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Polyethylene glycol (PEG) was genetically incorporated into a polypeptide. Stop-anticodon-containing tRNAs were acylated with PEG-containing amino acids and were then translated into polypeptides corresponding to DNA sequences containing the stop codons. The molecular weights of the PEG used were 170, 500, 700, 1000, and 2000 Da, and the translation was confirmed by mass spectrometry. The PEG incorporation ratio decreased as the molecular weight of PEG increased, and PEG with a molecular weight of 1000 Da was only slightly incorporated. Although improvement is required to increase the efficiency of the process, this study demonstrates the possibility of genetic PEGylation.
Citation: Tada S, Andou T, Suzuki T, Dohmae N, Kobatake E, Ito Y (2012) Genetic PEGylation. PLoS ONE 7(11): e49235. doi:10.1371/journal.pone.0049235
Editor: Nediljko Budisa, Berlin Institute of Technology, Germany
Received: March 19, 2012; Accepted: October 8, 2012; Published: November 8, 2012
Copyright: © 2012 Tada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: These authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Synthetic polymer–protein hybrids have been developed for use as therapeutic proteins or bioreactor enzymes [1]–[10]. Polyethylene glycol (PEG), which is nontoxic, nonimmunogenic, highly soluble in water, and approved by the U.S. Food and Drug Administration (FDA), is very useful in the preparation of therapeutic proteins [11], [12]. Some proteins trigger immune reactions, and proteases and other compounds inside the body can rapidly degrade them and remove them from the body. Many PEGylated protein drugs have been developed since the pioneering work of Abuchowsky et al. on the PEGylation of proteins [13], [14]. Although protein PEGylation has proven very valuable, many of the first-generation PEGylation products suffered from a severe loss in bioactivity [5]. This reduction in activity was mainly attributed to the chain lengths of the attached polymers and the site on the protein to which they are coupled. To overcome this difficulty, a more specific modification was achieved by exploiting the difference in the pKa value of the amine in the lysine side chain or the replacement of lysine residues with other amino acids [15]–[18]. The thiol groups in cysteine residues, the phenol groups of tyrosines, the amide groups of glutamines, or the incorporated His tag have also been used for this specific modification [19]–[29]. The site-specific polymer attachment has also been achieved with the complete synthetic construction of an erythropoietic protein [30], [31], consisting of an α-amino acid polypeptide chain of 166 residues by using native chemical ligation. Recent development of ligation methods has significantly expanded the possibility of bioorthogonal chemistry [32]–[36].
A genetic-encoding approach was first reported in 1989 as an alternative method for the site-specific incorporation of nonnatural amino acids into peptides or proteins [37], [38], and various amino acids have been incorporated in this way [39]–[43]. The method utilizes the UAG codon (the amber nonsense stop codon), which normally directs the termination of protein synthesis, to encode instead a nonnatural amino acid that is loaded onto the complementary tRNA. Deiters et al. [44] made 20 different versions of human growth factor, each of which had a nonnatural amino acid, p-acetylphenylalanine, inserted at a different site using the misacylated tRNA method. They linked a single PEG molecule to each keto group as a posttranslational modification. Johnson et al. [45] enhanced the efficiency of the ribosomal incorporation of unnatural amino acids at multiple sites by RF1 knockout in a live cell. However, it is difficult to precisely insert more than two PEG chains of different lengths or two different unnatural amino acids into each desirable position in one protein molecule using this posttranslational modification method.
Sisido and co-workers developed a frameshift-suppression method, in which nonnatural amino acids are incorporated into proteins using four-base codon–anticodon pairs instead of the stop codon [46]. Using the four-base codon method, Shozen et al. [47] recently attempted to incorporate a short polyethylene glycol chain into a polypeptide, although its production was not directly confirmed by mass spectrometry, and the incorporation of a long PEG chain was not attempted. Therefore, in this study, we attempted to add tRNAs that recognize a stop codon, to which PEG of various molecular weights was attached, into a translation system, as shown in Figure 1. Here, the incorporation of PEG with a molecular weight of 1000 Da using the in vitro translation system was directly confirmed by mass spectrometry.
Materials and Methods
Ethylene glycol tetramer (PEG4, Mw 170 Da)- or ethylene glycol dodecamer (PEG12, Mw 500 Da)-conjugated aminophenylalanyl tRNAs containing a CUA anticodon were purchased from Protein Express (Chiba, Japan). The single-molecular-weight PEG compounds m-dPEG®16–N-hydroxysuccinimide (NHS) ester (PEG16–NHS, Mw 700 Da) and m-dPEG®24–NHS ester (PEG24–NHS, Mw 1000 Da) were purchased from Quanta Biodesign (Powell, OH, USA). Methoxypoly(ethylene glycol)–NHS ester of molecular weight 2000 Da, corresponding to PEG48–NHS, was purchased from NOF (Tokyo, Japan). PURESYSTEM classic II for in vitro translation and the PURExpress In Vitro Protein Synthesis Kit were purchased from BioComber (Tokyo, Japan) and New England Biolabs (Ipswich, MA, USA), respectively. Monoclonal anti-FLAG M2 antibody was purchased from Sigma-Aldrich (St Louis, MO, USA).
Preparation of PEGylated tRNA
The acylated tRNAs were prepared as previously reported [48]. Aqueous solutions of PEG16, 24, and 48 (25 µM, 40 µL) were mixed with aminophenylalanyl–pdCpA (5 µM, 40 µL) in aqueous pyridine-HCl (5 M, pH 5.0, 80 µL). The product is referred to as PEG–AF–pdCpA. After incubation at 37°C for 3 h, PEG–AF–pdCpA was purified by reversed-phase HPLC (Waters XTerra C18; 2.5 µm, 4.6 mm×20 mm) at a flow rate of 1.5 mL/min, with a linear gradient of 0%–100% acetonitrile in 0.1% trifluoroacetic acid (TFA) for 10 min. The PEG–AF–pdCpA products were confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI–TOF–MS; Voyager DE-PRO, Applied Biosystems, Foster City, CA, USA): PEG16–AF–pdCpA, calculated 1543.61 for (M–H)–, found 1544.09; PEG24–AF–pdCpA, calculated 1895.82 for (M–H)–, found 1896.41. PEG–AF–pdCpA was ligated to a yeast phenylalanine tRNA that contained a CUA anticodon and lacked the 3′-terminal dinucleotide. The ligation reaction mixture (20 µL) contained tRNA lacking the 3′ dinucleotide (0.5 nmol), PEG–AF–pdCpA in water (4.4 nmol, 2 µL), HEPES-Na (55 mM, pH 7.5), ATP (1 mM), MgCl2 (15 mM), DTT (3.3 mM), BSA (20 µg/mL), and T4 RNA ligase (30 U). After incubation at 4°C for 2 h, potassium acetate (pH 4.5) was added to a final concentration of 0.3 M. PEG4– and PEG12–AF–tRNA were purified with the RNeasy Mini Kit (Qiagen, Hilden, Germany). PEG16–, PEG24–, and PEG48–AF–tRNA were purified by reversed-phase HPLC (Applied Biosystems POROS R2/10; 10 µm, 4.6 mm×100 mm) at a flow rate of 1.0 mL/min, with a linear gradient of 0%–100% acetonitrile in 0.1% triethylammonium acetate for 20 min. The purified PEG–AF–tRNAs were lyophilized and stored at –80°C. For the experiments, the PEG–AF–tRNAs were dissolved in potassium acetate (1 mM, pH 4.5) and stored at –80°C.
DNA Templates
The DNA templates for the cell-free translation of mRNAs that encode the peptide or proteins shown in Figure 2 were constructed by ligating complementary oligonucleotides with the appropriate single-stranded overhangs into pCR2.1 (Invitrogen), previously cut with NotI and HindIII. The plasmid DNA was prepared from ampicillin-resistant transformants and used as the template in PCR reactions with primers corresponding to the T7 RNA polymerase promoter and terminator sequences. The PCR products were purified using the QIAquick PCR Purification Kit (Qiagen) and used as the templates for cell-free translation reactions.
Cell-free Translation
Cell-free translation was performed using PURESYSTEM classic II (BioComber) or the PURExpress In Vitro Protein Synthesis Kit (New England Biolabs) according to each manufacturer's protocol. For the incorporation of PEG4, PEG12, PEG16, PEG24, or PEG48, the translation reaction was performed in the presence of 8, 8, 20, 40, or 60 µM, respectively, of each PEG–AF–tRNA. The reaction mixture was incubated at 37°C for 2.5 h, unless otherwise stated.
Mass Spectra Measurements
The samples were prepared for mass spectrometry as previously reported [39]. The translated peptides were purified from 50 µL reactions using prewashed FLAG M2 agarose (Sigma). After two washes with buffer (50 mM Tris-HCl, 300 mM NaCl, pH 8.0), the peptides were eluted from the matrix with 0.2% TFA. For the mass analysis, the peptides were desalted using ZipTip μ-C18 (Millipore) and mixed with 2,5-dihydroxybenzoic acid or 3-hydroxy-2-pyridinecarboxylic acid as the matrix. The samples were subjected to MALDI–TOF–MS analysis on an Ultraflex spectrometer (Bruker Daltonics) in linear or reflector mode.
Western Blotting
The reaction mixtures of the translated products (6 µL) were mixed with 3× loading buffer and boiled at 95°C for 3 min, before they were subjected to SDS–PAGE (16.5% acrylamide separation gel and 4% acrylamide stacking gel). The products were detected after western blotting by analysis with horseradish-peroxidase-conjugated anti-FLAG M2 monoclonal antibody (Sigma).
Results and Discussion
Preparation of PEGylated Phenylalanyl–tRNAs
To prepare the nonnatural amino acids carrying PEG chains, PEG was conjugated to aminophenylalanyl–pdCpA. The nonnatural amino acid p-aminophenylalanine has been found to be a good substrate for the in vitro translation system [48]–[51]. The PEG–aminophenylalanyl–pdCpA conjugate was connected to the truncated tRNA with ligase. The synthesis was confirmed by mass analysis, as shown in Figure 3.
The molecular weights of PEG16–tRNA, PEG24–tRNA, and PEG24–tRNA were calculated to be 24485.69, 24838.10, and 25983.45, respectively.
PEGylation Conditions
Thioredoxin (Trx) was synthesized by in vitro translation using PEG–AF–tRNA (Figure 4). The synthesis of Trx using PEG4 and PEG12 was confirmed by western blotting. The amount of PEGylated Trx produced increased with the addition of increasing amounts of PEG–AF–tRNA (Figure 4a). In the presence of 8 µM PEG–AF–tRNA, more PEGylated product was produced at 30°C for 4.5 h than that at 37°C for 2.5 h (Figure 4b). The yield of Trx protein that contained no amber codons was also increased in the translation reaction at 30°C for 4.5 h. Thus, the efficiency of the cell-free translation was greater at the lower temperature, so the yield of PEGylated protein increased. Bundy and Swartz reported similar results in that the protein yield of a cell-free translation reaction was higher at 30°C for a longer reaction period than at 37°C [52]. They attributed the difference in the protein yields to the rapid reduction of the translation rate at 37°C after 1 h from the beginning of the translation reaction, whereas the reduction in the translation rate at 30°C was relatively slow. The influence of temperature change on cell-free translation and the incorporation of unnatural amino acids requires further investigation.
a. Dependence of protein synthesis on PEG–AF–tRNA concentration. b. PEG-incorporated protein synthesis under different conditions.
PEGylation with Long Chains
Under the conditions described above, FLAG-labeled peptide was prepared by an in vitro translation reaction using PEG4, PEG12, PEG16, PEG24, and PEG48 (Figure 5). To enhance the efficiency of PEG chain incorporation, a peptide sequence containing the ProX tag was used (Figure 2). The sequence of the ProX tag is optimized for the effective incorporation of a nonnatural amino acid into a protein, with minimum irregular product [49]. The translation reactions were performed at 30°C for 7 h and the products were confirmed by mass analysis (Figure 5a). PEG4 or PEG12 was successfully incorporated in the presence of 8 µM PEG–AF–tRNA. However, PEG chains longer than PEG24 were not incorporated. Therefore, the amount of PEG–AF–tRNA in the translation system was increased. PEG16 or PEG24 was incorporated in the presence of 20 µM or 40 µM PEG–AF–tRNA, respectively. However, no incorporation of PEG with a molecular weight of >2000 Da was observed, even in the presence of 60 µM PEG–AF–tRNA.
a. Mass spectra of polypeptide incorporated with poly(ethylene glycol) chain. PEG4–FLAG, calculated 2681.177 for (M+H)+, found 2681.152; PEG12–FLAG, calculated 3033.386 for (M+H)+, found 3033.972; PEG16–FLAG, calculated 3209.492 for (M+H)+, found 3209.529; PEG24–FLAG, calculated 3563.890 for (M+H)+, found 3563.712; PEG48–FLAG, calculated 4709.244 for (M+H)+, not found. b. Molecular weight dependence of coefficient of incorporation of poly(ethylene glycol) into a polypeptide by in vitro translation.
The dependence of the translational incorporation of PEG on its molecular weight was roughly estimated by mass analysis. Each product peak was compared with a standard peak at a molecular weight of 4364 Da, attributed to ribosomal protein L36 in the cell-free translation system, and the corresponding value was plotted, as shown in Figure 5b. The higher the molecular weight, the less translation product was produced. We inferred that the longer PEG chains sterically hindered the processing of the polypeptide because the tunnel space in the ribosome is narrow. It is also possible that the PEG groups hinder the binding of EF-Tu to the acylated tRNA.
Site-specific PEGylation will be important for the preparation of defined protein drugs. In the future, some modifications to the ribosome should be investigated that enlarge the entrance and exit spaces or increase the binding of EF-Tu to allow the incorporation of longer PEG chains.
The authors thank Dr R. Abe at Protein Express Company for his technical support and useful discussions. The western blotting experiments were performed by Ms H. Shirai and Dr A. Wada.
Author Contributions
Conceived and designed the experiments: YI. Performed the experiments: ST TA TS. Analyzed the data: ST ND. Contributed reagents/materials/analysis tools: EK. Wrote the paper: YI.
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Presents a recipe-augmented family history that traces the origins of the author's love affair with food to her Midwestern youth and her parents' San Francisco pizza parlor, where signature dishes created sumptuous memories.
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- SDGE: We have 1.4 million customers without power. ->
- The scale of this CA outage is difficulty to comprehend/communicate. Really highlights fragility of aging US power grid. ->
- SDGE press conference underway. Saying both major lines into SoCal down, "an event" happened, & power could be out into tomorrow. ->
- Almost an hour into unprecedented SoCal power outage and @SDGE just said it still doesn't know cause. ->
- LAT on power story, but no new info: Massive power outage hits San Diego – http://t.co/3PbuREa ->
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By September 9, 2011 · ··
gee, you think it could have been the 2 x-class solar flares, and the 2 m-class solar flares over the previous 48 hours?
It was caused by a maintenance issue at a substation in AZ, total operator error. BTW power grids don't age. That thesis is a crock.


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Arts Lately at McLeod
posted by June 27 at 15:08 PMon
You know that haunted little room off the foyer at McLeod Residence where the 19th-century paintings used to hang? Through this week, Mandy Greer's show Parlor (above) is in there, with individual works for sale like this one, titled Little White Lion,
and this one,
titled White Milk Balls.
There's a closing party Thursday night (tomorrow), but the gallery doesn't turn over until after Saturday.
Then, opening July 6 is what promises to be an ambitious group show of interactive works (its title, Interactivity, seems criminally plain given the names of some of the works in the show: Biomimetic Butterflies, Running Plaid, Contexture).


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Published: Oct 30, 2007
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Authors: Inuburo (Story & Art)
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text:
|Publication number
|Publication type
|Publication date
|Feb 9, 1971
|Filing date
|Jul 22, 1968
|Priority date
|Jul 22, 1968
|Publication number
|Kovach Leslie J
|Original Assignee
|Kovach Leslie J
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (4), Referenced by (67), Classifications (7)
|External Links: USPTO, USPTO Assignment, Espacenet
" United States Patent FOREIGN PATENTS [72] Inventor LeslieJ.Kovach [54] DENTAL CLEANING AND MASSAGING DEVICE 9 Claims, 3 Drawing Figs.
DENTAL CLEANING AND MASSAGING DEVICE BACKGROUND OF THE INVENTION The present invention relates generally to improvements in dental cleaning and massaging devices and it relates particularly to an improved method and device for the cleaning of teeth by use of a liquid jet.
A common method for cleaning they teeth is by means of a fine, high-velocity water jet directed onto the dental area to be cleaned. The water jet is also employed for massaging the gums since the jet produces a pressure in the region of the gums subjected to the jet and the successive application and relief or variation of such pressure effects the massaging of the gums. Many forms of [water jet dental cleaning devices have been employed and proposed but these possess many drawbacks and disadvantages, particularly when used domestically as distinguished from professionally. A conventional apparatus includes a water tank, an electrically driven pump and a hand held nozzle connected to the pump outlet by a pressure hose. This apparatus is expensive, bulky, highly inconvenient and unreliable and requires the use of an electrical outlet with its attendant drawbacks. lt has been proposed to connect the jet nozzle by way of a pressure hose and coupling member to the domestic faucet nozzlebut such arrangement is likewise highly inconvenient, difficult to control and manipulate, of very limitedapplication and otherwise leaves much to be desired.
i SUMMARY OF THE INVENTION It is, therefore, a principal object of the present invention to provide an improved dental cleaning method and device.
Another object of the present invention is to provide an improved dental cleaning device of the water jet type.
Still another object of the present invention is to provide an improved water jet dental cleaning device which obviates the need for any external connections such as to an electrical outlet or to a pressurized water supply.
A further object of the present invention is to provide a compact, self-contained water jet dental cleaning device.
Still a further object of the present invention is to provide a dental cleaning device of the above nature characterized by its convenience, reliability, simplicity and ease of use.
The above and other objects of the present invention will become apparent from a reading of the following description taken in conjunction with the accompanying drawing which illustrates a preferred embodiment thereof. r
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a vertical longitudinal sectional view of a dental cleaning and massaging device embodying-the present invention illustrated with the gas cartridge being urged into engagement with the cartridge piercing needle;
FIG. 2 is a side elevational view thereof; and
FIG. 3 is an enlarged plan view of a valve spindle forming a part thereof.
In a sense, the present invention contemplates the provision of a dental cleaning device comprising a liquid reservoir, a nozzle member carried by said reservoir, and connected to the lower part thereof, a compressed gas cartridge, a manually operable valve normally biased to a closed position and including a first outlet with said reservoir and a first inlet, and means for connecting said valve inlet to said gas cartridge.
According to the preferred form of the improved dental cleaning device the reservoir is a` cylindrical tank provided at one end with a screw cap which axially supports the outwardly directed nozzle. An open ended housing is axially end to end to the opposite end of the tank and defines a handle. A threaded pressure regulator housing bushing extends through the abritting walls of the tank and housing and includes a piercing tube at one end in the housing and an outlet coupling tube in the tank. A separable threaded cartridge casing releasably engages the bushing and holds a CO, cartridge which is pressed against the piercing tube to efect the puncturing thereof. A spring biased normally closed slide valve extends across the upper part of the tank and includes an outwardly projecting push button actuator. The slide valve includes a first inlet port tube connected t0 the cartridge piercing tube and an associated first outlet port tube connected to the bottom of the tank, a second inlet port tube connected to the bottom of the tank and an associated second outlet port connected to an upwardly directed axial coupling tube which releasably engages a mating cap carried coupling tube communicating with the nozzle. A liquid pulsing device is located between the second outlet port and the nozzle.
The improved dental device is compact, easy to control and manipulate, requires no external water or power source and is highly reliable and versatile.
DESCRIPTION OF THE PREFERRED EMBODIMENT Referring now to the drawing which illustrates a preferred embodiment of the present invention, reference numeral l0 generally designates the improved device which comprises a water reservoir section l1, a noule and closure member l2, a valve assembly 13, and a pressurized gas cartridge section 14. Reservoir section ll and cartridge section 14 are assembled to form a handle which conveniently and easily may be held in the hand and its operation controlled in use.
i Reservoir section Il comprises an elongated cylindrical open topped tank or body 16 including an upwardly slightly diverging peripheral wall 17 provided with an externally' threaded upper peripheral border 18. Formed on the outer upper face of wall I7 are opposite coaxial bosses 19 and 20, boss 20 having a tapped axial bore and boss 19 having an axial well in its inner face. Tank 16 has a flat bottom wall 2l provided with a circular central opening.
Section 14 comprises an open-bottomed cylindrical housing 22 disposed below and arranged coaxially end to end with tank I6 and includes a centrally apertured top wall 23 coincid ing with wall 21. A cylindrical casing 24 houses a conventional pressure reducing regulator valve and includes a threaded upper section 26 registering with the openings in walls 2l and 23 and provided at its base with a peripheral flange 27 abutting the underface of wall 23. A nut 28 engages threaded section 26 and is tightened onto a washer 29 overlying wall 2l firmly and hermetically to interconnect sections l l and 14. Integrally formed with the casing upper section 26 is an upwardly directed outlet coupling tube 29a. The regulated outlet pressure of the regulator valve is preferably of the order of 25 to 50 pounds per square inch, the normal inlet pressure ranging up to about 900 pounds per square inch.
Casing 24 includes a threaded lower section 30 depending below flange 27 and having an axial well 32 formed in the underface thereof. integrally formed with casing 24 is a piercing tube 33 which is coaxially disposed in well 32 and is provided with a sharpened tip, tubes 29a and 33 communicating through the regulator valve in casing 24. A cup-shaped magazine or casing 34, internally threaded at its upper border, releasably engages section 30 and is provided at its lower part with radially projecting wings 36 to facilitate the tightening and removal of casing 34 from threaded section 30. A conventional pierceable compressed carbon dioxide cartridge 37 is separably housed in casing 34 and includes a neck portion the upper end of which is insertable into well 32 so that tightening of casing 34 by clockwise rotation thereof forces the cartridge against piercing tube 33 to eect the aperturing of cartridge 37 and communication between the pierced cartridge and coupling tube 29. t
A threaded plug 38 registers with tapped boss 20 and includes an outer enlarged head provided in its inner face with an annular groove, which holds a resilient ring 39 bearing on the outer face of boss 20 to form a seal therewith. An axial well 40 is formed in the inner face of plug 38 and communicates with the outer face thereof through coaxial bore 4l of reduced diameter. An annular groove is formed in the face of the well 40 and holds a resilient sealing ring 40a.
Valve assembly l3 comprises a tubular valve body member 42 one end of which nests in well 40 and sealed by the resilient ring therein and the other end 43 of which is enlarged an and tapped and closed by a threaded plug 44, end 43 and plug 44 nesting in a suitably dimensioned well in boss 19. integrally formed with and depending from valve body member 42 are first longitudinally spaced inlet and outlet tubes 46 and 47 respectively which communicate with the valve body member axial bore 48 through corresponding inlet and outlet ports. A second valve inlet tube 49 spaced from the first inlet tube 46 depends from body member 42 and communicates with bore 48 through a corresponding second inlet port. A second valve outlet coupling tube 50 is directed upwardly from valve body member 42 coaxial with tank 16 and communicates with bore 48 through a corresponding second outlet port. Coupling tube 50 is upwardly tapered and terminates at a point below the top of tank 16.
A valve shaft 51 is longitudinally slideably disposed in valve body bore 48 and has an axialcylindrcal pushbutton 52 integrally formed therewith and projecting through plug bore 4l. Valve sheet 51 includes enlarged inner and outer end sections 53 and 54 respectively, and an enlarged intermediate section 56, end section 54 being disposed shortly inwardly of pushbutton 52. Shaft sections 53 and enlarged section 56 are jcined by an integrally fonned coaxial rod 57 of reduced cross section and spool sections 54 and 56 are joined by an integrally fonned coaxial rod 58 of reduced cross section, rods 57 and 58 delineating passageways with the face of bore 48. A pair of spaced annular grooves 59 spaced inwardly of end section 53 are provided and hold resilient sealing rings 60, a pair of spaced annular grooves 6l formed in intermediate section 56 are provided and hold resilient sealing rings 63, and an annular groove 64 between end section 54 and button 52 is provided with a resilient sealing ring 65. Rings 60, 63 and 65 slideably engage the face of bore 48 in the valve body to form a seal therewith.
A helical compression spring 66 is entrapped between plug 44 and the inner end of spool 5l to bias the spool to its outer closed position, with spool section 54 abutting an inwardly directed flange 67 at the corresponding end of valve body 42. ln the spring-biased closed position of the valve, as seen in FIG. 2, valve section 53 registers with the second inlet port thereby closing communication between coupling pipes 49 and 50, and valve shaft section 56 registers with the first inlet port thereby closing the communication between coupling pipes 46 and 47. Movement inward of button 52 slides shaft l inwardly to open communication between coupling pipes 46 and 47 around shaft section 58, and between coupling pipes 49 and 50 around shaft section 57.
A flexible tube 68 engages coupling tube 49 and extends to the to bottom of tank 16, while a flexible tube 69 engages and interconnects coupling tubes 29a and 46, and a flexible tube 70 engages tube 47 and extends to the bottom of tank 16.
The upper end of the tank 16 is closed by a separable screw cap 7l including a top well 72 and a depending internally threaded skirt wall 73 which engages the tank threaded border 18. A nozzle 73, of known construction projects coaxially upwardly from the cap top wall 72 and terminates in an angularly direct discharge or jet portion 74. A liquid pulsing device 75 is positioned at the base of the nozzle 73 affording communication between the inlet and outlet thereof, the device 75 regularly intennittently varying or stopping the liquid flow through noule 73 and may be of any suitable mechanical self energized type of maybe of a fluidic type for example, a fluidic multivibrator or oscillator. Depending coaxially from and integrally fonned with wall 72 is a coupling tube 78 communicating with the nozzle and having a tapered socket 76 fonned therein mating coupling pipe 50. When cap 7l is in closed position, coupling tube 50 snugly engages socket 76.
Considering now the operation of the dental cleaning device described above and the practice of the improved method, casing 34 is unscrewed and removed and a pressurized CO2 cartridge 37 positioned therein. The casing is then engaged with and tightened on threaded section 30 to force piercing tube 33 into and through the cartridge closure and into communication with the pressurized gas therein. Cap 71 is removed, tank 16 filled with water and the tank closed, with cap 7l coupling nozzle 73 to outlet pipe 50. The device is then ready for use.
The device is held by grasping the handle defining sections ll and 14 and the nozzle 73 is directed toward the tooth and gum area to be treated. Button 52 is depressed to open communication between the corresponding valve outlets and inlets whereby to introduce gas at the regulator valve reduced pressure, into tank 16 from cartridge 37 through tubes 69 and 70 and valve 13. The pressurized gas in the tank 16 forces the water therein through tube 68, valve 13 and pulsing device 75 to nozzle 73 which directs a pulsating high pressure water jet onto the area to be cleansed and massaged, the jet being swept across and directed onto the desired area. lt should be noted that an appreciable fraction of the pressurized carbon dioxide dissolves in the water in tank 16 to form a carbonic acid ora supersaturated solution at atmosphere pressure of the carbon dioxide in water, which carbon dioxide carrying water is directed by the nozzle onto the treated area. The carbonic acid provides desireable advantages over the use of straight water jets for among other reasons that upon impact on the dental surface the carbon dioxide is rapidly released and produces high foaming which greatly improves the cleaning action. After completion of the cleaning and massaging operation, which generally does not require more than a tankful of water, button 52 is released to close valve 13 and seal off com,- munication between tank 76 and nozzle 73 and cartridge 37. Tank 16, in the valve-closed position, retains its valve regulated pressure and the water therein is charged with carbon dioxide, and the device is ready for further use. Upon depletion of water on tank 16, cap 7l is removed, the water in the tank replenished and cap 71 reapplied. A single conventional CO2 cartridge 37 is generally sufficient for at least several full tanks of water and is easily replaced when spent. lt should be noted that various ingredients may be added to the treating water if desired, such as gen'nicides and the like, and the device is easily cleaned to remove any residues.
While there has been described and illustrated a preferred embodiments of the present invention, it is apparent that numerous alterations, omissions and additions may be made without departing from the spirit thereof.
l. A dental cleaning device comprising a pressurized gas cartridge, a liquid reservoir, a nozzle member carried by said reservoir, and communicating with the lower part thereof, a manually operable valve normally biased to a closed position and including a first outlet communicating with said reservoir and a first inlet, means for connecting said valve inlet to said gas cartridge and a pressure reducing regulator valve connected between said gas cartridge and said reservoir.
2. The dental cleaning device of claim 1 including a magazine member separably secured to said reservoir and releasably housing said cartridge, said cartridge connecting means including a piercing tube projecting into said housing and communicating with said valve first inlet.
3. The dental cleaning device of claim l wherein said valve includes normally closed associated second inlet and second outlet, said second outlet being connected to said nozzle, and means connecting said second inlet to the lower part of said reservoir.
4. The` dental cleaning device of claim 3 including a magazine member separably secured to said reservoir and for releasably housing said gas cartridge connecting means including a piercing tube projecting into said housing and communicating through said pressure regulator valve with said valve first inlet.
5. A dental cleaning device comprising a pressurized gas cartridge, a liquid reservoir, a nozzle member carried by said reservoir, and communicating with the lower part thereof a manually operable valve nonnally biased to a closed position and including a first outlet communicating with said reservoir and a first inlet, meansfor connecting said valveinlet to a gas cartridge, and a liquid actuated pulsating device disposed between the outlet of said nozzle member andV said reservoir.
6. A dental cleaning device comprising a pressurized gas cartridge, a liquid reservoir, a nozzle member carried by said reservoir, and communicating with'the lower part thereof, a manually operable valve normally biased to a closed position and including a first outlet communicating with said reservoir andra first inlet, means for connecting said valve inlet to a gas cartridge, and a housing secured to and positioned end to end with said reservoir and defining a handle therewith, said nozzle being mounted on to the outer end of said reservoir, said valve including a tubular body member positioned in and extending across said reservoir and having longitudinally spaced first inlet and outlet ports defining said first inlet and outlet respectively, a valve shaft longitudinally movable in said body member between alternative first and second positions respectively closing and opening communication between said first inlet and outlet ports and normally biased to said first position and provided with a pushbutton projecting from said shaft outwardly of said valve body member and reservoir, and said cartridge connecting means including a piercing tube projecting into said housing and communicating with said valve first inlet.
7. The dental cleaning device of claim 6 wherein said valve body member has longitudinally spaced second inlet and outlet-dening ports formed therein, communication between said second ports being alternatively closed and open by said valve shaft when in said first and second positions respective- Iy, said second outlet port being connected to said nozzle and said inlet port communicating with the lower part of said reservoir. i y v 8. The dental cleaning device. of claim 6 wherein said valve body member has longitudinally spaced second inlet and out let defining ports formed therein, communication between said second4 ports being alternatively closed and open by said valve shaft when in said first and second positions respectively, a first tube directed upwardly from said valve body member coaxial with said reservoir and communicating with said second outlet port, said reservoir having an opening in the top thereof, a cap member releasably engaging said opening, said member and depending therefrom, an externally threaded .peripheral wall depending from and integrally formed with said casing member, a magazine member supporting said car-
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|Reservoir for water flosser
|Sep 4, 2013
|Dec 2, 2014
|Water Pik, Inc.
|Base for water flosser
|Sep 12, 2013
|Jun 9, 2015
|Water Pik, Inc.
|Reservoir for a water flosser
|Sep 4, 2013
|Oct 13, 2015
|Water Pik, Inc.
|Water flosser base unit
|Apr 15, 2013
|Dec 22, 2015
|Sonendo, Inc.
|Dental handpiece
|Apr 25, 2014
|Jan 12, 2016
|Water Pik, Inc.
|Handheld oral irrigator
|Nov 7, 2014
|Apr 19, 2016
|Water Pik, Inc.
|Handle for a water flosser
|Jul 12, 2013
|May 17, 2016
|Water Pik, Inc.
|Oral irrigator tip
|Jun 21, 2012
|Apr 29, 2015
|Device and method for providing pressurized fluid
|Feb 3, 1982
|Aug 11, 1983
|Paul Hirsch
|Jun 12, 1992
|Jan 21, 1993
|Fan Chin Fu
|Universal medication port
|Dec 21, 2005
|Jun 29, 2006
|Koninklijke Philips Electronics, N.V.
|Gas-assisted system for fluid droplet generation in an oral care system
|Jun 21, 2012
|Dec 27, 2013
|Pinchas Shalev
|Device and method for providing pressurized fluid
|U.S. Classification
|601/162, 604/249, 604/140
|International Classification
|Cooperative Classification
|European Classification


text:
For the friends you have not met yet.
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Come Get Your Loveby E.C. Scott
Product Details
- Release Date:
- 04/15/1995
- Label:
- Blind Pig
- 0019148501928
- catalogNumber:
- 5019
- Rank:
- 161035
Album Credits
Performance CreditsE.C. Scott Primary Artist,Vocals,Background Vocals
Chris Cain Guitar
Jeanie Tracy Background Vocals
Larry Batiste Trombone,Trumpet,Background Vocals
Vernon "Ice" Black Guitar
John Burr Keyboards
Chris Cobb Guitar
Michael Fellows Drums
Michael Harper Bass
Derek Jones Bass
Eric McCann Bass
Norbert Stachel Saxophone
Annie Stocking Background Vocals
Randy Singer Saxophone
April Spikes Background Vocals
Tia Carroll Background Vocals
Chris Durbin Keyboards
Amanda Elliott Background Vocals
Greg Goneaway Drums
Jay Goudeau Bass
Tim Landis Guitar,Rhythm Guitar
Mark Little Keyboards
Alex Marlowe Bass,Drums,Keyboards,keyboard bass
Tracy McGee Background Vocals
Curtis Nutall Drums
Gary Brown Bass
Technical CreditsElton John Composer
Dave Davies Composer
Larry Batiste Producer
Chris Cobb Contributor
Pat Coughlin Engineer
Lee Hildebrand Liner Notes
Steve Savage Engineer
E.C. Scott Producer,Executive Producer
Alex Marlowe Producer,drum programming
Customer Reviews
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text:
Atelier Totori Plus for Vita goes on sale in Japan on November 29th for 6090 yen ($77.71 US). A limited-edition premium box comes with a PS Vita skin and a paper weight for 8190 yen ($104.51 US). First-print runs include a costume code for two swimsuits called Angel Swimsuit and Little Devil Bikini. Take that as you will.
Boot Hill Heroes July 24 • 9:00am PDT/12:00pm EDT
Tales from the Borderlands July 31 • 9:00am PDT/12:00pm EDT
Breath of Fire IV Continues! Every Monday • 5:00pm PDT/8:00pm EDT
Grandia II Continues! Every Wednesday • 2:00pm PDT/5:00pm EDT


text:
Cubs Rumors from Around the Globe
- Alfonso Soriano had a "scheduled" off day on Wednesday versus the Diamondbacks despite some gaudy career numbers against Ian Kennedy (6-for-13, 3 HR's, 7 RBI's, 3 BB's). The Twitter-verse was having none of it and the conspiracies flowed that the Cubs were just awaiting his approval on a deal. Soriano showed up though for a pre-game chat with the reporters and spilled the beans that he would accept the a trade to the Yankees and apparently gave TheJedi a list of a few other teams he'd be willing to say yes to...so it's Soriano waiting on the Cubs and the rest of the league. As of now, a trade has not been made, but somehow Soriano didn't manage to even get an at-bat in a 12-inning affair last night that the Cubs eventually won 7-6.
- Speaking of Wednesday's game, the bullpen is pretty taxed, wonder if they'll try and get someone up to the club by gametime. Carlos Villanueva is starting Thursday which could going to the pen early and they'll certainly be without Gregg and Rondon as you can see below (and possibly Guerrier if they don't want to go a 4th day with him although his pitch counts have been low). That leaves Russell, Parker, Strop and Bowden for the most part.
- The other major rumor was that the Pirates and Braves seem keen on James Russell.
- Matt Garza pitched a gem in his first start for Texas: 7.1 IP, 0 ER, 0 BB, 5 K with the only unearned run courtesy of his own throwing error. The more things change, the more they stay the same. Also, the Yanks had Lyle Overbay batting cleanup and Vernon Wells is a regular batting 5th...so don't get too excited yet Ranger fans.
- In the minors, Kris Bryant got his first hit with Boise with a double, ending up 1-for-4 on the night. Javier Baez doubled and hit his 6th home run in AA (23rd on the season). Dae-Eun Rhee pitched for the Smokies in that game and went a solid 5 innings giving up a run and racking up 6 K's against 3 BB's. Mike Olt made his debut for Iowa and went 1-for-5 with 3 K's. Speaking of the minors, check out MLBFarm.com...cool stuff.
wonder what he's worth...he's
wonder what he's worth...he's a pure platoon guy who is easily squashed by a lefty.
he's got a year of club control and an excellent RF arm, though.
b.barnes...j.bell...k.mcpherson if they're selling low on his bum shoulder...maybe t.glasnow if they throw in russell
Interesting though on
Interesting though on Schierholtz...
career numbers:
vs RHP: .270/.323/441
vs LHP: .276/.317/.374
that is interesting
that is interesting considering his last 3 seasons
.234/.265/.297 - 2011
.175.206/.238 - 2012
.192/.313/.192 - 2013
he actually owned them in 2007-2010, a few of those years doing better than vs RHB.
Getting worse...interesting.
Getting worse...interesting.
Either way, he's a nice platoon guy...good defender...inexpensive...but I'm not going to boycott if they trade him.
He's the kind of guy that
He's the kind of guy that could go all Jim Leyritz in a World Series, I think.
AA RHP Nick Kingham's name
AA RHP Nick Kingham's name was thrown out there about a week ago by a Pittsburgh writer.
So sori deciding if he wants
So sori deciding if he wants to move into pressure situation to win, or stay in current situation for the same money.
Do the Cubs owe KC a prospect
Do the Cubs owe KC a prospect for not putting Santana on the trade market until Garza was dealt? Trevor Gretzky sounds about right.
Shaw Media today announces
Shaw Media today announces the launch of HubArkush.com, a website dedicated to in-depth news and analysis of the Chicago Bears.
"Our plan for Hubarkush.com is to bring football lovers everywhere the best of what I've done at Pro Football Weekly for the last 35 years with a hyper-local focus on the Chicago Bears and the NFC North, 24 hours a day, seven days a week. If you love football and you love the Chicago area, you'll love Hubarkush.com." Arkush said.
Alderman Tunney, also
Alderman Tunney, also propieter of "stickey buns", uses interesting threat against Cubs
Just let that one sit there a
Just let that one sit there and breathe.
So you could say Alderman
So you could say Alderman Tunney is going to be anal about checking up on the Cubs?
It had to be said.
It had to be said.
I love Nate.
I love Nate.
I wouldn't mind seeing him in Wrigley another year at all.
He's cool, but I see him more
He's cool, but I see him more as a great piece for a contender. But just giving him away for unlikely to get the "bring him up" type of treatment type of prospect would be stupid. The other consideration is that you do want grinders on your club for the younger guys to be around - he seems like that type of guy.
WSox Reed had "setback",
WSox Reed had "setback", Russell talk should heat up.
you mean Jessie Crain (not
ooops him too
ooops him too
robert fick admits to roiding
robert fick admits to roiding...still waiting on a followup report to see who cares besides e.karros.
When I get home, I am going
When I get home, I am going to burn all my Robert Fick memorabilia. All of it.
My God, who wasn't 'roiding'
My God, who wasn't 'roiding' from 1990 to 2005?
Maddux. Kruk. That may
Maddux. Kruk. That may cover it.
My God, who wasn't 'roiding'
My God, who wasn't 'roiding' from 1990 to 2005?
George Brett was 'roiding in the 1980's. Back then, 'roids took a little "PREPARATION"
I'm not below a little butt humor too.
Big Z released from Phils AAA
Big Z released from Phils AAA.
He should be available for the Kerry Wood Wiffle ball game in August.
Keith Law, from his blog, an
Keith Law, from his blog, an older post...but WOW:
Mike (Chicago)
Is Junior Lake a good prospect or just a one week wonder?
Klaw (1:07 PM)
This is a great place to hit, so please take all AFL hitter stats with a major grain of salt. His feel for the game - including instincts on defense and ability to work the count or recognize offspeed stuff - is so limited that there's a good chance he ends up on the mound.
even back in the day...and
even back in the day...and leading up to now...
there was always a feeling that he could hit 15+ HR, a good amount of doubles, make good contact, not walk much...but doubtful to stick at SS/3rd.
at best, i get the feeling like a lot of people project him to be a .280/.330 avg/ob% type guy who could hit a slew of doubles with 15-20HR pop.
not exciting for a corner OF...good enough for a CF'r...awesome for a bench guy + injury replacement.
Yahoo! I can't remember a
Yahoo! I can't remember a manager ever commenting on an imminent trade as close. Sveum just did.
Ps - "yanked" I see what you did there.
I cannot even imagine how
I cannot even imagine how pedestrian a 'lower tier' Yankees prospect is. Sigh.
Olney tweet...
Olney tweet x2...
Cubs would get a lower-tier pitching prospect if they finish the Soriano deal with the Yankees. They are waiting for his formal waiver.
If the Yankees' deal with the Cubs happens, Chicago would eat the bulk of the money owed to Soriano, about $25m.
Recent comments
That's a hell of a first impression by Montgomery. Brian Cashman having a good laugh on that debut.
...and it's a 3 run homer.
hey, vogelbomb had a HR on his 1st game with SEA AAA, too!
montgomery comes on with men on 1st/2nd, 2 out, in the 8th.
from rotoworld...
"Tommy Stokke of FanRag Sports reports Chris Sale was sent home from U.S. Cellular Field on Saturday after cutting up throwback jerseys that he did not want to wear.
I thought the same. It'd be great luck to face these non-contenders after the trade deadline.
...why isn't j.lucroy playing for TEX yet?
2r HR on a 12-pitch AB.
nathan to join the cubs tomorrow.
Wow in deed.
FOX Sports @MLBONFOX
Chris Sale was scratched from tonight's scheduled start due to a clubhouse incident before the game
he was sent home by the team, too. the wsox released a press statement and everything. they stated it was non-physical in nature.
He was scratched from his start today. No reason given.
At the start of the season the book was that he was trying to pitch to more contact so he could stay in the game longer and it seems to be working so far. Contact against is 77.5% this year and it was 70.2% the year before. He averaged 6.7 IP/game last year and so far it's 7 IP/game. His actual pitches per game are only down to 106.1/game from 107.2/game last year but if he's able to go a bit farther into games without throwing more pitches and without giving up more runs that is a good thing.
sale's skills and insane value makes it almost too hard to have a market for the guy...he's got 3/38m owed to him over 3 seasons (2 team options). he could easily pull in 30m/yr if he was on the market as a FA.
he's throwing a bit differently this season, especially with more sliders and less changeups like earlier in his career, but all his stuff still looks great even if the HRs are a little elevated and the Ks are down.
Torres, Happ, McKinney, Jimenez, and Candelario for Sale. Deal or no deal?
"The White Sox are reportedly asking for "five top prospects" for Chris Sale, FanRag Sports' Jon Heyman reports."
Unless he develops 30+ HR power and keeps his walk rate close to his K rate at the MLB level, he's not going to turn into Prince Fielder. And even if he does turn into Prince Fielder, he's gonna have a short prime. His very limited athleticism is likely to also detract some value from his ability to reach base--I don't buy making an out as being preferable to base clogging, but you'd certainly prefer just about any base runner other than Vogelbach, David Ortiz, etc.
seeing as arod has played a total of 27.1 innings of D at 1st/3rd and somehow managed a -0.5 dWAR with his 1 error at 1st and an overall positive total zone rating...he might end up even more in the shitter via the characteristics/flaws/whatever of how some sites determine various WAR values. dWAR doesn't directly lead to a WAR value, but the 2 main entities pushing the most popular variations of WAR sometimes lead to some interesting discrepancies in value.
I have a lot of faith in Baez that he's going to turn into a more consistent, solid player. It looks like it took him about a half season or so of futility at the plate to figure out he was not talented enough to get away with the crazy approach he had. I think his running game will eventually have a more measured aggression.


text:
- Anonyme
- États-Unis, Femme, 18-24
- Voyageur passionné
- 11 Avis
The dorm beds are horrifying. They feel like they are going to fall at any moment. I'm a 115lb female and as I got on to the top bunk I thought I was going to break it. The kitchen is only opened from 7-7 and the options are very limited. I decided to cut my stay short and go elsewhere.
- Anonyme
- Afrique du Sud, Homme, 31-40
- Nomade novice
- 2 Avis
Pros: - Very friendly security guards and some of the staff are also friendly and willing to help well except one. - They make the best food (Nshima and beef stew was the best). - Reliable, fast and free wifi. - Daily shuttle to Victoria Falls at 10H30 Cons -- Although I booked 4 male dorm I was made to share the first night with a girl, second day with 3 other males and the third day with 3 ladies!!!! - Third night a 5th guy was shown to our room after midnight but we had no space. -
- Anonyme
- États-Unis, Homme, 31-40
- Globe-trotter
- 50 Avis
Excellent hostel. Worth a stay there and it's a very good alternative to the other popular backpackers in town. Good facilities and overall no issues whatsoever
- Anonyme
- Canada, Homme, 18-24
- Nomade novice
- 1 revue
Comfortable, peaceful, friendly place. Very private and safe.
- Anonyme
- États-Unis, Femme, 25-30
- Nomade novice
- 4 Avis
The set up is nice with the lounge area by the pool and the bar nearby very centrally located within Livingstone. The dorm rooms are very small and unfortunately ended up on a top bunk which is far too close too the ceiling, especially if you want to sleep under the mosquito net then you have to deal with having the mosquito net touching your entire body which is not an enjoyable experience. There was no fan in the room first night and no plugs for charging. Also the noise level was quite high
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text:
Dutch Oven Carnitas
|Pork shoulder
|5 Pound
|4 Large
|Filtered water
|4 Cup (64 tbs)
|Bay leaf
|2 Medium
|5 Teaspoon
|Everyday seasoning
|3 Teaspoon
|Coriander powder
|2 Teaspoon
|Chipotle powder
|2 Teaspoon
|2 Teaspoon
|Cumin powder
|2 Teaspoon
|Olive oil
|1 Teaspoon
|1 Large, chopped
|4 Clove (20 gm)
|2 Large
|Chicken broth
|2 Cup (32 tbs)
1. In a large stainless steel bowl, place the pork shoulder.
2. Cut the lemons and squeeze in the lemon juice.
3. Pour in the filtered water.
4. Drop in the bay leaves and add the salt.
5. Sprinkle in the Everyday seasoning.
6. Allow the meat to rest in the marinade for 6 hours or more in the refrigerator.
7. Before you are ready to cook, pre heat the oven to 275 degrees Farenheit.
8. Chop the onions and the garlic roughly.
9. Split open the jalapenos, remove the seeds and cut into strips.
10. In a bowl, mix in the coriander powder, cumin powder, chipotle pepper powder and paprika.
11. Take the meat out from the marinade and pat it dry with paper towels.
12. In a sheet pan, place the dried pork shoulder.
13. Generously sprinkle in the spices on all the sides, pressing it in with both hands so that it forms a crust.
14. Heat a Dutch oven and pour in the olive oil.
15. Place the meat in it with the fat side down and give it a sear on all sides about 4 minutes on each side.
16. Add the chopped onions and garlic in it.
17. Place the sliced jalapenos on top of the pork shoulder. Take care to have the fat side on top so that as the fat is rendered, the meat remains soft.
18. Add chicken broth to the pan.
19. Set the oven rack such that the Dutch oven receives equal amount of heat from all sides.
20. Let it sit in the preheated oven for 4 hours.
21. Take it out of the oven and remove the chilies from the top.
19. In a roasting pan, lift and transfer the pork shoulder.
20. Use two forks and pull the pork from the bone and shred it.
21. Season the meat with a little salt and everyday seasoning.
21. Set the oven to Broil at 450 degrees Farenheit and place the roasting pan on the top rack for 15 minutes for the meat to crisp up.
22. Take it out from the oven.
24. Serve the Carnitas on a Napa cabbage leaf with chipotle mayo sauce on top or on a bun as in a pulled pork sandwich.
Recipe Summary
Rate It
Nutrition Rank
Nutrition Facts
Serving size
Calories 463 Calories from Fat 264
% Daily Value*
Total Fat 29 g45%
Saturated Fat 10 g50.1%
Trans Fat 0.3 g
Cholesterol 140.6 mg46.9%
Sodium 1716.3 mg71.5%
Total Carbohydrates 10 g3.2%
Dietary Fiber 3.4 g13.8%
Sugars 1.9 g
Protein 41 g82.1%
Vitamin A 22.4% Vitamin C 52.9%
Calcium 8.9% Iron 21.6%
*Based on a 2000 Calorie diet


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The objective of this paper is to present a feature model as a main deliverable of a domain analysis for context-aware Mobile Patient Monitoring Systems (MPMS). This model is a part of ongoing work to design an application framework to develop context-aware MPMS. These systems will enable elderly populations and patients with chronic diseases to undertake monitoring of themselves during their daily life. Unfortunately, developing these systems is very complex. An application framework, as an ideal reuse technique, is one of the most suitable solutions to simplify the development of such systems and overcome their development complexity. The scope of this paper is limited to construction process for context-aware MPMS feature model. The expected benefits of the resulted model are twofold. First, it enhances the understanding of the domain of context-aware MPMS. Second, it supports designing frameworks that satisfy the main characteristics of application frameworks, which are framework extensibility and reusability.
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