text:
A method for photoeluting photocleavable linker-attached chemical compounds, and an apparatus suitable for implementing the method, are disclosed. According to the method, photocleavable linker-attached library compounds are photoeluted from solid support media under conditions of controlled light exposure and controlled temperature. An apparatus suitable for carrying out the present photoelution method includes means for substantially evenly illuminating the photocleavable linker, means for controlling illumination time and intensity, and means for controlling sample temperature.
1. In a method for photoeluting chemical compounds from a support, wherein photocleavable linkers that link said chemical compounds to said support are subjected to irradiation to release said chemical compounds, and wherein said chemical compounds that are released are then eluted, the improvement comprising:
terminating said irradiation after a period of time that:
is sufficient to release some but not all of said chemical compounds, wherein the chemical compounds that are released define a first released group;
is limited to prevent degradation, by further irradiation, of said first released group of chemical compounds; and
controlling elution temperature to a temperature that is within the range of about 20� C. to about 70� C.
2. The method of
3. The method of
4. The method of
irradiating uncleaved photocleavable linker molecules to release at least some of the chemical compound that remain linked to said support, the released chemical compound defining a second released group;
terminating the irradiation of said uncleaved photocleavable linker molecules before degradation of said second released group of chemical compounds; and
eluting said second released group of chemical compound, wherein said irradiation of said uncleaved photocleaved linker molecules occurs after eluting said first released group of chemical compounds.
5. The method of
6. The method of
7. The method of
8. The method of
9. The method of
10. The method of
The present invention relates to the field of solid-phase chemistry. More particularly, the present invention relates to a method and apparatus for eluting photocleavable-linker attached chemical library compounds.
Combinatorial chemistry libraries or single chemistries can be produced by a method known as solid-phase synthesis. That process involves linking a first chemical �base structure� molecule to solid support media and subsequently adding, seriatim, chemical building blocks, or, alternatively, effecting chemical structural changes to the base structure, e.g., ring opening or closing. The base structure molecule participates in one or more reaction steps with the added chemical building blocks. Chemical compounds, referred to as library compounds, descended from the base structure molecule, are thereby generated. Extremely large, diverse chemistry libraries can be synthesized in this manner.
Each library compound, and its base structure molecule precursor, is typically attached to the solid support media, typically inorganic or polymer beads, via a cleavable linker that covalently links the compound to the support media. The synthesized library compound remains linked to the support media until such time as it is deliberately removed therefrom. A synthesized library compound can be separated from the support media by cleaving the linker. One class of linkers, referred to as photocleavable linkers, are cleaved by exposure to light, such as long-wave ultraviolet light (UV). The process by which a synthesized compound is cleaved from the photocleavable linker and removed from the environment of the solid support media is termed photoelution.
Currently, chemists use mercury spot lamps for photoelution. While such a spot lamp generates sufficient light output, it provides uniform illumination across a relatively small circular region or spot on the order of 5 centimeters or less in diameter. As such, they are suitable for illuminating only one sample at a time. As conventionally practiced, a spot lamp and sample are placed inside a hood. Due to the amount of bench-top area required, only one or two lamps are typically placed within a given hood, limiting the amount of samples that can be photoeluted. Moreover, the small size of the uniformly illuminated region disadvantageously increases the likelihood of sample-to-sample variation in the amount of received radiation.
As such, it would be desirable to have a method and apparatus for simultaneously photoeluting a multiplicity of samples and for providing a substantially uniform dosage of radiation thereto.
A method for photoelution, and an apparatus suitable for implementing the method, are disclosed. According to the present method, photocleavable linker-attached library compounds are photoeluted from solid support media by (i) exposing the solid support media for a portion of the photoelution time to light having a spectral energy distribution appropriate for cleaving the photocleavable linker from the solid support, and (ii) eluting the library compound from the solid support with a solvent under controlled temperature with or without UV exposure.
An apparatus suitable for carrying out the present photoelution method includes means for substantially evenly illuminating the sample, means for controlling illumination time and intensity, and means for controlling sample environment including temperature and, optionally, atmosphere. In some embodiments, means for substantially evenly illuminating the sample includes means for stirring or agitating the sample.
Further features of the invention will become more apparent from the following detailed description of specific embodiments thereof when read in conjunction with the accompanying drawings, in which:
FIG. 1 represents a library compound linked to a solid support media via a linker;
FIG. 2 shows a flow diagram of a method according to the present invention for photoeluting a photocleavable-linker-attached chemical library compound;
FIG. 3 shows the photocleavage reaction for o-nitrobenzyl linker;
FIG. 4 shows a plot of percent theoretical yield of photocleaved linker as a function of time;
FIG. 5 shows a functional representation of an apparatus according to the present invention for photoeluting a photocleavable-linker-attached chemical library compound;
FIG. 6 shows an exemplary first embodiment of the apparatus of FIG. 5 wherein a vial is used for retaining the solid support media and linker-attached library compound; and
FIG. 7 shows an exemplary second embodiment of the apparatus of FIG. 5 wherein a microtiter plate retains the solid support media and linker-attached library compound.
The present invention is directed to a method and apparatus for photoeluting linker-attached chemical compounds from solid support media. As used in this specification, the term �photoeluting� refers to a method by which (i) photocleavable linker is cleaved, thereby releasing the chemical compound from the solid support media, and (ii) the chemical compound is eluted out of the solid support media and into a solvent. The compounds, either attached, via linker, to the solid support media before photoelution, or in a linker-free or released state after photoelution, will be referred to herein as library compounds. It should be understood that such compounds may or may not be part of a chemical library.
FIG. 1 shows a simplified conceptual illustration of a library compound 6 linked to solid support medium 2 via a photocleavable linker 4. As used herein, the term �photocleavable linker� or �linker� means any component capable of being photolytically cleaved to release the library compound from the solid support media. See, e.g., Greene and Wuts, �Protective Groups in Organic Synthesis,� 2d. ed., Wiley, 1991, incorporated by reference herein. In a preferred embodiment, the linker is o-nitrobenzyl. Solvents suitable for eluting released library compounds include, without limitation, acetonitrile, alcohols, such as ethanol, isopropanol, methanol, and the like, methylene chloride, water, and various stoichiometric and ratiometric mixtures thereof.
Solid support media 2 suitable for use in conjunction with the present invention include, without limitation, beads, pellets, disks, fibers, gels, or particles such as cellulose beads, pore-glass beads, silica gels, polystyrene beads optionally cross-linked with divinylbenzene and optionally grafted with polyethylene glycol and optionally functionalized with amino, hydroxy, carboxy, or halo groups, grafted co-poly beads, poly-acrylamide beads, latex beads, dimethylacrylamide beads optionally cross-linked with N,N′-bis-acryloyl ethylene diamine, glass particles coated with hydrophobic polymer, etc., i.e., material having a rigid or semi-rigid surface; and soluble supports such as polyethylene glycol or low molecular weight non-cross-linked polystyrene. In a preferred embodiment, 200 micron PEG-grafted polystyrene beads (sold under the trademark �TENTAGEL�,� by Rapp Polymere of Tubingen, Germany) are used as the solid support media. In other embodiments, beads having a diameter within the range of about 0.01 to 10 millimeters (mm) may suitably be used.
Notwithstanding the designation as �solid,� the solid support media 2 are characteristically porous so that substantially more than simply the external surface is accessed by library compounds 6. As such, it should be understood that while FIG. 1 shows linker 4 and library compound 6 apparently attached to an external surface 8 of the solid support media 2, a substantial amount of linker 4 and library compounds 6 are attached to inner surfaces, i.e., the surfaces of pores, within the solid support media 2.
In a method according to the present invention, photoelution reaction conditions are controlled to an extent not hitherto practiced in the art. More specifically, as illustrated by the flow diagram in FIG. 2, photoelution is carried out under conditions of controlled duration and intensity of light exposure and controlled temperature. Exemplary apparatuses for implementing the present method are described later in this specification.
As indicated in operation block 201, photocleavable linker is evenly irradiated for a predetermined time period by light having a spectral energy distribution appropriate for cleaving the linker from the library compound. The photocleavage reaction for o-nitrobenzyl linker is shown in FIG. 3. As shown in that Figure, o-nitrobenzyl linker 4 a is attached to a library compound 6 a and solid support media 2 a. The reaction liberates the library compound 6 a as a secondary amide 6 b. Other leaving groups may result when different photocleavable chemistries are used.
Linker photolytic cleavage is dependent on the wavelength of the irradiating light, its intensity and duration. Long-wave UV, i.e., UV-A, which has spectral energy in the range of about 320-400 nanometers (nm), is suitable for cleaving o-nitrobenzyl linker. It should be understood that the aforementioned range is a compromise between using shorter wavelengths that may damage the library compound and using longer wavelengths that are less effective at cleaving the linker. Light having other spectral energy distributions may be required for cleaving other photocleavable linkers. Such other energy distributions are known to, or can be readily determined by, those of ordinary skill in the art.
It will be appreciated that due to the relatively small size of the solid support media, i.e., the beads, a relatively large number of such beads may be retained within a vial or other vessel for carrying out photoelution. Irradiating light should be delivered substantially evenly to all such beads. This is best accomplished, in certain embodiments, using an agitating or stirring device. An exemplary stirring device is a standard stirring bar activated by a motor-driven magnet. Thus, in block 201, the operation of evenly irradiating the linker may further include a controlled mixing or agitating operation. It will be understood that if the solid support media are retained within a plate having relatively shallow sample-receiving regions or wells, such as a microtiter plate, a stirring device may not be required to achieve substantially uniform illumination.
Continued UV irradiation after linker photocleavage may degrade released library compounds. In particular, library compounds that have been released from the linker but that have not diffused out of the solid support media are particularly vulnerable to such degradation. As such, it is desirable to limit the extent of UV irradiation to no more than that required for cleaving a desired fraction of total linker bonds. With a suitably intense light source, the time required for UV irradiation is shorter than the total time required for released library compounds to be cleaved from the supports and to diffuse out of the solid support media. Thus, in operation block 201, the predetermined time period for illumination is suitably short for limiting degradation of released library compounds.
The fractional extent of linker cleavage, i.e., the proportion of linkers cleaved out of the total of linkers present, can be controlled by irradiation time. Moreover, reaction rate will be affected by the spectral energy distribution of the irradiating light, as well as its intensity. It has been experimentally determined that photocleaving reaction kinetics follow a first order decay below about 50 milliwatts per square centimeter (mW/cm2) in the UV-A range mentioned above. FIG. 4 shows a plot of the percentage of theoretical yield of photocleaved linker (as determined by measurement of eluted compound) as a function of irradiation time for a given solvent, bulb type, light intensity and linker and library compound chemistry. The photocleaving rate expression can be readily determined from such data. The rate equation for other solvents, light sources, light intensities, linker and library compound chemistries can be determined with simple experimentation by those of ordinary skill in the art.
In one embodiment of the invention, illumination occurs in one or more timed doses separated by equilibration periods. Sufficient light intensity is provided so that a dose lasts for a time period within the range of about one minute to five hours. Light intensity, as measured at, the solid support media, in the range of from about 0.2 to about 10 (mW/cm2) at 365 nm with a 10 nm bandpass is suitable for attaining dosing periods within the prescribed range. It will be understood that the present method can be practiced using a lower than recommended light intensity. Such a practice lengthens the illumination period. Shorter illumination periods are presently preferred so as to minimize overall photoelution time.
After each illumination period, the system can be allowed to equilibrate wherein linker-released library compounds elute out of the solid support media and into the solvent. Such an equilibration period is typically within the range of about one to twelve hours for the 200 micron TENTAGEL� as a function of temperature.
With continuing reference to FIG. 2, in a method according to the present invention, photoelution temperature is controlled as indicated in operation block 203. Preferred photoelution temperature is selected based on several parameters, including, without limitation, the particular solid support media used, the linker composition, and the solvent. Moreover, to the extent that at least some of the photoeluting library compounds are temperature-sensitive, as is often the case, the presence of such compounds may limit the maximum acceptable photoelution temperature. A photoelution temperature within the range of about 20� to 70� C. is suitable for photoeluting with o-nitrobenzyl linker, methanol as the solvent and TENTAGEL� beads as the solid support. The aforementioned range of photoelution temperatures is satisfactory if other linkers, solid support media and solvents are used, as well. To the extent that such a temperature range is unsuitable for use with certain other systems, those skilled in the art can readily determine such suitable conditions for such other systems in view of the present teachings.
According to the present method, it may be also desirable to expose samples to heat, but not light, e.g., UV, for some portion of time during photoelution.
Prior art apparatuses or arrangements for photoelution are, at best, poorly suited for implementing the present photoelution method. Accordingly, an apparatus suitable for providing the requisite control over photoelution operating conditions and, if desired, for providing heating in the absence of illumination, is described below. Such an apparatus, illustrated in FIG. 5, is functionally described as including means 51 for supplying uniform illumination and controlling illumination intensity, means 53 for controlling illumination time and means 55 for controlling sample temperature. Such an apparatus optionally includes means for controlling sample atmosphere.
Means 51 for supplying uniform illumination is typically a lamp having a spectral energy distribution suitable for cleaving the particular photocleavable linker being used in conjunction with the library compound. For example, as previously described, long-wave UV having some spectral energy in the range of about 320-400 nanometers (nm) is suitable for cleaving an o-nitrobenzyl linker. A bulb providing a light intensity at the sample in the range of about 0.2 to about 10 mW/cm2 at 365 nm with a 10 nm bandpass has been found to be suitable for such purposes. Such intensity can be obtained using, for example, chemists' mercury spot lamps, available from UVP of California and BL9 phosphorescent bulbs, four feet long, 110 watts, available from Light Sources of Milford, Conn.
In some embodiments, means 51 for supplying uniform illumination further comprises means 57 for stirring, vibrating or agitating the sample to ensure that substantially all solid support media and attached linker and library compound receive about the same amount of illumination. One implementation of such means 57 is a magnetic stirring system. Other means of vibrating, shaking, or agitating are known to practitioners in the art and may suitably be used.
In a first basic embodiment, means 53 for controlling illumination time is simply an �on-off� switch for controlling power to the illumination source. In a somewhat more sophisticated second embodiment, a plurality of such switches are provided, one for each illumination source, i.e., bulb. In a third embodiment, means 53 comprises a �shield,� optically opaque at the relevant wavelengths and physically adapted for placement between a sample and means 51 for supplying illumination. In a fourth embodiment, means 53 for controlling illumination time includes a suitably configured photoeluting apparatus to allow insertion or removal of individual vessels containing respective samples. In a fifth embodiment, means 53 includes a conveyor by which samples are passed through an illumination zone, the samples thereby receiving a desired amount of illumination.
In some embodiments, means 53 may be configured so that, if desired, only a selected portion of the samples are illuminated. Additionally, means 53 can be automatically controlled, such as, for example, by using a simple timer, computer or the like.
Means 55 for controlling sample temperature may suitably include, for example, a temperature-controlled fluid, preferably a liquid, in contact with the exterior of a sample-containing vessel. Alternatively, such means 55 may include a temperature-controlled surface in contact with the sample-containing vessel.
Other implementations of means 51 for supplying uniform illumination and controlling illumination intensity, means 53 for controlling illumination time, means 55 for controlling sample temperature and means 57 for stirring, vibrating or agitating known to those of ordinary skill in the art may be used in lieu of those described above.
Photoelution is typically practiced in one of two formats. Such formats are characterized or distinguished by the configuration of the vessel containing the solid support media. In particular, in a first format, the solid support media are retained within vials or other similarly-configured vessels. In a second format, the solid support media are retained in a flat vessel containing a multiplicity of shallow wells, such as a microtiter plate. A first and a second exemplary apparatus suitable for practicing the present method, using the respective first and second formats, are described below.
FIG. 6 shows an exemplary first embodiment of the apparatus of FIG. 5 wherein a vial or similar cylindrical vessel is used for retaining solid support media with linker-attached library compound. For the exemplary apparatus 60 of FIG. 6, illumination is provided by two bulbs 61 a, 61 b, which provide light having suitable spectral energy distribution and intensity as required for cleaving the selected photocleavable linker. The bulbs 61 a, 61 b are positioned, relative to a plurality of sample-containing vials 67, for providing uniform light exposure to such vials 67. In the embodiment shown in FIG. 6, the bulbs 61 a, 61 b flank the sample-containing vials 67. It should be appreciated that in other embodiments wherein the photoeluting apparatus is configured differently than in FIG. 6, fewer or additional bulbs, located in other positions, may suitably be used to provide uniform light exposure to the sample-containing vials 67.
In a presently preferred embodiment, two BL9 phosphorescent bulbs, four feet long (110 W) are used in the photoeluting apparatus 60. Such a longer-length bulb, in contrast to spot lights, advantageously provides substantially uniform illumination over most of its length. Such uniform illumination facilitates simultaneous photoelution of a plurality of samples, such as are contained in the plurality of sample-containing vials 67. A variety of different-sized vials may be so illuminated. Such an arrangement, allowing photoelution of samples contained in multiple vials in a relatively small space, i.e., about four feet of bench surface, represents a significant improvement over prior art photoelution apparatuses.
During at least a portion of the photoelution time, the sample-containing vials 67 are situated in a carrier exemplified by trough 69. The trough 69 is suitably configured to receive a flow of a temperature-controlled fluid, not shown, such as can be provided by an external fluid bath, such as a water bath, also not shown. Side walls 71 a, 71 b of trough 69 have a height h suitable for substantially submerging the sample-containing vials 67 within the received flowing temperature-controlled fluid. The flowing temperature-controlled fluid provides a stable, temperature-controlled environment for the vials 67 and the samples contained therein. In the exemplary photoelution apparatus 60, the external fluid bath and trough 69 embody the means 55 for controlling sample temperature.
To further control sample temperature, at least a partial thermal barrier, partition or the like between a sample-containing vial and the illumination source may be utilized. The barrier should be transparent to the illuminating light at the appropriate wavelengths. In addition, an infrared filter may be used between the bulbs and the samples.
In the exemplary first embodiment shown in FIG. 6, sample-containing vials 67 may be disposed within the trough 69 during illumination. When so disposed, the side walls 71 a, 71 b of trough 69 are positioned between the vials 67 and respective bulbs 61 a, 61 b. Such side walls 71 are light (UV) transparent so that bulbs 61 a, 61 b provide a penetrating light exposure to the vials 67 through said side walls. Even illumination of the sample-containing vials 67 is thereby promoted. Suitable UV-transparent materials include, without limitation, glass, substantially UV-transparent polystyrene or acrylic, such as SUVT� from Polycast Technology Corp. of Stanford, Conn.
The apparatus 60 further includes a retaining or hold down device 75, which may be configured, as in the exemplary apparatus 60, as a flexible string formed from a resilient and chemically stable material such as, for example, silicone tubing. Such a retaining device 75 secures sample-containing vials 67 against the bottom of the trough 69 to prevent floating of such vials 67 when flowing temperature-controlled fluid is present in the trough 69. Such a retaining device 75 is further physically adapted to avoid nonuniform illumination of the sample-containing vials 67, i.e., to avoid shadows.
As discussed in conjunction with FIG. 5, an apparatus for photoeluting according to the present invention includes means 53 for controlling illumination time. Such means may be implemented in numerous ways. For example, in the embodiment shown in FIG. 6, the trough 69 is accessible from a top 73 of the apparatus 60. Such access allows sample-containing vials 67 to be placed within, and removed from, the trough 69. Thus, at the end of a scheduled illumination period, one or more of the sample-containing vials 67 may be removed from the apparatus as required. Alternatively, opaque shields, not shown, can be placed between the bulbs and the samples. In one embodiment, the opaque shield is a UV-opaque cylinder open at least at one end. Such a cylinder is placed over a sample-containing vial 67, thereby preventing UV radiation from reaching the enclosed sample-containing vial 67 while maintaining sample temperature control.
The apparatus 60 further includes means for stirring or agitating the samples within the sample-containing vials 67 during photoelution. Agitating the sample during illumination promotes uniform illumination.
In the exemplary first embodiment shown in FIG. 6, the agitating means include one stirring bar 79 for each sample-containing vial 67. A plurality of motor-driven magnets 89, one for each sample-containing vial 67, are positioned beneath the trough 69. One motor-driven magnet 89 is located directly beneath each sample-containing vial 67.
Each motor-driven magnet 89 comprises a magnet 81 attached to a shaft 83 of a motor 85. Each motor 85 is controlled by an adjustable speed regulator 87. The motor-driven magnet 89 and stirring bar 79 are placed sufficiently close to one another so that the stirring bar 79 is actuatable by the magnetic field generated by the magnet 81. As the magnet 81 is rotated or otherwise moved by shaft 83 under control of the adjustable speed regulator 87, the stirring bar 79 moves in complimentary motion within the sample-containing vial 67. Such motion agitates the solid support media contained within vials 67.
Agitation of solid support media is monitored through optically transparent outer walls 63 and trough walls 71 a, 71 b. While transparent to light in the visible wavelength range, the outer walls 63 are substantially opaque to UV for safety considerations. Agitation is adjusted, via the adjustable speed regulator 87, to provide a sufficient amount of agitation to the solid support media. In the present context, �sufficient agitation� is the amount of agitation required for substantially uniformly illuminating all support media in a sample-containing vial. It has been found that if the stirring bar speed is adjusted to generate a vortex within a sample-containing vial 67, the solid support media are sufficiently agitated for the present purposes. It will be appreciated that agitation speed for sufficiently agitating the solid support media is a function of the size of the stirring bar 79, the size of the sample-containing vial 67, the physical characteristics of the solid support media, and solvent viscosity and density, among other considerations.
It may be desirable to maintain the sample-containing vials 67 under an inert atmosphere such as, for example, nitrogen or argon. If so, the vials 67 can be sparged and then capped.
FIG. 7 shows an exemplary second embodiment of the apparatus of FIG. 5 configured for photoeluting samples, comprising the solid support media with linker-attached library compounds, which are retained in microtiter plates 101. An example of plate 101 is a microtiter plate containing 96 wells.
Exemplary apparatus 90 of FIG. 7 includes a source of illumination having suitable spectral energy distribution and intensity as required for cleaving the selected photocleavable linker from the selected solid support media. In the exemplary embodiment shown in FIG. 7, the illumination source is five bulbs 91 a- 91 e. The five bulbs 91 a- 91 e are preferably the previously-described BL9 phosphorescent bulbs (110W). The bulbs 91 a- 91 e are positioned, relative to a plurality of sample-containing plates 101, for providing uniform light exposure to the bottom of the wells contained in such plates 101, and to minimize shadows. Illumination intensity is controllable by simply changing the number of bulbs used for illuminating the sample-containing plates 101, via wattage selection or by regulating voltage which results in proportional changes in illumination intensity. Moreover, a neutral density filter 103 can be placed between the illumination source and individually-selected plates to moderate light intensity to the selected plates. Spectral or infrared filters may be used, as well.
In the embodiment shown in FIG. 7, the five bulbs 91 a- 91 e are located above the sample-containing plates 101. It should be appreciated that in other embodiments wherein the photoeluting apparatus is configured differently than in FIG. 7, fewer or additional bulbs located in other positions may suitably be used to provide uniform light exposure to the sample-containing plates 101. As previously described, long cylindrical bulbs, such as BL9 phosphorescent bulbs, advantageously provide more uniform illumination for photoeluting multiple samples than spot lights, and are used in preference thereto.
The apparatus for photoeluting illustrated in FIG. 7 also includes means for controlling illumination time. In the embodiment of FIG. 7, the sample-containing plates 101 are accessible from a side of the apparatus. Thus, plates 101 can be removed and inserted as required to control light exposure. Additionally, like the exemplary first embodiment, the exemplary second embodiment preferably incorporates a shield, opaque to the relevant wavelengths of light, which is positionable between the illumination source and a selected few or all of the sample-containing plates 101. In FIG. 7, the shield is implemented as a shutter 99 that is extendable, as required, across the surface of a thermal shield 97. The shutter is extended as far as necessary to prevent light from illuminating the selected few or all plates 101. In FIG. 7, the shutter 99 is shown extended about fifty percent of the distance across the barrier 97. Alternatively, a �Venetian blind� type of shield may be used.
In the embodiment of FIG. 7, temperature control is provided, primarily, by a temperature-controlled carrier, exemplified by surface or platen 93. Sample-containing plates 101 are placed on top of the platen 93 and receive heat therefrom. The temperature-controlled platen 93 may include resistive elements, not shown, for generating heat on application of a current. Such current can be regulated by a servo that uses a temperature measurement of platen 93 or one of the wells of the sample-containing plates 101.
In one preferred embodiment, a cover 95, transparent to the illuminating light at the relevant wavelengths, is disposed on the platen 93 so as to substantially cover the sample-containing plates 101. The cover 95 provides additional temperature stability in the immediate vicinity of the sample-containing plates 101 by reducing convective heat transfer. In the exemplary photoelution apparatus 90, the temperature-controlled plate 93 and optional thermal barrier 97 embody the means 55 for controlling sample temperature.
The thermal barrier 97 segregates the apparatus 90 into first and second independently temperature-controllable regions. The first region includes the illumination source, e.g., the bulbs, and the second region includes the sample plates. The second region may optionally include a tap, not shown, for introducing and establishing an inert gas environment. Alternatively, the cover 95 can be fitted with a tap so that the inert gas may be introduced to the region underneath the cover 95.
Although a number of specific embodiments of this invention have been shown and described herein, it is to be understood that such embodiments are merely illustrative of the many possible specific arrangements that can be devised in application of the principles of this invention. Numerous and varied other arrangements can be devised in accordance with those principles by those of ordinary skill in the art without departing from the spirit and scope of the invention.
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Rosebud Luxury Bathroom Set
product code: 139091
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The Rosebud house bathroom set includes everything a luxurious dolls' house bathroom needs. The bathroom set includes a bath, separate shower, toilet and basin unit with a mirror. It also comes with accessories including a bathmat, towel rail and hand towel. Because Rosebud House has such a flexible open-plan design, your child can choose where to put the bathroom, and move it around the house as often as they like. The nicely coordinating bathroom set makes your child's imaginative dolls' house play fun and realistic: they can help their dolls shower and get ready for school or work in the morning, and enjoy a relaxing bath after a long day.
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Fi News #104: Cormariae Launch and Blessing
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Ave Maria! TheĀFranciscans ofĀtheĀImmaculate inĀNew Bedford, Massachusetts have launched theĀfirst Catholic radio station inĀtheĀDiocese ofĀFall River. Like our other station inĀUp-State New york theĀcontent ofĀtheĀradio is aĀfeed from EWTN, but over time, little byĀlittle, we'll produce our own content. Ave Maria! To Download Audio go to http://airmaria.com?p=18735
Blessing CorMariae Launch New Bedford Radio
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text: Previous Saturday, November 22, 2014 Next View Programs By: Day Week Month 22 Nov Fr. Woody Wrap Party 9:00 AM-1:00 PM Regis will be hosting the annual Fr. Woody Wrap Party in the Main Cafe in the Student Center. Father Woody's Wrap Party is a service project that supports the Regis University mission project: Father Woody's Christmas Party. All participants at the Wrap Party wraps gifts for Denver's homeless and disadvantaged population. The wrapped gifts will be distributed at Father Woody's Christmas Party in December. For questions, information, or other inquiries please contact Dr. Victoria McCabe at 303.458.3572 or Connie Gates at 303.458.4148. Location: Student Center Main Cafe Rm 105 22 Nov RU Men's Soccer Play Day 9:00 AM-4:00 PM http://www.regisrangers.com/landing/index"> Location: West Field 22 Nov RU Women's Basketball vs. McMurry State 5:00 PM-8:00 PM http://www.regisrangers.com/landing/index"> Location: Field House Gymnasium 22 Nov Concert for a Cause 7:30 PM-10:30 PM See Student Activities for more details. Location: St. Peter Claver, S. J. Hall Rm 125


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US: Gay rights protester interrupts Michelle Obama's speech
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To paraphrase the line from the old Weekend Update segment on SNL (Sat. Night Live): Ellen, you ignorant s***!
Being in-your-face rude doesn't work, it triggers disgust in the average citizen and makes us all look bad.
Isn't it also rude to constantly ignore the human rights of others? If the Obama's chose to be in the political domain sometimes people will get political when they least expect it – rough with the smooth!!! It ain't all Oprah & Ellen.
The Obamas have done a hell of a lot for the rights of LGBT people. I'd hardly call what they do 'ignoring' human rights.
And yeah, rough with the smooth, but the rough in this case chose to be rough. What an ignorant, rude woman Ellen seems like.
I agree with Mijacmad wholeheartedly. Michelle Obama could have easily responded to Ellen Sturtz by telling her that she and her husband have done allot for gay rights and that if Ellen wanted to discuss the matter, she would do so later. Instead, she used her position as First Lady to intimidate the woman. For the wife of a head of State to tell a protestor, "you can take the mic, but I'm leaving. You have one choice" was bullying. She had to know the ripple of fear she would create in Ellen and the benefit attendees around her. Ellen Sturtz was making a crucial point: gay people are the only people who are treated as second class citizens in the U.S. Someone should remind the First that when African Americans were fighting for their civil rights, they didn't just annoy a First Lady (like Eartha Kitt did Lady Bird Johnson) they also rioted and used violence. Ellen Sturtz may have been out of place but she was not out of line.
Whilst I agree with what Ellen was campaigning for I disagree with her methods…heckling Michelle is not the right way of doing things especially as she has constantly supported LGBT rights
Isn't the problem with executive orders that they can easily be rescinded by a new President?
Even so, even a temporary fix like that may be helpful, – but then maybe there are political deals going on that we know nothing about.
Personally I found the 1st Lady's aggressive response a bit disturbing, there are better ways of talking to your supporters. She could just have said "Thank you, I'll pass that on to the President" instead of making a scene. Look at the decorum in the House of Lords between people with drastically opposed views!
It seems Mrs O's response was not any different to anyone else there given the comment from Ellen about " how negative the crowd seemed to be". People were there for a purpose, and that purpose was derailed by one person's stunt. I'd guess there was also probably a reasonable element of alarm in their reactions to the interruption, since these days we are all very aware of the lengths that some people go to in order to get their message heard.
In terms of your suggestion I rather think that committing to do that would set a precedent that heckling the first lady gets you a hotline to the white house. She might have found a more placatory way but its not like she told her to STFU after all.
Second class citizens should remember their place?
Well put Karen.
Michelle announced she was not good at handling such situations, and then proved herself right.
I totally understand a need to make a stance with regards to our rights. But there's a time a and place and sometimes you can do more harm than good.
Obama has done a lot of LGBT rights in the US. As much as Ellen may like everything to change over night, it's not possible, as they say, tiny steps and frankly to do this to Michelle Obama was damn right rude.
She IS the first lady and not the President. She does a lot of various charitable stuff, but she has no say in how her husband runs the country.
Really? You think Nancy Reagen had no say in how Ronnie ran the country?
Take the T out of LGBT and see how fast Obamarama moves….the T is diluting our struggles
Yeah! Get rid of those icky Mudbloods!
These comments are un-moderated and do not necessarily represent the views of PinkNews.co.uk. If you believe that a comment is inappropriate or libellous, please contact us.
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Can Christians Trust Talesfrom Heaven? Yes
Millions have read the testimonies of those who have been to heaven and returned. But what do these stories mean for Christians? How do they fit with what the Bible teaches? What do they say about who goes to heaven? Debate has raged throughout the church about whether we should trust these testimonies, since they don't always align with what we think the Bible teaches. Reverend John Price, a pastor who has been a pioneer in integrating near-death accounts into ministry, surveys the Bible and Christian doctrines to discover that these firsthand accounts of encounters with God are fully compatible with Christian spirituality.
Price began his ministry not believing in heaven. In Revealing Heaven, after hearing over two hundred accounts of near-death experiences, Price narrates the stories of those who helped change his mind and now makes a case not only for why Christians can trust near-death accounts but for why we should treat these amazing stories as precious gifts from God.


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West Jefferson House Rental Photos and Description
Custom 5 Br, 3.5 Ba 3 Level Home, 2500 Square Feet, Nicely Furnished,Mtn. Views
This custom mountain home has 5 bedrooms, 3.5 baths, and many upgrades. Granite counter tops, stainless appliances, gas fireplace, beautiful wood throughout home, large deck over looking mountains, and a stone and wood covered entrance way. Satellite, internet, phone, and HDTV's.
Full size washer/dryer in laundry room.
Recreation room with pool table, board games, and books.
A great place to relax with plenty of things to do within a short drive. 5 minutes from downtown West Jefferson shopping. Many other attractions close by including the
New River, Churches of the Frescoes, Blowing Rock, Boone, Blue Ridge Parkway and the list goes on :)
- Suitability:
- Minimum Age Limit for Renters
- children welcome
- non smoking only
- pets not allowed
- wheelchair inaccessible
About Kathy& Steve
Family of 5. Husband, wife, and 3 girls in age ranges 12 to 19 located outside Charlotte, NC.
We enjoy the North Carolina Mountains and the South Carolina Beaches and are fortunate enough to have properties in both locations (all listed on VRBO #'s 335239, 412912 and now this one 503406 ).
We try to spend our travel time relaxing at the different locations when not having to do the less fun things like working to pay for the homes and going to school :)
Kathy& Steve purchased this house in 2013
Why Kathy& Steve chose West Jefferson
In 'Our Point of View' this home is the place to be when wanting to enjoy the Blue Ridge Mountains. Home is custom built, full of everything you could need on vacation, on a beautiful private mountainside lot where feel away from it all and yet be able to be back into civilization within minutes.
We hope you choose to stay with us as our guests for your next family vacation.
What makes this house unique
We have listed quite a few things our home has in this listing, and it has many beautiful features. Best thing is to look at our attached photos because seeing is believing.
We have been dealing with renting our homes on VRBO for several years now and we know how to make your stay as enjoyable as possible.
You can look at our other listings and read the feedback on how we care for our homes and our guests (VRBO #'s 503406, 335239 and 412912).


text: Pancakes « Seasalt Blog shop online our shops meet the bloggers contact us Pancakes posted on February 20th, 2012 by rosie Tweet Leave a Reply Name (required) Mail (will not be published) (required) Website previous: easy peasy pancakes RECENT POSTS How to Make a Rope Wreath 11-21-2014 A Christmas Market Guide 11-20-2014 Truro City of Lights 11-19-2014 Have You Made Your Cake Yet? 11-14-2014 WIN your Wish List! – Up to the value of £250 11-11-2014 ARCHIVES Cornwall Devon Shops Coastal Recipes Jobs Gig Rowing Sailing Gardening Walking Competitions Behind the scenes Seasalt Limited trading as "Seasalt" & "Seasalt Cornwall" | Registered in England & Wales | Company No: 2259954 Registered Office: Unit 8 Falmouth Business Park, Bickland Water Road, Falmouth, Cornwall TR11 4SZ © Seasalt Limited 2005- all rights reserved


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shop to let
shop to let dunscroft area, currently being used as hairdresser/barber shop. but would suit a veriety of businesses from general store to cafe or pizza shop ect ect. the premises are located on broadway dunscroft on a parade of shops adjacent to a ch
- Date available: 01 Dec 2014


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Secret Keeper Girl Friendship Pak: 8 Great Dates for You and Your DaughterMultiple copy pack
List price $25.07
You save $5.10 20% off
Free delivery worldwide
Dispatched in 1 business day
When will my order arrive?
- Publisher: Moody Press,U.S.
- Format: Multiple copy pack | 96 pages
- Dimensions: 142mm x 267mm x 8mm | 454g
- Publication date: 1 October 2008
- Publication City/Country: Chicago
- Illustrations note: black & white illustrations
- Sales rank: 388,265
Product description
Finally! Some fun friendship truth for your daughter from the trusted team of Dannah Gresh, Family Life, and Moody Publishers. Secret "Keeper Girl-The Gift of True Friendships" promises to be one of the greatest tools moms have to connect with their 8-12-year-old daughters, while at the same time teaching them vital truth about friendship in a world that bombards them with lies. Giving you everything you need for a creative and focused mother/daughter date, "Secret Keeper Girl- The Gift of True Friendships" will guide you as you guide your daughter to godly friendships. During eight fun and easy-to-plan dates, you will tackle many questions including: How can I have and be a friend? Just what is real friendship? What's the source of friendship? The Secret Keeper Girl Kit 2 includes: An easy to use mother's planning guide A cool daughter's diary A music CD and poster SKG stickers
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DANNAH GRESH is a bestselling author and co-founder of Pure Freedom. She has sold over 750,000 copies of her books, including "And the Bride Wore White ," "What Are You Waiting For: The One Thing No One Ever Tells You About Sex," and "Lies Young Women Believe" (co-authored with Nancy Leigh DeMoss), in addition to the Secret Keeper series. She is also a frequent guest for national radio, TV and print mediums. Dannah lives in State College, Pennsylvania, with her husband, Bob, and their three children.


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Nyack News
Third Annual Student Research Conference at Nyack Rockland
The Center for Scholarship and Global Engagement will host its Third Student Research Conference, Thursday, April 10 on Nyack's Rockland County campus from 9:00 a.m. until 3:00 p.m. in Bowman Gymnasium. With the theme, "Making a Difference: Contributions from our Disciplines" CSGE will welcome keynote speaker, Dr. Marcy Kelly, professor and assistant chair of the department of Biology and Health Sciences at Pace University in New York City.
Dr. Kelly earned her Ph.D. in 2000 from the Department of Microbiology and Molecular Genetics at Rutgers University-Newark. In addition to her teaching accomplishments with undergraduate biology and pre-health majors in the classroom and teaching laboratory at Pace University, Dr. Kelly maintains two active research programs. Her undergraduate research laboratory work focuses on the interaction between a model organism for tuberculosis, Mycobacterium bovis-BCG, and molecules produced by the human immune response. She is also currently in contract to develop a first-year biology major laboratory manual to introduce students to scientific research. Dr. Kelly has two publications in peer-reviewed educational journals and she is currently the Research Editor for the American Society for Microbiology (ASM) education journal, Journal of Microbiology and Biology Education. She is the Lead Facilitator for the ASM Biology Scholars Program Transitions Residency to assist undergraduate faculty with the development of educational assessment manuscripts for publication.
Click here to learn more about CSGE and upcoming events.
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There's a certain confidence that radiates when Avant sings. It could have something to do with the way women react when he hits his falsetto or how his voice rides the beat like a surfer cruising the waves.
Avant first appeared on the music scene with his summer anthem "Separated," that peaked at number one on the R&B charts. He kept us interested with hits "My First Love" and set the bedroom ablaze with "Making Good Love."
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November 17-23: This Week in Black History
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text: Vintage Enamel Shaker And Cookie Cutter by Ella James £6.95$13.25€9.15$11.63 In stock £2.75$5.24€3.62$4.60 mainland UK delivery - Order now and receive this item on or before Thursday 4 December £2.75$5.24€3.62$4.60 mainland UK deliveryEstimated delivery: 2-5 days £9.70$18.50€12.77$16.24 Express Next Day 1pm - Order now and receive this item on or before Monday 1 December Express delivery available £15.70$29.95€20.67$26.28 Saturday delivery - Order now and receive this item on or before Saturday 29 November International delivery available add cookie cutter tin and 5 cookie cuttersadd cookie cutter tin and 5 cookie cutters (required)Yes , please (+ £15)No , thanksadd cookie cutter tin and 5 cookie cutters (required)Yes , please (+ $28.61)No , thanksadd cookie cutter tin and 5 cookie cutters (required)Yes , please (+ €19.75)No , thanksadd cookie cutter tin and 5 cookie cutters (required)Yes , please (+ $25.11)No , thanks quantity by Ella James Location: Oakham, GB read seller's profile see seller's complete range more items from this seller Pink Ceramic Cake Stand £26$49.60€34.23$43.53 Retro Style Enamel Kitchen Scales £25$47.69€32.91$41.85 Set Of Six Milk Bottles In A Crate £14.50$27.66€19.09$24.27 Willow Teacup Planter £14.95$28.52€19.68$25.03 new Cast Iron Reindeer Or Tree Stocking Holder £18$34.34€23.70$30.13 Bank Note Tea Towel £9.50$18.12€12.50$15.90 view all you may also like PRODUCT DETAILS DELIVERY RETURNS ask seller a question Cute duck egg blue country style enamel shaker . This lovely little sugar shaker with a will be a cute addition to any kitchen . It is perfect for dusting icing sugar , flour or chocolate powder. A coordinating cookie cutter tin with five traditional cutters is also available to complete a gift for a keen baker . Easy to fill and clean its also an ideal gift for a junior pastry chef. made from: Enamel dimensions: H 12.5cm x W 7cm product code: 259547 This product is dispatched to you by Ella James. MAINLAND UK order now and receive this item on or before price Standard Delivery Thursday 4 December £2.75$5.24€3.62$4.60 Express Next Day Monday 1 December £7.70$14.69€10.13$12.89 Express Next Day 1pm Monday 1 December £9.70$18.50€12.77$16.24 Saturday Delivery Saturday 29 November £15.70$29.95€20.67$26.28 NON-MAINLAND UK estimated delivery price Highlands & Islands of Scotland 2-5 daysfrom dispatch £2.75$5.24€3.62$4.60 Northern Ireland 2-5 daysfrom dispatch £2.75$5.24€3.62$4.60 Other UK Islands 2-5 daysfrom dispatch £4.95$9.44€6.51$8.28 INTERNATIONAL DELIVERY estimated delivery price Western Europe 2-5 daysfrom dispatch £9.95$18.98€13.10$16.65 Rest of Europe 5-10 daysfrom dispatch £9.95$18.98€13.10$16.65 USA & Canada 5-10 daysfrom dispatch £17.95$34.24€23.63$30.05 Far East & Australasia 5-10 daysfrom dispatch £17.95$34.24€23.63$30.05 Rest of the world 5-14 daysfrom dispatch £17.95$34.24€23.63$30.05 You have 28 days, from receipt of cancellable goods, to notify the seller if you wish to cancel your order or exchange an item. Please note: goods that are personalised, bespoke or made-to-order to your specific requirements, perishable products and personal items sold with a hygiene seal (cosmetics, underwear) in instances where the seal is broken are non-refundable, unless faulty. Read more about our returns policy.Should you choose to return or exchange your order you will need to deliver the item(s) to the UK, where this seller is based. Ella James's return policy


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Leo Panitch is a Distinguished Research Professor, political economist, Marxist theorist and editor of the Socialist Register.
In this interview Leo Panitch discusses "The Making of Global Capitalism" and the intimate relationship between modern capitalism and the American state, including its role as an "informal empire" promoting free trade and capital movements. He also discusses how the US has superintended the restructuring of other states in favor of competitive markets and coordinated the management of increasingly frequent financial crises.
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Find Out The Meaning Behind The Numbers At The Gas Pump
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Las Vegas, Nevada (NAPSI) - Are you one of the millions of Americans who will load up their car this summer and head out for a weekend getaway?
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Las Vegas, Nevada (NAPSI) - There's good news for those who get a kick out of soccer and are trying out for a team in the near future. Taking a few practical steps before the tryout can help them stand out on the field and make the most of their opportunity.
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Carson City, Nevada - The Nevada Division of Public and Behavioral Health (DPBH) today announced the launch of two new Nevada-specific websites to help schools protect students from sexual assaults on college campuses.
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Washington, DC - U.S. Customs and Border Protection, the agency responsible for securing U.S. borders from all threats, is accepting applications nationwide for CBP officer positions at air, land and sea ports across the country.
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Washington, DC - A Las Vegas-based former Department of Defense contractor has been extradited from Iraq to the United States to face fraud and conspiracy charges for attempting to bribe U.S. officials in order to secure government contracts for his companies.
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Las Vegas, Nevada (NAPSI) - Whether you are a committed clipper or you have a more laid-back relationship with coupons, there's good news.


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Table No. 10
- Address:
369 10th Avenue
San Diego, CA 92101Neighborhood:
Downtown / Gaslamp
- Cuisine:
Contemporary AmericanPrice: $30 and under
Table No. 10
- Dining Style: Casual Elegant
- Website: http://tablenumber10.com/
- Phone: (619) 550-1262
- Hours of Operation:
Dinner: Tuesday - Thursday: 5:30pm - 10:00pm; Friday & Saturday: 5:30pm - 12:00am; Sunday: 5:30pm - 10:00pm
Brunch: Saturday & Sunday: 10:00am - 2:00pm
- Payment Options: AMEX,Discover,JCB,MasterCard,Visa
- Cuisine: Bar / Lounge / Bottle Service, American, Contemporary American
- Executive Chef: Jason Gethin
- Dress Code: Smart Casual
- Accepts Walk-Ins: Yes
- Additional Details: Banquet/Private Rooms, Bar Dining, Bar/Lounge, Beer, Chef's Table, Counter Seating, Entertainment, Farm to Table, Full Bar, Gluten-free Menu, Happy Hour, Late Night, Non-Smoking Restaurant, Personal wines welcome, Personal wines welcome (corkage fee applies), Private Room, Weekend Brunch, Wine
A word from Table No. 10
Table No. 10 offers "Contemporary American Tapas" created by Executive Chef Jason Gethin. With a focus on shared dining and handcrafted, fresh unique cocktails will make Table No. 10 the spot in the East Village. American whiskeys are augmented by an extensive list of whiskeys from Europe and beyond as well as a selection of all-bourbon cocktails. A field of pendants suffuse the space with a tawny glow that sets a mood of sophisticated conviviality for both drinking and dining.Continued
Foodspotting photosSee all photos
Awards voted by OpenTable diners
- Diners' Choice WinnerFit for Foodies
- Diners' Choice WinnerHot Spot
- Diners' Choice WinnerContemporary American
Table No. 10 - Best Restaurants in Downtown / Gaslamp ›
Table No. 10 reviews from OpenTable diners
63 reviews since July 31, 2014
- Food4.5Service4.5
- Ambiance4.5Noise LevelModerate
fit for foodies (55)neighborhood gem (37)hot spot (32)special occasion (24)romantic (23)vibrant bar scene (21)notable wine list (18)good for groups (17)late-night find (11)scenic view (8)great for brunch (5)great for outdoor dining (3)Show More
- Great Atmosphere - food a little lackingJanlovestoEatDined on 11/11/2014This place had a wonderful ambiance. We had a small group (6) people and scheduled to sit downstairs around the kitchen. We were "upgraded" to the table near the kitchen. We started with appetizers that mostly hit the mark. The main dishes were not as successful. The hanger steak was not flavorful while the brisket was over-sauced with scary large pieces of bread overwhelming the plate. The risotto looked promising when large pieces of truffle was shaved on top. However the truffle flavor instead of being overwhelming was in fact, barely discernible. I did find the deconstructed ravioli to be exciting and fun to eat; the pork a nice variation. Good service and we will be back to try again.Special Features:I would recommend this to a friend.
- One of SDs bestfoodlovingcoupleDined on 11/7/2014I was very impressed through my entire meal. Starting with our pre-dinner cocktails down to the desert, nothing disappointed. All of the staff was very engaging, gave great recommendations and made us feel welcome. We were lucky enough to sit right alongside all the action by grabbing seats at the bar top 'chefs table'. I heard good things about the scallops and pork belly and it did not let us down. The rolls with bone marrow butter were delicious, though I would happily of just taken the whole bone. The deviled eggs were delicious, and the texture they achieved on the sous vied octopus was delightful, the flavors of the dish were wonderful. It was amazing experience, the kitchen staff was great. I felt I got more then my moneys worth!Special Features:
- Exceptionalroberry82Dined on 10/23/2014An already amazing evening was turned exceptional when we sat down at Table No. 10. Our server, Max, was fun, knowledgeable and made us feel like we were his only table. We shared our way through a few small plates, and were lucky enough to snag their special of the night along with the best risotto I've ever had! We paired the evening's food with one of our favorite bottles of red wine, which we're only able to find at two other restaurants in San Diego! Looking forward to going back!Special Features:I would recommend this to a friend.
- Good food, but not accomodatingpleasenonicknameDined on 10/17/2014They worked us right in even though we were 10 minutes early. It's located in an old downtown building but no views. The food was good and unique. But when we wanted just the ice cream from one of the deserts, there was a quick "no we can't do that". Really? Our check was over $150 for 2 and you can't take a special request? Fail. You can't be in business doing that. Would not go back.Special Features:
- Great food and serviceYamahazingVIPDined on 10/1/2014Great new spot, very interesting food, the brisket is out of this world!Special Features:
- Sat by the kitchen staff. Loved it!A1datenightDined on 9/28/2014Friendly staff, delicious unique dishes - we loved every aspect of the experience! We will definitely go back for another date night! We tried 6 different small plates, devoured the rolls and finished up with the donut holes. The talents of the kitchen staff made for an amazing evening!! Kudos to Table # 10!Special Features:
- valpalDined on 9/28/2014Excellent food, excellent service, interesting drink menu. All the dishes are beautifully presented and have a mix of interesting textures and flavors. Everything we tried was awesome.Special Features:
- aokpaintingDined on 9/28/2014There was 6 guest at our table we ordered 7 different dishes and we shared all dishes all six guest thought the menu was over priced and every dish we ordered was Very SALTY even the dinner rolls were salty the service was great the drinks were good the food was way over priced>Special Features:
- Great food but too priceyOpenTable Diner Since 2009Dined on 9/26/2014Small plates are good but really small and expensive The roasted vegetables were awesome but such a small portion for price. Brussels sprouts were very good too.Special Features:
- Foodie and cocktail dreamBonzoDined on 9/12/2014Service was outstanding, salads were extraodinary, really liked everything about our evening. We had the citrus salad and ceaser salad. Ceaser was made w Brussels sprouts. Different but so flavorful. We had duck and brisket. So much flavor and tender. Cory is an amazing mixologist and made a killer manhattan correctly. Delivered the drink to our table and the men complemented each other's beards! We finished with tieramisu donuts! A great night for east villagers!Special Features:I would recommend this to a friend.
- Great foodOpenTable Diner Since 2008VIPDined on 9/12/2014But air conditioner was leaking on our table and people sitting at the booth upstairs. The server finally moved us. The good was great.Special Features:I would recommend this to a friend.
- Amazing FoodvalpalDined on 9/9/2014The food was beautifully presented, with an amazing array of flavors and every morsel was delicious. The desserts were the best I've had anywhere. Imaginative and a taste sensation.Special Features:
- Great food and staffFromLove2FoodDined on 9/6/2014It's all about the food here. It's well crafted and beautifully plated. But best of all it tastes amazing. I would highly recommend the desserts. The Moscato was perfect. Our waiter was knowledgeable about the food and good at conversation. It just got really crowded at 830ish and our service suffered (couldn't flag our waiter down and things we ordered came later than expected). I am definitely coming back but only during the early hours of opening.Special Features:I would recommend this to a friend.
- AmazingJennzimm14Dined on 8/30/2014A must if in the east village. Amazing food for all different taste buds.Special Features:I would recommend this to a friend.
- serviceloreelDined on 8/29/2014Our server was awsome. Best service we have had in a whileSpecial Features:
- TerribleJennieKDined on 8/23/2014This restaurant was a huge let down. Very loud, food was not good! Brussel sprout Caesar had plops of dressing that was way to salty. The chicken skins were only made of fried bread crumbs, and the Branzino was in edible because our waitress,who filleted the fish at the table had no idea what she was doing and made a mess of the fish and it still had bones through both sides. We left hungry and annoyed to have spent the money on this place!
- Fantastic Food and Atmosphere!jinxiDined on 8/22/2014Had a wonderful meal here at Table No. 10, one of San Diego's hottest new restaurants! Here's what we ordered: - I'm Messin' With Texas cocktail - brisket fat-infused whiskey cocktail; loved the smoky flavor. - Deviled Eggs ("Bites") - Mushroom & Grits ("Small Plates") - Octopus & Portuguese Sausage ("Small Plates") - Scallops & Pork Belly ("Small Plates") - BBQ Brisket ("Large Plates") - Creme fraiche panna cotta (Desserts) Loved all the dishes; I especially recommend the mushroom and grits - the grits are made in-house and have a distinct sweet corn flavor. Absolutely my favorite dish of the meal (although I loved everything else, too!). Fantastic service and lovely atmosphere - this is a perfect date night or hang out spot!Special Features:
- Fun, great foodMarKDined on 8/21/2014The service was outstanding and I really love the way they remodeled and decorated the place. Very clean and bright. Food is amazing but definitely better to go with a group so you can sample a few things. More tapas style.Special Features:
- Should have heeded OT's adviceefoodieVIPDined on 8/17/2014There's something off about this restaurant. It is beautifully laid out, but it doesn't know who it is. I heard servers present the restaurant both as a tapas place and as a regular restaurant. It surprised me tremendously when ALL of our courses (salads and entrees) came out at the same time. They used liquid smoke on my dish - inappropriately - which made it hard to digest. Their cocktails were good and their doughnut dessert (which took a lifetime to arrive) was to-die-for. I can't honestly recommend this place. They need to grow up a little and refine their service.
- Great food and wineAndyDined on 8/16/2014My son and I took my wife to Table No. 10 for her birthday. The food was excellent, I recommend the octopus starter and the BBQ brisket. their wine list caters to all taste levels. Service was excellent. We will definitely will go backSpecial Features:I would recommend this to a friend.
- Took me by surpriseApparitionDined on 8/15/2014Was not sure what to expect but we had a fantastic time. Wonderful food and excellent service. We took every recommendation from the waiter and were not disappointed. The brussel sprout cesar salad, brisket sandwich and fried chicken was all incredibly great.Special Features:
- PotentialseriousaboutfoodDined on 8/9/2014Table 10 is a new restaurant with a great décor. Loved the building, parking difficult. We were there relatively early & no street parking, lot across from the restaurant pricey at a flat 10 dollar rate. Our table upstairs in loft like atmosphere had open ceiling to outside. Lovely. Service was very good, server knowledgeable. Menu very nice. Made a luke warm martini heavy on the vermouth. Chicken skins very salty. Ordered Duck and it was too rare although presentation was amazing. The Ravioli with suckling pig excellent. We ended up sending the Duck back and it took forever. The potatoes were hard on the second plate. They were accommodating but should have made more of an effort to correct errors.Special Features:I would recommend this to a friend.
- My New Favorite Place!EastVillageFoodieDined on 8/5/2014Table No. 10 just opened recently and it is a foodie's cream. Make their own craft beers and even sodas. Everything fresh, local sourced. When I o by at 7 am they're in there working in the open kitchen already, even though they don't open til 6 pm. Homemade fries were the best I've ever had. Even the grilled vegetables were succulent. Really creative and tasty entrees, with gluten-free options. And the deserts are worth a flight from Australia!Special Features:I would recommend this to a friend.
- A Must Experience RestaurantOpenTable Diner Since 2013Dined on 8/1/2014The food, The service, The experience was amazing. I highly recommend Table No. 10 I had two friends visiting from Chicago and we all loved it.. Their cocktails are incredibly creative. Their desserts were incredible and we loved all the small plates we shared... This is a must experience for foodies..Special Features:
- The following 4 reviews are from the Table No. 10 reviews archive.
- Best Meal in SDOpenTable Diner Since 2014Dined on 7/25/2014This place is my new all time favorite. I haven't had a meal this good since I moved from SF. I sat right at the kitchen with my party and the chef took care of us personally. Everyone in the kitchen chatted with us and since the chef's wife is a celiac there's a gluten free option for nearly everything on the menu. The bartender is an expert in anything that goes in a glass and once you try the food you'll understand why I've already booked two more reservations to eat with friends and family.Special Features:
- fun placeOpenTable Diner Since 2013Dined on 7/22/2014My table of four attended this restaurant on Tuesday night; I live in the Icon building on the same block. I like the renovations and the food and service were excellent. Everyone should try to Flux Capacitor!Special Features:
- Had great expectationschrisVIPDined on 7/17/2014It may not be a fair review because we had very high expectations for Table No. 10. The menu wasn't very clear and there were not a lot of options. Basically only 3 options if you take away the two sharing options. The drink list was great though. The food was very good, just not a lot of options.Special Features:I would recommend this to a friend.
- Just what the neighborhood neededCHfilesVIPDined on 7/17/2014From the moment we sat down everything unfolded perfectly. The service was caring. The food was inventive and beautiful. The vibe was energetic and fun. We will definitely will make this a regular place.Special Features:


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4405V00002B - Dvd-rom
Mfr Name: LG Electronics
Mfr Number: 4405V00002B
See all items in LG
83-14593 - LG 24X DVD Burner with M-Disc
Instantly enhance any system and enjoy a higher level of disc writing performance at a max speed of 24x. This increased speed lets you burn more discs in less the time, therefore allowing you to enjoy greater time management and overall efficiency.
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83-13498 - 3D Compatible 12X BD-R/RE Blu-ray Drive
The BDR-207DBK drive is perfect for system builders, for those looking to upgrade to a Blu-ray burner, or for those who already have software.
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83-13533 - 18X Sata Dvd-rom Drive Black Drive Only
Lite-On Optical 18X DVD, 48X CD-Rom SATA internal drive
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Burn disc with enhanced data protection and intuitive Disc Encryption in just 3 quick steps with this slim external DVD±RW drive.
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CU-VD3US - Everio Sharestation External DVD Burner
Everio's DIRECT DVD button enables one-touch launching of the DVD-Video disc burning process. It's smart so you can even use it to automatically transfer only newly recorded data to the burner, just the scenes you manually select, or pre-select using the Playlist.
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83-11296 - DVD+R DL 8X 25pk
High capacity, portable storage for both digital video and data recording
Philips 8X DVD+R double layer media is ideal for sharing and archiving data, home videos, and photos
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83-14598 - 12x Blu-Ray Writer
Enter a new era of high definition visuals with the BC-12B1ST Blu-ray drive.
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The ASUS Blu-ray writer combines multiple technological innovations, easily integrating many advantages in a user-friendly environment. The stylish appearance and functionality of this product provides consumers with an ideal choice for both business and entertain...
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4.7GB capacity can store up to 2 hours or 133 minutes of high quality video and up to 3 hours of VH...
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The M-DISK system uses a patented rock-like recording surface instead of organic dye to etch your data onto a disc. The M-DISC has been tested and proven to outlast standard DVDs currently on the market. M-Disks can be read by any standard DVD drive and have a pr...
Mfr Number: GE24NU40
It was very easy and convenient to order. The delivery was in 3-4 days. Wow...Very impressed


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Queerty is better as a member
Queerty, you have outdone yourselves today. That hilarious interview with the wonderful Miriam Margolyes, and naked (if blacked out) pics of AFP. Awesome. Thanks!
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The Way He Looks — Best Gay Teen Romance Movie Ever?
Shape Up! Here's A Workout That Will Make You Thankful
UPDATE: Dad Who Accidentally Discovered Son Is Gay Proves Yet Again That He's Doing It Right
PHOTOS: Yummy Guys Show Off Their Tasty "Manspreads" Just In Time For Thanksgiving


text: Aarkstore.com announces, a new market research report is available in its vast collection: Flooring- America http://www.aarkstore.com/reports/Flooring-America-149588.html Summary This package contains 4 flooring market analyses from the following American countries: Brazil, Canada, Mexico and the United States The flooring market analyses give an overview of the actual situation, trends and future outlook of the flooring markets in different American countries. The market analyses provide essential market information for decision- makers including: * Overall market for flooring, 2004-2010 * Market for flooring by type (resilient, non-resilient, carpets and rugs) * Forecasts and future outlook of the market till 2016 * Country overview, macroeconomic indicators and indicators of doing business These market analyses answers to questions such as: * What is the size of the flooring market in different American countries? * How is the flooring market divided by material? Which material groups are growing fast? * How the flooring market has been developing in different countries? How does the future look like? * What is the potential for flooring market in different countries? * How the indicators of doing business look like? For example, how easily the contracts are being enforced, or what is the inflation rate in and how is it developing? For More Related Reports Please follow the link : http://www.aarkstore.com/search/viewresults.asp?search=Flooring &PubId=&pagenum=1 For more information, please visit : Contact: Jenny Ph.No.918149852585 Email : firstname.lastname@example.com/ URL: http://www.aarkstore.com/


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'12-12-12' Concert for Sandy Relief Plays Madison Square Garden
It was announced today that Clear Channel Media and Entertainment, The Madison Square Garden Company and The Weinstein Company -- the same group that produced and sponsored the historic 9/11 benefit "The Concert for New York City" -- have come together once again to present "12-12-12" (A Concert For Sandy Relief). The special one night only live music event will help provide assistance to the millions of people throughout the tri-state area who have been affected by Hurricane Sandy. "12-12-12" (A Concert For Sandy Relief) will occur on December 12, 2012 at Madison Square Garden in New York. More details on the event and the artist line-up will be released in the coming days. All money raised will be administered directly to those who need it most, through the Robin Hood Relief Fund.
As the tri-state region fully realizes the true scope of Sandy's stunning and acute devastation on the coastal areas of Long Island, Queens, particularly Breezy Point and the Rockaways, Staten Island and New Jersey, the enormous task of rebuilding both the infrastructure and thousands of shattered lives becomes dauntingly clear. Robin Hood - New York City's largest poverty fighting organization - has re-established the Robin Hood Relief Fund, which it spearheaded following 9/11, to help those most affected by Hurricane Sandy.
The needs are enormous: Sandy has created a devastating short and long-term housing crisis, with tens of thousands of people, including many first-responders, in need of significant rebuilding assistance. Many victims of Sandy are undocumented, non-English speaking residents who are especially vulnerable during a crisis, particularly relating to navigating complicated insurance and legal requirements. Thousands of New York City schoolchildren have lost essential tools, such as books, computers and supplies, while also enduring displacement, with their schools either damaged or turned into emergency shelters. Food banks throughout the region are struggling to maintain their daily complement of services, as they dramatically increase their operations to feed the huge influx of people affected by the storm. Additionally, the psychological scars of Sandy will linger for years to come, with those affected in need of ongoing emotional counseling and support.
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May 22, 2014
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According to an article in today's MediaPost, Borrell Associates' newest local forecast is quite upbeat about geotargeted ad growth across categories, but especially in paid search.
Borrell predicts a 32% increase in local advertising online, to $7.7 billion by 2007. The firm also estimates local paid search will amount to $1.8 billion by next year. By 2010 geotargeted email and paid local search will together represent 50% of online local advertising. And the overall value of the local online ad market will approach $10 billion at the end of that forecast period, according to Borrell.
There's some additional analysis on my blog. We're waiting for a copy of the report and will follow up with additional posts after we get a chance to take a look.
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Forecast more >
A weak cold front will move through our area tonight with temperatures a little cooler for Thanksgiving. A warming trend will begin this weekend with a slight chance of light showers Sunday.
Lakes ...
Search Results
Beaumont man sentenced to 25 years for aggravated robbery and attempted capital murder of a police officer
A Jefferson County judge sentenced a Beaumont man to 25 years behind bars for aggravated robbery and attempted capital murder of a police officer.
Ronnie James Lafleur admitted he pointed a pistol at the store clerk during a robbery at KRS Food Mart located in the 3000 block of Pine Street in December of 2012.
Lafleur pulled the trigger but the gun did not discharge.
Then Lafleur shot at officers while trying to the leave the Mart.
Lafleur has 13 prior felony convictions and nine prior misdemeanor convictions.


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Travel Blogs from Montreal
Oust et la pomplemousse?!
... made our way down along the pier to look out across the river. Whilst walking back the the centre we stopped by the pedalo station opposite the Tutankhamen exhibit and dangled our feet in the water. We headed back up Rue Notre-Dame and ate a share platter of nachos with lots of tasty added extras! We then meandered to Place Jacques Cartier where so many stalls of caricature artists clamoured for models. We stopped and watched ...
We're Back!
... them anyway?
Since we now have our bags Peter called the Holiday Inn where we had left the car (if you stay one night then you can leave your car for a long term stay in their lot—for an extra charge, of course). The van came and we waited for some others to arrive who had called for the van but after about 15 minutes when they didn't arrive the driver took us to our car. When you call for the Stay and Park van you are not supposed ...
It's the Final Countdown
... to one country when you can go to two?
Better yet, why deny the opportunity a 13 hour layover to visit MK's motherland (the Netherlands) presents?
After all it has been almost four years since the Dutch-one has had a chance to fill up on authentic Dutch delights: frikandel speciaal, market-fresh stroopwafels, Chocomel, vla...to name a few, as well, MS has ...
Walking Mont Royal and the Canadiens
... of the park's trees are more than half a century old. Thought that might wake some of you up! There was a fellow there who was obviously doing some sort of film....lets say his subject was dressed....oddly. See for yourself. I would have tried to film him when he stood up but...I don't think it would have been appreciated. I guess having half an animal costume on is better than nothing at all on a day that was not going anywhere past 6 degrees..... Anyway, we walked some ...
Montreal Fun!!
... art which adds further exuberence to the square. Around the fringes of the square street artists and musicians entertain the crowds and provide auditory delight to this fun community space. As you walk up the square you notice tiny alley like streets extending away from the square including one such alley which is filled with venders selling artworks known as artist alley. At the top of the square there is a noticeable column with a man perched on top of it. The column strikes ...
Other places to stay in Montreal
Marriott Chateau ChamplainDowntown, Montreal | 4 star hotelfrom $192
- An anniversary getaway to remember!
- Couln't ask for more
- Chateau Champlain was wonderful!
Holiday Inn Montreal MidtownJeanne-Mance, Montreal | 3 star hotelfrom $127
- We were very pleasantly surprised with the Holiday Inn Midtown
- Great place
- Not awful at all
Sheraton Le Centre Montreal HotelDowntown, Montreal | 3 star hotelfrom $161
- Always stay here!
- The View? Cheers! The Staff? Jeers!
- Wonderful stay
InterContinental MontrealSaint-Jacques, Montreal | 5 star hotelfrom $168
- Great Hotel
- There are better options in Montreal
- Rude service, dust on the curtains and mold in the bathroom
Hyatt Regency MontrealDowntown, Montreal | 4 star hotelfrom $181
- Avoid this place if you can
- The Good and the Bad
- Excellent location and much more
Delta Montreal HotelSquare Mile, Montreal | 4 star hotelfrom $183
- Great way to end our trip!
- Disgusting
- Not a 4-star hotel
Delta Centre-VilleDowntown, Montreal | 4 star hotelfrom $183
- Only tried the revolving restaurant
- A nice place for families
- Right in between St. Catherines and Vieux-Montreal
Holiday Inn Montreal AirportSaint-Laurent, Montreal | 3 star hotelfrom $110
Hotel Omni Mont-RoyalPeter-McGill, Montreal | 4 star hotelfrom $172
- The best in Montreal
- Omini Mont Royal Just Right
- Great weekend getaway
Holiday Inn Select Montreal Centre-VilleDowntown, Montreal | 3 star hotelfrom $164
- We recommend this hotel
- A pleasant surprise
- Hotel was good enough for our stay
Fairmont The Queen ElizabethDowntown, Montreal | 4 star hotelfrom $180
- Loved every moment
- Bugs
- Couldn't be better
Hotel Gouverneur Place Dupuis MontrealDowntown, Montreal | 4 star hotelfrom $132
- Best Location For Gay Village
- Tired Hotel
- Beautiful, Clean, Great service
Hotel Le Cantlie SuitesSquare Mile, Montreal | 4 star hotelfrom $140
- Nice, inexpensive hotel
- Gestapo at the front desk
- Cantlie ignorance
Sofitel MontrealSquare Mile, Montreal | 4 star hotelfrom $209
- Rather Impressed
- Beds to die for..
- Terrific French Hotel in the Quintessential French City
Crowne Plaza Hotel Montreal AirportSaint-Laurent, Montreal | 3 star hotelfrom $120
BEST WESTERN PLUS Montreal Downtown-Hotel EuropaSquare Mile, Montreal | 3 star hotelfrom $138
- Small but servicable
- Small with Big Attitude
- Excellent location
Novotel Montreal CenterVille-Marie, Montreal | 3 star hotelfrom $138
- Good price, good location
- Pricy but worth it!!!
- Not a wonderful experience
Travelodge Montreal CentreDowntown, Montreal | 2 star hotelfrom $98
- Get what you pay for
- Tiny rooms filled up with smoke
- Tiny Room and Shower
Hilton Garden Inn Montreal Centre-villeJeanne-Mance, Montreal | 5 star hotelfrom $167
BEST WESTERN Ville-Marie Hotel & SuitesSquare Mile, Montreal | 3 star hotelfrom $142
- Would not stay at this hotel again.
- Very nice
- If you are looking for Peace and Relaxation. STAY AWAY from it
Hotel Maritime PlazaSquare Mile, Montreal | 3 star hotelfrom $109
- Not as bad as these reviews say...
- Not as advertised...
- Recommended to friends
Embassy Suites MontrealVieux-Montreal, Montreal | 4 star hotelfrom $169
- Great location and lovely suite
- Una excelente ubicaci�n y una suite encantadora.
- Tr�s bon emplacement et suite ravissante
Quality Hotel Downtown MontrealLe Plateau-Mont-Royal, Montreal | 2 star hotelfrom $105
Hotel Espresso Montreal Centre-Ville/DowntownPeter-McGill, Montreal | 3 star hotelfrom $117
Hotel Ruby Foo'sCote-des-Neiges-Notre-Dame-de-Grace, Montreal | 3 star hotelfrom $151
Holiday Inn Express Montreal Centre-VilleQuartier Latin, Montreal | 2 star hotelfrom $138
- Highly Recommend!!
- Nice stay
- Great Stay!