $250; $500; $1,000; $2,500; $5,000; and $10,000 per member per coverage period. Family deductible – maximum of 2 deductibles per family per coverage period
- Coverage area – Two options: 1. Worldwide including US/Canada; or 2. Worldwide excluding US/Canada
- Coinsurance – 100% for eligible medical expenses outside the U.S. and Canada and within the PPO in US and Canada after the deductible has been met. If outside PPO 90% of the next $5000 of eligible expenses, then 100%.
- Organ Transplants – Up to $2,000,000 for Covered Transplants
- Pre-existing cover – If disclosed on the application and not limited or excluded by rider, covered after 12 months same as any other illness
- Maternity cover – Automatically included with coverage up to $100,000 maternity coverage. There is a 12 month waiting period before full maternity benefits start. There is a separate maternity deductible of $5,000.
- Vision Benefit – $250 per Coverage Period for exams and materials (after 1 year).
- Emergency evacuation – $110,000 maximum limit for under 65 years young. $55,000 maximum limit for ages 65 onwards
- Wellness-Adult (over 25): $350/year after 90 days waiting.
- Wellness-Child: $200 after 60 days
- Optional Dental and Extreme Sports Riders
- Many more benefits (see brochure)
- Medical coverage – $5,000,000 Maximum Limit
- Deductibles choices – $500; $1,000; $2,500; $5,000; and $10.000 per member per coverage period, Family deductible – maximum of 2 deductibles per family per coverage period.
- Coverage area – Area 1 worldwide coverage to include the U.S. and Canada | Area 2 worldwide excluding the U.S. and Canada
- Coinsurance – 100% for eligible medical expenses outside the U.S. and Canada and within the PPO in US and Canada after the deductible has been met. Outside of PPO: 80% of the next $5000 of eligible expenses, then 100%.
- Pre-existing condition cover – After 24 months of continuous coverage, $10,000 per year with a $50,000 lifetime maximum limit
- Selecting the maternity rider at the start of the policy exempts the maternity waiting period however you cannot already be pregnant at time of actual enrollment date. Maternity benefits start right away. Maternity coverage is $10,000 per delivery and a $50,000 life time limit.
- Optional Dental and Extreme Sports Riders
- Wellness-Adult (over 25): $250/year after 180 days waiting.
- Wellness-Child: $170 after 90 days
- Medical Evacuation – NOTE that this plan is limited to $50,000 ($25,000 for ages 65 and older) maximum medical evacuation
- Many more benefits (see brochure)
More to like about the Azimuth Meridian International Health Plan:
- You are allowed up to 30 days of coverage in the U.S. at the start of the insurance period
- They will cover up to 6 months in the U.S. each policy year
For Unlimited maternity coverage, you may want to consider Global Navigator


text:
Hostal Lima
This neighborhood is a great choice for travelers interested in ancient landmarks, architecture and monuments – Check location Laurel De Las Tablas, 17, Granada City Center, 18002 Granada, Spain – This neighborhood is a great choice for travelers interested in ancient landmarks, architecture and monuments – Check location
Excellent location – rated 9.5/10! (score from 1299 reviews)
Rated by guests after their stay at Hostal Lima.
|Room Type
Deluxe Single Room
Double or Twin Room
Single Room
Superior Deluxe Double Room
Superior Double Room
Area Info – This neighborhood is a great choice for travelers interested in ancient landmarks, architecture and monuments – Check location Guests loved walking around the neighborhood!
Closest Landmarks
- Facultad de Derecho 0.1 miles
- Alcaiceria 0.2 miles
- Granada Cathedral 0.2 miles
- Bib-Rambla Square 0.2 miles
- Royal Chapel of Granada 0.2 miles
- Royal Chapel 0.2 miles
- Elvira Street 0.3 miles
- Plaza Nueva 0.4 miles
- Calle Navas 0.4 miles
- Albaicin 0.4 miles
Most Popular Landmarks
- Hammam Arab Baths 0.5 miles
- Carrera del Darro Street 0.5 miles
- Granada Train Station 0.6 miles
- San Nicolas Viewpoint 0.6 miles
- Sacromonte 0.6 miles
- Paseo de los Tristes Boulevard 0.7 miles
- Plaza de Toros 0.7 miles
- Alhambra and Generalife 0.8 miles
- Granada Science Park 1.1 miles
- Museum Federico Garcia Lorca 10.5 miles
Restaurants & Markets
- TODOS, CENTRO CIUDAD Restaurant 0 miles
- LIMA, GUERRERO,GOYA,,,,,, Cafe/Bar 0 miles
- MERCADO GRANADA Market 0 miles
- DIA, DANI, LOS ALMENDROS Supermarket 0 miles
Closest Airports
- Federico García Lorca Airport 9.6 miles
- Malaga Airport 59.9 miles
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4 Reasons to Choose Hostal Lima
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Prices you can't beat!
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The staff speaks English
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Facilities of Hostal Lima Great facilities! Review score, 8.5
Most Popular Facilities
- Ski Storage
- Horseback Riding (additional charge)
- Diving (additional charge)
- Hiking (additional charge)
- Bicycle Rental (additional charge)
- Skiing
Food & Drink
- On-site Coffee Shop
- Parking Garage
- Secured Parking
- Daily Housekeeping
- Baggage Storage
- Tour Desk
- Honeymoon Suite
- Room Service
- Air Conditioning
- All Spaces Non-Smoking (public and private)
- Heating
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- Non-smoking Rooms
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- French
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Cancellation and prepayment policies vary according to room type. Please enter the dates of your stay and check what conditions apply to your preferred room.
Children and Extra Beds
Children cannot be accommodated at the hotel.
There is no capacity for extra beds in the room.
Pets are not allowed.
Hostal Lima accepts these cards and reserves the right to temporarily hold an amount prior to arrival.
Please note reception is open from 08:00 to 00:00.
Please note that guests must present the credit card used to make the reservation on arrival. If you are not the owner of the credit card used to make the reservation, please contact the property in advance.
Guests are required to show a photo ID and credit card upon check-in. Please note that all Special Requests are subject to availability and additional charges may apply.


text: This week I'm sharing a tiny, scruffy, and semi-competently spread Nepticulidae in the genus Stigmella from the same light trap of Prescott Arizona as the past few Monday Moths. I usually wouldn't share a photo of a moth that isn't in the best condition, but I'm using this as an example of technique. Not only was this 4mm moth pulled out of the bottom of a light trap, but it was field pinned and dried for over a year and a half. I've always heard that it can nearly be impossible to deal with the smallest of the small; and for the most part I haven't. I used to think you need to capture them off of a light sheet alive in a vial and euthanize moments before spreading, all while never, ever let them dry the tiniest bit beforehand. But as it turns out, you can get away with a decent specimen by relaxing 24 hours and spreading upside down. Of course if you have a perfectly fresh specimen that avoided the blender of a bucket-trap it would make for a far superior specimen. Better yet, you pulled the leaf mine and reared the moth yourself. Most of these Nepticulidae are host-specific and far more diverse than we have given them credit. I've heard there could be at least 100 new species awaiting discovery in the US alone.


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This item has been discontinued and we do not expect it to be offered again.
Our Boy's basket is sure to please! Each gift box is overflowing with treats any boy would love! We top it with the balloon design of your choice - from Planes to Spiderman! Inside they'll find two Theater Size Candy Boxes, four Regular Size Candy Bars, one Share Size Candies, three Lollipops, four Fun Size Candies, two Mini Candies and 1 Pack of Gum.
Item Number: CF-kid026
Note - This item includes a personalization, color, size or design option: Select Balloon Design (View Choices)
(Free of charge).
You may specify this information during our checkout process.


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NY offering free air conditioners for vulnerable to heat
NEW YORK (FOX 5 NY) - Residents in New York who are vulnerable to the heat during the warm weather months may be eligible for a free air conditioner and installation.
"The heat and humidity during the height of the summer can be uncomfortable for some, but potentially life-threatening to others with medical conditions exacerbated by high temperatures," Governor Cuomo said. "This program will ensure that some of the most vulnerable New Yorkers can remain safe and cool in their homes when the summer weather is at its worst."
Residents must meet income requirements in order to qualify. Click HERE for guidelines.
Some of the most vulnerable to the extreme heat include the elderly and people with breathing ailments such as asthma.
In New York City, 693 households received assistance to beat the heat last year.
Eligible households can apply for cooling assistance through the New York State Office of Temporary and Disability Assistance's Home Energy Assistance Program beginning May 2.
To apply, visit: http://otda.ny.gov/programs/heap/HEAP-contacts.pdf.
Last summer, more than 4,100 households received cooling assistance.


text:
Course Offering
- IT-Training by Fast Lane»
- Digital Transformation
- Training by Technology
- Big Data & Analytics
- Cloud Computing
- Collaboration
- Data Center
- Enterprise Mobility
- FlexPod
- Internet of Things (IoT)
- IPv6
- Security
- VersaStack
- Virtualization
- Wireshark / Packet Analysis
- Training by Vendor
- Amazon Web Services»
- Apple»
- Azeti Networks
- Barracuda
- Blue Coat
- Brocade»
- Check Point
- Cisco»
- Cisco Learning Services»
- Cisco Sales & Business
- Citrix
- Cloud Security Alliance
- Cloudera
- CompTIA
- Cybersecurity First Responder
- Davra Networks
- Fortinet
- Gigamon
- Juniper»
- Kaspersky Lab
- Microsoft»
- NCTA Cloud
- NetApp»
- NotSoSecure
- Oracle»
- Palo Alto Networks
- Pivotal / Spring»
- PTC ThingWorx
- Red Hat Linux / JBoss»
- Relayr
- Salesforce»
- Symantec»
- Veeam
- Veritas
- VMware»
Dimensions Administration (Paper) Paper Only SPVC
Who should attend
This course is recommended for anyone responsible for creating the ´look and feel´ of IBM SPSS Data Collection paper surveys.
You should have:
- Familiarity with Microsoft Word.
- Understanding of survey creation with IBM SPSS Data Collection.
Product Description
This is the self paced training version of ´Dimensions Administration (Paper) Paper Only´ classroom course. The Dimensions Administration (Paper) Paper Only self paced training consists of 2 parts: Questionnaire Creation and Questionnaire formatting. The SPSS Paper Solution begins with designing the questionnaire. This course gives designers a thorough understanding of Quanquest GUI features applicable to constructing scripts for paper questionnaires. Next, we export the document to Paper Paper has been designed for ease of use. Yet, it is incredibly powerful and flexible. Through the use of Looks or ´themes´, anyone, even with minimal computing skills, can create stylish paper questionnaires.
If you are enrolling in a Self Paced Virtual Classroom or Web Based Training course, before you enroll, please review the Self-Paced Virtual Classes and Web-Based Training Classes on our Terms and Conditions page, as well as the system requirements, to ensure that your system meets the minimum requirements for this course.


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This is a delicous summer salad, great for a light lunch, or as a starter for a dinner party.
- Yield
- Makes 2 main course serves, or 4 starter size
- 8 slices smoked salmon - cut into thin ribbons
- 1 head of fennel - trimmed and finely sliced
- 2 cups washed rocket leaves
- 2 cups washed cos lettuce leaves torn into bite sized pieces
- 1 red onion finely sliced
- 1 teaspoon preserved lemon finey diced
- 2 teaspoons baby capers (rinsed)
- 1 Yellow bell pepper, seeds removed - cut into fine strips about 2" long
- 1 telegraph cucumber, cut into fine strips about 2" long
- Dressing
- Half cup good quality olive oil
- 2 teaspoons tarragon vinegar
- 2 teaspoons chopped chives
- salt and freshly ground black pepper to taste.
- Combine fennel, rocket and cos lettuce in a large serving bowl. Toss in yellow peppers, cucumber, red onion and combine. Scatter baby capers and preserved lemon over the salad and arrange smoked salmon ribbons on top. Mix dressing ingredients together and drizzle over salad.


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à bientôt!
Why hello again! We have sadly, been very quiet in cyberspace, and we've decided to officially take a short hiatus until Honey finishes her doctoral thesis. We have still been busy enjoying food in all its glory where we can, and have had delicious experiences in Singapore, Bali, Malaysia, Canberra and Sydney over the last few months, and hopefully we will be able to share these with you very soon when we come back to regular blogging.
In the meantime, we wanted to share some good news with all of you: we finally bit the bullet and are one step closer to living sustainably- we got chooks!
Chickpea and Mrs Brown are 20 weeks old and seem to be settling into their new home in our backyard. There have been a few escape attempts and hilarious episodes of us chasing them around the garden, but we have now safely clipped their feathers so they should happily remain within their fence, away from our veggie garden! As we learnt from Celia, the chooks are in a moveable pen so they will move all around our backyard, helping us to till the soil and keep our grass in control. It has been fascinating watching them so far, scratching around and digging holes for dust baths.
The girls happily pecking away from the feeder that Soy so proudly made from scratch!
After 2 weeks of waiting, we got our first egg 2 days ago! We hope all of you are doing brilliantly, and until next time, we wish you many new and exciting food adventures!


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Southwest Ice Arena is a family owned and operated business since 1975. Since then we have serviced many hockey clubs, ice skating classes, public skating sessions and private parties. Our professional staff will assist you in any aspect of ice skating you require. We hire only certified instructors to teach our learn to skate classes.
About Us & Staff Southwest Ice Arena


text: This Bosch wiper is made for many Asian and European vehicles requiring a 21" curved wiper blade. High Quality Rubber A high quality rubber spine enables effective flip over functions. A precision cut cleaning edge ensures smear free wiping. Ultimate Visibility Bosch Specific Fit provides exceptional performance and a significant reduction in juddering and screeching. Minimal Noise Precision cut rubber makes the wiping action smoother and reduces noise levels significantly. Extended Blade Life Bosch blades performs better than other blades after 300 hours use. Often inferior and cheaper blades will not reach 300 hours of service For Hooked/Retro Wiper Arms only Part Number SP21JS


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This blog entry was posted on Sept. 13, 2005.
It was two weeks ago tonight that the death and destruction of Hurricane Katrina really sank in. It was already clear that hundreds, maybe thousands, had perished, washed away in storm surges or rising floodwaters from a ruptured levee. This is how we began the story that we wrote for the Philadelphia Daily News 14 days ago:
FRANK MILLS had just watched two bodies float by, and he was sure he was next.
Mills, 56, lived in a boarding house with three elderly residents in the 9th Ward of New Orleans, a low-income section that has borne some of the brunt of the flooding that followed in the wake of Hurricane Katrina.
That's where Mills was early yesterday, when the floodwaters from the city's breached levees began swirling into the house, rising toward its ceiling. Hours later, he told a reporter that he had headed for the front door, but one of the other men went to a bedroom to retrieve something, and a woman went with him.
"And when I saw her in the hallway, she was floating face up," Mills told the Associated Press yesterday, adding that he never saw the other man again. Mills changed direction and made it to the roof of the one-story home's porch.
There, he tried desperately - and unsuccessfully - to pull another elderly man to safety. But that man slipped away.
Frank Mills didn't know their names. Neither did we. Two weeks later, we still don't.
And that is a national disgrace.
For days we have seen the pictures -- bodies floating down waterlogged streets, face down, bloated, completely stripped of the humanity that once coursed through them, and completely stripped of dignity as well.
Most of the corpses are alone, like this one that a New Jersey-based rescue team found in a bedroom in three feet of water. But some are in groups, like the five corpses that a Marine amphibious team saw floating in a row on a street in the lower 9th Ward of New Orleans.
We've seen stories about the larger clusters, like the nursing home where 34 elderly people were left to die. We've read lots of articles about the cavernous morgue in St. Gabriel, La., where bodies are said to arrive by the truckload. We heard today that the state of Louisiana had to hire a mortuary company because FEMA couldn't get it together to award a contract to process all the corpses.
We even saw a number today: 423 just in New Orleans (with more than 200 fatalities in Mississippi a seeming afterthought).
But we haven't seen a name -- not officially anyway. Not one single name -- the thing that turns an empty corpse back into a person. So far we've seen one story (in the Washington Post) that took a massive amount of reporting to come up with the life stories of five of the dead -- five lonely faces out of the hundreds.
So much death.
And not a single funeral.
It's been 14 days now. Where are the funerals?
New Orleans is famous for its funerals, you know. Jazz funerals -- an untidy gumbo of grief and joy, pouring out through the streets of a timeworn city, punctuated by the music of the living. We've never been to one, but here's a description of the recent funeral for a prominent jazz musician. Anthony "Tuba Fats" Lacen:
A line of tubas, a man with a red tuba, all the celebrants filled with sorrow, but also exalting Tuba Fats with signs and pictures, in fine suits and fancy dresses, hot colors and cool hairdos. They were alternately somber or cheered as the mood of the music changed: slow dirge, medium hymn, fast march. Probably 2,500 made their way with the horse drawn casket to the French Quarter, down Bourbon Street a rare honor due to Tuba's daily play on Jackson Square where tourists gawked and clamored. A somber stop at St. Louis Cathedral, where a priest blessed the bier while those who knew Tuba Fats cried out his goodness. Starting up and out of the Quarter the several blocks long throng sang "Down By the Riverside" with the line "Ain't gonna study war no more" resonating about life here and abroad.
Now, New Orleans has been overrun by death, and yet there are no funerals. And if our government has its way, they could be weeks away. They are taking their time in collecting and tallying the dead, and shipping the bodies to that remote place, far from home. When journalists get too close to the reality of death, they are driven back:
The 82nd Airborne soldier told reporters the Army had a policy that requires media to be 300 meters -- more than three football fields in length -- away from the scene of body recoveries in New Orleans. If reporters wrote stories or took pictures of body recoveries, they would be reported and face consequences, he said, including a loss of access for up-close coverage of certain military operations.
The names will come in good time -- most of them, anyway -- but they want us to look the other way for now, hoping we will forget. Because when the names, and the tales of love and loss that accompany them, finally come known, that will bethe day when America truly realizes the horror of the humanity that was lost along the Gulf Coast -- including the people who could have been saved by a speedy government response.
And so we will not forget.
But it is up to us. We can't trust the government. We, the American people, will have to keep our own book of the dead. Hopefully, there will be Web sites along the lines of this one, dedicated to Iraq casualties. An accurate count is the only way to keep them honest.
And we must not just tally their number, but we must tell their stories, once we learn who they are. We promise to do what we can here at Attytood. Hopefully, others in the broad community of writers and bloggers out there will do the rest.
We can argue until Kingdom Come about policy, and who's to blame -- and we should. But until we give the dead their proper burial, and until we hear their jazz, New Orleans -- and America -- will not be whole again.


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Colonial Pipeline announced completion on July 31 of the final phase of a 75,000 bpd increase to the capacity of its primary distillate pipeline, which originates in Houston and serves the Southern and Eastern U.S.
The previously announced project was accomplished through the enhancement of pumps, motors and existing operations at 17 Colonial locations but did not require laying additional pipe, Colonial CEO Tim Felt said in announcing the 15-month project's completion.
The distillate line, which generally runs parallel to Colonial's main gasoline pipeline from Houston to Greensboro, NC, carries diesel fuel (including Ultra Low Sulfur Diesel or ULSD), jet fuel for commercial aviation, military fuels and home heating oil as well as other refined petroleum products.
The line supplies Colonial's large tank farm in Greensboro from where additional Colonial pipelines transport the products for further delivery to markets in the Northeast. The Houston-to-Greensboro line's overall capacity is now approximately 1.15 million barrels – or about 50 million gallons – a day.
"We are extremely pleased to complete this project at a time when our customers increasingly are relying on Colonial to serve their markets," Felt said. "In addition, I am very proud of the careful planning and review that went into ensuring this improved service was done safely, as all of our operations must be."
An initial phase of the project added 20,000 bpd to Colonial's capacity, while the final phase achieved an additional 55,000 barrels of daily capacity for Colonial's main distillate line.
As the additional capacity is phased into the Colonial system, customers should see increases in their allocation levels that reflect the increased available capacity.
Felt said customers' input into Colonial's expansion plans continues to help guide the company's growth. A 100,000 bpd increase in capacity for the Northeast was completed in late 2011.
Colonial is also currently constructing two additional mainline capacity expansions: 100,000 bpd capacity increase on Colonial's main gasoline line from Houston to Greensboro, and an additional capacity expansion of 60,000 bpd for the line serving the Northeast. Each of these expansions is under way and scheduled to be operational by mid-2013.


text:
Pentagon, VA Call Off Interagency Health Database
Secretary of Defense Leon Panetta and Secretary of Veterans Affairs Eric Shinseki announced in December that they were looking at ways to speed up the project, expected to cost around $4 billion by its 2017 completion date. But the new...
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text:
Discover some of Spain's less touristic sites and unwind away from other tourists flocking Spain.
Spain has numerous tourist attractions and amazing sights to visit all over the country, yet it also has many hidden jewels that are not frequented by the masses. In short, Spain is a land of contrasts and beauty. Here are Spain's top off-the-beaten-path summer destinations.
1. Ronda, Málaga
The spectacular views from the top of the cliffs and mountains of Ronda make this town in Málaga one of the most magical in Spain. Ronda is one of the oldest cities on the peninsula, and is found 750m above sea level on the edge of a precipice that ends at the mouth of the River Guadalevín.
2. La Albufera, Valencia
The Albufera is a natural park south of the city of Valencia. It's a huge freshwater lagoon and contains the largest lake in Spain, which is home to thousands of different species of wildlife that you won't find anywhere else. A natural haven of peace and tranquillity, you can tour the lake and park by bus or boat.
3. Sa Calobra, Mallorca
Sa Calobra, which means 'the snake' in Mallorquin, is one of the most beautiful beaches in the country. While it's not easily accessible – you have to drive down through the mountains along a very windy road to reach it – it's definitely worth the effort.
4. The Roman Bridge of Córdoba
The Roman bridge that sits above the Guadalquivir River was built more than 2,000 years ago. It has 16 arches and measures in excess of 300m in length, making it one of the most important crossing points in Spain.
5. Playa de las Catedrales, Lugo
This beach has been declared a 'Natural Monument' and is famous in Spain due to its extraordinary beauty. It is located on the Galician coastline, on the border with Asturias. The spectacular giant rock formations that have been shaped over thousands of years by the winds and water make this place totally unique.
6. El Monasterio de Piedra, Zaragoza
This impressive monastery was built in the 12th century by 13 Cistercian monks. It is surrounded by the Piedra River, which shaped the land around it over several centuries. Waterfalls, lakes and natural caves are just few of the breathtaking sights you can see in the area.
7. The Amphitheatre of Mérida
For those who like to visit historical sites, this famous Roman amphitheatre, where gladiators fought and lost their lives centuries ago, in Mérida is a must.
8. Bárdenas Reales, Navarra
As one of the settings for the latest series of Game of Thrones, the natural desert-like park of 42,000 hectares in Navarra has suddenly been thrown into the spotlight. This is another place that has been shaped by the natural elements creating something rather spectacular.
On the Pulse of Spain / Source: www.diarioinformacion.com / Expatica
Photo Credits: Bert (Ronda), Marc Ryckaert (Sa Calobra), Jaume Meneses (Playa de las Catedrales), Håkan Svensson (The Amphitheatre of Mérida).


text:
first edition Hardcover
1982 · Surrey
by Hislop, Richard, ed
Surrey: Art Sales Index Ltd, 1982. First printing. Hardcover. Very Good. Two volumes, complete. First edition, 1982. Quartos, red cloth hardcovers, 1402 pp., clean unmarked text, Very Good copies, both volumes with label ghost on titlepage, a bit of age-toning to some pages and to the page-edges, light discoloration to the covers, rubbing and some wear to the edges of the covers of the books, no dust jackets. (Inventory #: s00020308)


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'The cull could be promising for our new venison line'
My week: Denis Carroll, farmer, Killarney, Co Kerry Ring of Kerry Quality Lamb
Things are getting busy down on Denis Carroll's mixed farm just outside Killarney with some 50 Scotch ewes being sent to the ram next week while a further batch from the 150-strong flock are due to lamb themselves in the run-up to Christmas.
And then there is the daily round of milking a 58-strong herd of Holsteins to say of nothing of his commitments to the Ring of Kerry Quality Lamb group who are producing prime product for restaurants and hotels in Kerry and Dublin and also exporting to London.
Denis took over the home farm from his parents, Daniel and Francis - who bought the property as returning emigrants from the United States in the sixties - on what he calls "the most auspicious day of January 1, 1984 when the EU milk quota regime was first introduced".
"What a day to start wearing wellingtons on a full-time basis," he remembers.
So is he impressed by the milk price being paid by the Kerry group now that we are in the post-quota era?
"Absolutely not. They are paying 24c/l and 34c/l on the fixed price on 20pc of the milk. It should be up in the mid-thirties," he says with an accusatory firmness.
Denis, who is married to Kay, a medical secretary, and has two daughters - Denise, a teacher, and Michelle, who is studying to be a dietician - is helped on the 130-acre enterprise by his son, Shane, a 22-year-old student completing his Green Cert studies part-time at Pallaskenry in Limerick.
"I do the milking and Shane does the grassland management," he says of the division of the farmyard workload.


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The White House on Tuesday denied the US media report that the Obama administration has decided to suspend aid to Egypt.
"The reports that we are halting all military assistance to Egypt are false," said the White House National Security Council spokesperson Caitlin Hayden in a statement on Tuesday evening.
"We will announce the future of our assistance relationship with Egypt in the coming days, but as the president made clear at UNGA (the UN General Assembly), that assistance relationship will continue," said Hayden.
CNN reported earlier on Tuesday that the Obama administration has planned to cut off military aid to Egypt, which costs about 1.3 billion billions annually.
The network cited a US official who requested anonymity as saying "an accumulation of events" in Egypt, including recent violence against protesters with dozens killed over the weekend, has prompted the decision of the full suspension of foreign aid to the country.
The official told CNN the suspension will formally take effect in the coming days.
CNN also reported that the United States has not yet notified the Egyptians of the decision and the announcement has already been pushed back a few times.
简明释义:周二,白宫否认美国媒体"奥巴马政府已决定暂停对埃及的援助"的报道。白宫国家安全委员会发言人凯特琳海在周二晚间一份声明中说: "我们停止所有军事援助埃及的报告是假的, " 。


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EDRA43 Seattle / Symposium
Hard Space, Soft Space, and Architectures of Appropriation
My spring-term field trip to Europe culminated in Seattle, at the 43rd Annual Meeting of EDRA researchers. It was wonderful to connect back with friends, colleagues, and precious mentors at EDRA, and equally brilliant to interview one of the members for my dissertation research at the venue. Whilst details of my field work will be forthcoming, here is a snippet of the symposium I led and participated in at EDRA.
The theme of EDRA43 conference was "emergent placemaking." My session entitled, "Hard Space, Soft Space, and Architectures of Appropriation" discussed the notion of "emergence" in terms of the social makings of an environment through design. It focused attention on architectural and urban design frameworks that allow distinct social groups to take ownership of space and negotiate harder aspects of space. The panel saw hard space as material space: space as defined by physical elements such as walls and boundaries; it discussed soft space in terms of the everyday social coding of space: space made and remade by human activity through everyday social interactions with material space; finally, it imagined appropriation as a dialogic relationship between harder and softer aspects of space: the practice of space, both real and imagined.
Overall, the symposium looked at each of these three components as key interrelated elements of emergent placemaking. Specifically, it sought to position space as an agent in the discourse on emergence, and ask: How is space defined through use patterns of its inhabitants? What kinds of design strategies afford possibilities for spatial appropriation? In what ways does space provide agency to its inhabitants, if any? The aim of this session was to bring theoretical and descriptive work on design and localized use together in a conversation. Continuing the conversation from last year, one of my goals at this meeting was to clarify the social meanings of environmental design with diverse perspectives from design researchers and academics and to seek connections between and among spatial concerns, both old, new, and ongoing.
– K. Franck, Professor, College of Architecture and Design, New Jersey Institute of
– K. Patel, PhD Candidate, Architecture, University of Michigan
– P. Aeschbacher, Assistant Professor, Architecture and Landscape Architecture, Penn State University (in spirit!)


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The missing link
To live unbroken we need all the links in the chain to connect.
As avid fitness enthusiasts we devote a lot of time to 'recovery'. Spending our evenings meal prepping or RomWODing etc etc. One of the major areas of recovery and wellness, that is overlooked more often than not, is mental recovery. Now why the hell is that important?
Correct me if I am wrong, but a large percentage of you get up at stupid o'clock in the morning to battle with the London transport system on the way to a stressful day's work that you might not even enjoy. Upon finishing your days work you get straight to the gym and get your fitness on (and righty so).
All this stress builds and builds. It ends up making us tired and run down. Make our brains slow and sluggish and, due to the brains (central nervous system) effect upon physical performance, makes our body's sluggish too.
So what can you do to to let your brain recover?
If you are a goal driven, constantly busy person you could probably do with slowing down and taking some 'me' time. Immerse yourself in a good book, take a quiet walk, have a spa treatment, anything that shuts your brain off from the million and one things going on.
If the need to be mentally stimulated is what is making your brain tired. I.e. Boring job that doesn't fulfil your creative brain, then get out and explore new places and things with the people that make you happy. Go on a hike or take up a new sport. Find an interest outside of work and the gym that requires you to be creative and challenges you.
Remember that your brain and body are one. If one isn't functioning optimally the other can't be either. To become the best version of yourself, you must look after both.


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MPI may climb to 5th floor soon?
The Kijun Sen line provided a support to hold the price from falling down and currently MPI is sitting above the 23.6% Fibonacci Retracement level which was our immediate support last week. This time it is now our newly found support. The question is, will it hold? Although last time it close above this line it wasn't able to sustain, this time might be different because last time it was the Kijun Sen resisting the price from moving up while this time Kijun Sen act as our support.
The flat Kumo or Cloud may attract the price, if that happens then MPI may go to the 5th floor. Immediate resistance is at 4.93 Too much room for the buyers as the stock is not yet overbought based on RSI or Relative Strength Index
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text: I'm on a real PINK kick lately - and was just wondering...would a Framboise Lexington fit the bill as an out-to-dinner or light trips/quick-errands bag used for carrying a: - Ludlow - 4-key holder - Phone (which is relatively compact) - Brush/comb - Pack of gum and maybe an iPod nano? Thoughts/opinions/advice/comments/images would all be greatly appreciated from those who have it, like it, love it or hate it! TIA