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United States, NC, Raleigh
Joined Jun 2005
1,789 Posts
Indoor flying - foamie & micro time slots?
With our indoor season underway, we've consistently drawn more pilots each time. This last weekend showed 26 pilots and several spectators. This time in-particular...the airspace was extremely crowded and busy.
We've had a couple people comment that they are scared to fly their micros when bigger foamies and helis are out there as the micros always take the bulk of the damage. Several younger pilots are becoming discouraged as they usually go home with broken planes, not to their fault. A suggestion was brought up to try and divide the time between foamies/helis/micros. While I see the argument, policeing the airspace every 15 minutes sounds like a pain, especially since we are there for 4+ hours at a time.
Can everyone else comment on how their airspace is handled when flying indoors?
West of California Speedway, East of LaLa, North of Disneyland
Joined May 2001
2,378 Posts
I fly with a group in a single-court gym. In the past, we had more members and a wide variety of small plane categories that guys brought. To preserve the integrity of the smallest planes, we had time slots for different categories, and it worked out well. The duration of the "slots" were slightly longer than the time the typical battery life for that category. As long as the time slots are organized so that similar speed planes fly together, the chances of mid-airs are reduced. For instance, we had several Cessna Miniums (remember those?) flying at once with similar-size-and-speed planes, then a slot with a gazillion (well........) Vapors, etc. Then we had an "open" slot where the larger (but fewer) planes went up. These slots were then cycled through again, allowing time for battery charges in between.
This all worked well, and our host and organizer was always open to suggestions.
As far as heli's are concerned, they are still relegated to the corners of the facility, where they have the least impact on planes which are turning, well clear of the corners.
Thats how its been at both local clubs' indoor events. 15 minutes for foamies, for helis and for micros. Some guys still don't like it and want to do a separate event for micros, which i wouldn't mind but i do fly helis as well so i am not terribly bothered by it.
West of California Speedway, East of LaLa, North of Disneyland
Joined May 2001
2,378 Posts
Joined Oct 2010
151 Posts
We also fly in a single gym sized area, and if there's a reasonable number of people there, we do slow planes, fast planes, and helis in separate sessions. I think our sessions are about 10 minutes each. We've got a 3 sided sign that says what the current session is and a timer to do the session timing. Personally I think it's worked out pretty well, and as far as I know hasn't generated any complaints. If the number of people gets low enough, then we drop the restrictions on what's flying.
Souderton Pa. USA
Joined Mar 2002
2,670 Posts
We fly in a single court gym. Most time is open flying and it's mostly cubs and champs with a few T-28's and extras, helis also fly in this time. We have a few Vapor flys for 15 minutes that include anything that flies "vapor like". Then a couple time slots for large 3D. If I ask I usually get the air to myself for a couple minutes to fly stick and tissue.
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With a New Year upon us, real estate brokers and developers are dampening their expectations for the retail market in Nevada over the next couple of months and for the rest of 2015. Nevertheless, all of them see positive trends for the market and some reason to remain optimistic. "We are clearly in a recovery," said Brendan Keating, principal with The Equity Group in Las … [Read more...]
Educating, Connecting Entrepreneurs; Median Home Price Hits $200,000; 5K to Raise Funds for Kids with Cancer
Las Vegas Will Launch 1 Million Cups to Educate, Connect Local Entrepreneurs 1 Million Cups, a program to engage, educate and connect entrepreneurs, launched in Las Vegas on Wednesday, August 13. The weekly event will be located in the inNEVation Center, powered by Switch. 1 Million Cups is a weekly gathering that is building startup communities over cups of coffee and … [Read more...]
VEA Encourages Community to Support Fill the Bucket Truck School Supply Drive on Aug. 2
PAHRUMP, Nev. – In an effort to support schools in southwestern Nevada, Valley Electric Association, Inc. (VEA), a member-owned electric cooperative headquartered in Pahrump, will host its annual Fill the Bucket Truck School Supply Drive on Aug. 2 at multiple locations in Pahrump. VEA encourages community members to participate by donating during the charitable event, which … [Read more...]
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Take Charge Indy on Track for Donn Handicap
Chuck and Maribeth Sandford's Take Charge Indy , winner of the $1 million Florida Derby (gr. I) in March, breezed three furlongs in :36 4/5 at Palm Meadows Dec. 21 in his first workout since finishing a game second in the Clark Handicap (gr. I) at Churchill Downs Nov. 23.
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Small specific binding molecules, such as single variable domain antibodies (Dabs) and Fv fragments, can be coupled to solid plastics surfaces or to tracers such as enzymes by means of linkers comprising polypeptides containing from 5 to 20 amino acids and which are hydrophobic and/or contain at least one lysine residue. The coupling can be achieved without significant loss of specific binding activity. The combined Dab/linker or Fv/linker can be prepared by expression in genetically-modified organisms.
1. A specific binding reagent, comprising:
(i) at least one variable domain antibody fragment which is essentially free from the rest of the originating antibody or antibodies;
(ii) a peptide linking group, which does not contribute to the specific binding properties of the reagent, said peptide linking group being attached at or near the end of the variable domain antibody fragment and wherein said linking group comprises from 5 to 20 amino acid residues, is hydrophobic and includes at least one lysine residue and at least two amino residues selected from the group consisting of valine, leucine, iso-leucine, phenylalanine, tyrosine, tryptophan, proline and alanine and
(iii) a solid surface or a tracer, coupled via the lysine residue of the linking group by covalent attachment to the variable domain antibody fragment.
2. A specific binding reagent according to claim 1, consisting of a single variable domain antibody fragment attached to a proteinaceous 'tail' which acts as the linking group, the 'tail' being coupled to a solid surface or to a tracer without significant loss of specific binding activity.
3. A specific binding reagent according to claim 1, wherein the linking group comprises the amino acid sequence:
set forth in SEQ ID NO:1.
4. A specific binding reagent according to claim 1, wherein the variable domain antibody fragment and the linking group have been produced together by expression in a genetically modified organism.
5. A specific binding reagent according to claim 1, wherein the solid surface is a surface of a solid structure formed from plastics material.
6. A specific binding reagent according to claim 1, wherein the solid surface is the surface of a latex particle.
7. A specific binding reagent according to claim 1, wherein the tracer is a protein, covalently coupled to the linking group via the e-amino group of a lysine residue in the linking group.
8. A specific binding reagent according to claim 5, wherein the protein is an enzyme.
9. A specific binding reagent according to claim 5 or claim 6, wherein the linking group contains at least two adjacent amino acid residues conferring hydrophobicity on the linking group.
10. The method of preparing a specific binding reagent according to claim 1 which comprises using a hydrophobic polypeptide containing from 5 to 20 amino acid residues as a linking group to attach to a solid surface a specific binding entity comprising at least one variable domain protein which is essentially free from any originating antibody or antibodies.
11. The method of preparing a specific binding reagent according to claim 1 which comprises using a polypeptide containing from 5 to 20 amino acid residues, and wherein at least two adjacent amino acid residues confer hydrophobicity on the polypeptide, as a linking group to attach a solid surface a specific binding entity comprising at least one variable domain protein which is essentially free from any originating antibody or antibodies.
12. A method according to claim 10 or claim 11, wherein the specific binding entity is a Fv or Dab antibody fragment.
13. A method according to any one of claims 9 to 11 wherein the polypeptide has the amino acid sequence:
set forth in SEQ ID NO:1.
14. In an immunoassay using a specific binding reagent, the improvement which comprises using, as said specific binding reagent, the reagent of claim 1.
This is a continuation of application Ser. No. 07/741,425, filed on Oct. 1, 1991, which was abandoned upon the filing hereof.
This invention relates to reagents having specific binding properties. The invention relates in particular to reagents comprising a specific binding agent linked to a solid surface or linked to a tracer.
Natural antibodies, either polyclonal or monoclonal, have been used widely as specific binding agents. When immobilised on solid phases, such as pegs, dip-sticks, wells and moisture-permeable membranes such as filters and strips, or when linked to various tracers (otherwise known as labels or markers), they can be used in assays.
Antibodies are large complex multi-chain proteinaceous structures. Although it has been appreciated for some while that substantial portions of these structures seem unrelated to the specific binding properties, the minimum portion necessary to provide adequate specific binding has been a matter of debate. It has already been shown that so-called Fv fragments, ie. an antibody fragment essentially comprising only a single heavy-chain variable region and its corresponding light chain variable region, can exhibit specific binding activity. Very recently it has also been shown by Ward et al (Nature, 1989, Vol. 341, p.544-546) that a single variable domain from an antibody can exhibit significant specific binding activity. The production of single variable domain antibodies (Dabs), as described by Ward et al, is also described in detail in EP 0368684 A1 (Medical Research Council) published on May 16, 1990.
To be of practical use in immunoassays, specific binding activity alone is not sufficient. The specific binding agent must also be capable of being linked to other material, for example a label such as an enzyme or a particle, or to a solid phase. This linkage must be achievable without any significant adverse effect on the specific binding activity. Such adverse effects can easily arise through chemical or conformational changes in the specific binding region, or simply by physical (stearic) hindrance of access to the specific binding region. In the case of conventional specific binding reagents, ie. whole antibody molecules or large portions of such molecules such as Fab fragments, the specific binding region or regions comprise only a minor proportion of the total molecule. The comparatively vast residual bulk of the molecule, which is apparently not directly involved in the specific binding activity, provides abundant scope for the existence of locations which can participate in chemical or physical linkage with other materials such as labels and solid phases. These regions can be relatively remote from the essential specific binding regions, and the resulting linkages need not interfere with the specific binding activity.
However, in the case of a specific binding entity essentially comprising only one or more variable domains unassociated with any substantial portion of the originating antibody or antibodies, eg. a Fv fragment or a single variable domain (Dab), the relative proportion of the molecule which participates in the essential specific binding activity is very much higher. Indeed, it would be expected that any attempt to link the small specific binding entity to another material will entail a very high risk that the essential specific binding activity will be adversely affected.
An objective of the present invention is to facilitate the linking of such small specific binding entities to other useful materials with less risk of damage to their essential specific binding properties.
The invention provides a specific binding reagent, comprising:
i) one or more variable domain proteins (VH and/or VL unassociated with any substantial portion of originating antibody or antibodies;
ii) a linking group, which does not contribute to the specific binding properties of the reagent, comprising at least 5 amino acid residues, and which is hydrophobic and/or includes at least one lysine residue, the coupling properties of the linking group thereby being enhanced; and
iii) a solid surface or a tracer, coupled via the linking group to the variable domain protein(s).
For the purposes of this specification, the "reagent" of the invention may be a water-soluble or water-dispersible material, or may be a solid device such as a bead, peg, dip-stick, or well or other container, having a surface on which the variable domain protein(s) are immobilised by means of the linking group.
Preferably the linking group comprises not more than 20 amino acid residues. Preferably the linking group is hydrophobic and includes at least one lysine residue. The presence of a lysine residue provides a very convenient site for covalent attachment to proteinaceous tracers, such as enzymes.
To provide the linking group with sufficient hydrophobicity to achieve the purposes of the invention, the polypeptide chain comprising the linking group should is contain a sufficient number (which may be as few as two, if the residues are adjacent) of amino acid residues selected from the group consisting of valine, leucine, iso-leucine, phenylalanine, tyrosine, tryptophan, proline and alanine. We have found that even if the majority of the amino acid residues in the polypeptide are other, relatively polar (and hence relatively hydrophylic), amino acid residues, the presence of merely a low proportion of residues from the above group can confer effective hydrophobicity on the polypeptide. The hydrophobic region or regions can be adjacent to regions of high charge density, ie. the peptide chain is of mixed character, without the essential hydrophobicity of the linking group as a whole being lost.
An important embodiment of the invention is a single variable domain protein (Dab) attached to a proteinaceous 'tail' which acts as the linking group as defined above, the 'tail' being coupled to a solid surface or to a tracer without significant loss of specific binding activity.
A particularly preferred linking group, especially for use in coupling to a solid plastics surface, comprises the "Myc" amino acid sequence(SEQ ID NO:1):
The linking group will normally be attached at or near one end of a variable domain protein. Normally, the point of attachment will be the amino terminus of the peptide linking group. This is the left hand end of the sequences A and B as seen in FIG. 2 of the accompanying drawings. Preferably, the variable domain protein(s) and the linking group have been produced together by expression in a genetically modified organism. The is polypeptide linking group may, for example, be synthesised (cloned) together with a variable domain protein and comprise a proteinaceous tail on one end of the domain sequence. The linking group will comprise at least about 5 amino acid residues, to confer sufficient length to "distance" the variable domain from the surface or tracer to which it is linked.
Actual coupling can be achieved, for example, by means of conventional bifunctional chemical cross-linking agents. Preferably, such a chemical coupling site is sufficiently remote, within the linking group, from the variable domain sequence itself that any molecule which becomes coupled to the linking group is held at a distance from the variable domain sequence.
Where the tracer is a protein, such as an enzyme, it is preferably covalently coupled to the linking group via the e-amino group of a lysine residue in the linking group. Examples of suitable enzymes are horse raddish peroxidase, alkaline phosphatase, beta-galactosidase, glucose oxidase and urease.
In one embodiment of the invention, in which the variable domain is attached via the linking group to a solid surface, the surface is a surface of a solid structure formed from plastics material, such as polystyrene, polyvinylchloride (PVC) or polyethylene teraphthalate glycol (PETG). Examples of surfaces to which it would be extremely useful to immobilise variable domains are so-called "latex" particles (which are minute solid particles of plastics material such as polystyrene, generally used in aqueous suspension), and the many other structures formed from plastics material such as beads, pegs and wells, commonly used in immunoassays.
The invention encompasses specific binding reagents composed of a plurality of variable domain proteins. These can be equivalent to natural Fv fragments, ie. a heavy chain variable region with a light chain variable protein, or they can comprise combinations of heavy chain or light chain variable region proteins. Such combinations are normally held together by relatively weak interactions. The linking group of the invention can be incorporated at or near one end of one of the variable region protein sequences, but more than one linking group, of the same or differing character, can be incorporated in the combination if desired, eg. region protein or at or near ends of the different variable region proteins. The individual variable domain proteins can be expressed separately during cloning. Generally they will combine naturally under mild conditions, which do not inhibit the weak interactions that can cause them to associate.
If desired, a reagent of the invention can be made to exhibit specificity for two distinct materials, by comprising a variable domain unassociated with any other substantial portion of its originating antibody, linked, by means of an intervening linking group, to a second variable domain of different specificity also unassociated with any other substantial portion of its originating antibody. Examples of particularly suitable combinations of specificities are anti-analyte and anti-enzyme.
The invention is not concerned in principle with novel ways of producing single domain antibody fragment or novel ways of producing combinations of such fragments with peptide tails. The Ward et al paper discloses methods that are adequate for these purposes. Indeed, Ward et al disclose the production of an anti-lyzozyme single domain antibody fragment having a "Myc" tail. This combination could be used in accordance with the present invention, but Ward et al only contemplate the use of the "Myc" tail as an epitope to assist them in their experimental identification and isolation of the anti-lysozyme Dab that they produced. Ward et al make no suggestion that the "Myc" tail might be ideal for immobilising the Dab on a plastics surface. Neither is this concept disclosed in EP 0368684 A1. Also, neither of these documents mentions the advantage of having a lysine residue in such a peptide tail.
Methods for the production of an activated variable domain fragment, a bispecific reagent containing 2 variable domains of different specificity, and conjugated products containing enzyme labels, in accordance with the invention, are given below purely by way of example.
a) Preparation of a vector containing the anti-lysozyme VH fragment D1.3 as a Pst1-BstEII cassette.
The anti-lysozyme VH fragment D1.3 is excised as a Pst1-BstEII fragment from the expression vector pSW1-VHD1.3-VKD1.3. This vector, and the other expression vector used in this example, pSW1-VHPOLY-TAG1, are fully described by the aforementioned Ward et al (1989) publications.
pSW1-VHPOLY-TAG1 is restricted with Pst1 and BstEII, and the anti-lysozyme Pst1-BstEII VH fragment of D1.3 is ligated into the opened vector. This ligation creates an expression vector with the VH D1.3 fragment inserted and is essentially the same as the expression vector pSW1-VHD1.3-TAG1 (Ward et al referred to earlier.), but with the Pst1 and BstEII restriction sites incorporated. We can refer to this expression vector as pVHD1.3-TAG1.
b) Cloning of a linking group sequence downstream of the cloned VH gene in pVHD1.3-TAG1.
The replacement of TAG1 by a linking group sequence downstream of the VH gene is done by the technique of site directed mutagenesis with large oligonucleotides as described in Verhoeyen et al., Science (1988), 239, 1534-1536.
Single stranded DNA template is prepared from mpl9VHD1.3-TAG1. This is the HindIII-EcoRI fragment from pVHD1.3-TAG1, containing VH D1.3 and TAG1, cloned in the HindIII and EcoRI sites of mp19. Single stranded DNA obtained from this clone contains the coding strand of the VH D1.3-TAG1 sequence. A DNA oligonucleotide is hybridized to the template to serve as primer to polyerize a second DNA strand. This oligonucleotide contains the required linking group sequence flanked on either side by 12 bases homologous to the site of integration. The double stranded molecule is transformed in E.coli, where a certain proportion of the molecules is 'repaired' by incorporation of the activation sequence structure. The 12 flanking bases, homologous to the site of integration, are the last four codons of VH D1.3 and the two stop codons followed by six bases present in pVHD1.3-TAG1. The oligonucleotide replaces the TAG1 gene sequence with that of the linking group gene sequence.
Convenient restriction sites can be incorporated in is the associated oligonucleotide to facilitate manipulation of the DNA sequences.
FIG. 1 of the accompanying drawings shows three oligonucleotide sequences I, II and III (SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4) useful in the above procedure. Sequences I and II are alternative sequences for producing an identical hydrophylic linking group, and III can be used to produce a hydrophobic linking group.
FIGS. 2A and 2B shows the cDNA and amino acid sequences of two linking groups A and B (SEQ ID NO:5 and 7 and SEQ ID NO:6 and 8). Linking group A is hydrophylic, and can be produced using either of oligonucleotides I and II. Linking group B is hydrophobic, and can be produced using oligonucleotides III.
FIG. 3 shows the calibration curve derived from the HRP conjugates of the Examples.
FIG. 4 shows the calibration curve derived from the biotin conjugates of the Examples.
Three plasmids derived in this manner, in which the linking group sequence structure contains 12 or 11 amino acids (n=1), and designated pVHD1.3-ADI, pVHD1.3-ADII and pVHD1.3-ADIII, are produced using sequences I, II and III. These plasmids are expressed in E.coli (as in Ward et al.).
Construction of a dual specificity reagent containing two variable domains.
A second VH domain, of a different specificity from VH D1.3 and prepared as a DNA fragment using standard recombinant DNA technology, is cloned in the unique Kpn1 restriction site of either pVHD1.3-ADI, pVHD1.3-ADII or pVHD1.3-ADIII. The resulting expression vectors now express VH D1.3 linked to a VH domain of different specificity by an amino acid 'bridge' containing a lysine residue to which other materials can be coupled.
Conjugation of the protein products derived from pVHD1.3-ADI, pVHD1.3-ADII and pVHD1.3-ADIII.
a) Conjugation of alkaline phosphatase.
100 μl of variable domain fragment protein with associated "tail" (2.5-5.0 mg/ml) is incubated with 100 μl alkaline phosphatase (10 mg/ml) and 5 μl glutaraldehyde (5%) at room temperature for 60 mins. Then 5 ml of Tris/ovalbumin buffer (0.05 M Tris, pH 7.5; 5% ovalbumin) is added and the mixture left at +4� C. for at least 24 hrs. Then the conjugate mixture is tested, quick-frozen and stored in aliquots at low temperature, eg. −20 to −80� C., until use.
b) Conjugation of horse radish peroxidase (HRP):
4 mg of HRP is dissolved in 1 ml distilled water. Then 0.2 ml of freshly prepared 0.1 M NaIO4 is added and the solution stirred for 20 mins. at room temperature. The HRP-aldehyde solution is then dialyzed against 1 mM sodium acetate buffer, pH 4.4, overnight at +4� C. After dialisis the pH of the solution is raised to 9.0-9.5 by adding 20 μl of 0.2 M sodium carbonate buffer, pH 9.5. Immediately 5 mg of the variable domain protein with associated "tail", in 0.01M sodium carbonate buffer, pH 9.5, is added, and the mixture is stirred at room temperature for 2 hrs. Then 0.1 ml of a freshly prepared sodium borohydride solution (4 mg/ml in water) is added and the mixture is left for 2 hrs at +4� C. After this incubation the conjugate mixture is chromatographed on a 35�2.5 cm column of Sephacryl S-200, equilibrated in PBS. The absorbance of each fraction (2 ml) is measured at 280 nm and 403 nm and the fractions comprising the desired conjugate peak are pooled. Bovine serum albumin is added to a final concentration of 10 mg/ml and aliquots are quick-frozen and stored at a low temperature, eg. −20� C. to −80� C., until use.
Monoclonal antibodies having binding specificities to linkers A and B (FIG. 2) are prepared for the purposes of detection of the variable domain fragments in the E.coli supernatant, for purification, and for construction of tracer immune complexes. After synthesis of the peptide (eq. by solid phase peptide synthesis) and conjugation macromolecules to provide immunogenic character (eg. conjugation to bovine serum albumin or keyhole limpet haemacyanin), monoclonal antibodies can be raised in mice using conventional techniques.
An immunoassay for lysozyme utilising variable domain antibody fragments with peptide tails
Experimental procedure
Anti-lysozyme VH fragments were produced as described in Example 1 and Ward et al (1989). Samples of fragments were prepared either with or without tails; two types of tail were used, one hydrophilic and the other hydrophobic, with sequences A and B respectively as shown in FIG. 2. Two conjugates were made from each of the three types of fragment, one conjugate with biotin and the other with horse radish peroxidase (HRP).
a) Conjugation with HRP. The method of Example 3b was followed, but using 0.042 mg of fragment for each conjugate.
b) Conjugation with biotin. A solution of fragment (0.5ml) at a concentration of 80 μg/ml (+/−10 μg/ml) was dialysed against carbonate buffer, pH 9.5. Biotin-N-hydroxysuccinimide (biotin-NHS, Sigma) was dissolved in dimethyl sulphoxide at a concentration of 1 mg/ml, and 75 μl of this was added to the dialysed solution of fragment. The reaction mixture was stirred and then left to stand at ambient temperature for two hours, after which the volume was made up to 2.5 ml with phosphate buffered saline, pH 7.2 (PBS). The diluted mixture was passed down a disposable gel filtration column (Pharmacia, PD10) to separate any unreacted biotin-NHS and unconjugated biotin from the conjugated fragments. Fractions containing the fragments were collected, pooled and dialysed against 2 litres of PBS for 24 hours at 4� C.
c) Preparation of solid-phase. Wells of a commercially-available polystyrene microtitre plate were dosed with looul aliquots of a solution of lysozyme at 100 μg/ml in PBS. The dosed plate was incubated at 37� C. for 2 hours to allow efficient adsorption of the lysozyme onto the polystyrene surface. The plates were washed 5 times in PBS containing Tween 20 (0.15% V/V, PBST) and were then treated with a 2% solution of skimmed milk protein (W/V), 150 μl per well, in PBS for a further 2 hours at 37� C. This second treatment was to block (with milk proteins) any unoccupied sites on the well surface with potential for protein adsorption, to minimise subsequent non-specific adsorption of assay components.
d) Generation of a standard curve for the lysozyme assay. A series of lysozyme calibration standards were prepared by dilution of a stock solution of lysozyme into appropriate volumes of PBST with 1% boving serum albumin (BSA, W/V), to give concentrations of 2�10−6M, 2�10−7M, 2�10−8M and 2�10−9M and 2�10−10M. Working strength solutions of the conjugates were prepared by diluting the conjugate stock solutions to {fraction (1/25)} for the biotin conjugate and {fraction (1/50)} for the HRP conjugate. Microtitre plates sensitised as in (c) were washed 5 times in PBST before appropriately labelled wells were dosed with equal volumes of conjugate and calibration standards (100 μl, total per well). This competitive binding assay step was continued for 1 hour at 37� C., after which the wells were washed 5 times in PBST.
For the procedure using biotin conjugates, the wells were dosed with a solution of streptavidin/alkaline phosphase conjugate (Sigma) and incubated at 37� C. for a further hour. The plate was washed 5 times again, and then dosed with Sigma 104 phosphatase substrate in 1M diethanolamine buffer, pH 9.8, at 1 mg/ml. Colour development was continued for 10 to 15 minutes at ambient temperature before the optical densities were read.
For the procedure using HRP conjugates, the wells were immediately dosed with a solution of tetramethylbenzidine (TMB) in phosphate citrate buffer, pH 6.5 and colour development was continued for 10-15 minutes at ambient temperature. Each well was dosed with 50 μl of 2M HCl before the optical densities were determined.
The calibration curves derived from the HRP conjugates are shown in FIG. 3 and those from the biotin conjugates in FIG. 4. In each figure it can be seen that the conjugate of VH with no tail fails to give a satisfactory calibration curve, whilst the fragments with either tail gave acceptable results, clearly showing the benefit of an appropriate linking group.
Efficiency of VH fragments in sensitising plastics surfaces—the effect of different peptide tails
Experimental procedure
Anti-lysozyme VH fragments were produced as described in Example 1 and Ward et al (1989), either alone or with a peptide tail. The two tail sequences A and B as in FIG. 2, and a third tail, identical to the "Myc" peptide as described by Ward et al (Nature, 1989, vol. 341 p.544-546), were used. The amino acid sequence (SEQ ID NO:1) of this "Myc" peptide is as follows:
Solutions of these fragments were used to sensitise wells of a microtitre plate by simple adsorption. The efficiency with which these fragments bound to the plastic surface, whilst still retaining their ability to specifically bind lysozyme, was assessed by means of subsequent immunochemical binding of a lysozyme/horse radish peroxidase (HRP) conjugate.
a) Conjugation of lysozyme with HRP. The method of Example 3b was followed, with purified lysozyme being used in place of activated VH.
b) Preparation of solid-phase. Wells of a microtitre plate (Costar "fastbinder" made with polyethylene teraphthalate glycol) were dosed with 100 ul aliquots of VH fragments in carbonate buffer, pH 9.8 at a concentration of 80 ng/ml. Some wells were treated with carbonate buffer to provide an unsensitised control. The dosed plate was incubated at 37� C. for 2 hours to allow efficient adsorption of the peptides onto the well surface.
c) Assessment of lysozyme capture efficiency. The wells of the sensitised plate were emptied and washed 5 times in phosphate buffered saline, pH 7.2, containing 0.15% Tween 20 (v/v, PBST). Each well was treated with a solution of lysozyme/HRP conjugate (diluted {fraction (1/100)}from stock solution, see Example 3b) in PBST containing 1% (w/v) bovine serum albumin. This immunochemical binding (or capture) step was continued for 1 hour at 37� C., after which the plate was emptied and washed 5 times again in PBST. The wells were dosed with a solution of tetramethylbenzidine in phosphate citrate buffer, pH 6.5, and the whole plate was maintained at ambient temperature until adequate colour had developed. At this point, 50 μl of 2M HCL was added to each well and the optical densities were determined.
The mean optical densities produced from each type of sensitisation are shown in Table 1. The capture efficiency of solid phases produced by adsorption of fragments with various peptide tails onto the PETG wells is proportional to the measured optical density.
These results clearly show the practical benefit of adding appropriate linker groups to fragments with immunochemical binding activity. Surprisingly, charged peptides containing short hydrophobic regions (of the Myc type) are the most efficient at these economical, low concentrations.
Similar results, demonstrating the advantage of hydrophobic linking groups, were obtained using commercially-available wells made from polystyrene and from polyvinylchloride.
Patent Citations
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Monday, October 01, 2012
Menu Plan Monday
Here it is, the first day of a new month. I always feel inspired at the beginning of a new month, so full of plans and ideas. . .
We are fresh off a long weekend getaway to the beach, and it's tough getting back into a routine. Add to that, limited on-hand groceries and lack of time for a trip to the store, and it's time to get CREATIVE!
So here is my creative, fall menu for the week (of course it's going to be in the 70s here all week):
Monday - Ham Slice, Potatoes & green beans
Tuesday - Spaghetti & Meatballs
Wednesday -Salmon, Couscous & vegetable
Thursday - Chicken Cutlets, Mashed Potatoes & Peas
Friday - Pizza Night
Saturday & Sunday - TBD
For inspiration or to link up your own plan, visit I'm an Organizing Junkie.
What's on your plan this week?
catch you soon -
Written By: Hillary Chybinski
Labels: food, menu plan, organization
Hillary is a wife, mom, Lifestyle Blogger, Social Media Strategist, crafter, reader and dreamer. She started My Scraps to record her memories of her kids' lives, and it's grown and flourished into a community where she shares her tips and advice for creating a simple and casual life.
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Senator Wyden Reintroduces His O&C Lands Legislation
After bringing his O&C lands bill close to passage last year,
Senator Ron Wyden (D-OR) picked up where he left off and reintroduced
his bill the very first week of this new Congress. While not a perfect
measure for either conservationists or timber interests, S.132 is a
balanced and reasonable approach to an issue that has troubled Oregon
for decades. The bill protects over 1.5 million acres of some of the
state's most wild and ecologically important
ancient forests while at the same time increasing current harvest
levels. Senator Wyden's commitment to getting this bill enacted
exemplifies how a true statesman can find compromise amongst diverse
interests to help bring both economic and environmental prosperity to
his state.


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Supply yourself with products that teach kids when to dial the 911 emergency number. Economical pack includes our Telephone For Help: Call 911 In An Emergency Educational Activities Book, My 911 Buddies Stickers, Dial 911 In An Emergency Laminated Ruler and Dial 911 In An Emergency Temporary Tattoo. You'll save 25% off of our regular individual prices.
3-in-1 value kit for grades K-2 includes: * What To Do In An Emergency Parent-Child Learning Activities Book * EMS "Color Me" Paper Ambulance * Non-Toxic Crayons
Check out our suggested products


text: http://www.linuxquestions.org – When I use my laptop. I share my destop like A|B In the left(A),this is my writing place. Maybe I opened a txt with gedit. In the right(B),this is my reading place.Maybe I opened a pdf to read. When I was writing in A place. Sometime I should read something in B. And I should move my mouse to B and scroll with mouse to see the whole paper (or type the key pg up/pg dn) Can I set some key to control the B place when I work at A? like this: When I writing in gedit(A place) , I type pg up key(or up key or scroll the mouse) , then pdf(in B place) moved. How can I use the different key to control different window at the same time? (HowTos)


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Fiber (disambiguation)
From Wikipedia, the free encyclopedia
|Look up fibre or fiber in Wiktionary, the free dictionary.
Fiber or Fibre may mean or refer to:
- Fiber, a long strand of material.
- Dietary fiber
- Myofiber
- Optical fiber
- Fiber (computer science)
- Fiber (mathematics)
- Myofiber, or muscle fiber, strands of muscle tissue
- Nerve fiber, strands of nervous tissue
- Fiber crop
- Fiber wire
|This disambiguation page lists articles associated with the title Fiber.
If an internal link led you here, you may wish to change the link to point directly to the intended article.


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Join us for the 2015 Copper Kettle Classics in Creemore on Saturday August 22nd
2015 classics
On August 22nd, enjoy an amazing day of classic cars, trucks and motorcycles in downtown Creemore on historic Mill Street. Register your 1990 or older car, truck or motorcycle and enjoy live music, shopping and a beer festival. This years show pays tribute to car and motorcycle clubs from near and far.
Last years event featured and incredible collection of over 400 vintage cars, trucks motorcycles. Vehicles from as far as Nova Scotia attended the show last year. Check out the results page to view the Best of the Best from 2014. Congratulations to each of you.
Creemore's Copper Kettle Classics has developed a reputation for the quality of nostalgic cars and picturesque setting in which it is held. A multitude of colours and chrome line one of Ontario's most beautiful downtowns one day a year
We are committed to the next generation of collector car enthusiasts. We invite you to join with us by making a donation to the RAY's PLACE auto restoration club of Creemore.
Register now for the 2015 Copper Kettle Classics. Space is limited on Mill Street so be sure to pre-register your classic car, truck or motorcycle to ensure you receive a spot in this historic event. Display your vehicle along Mill Street with our historic buildings as a backdrop.


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Click to expand
What do you think? Give us your opinion. Anonymous comments allowed.
Reply+91#7 - I Am Monkey (07/10/2013) [-]
I want to change my name to Yue Mad, go on an Asian dating site then when they meet me in person and find out I'm not Asian I'll just say "Yue Mad" and walk away.
Reply-2#36 to #7 - herpderpherpity ONLINE (07/10/2013) [-]


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Virus holds personal, business computers for ransom
It's that time of year again: colds, flu and viruses abound.
But viruses attack more than humans. Computer viruses have names and symptoms. Sometimes those viruses lie dormant in the system until a trigger releases their defective properties.
Keeping your computer safe from these invasive infections, as well as your bank accounts and credit cards, demands proactive defenses.
Two current, and particularly lethal, computer viruses, whose ultimate goal is monetary by gaining credit card information, are "CryptoLocker" and the one feigning as a "Microsoft helpline" phone call. They have wrecked havoc on local residents and even some businesses who inadvertently opened themselves up to contamination.
"We're getting about 200 calls a month about these viruses and others," said Klaus Schwanitz, owner of Act Computers in the Vero Beach K-Mart Plaza.
He advises that if you ever get a call from Microsoft, IMMEDIATELY hang up.
"Bill Gates and his people are just not going to call—ever," said Schwanitz. "Bill Gates has never called me."
These virus "technicians", call (oftentimes the phone numbers are blocked on caller-ID or come up as 000-000-0000) and introduce themselves as "Mike Smith" or Phil Jones," usually with a foreign accent.
They say they have important information regarding your computer's system and that they've received numerous alerts pertaining to your computer's current performance.
You may be asked, "Have you been getting many alerts recently?"or "Is your computer sluggish?"
If you answer, "yes", the caller immediately delves into how they know this and that they can certainly help, but they need you to go to your computer and type in some information.
By remote, they guide you to access files, in particular ones which will bring you to a bogus site.
The site asks for credit card information. You get to choose: American Express, Master Card, Visa, or others. Don't.
If you've managed to get this far—PLEASE hang up before it's too late. It may already be too late for your computer, but regardless, DO NOT give out precious personal information.
"These sites look real. Even we have been taken in by certain bad web-sites when we try to locate computer parts," explained Schwanitz. "It's so unnerving, even for us."
The CryptoLocker virus downloads into your computer and holds your files ransom until you consent to pay to have them released. Fees are upwards of hundreds of dollars.
CryptoLocker can also get into your computer by simply opening seemingly legitimate file attachments in unsuspecting emails.
Then the virus encrypts files. Most often, when the ransom is paid the files are released.
The on-going harm still latent in your computer remains to be detected. So far, researchers haven't been able to completely remove the CryptoLocker virus.
For more information about these computer problems, contact ACT Computer at 772-567-7888 or your own computer specialist.
Subscribe to TCPalm
Need Help? Call us at 1-877-710-6180.
Monday-Friday: 6am-3pm / Saturday: 6:30am-10:30am / Sunday: 7am-11am


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Yes! Steam supports paysafecard! Pro subscription here I come!
Type: Posts; User: PrOtOs_Angelus
Yes! Steam supports paysafecard! Pro subscription here I come!
A t4 CA/CTF player is looking for a clan.
2nd in Croatia in CA ELO (for ELO fans)
...please, a clan that is both skilled, polite and nice to play with.
Thanks in advance
As in the movie Lord of the Rings..."Is there any hope Gandalf; for Frodo and Sam?"...so I ask the same question. Is there any hope of seeing Quake Live in the European tournaments? Furthermore, for...
I am looking for a CA clan that is both active and skillful. "Protos_Angelus".....
My skillrating (based on empty serverinfo) is currently 861.
My current elo is 1956 [although it drops and rises...
Furthermore, keep in mind that we are a European clan and do not play on USA, Asia servers. Thank you
Dark Angels (DA) is recruiting! Looking for strong and active players to play CA. We will limit the player number of the clan to 10-15. Please if you are not an experienced player do not reply here....
Can you invite me too? Thanks
Add me please
Hello fellow QL players,
I am looking to join a CA clan preferably T4....I can do CTF but also only t4...thanks in advance
I was wondering if anyone knows if ID will ever bring up a server in or near Croatia?
Thanks in advance.
Found a clan, thank you. //ffs
3vs3 minimum
Mali Plac 1b, Varaždin :D moja adresa
...a good steady clan with not to many players on. Active clan and preferably tier 4 CA. I am a Croatian player (for Croatian clans) but flawless in English.
Thread CLOSED. CLAN FOUND
I play CA, CTF, FFA, and if I really have to TDM.... Open for business.
Hi, I am searching for a clan since I've been kicked out of one (he had to because a guy was cheating so he kicked everybody out) and whoever sends me an invite I'll be more than glad to accept. :)


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This position has been filled
Job Overview
Job Summary: The University of Utah, College of Nursing is seeking a qualified Family Nurse Practitioner for a clinical faculty appointment. This position will combine teaching, faculty practice and leadership in the primary care nurse practitioner (PCNP) doctoral program. This position is approximately 80% academic and 20% faculty practice.
Criteria for the position include: graduation from an accredited school of Nursing as a family nurse practitioner, Doctor of Nursing Practice (DNP) degree, national certification as an APRN, current Utah licensure as APRN with prescriptive authority (or qualifies for). Excellent leadership skills, interpersonal skills and the ability to work effectively with patients and other members of health care and academic team are essential. Academic teaching experience is required. Primary care experience with emphasis in adult/geriatric populations is desired.
Principle Functions and Responsibilities:
1. Provides didactic education for assigned courses in the PCNP, DNP program.
2. Participates as an active member of the PCNP, DNP program team.
3. Serves as a mentor/preceptor for students in the PCNP program.
4. Instructs and supervises/precepts primary care nurse practitioner students and other health care students as assigned. Ensures a positive learning environment.
5. Provides outpatient primary care in a faculty practice setting.
6. Collaborates with health care team in coordination of care for clients.
7. Participates in scholarship and continuing education activities.
8. Performs other duties as assigned.
Reporting Relationships:
1. Reports directly to the Chair of the Division of Health Systems and Community Based Care.
2. Reports indirectly to the Director of the Primary Care Nurse Practitioner, DNP program.
3. Yearly evaluation by meeting above requirements, functions and responsibilities and with review of set goals according to RPT clinical criteria.
Interested candidates should apply online at the following link: http://utah.peopleadmin.com/postings/21583
Questions may be directed to Cami Palo, Faculty Affairs and Office of the Dean at firstname.lastname@example.com
Surrounded by the Wasatch and Oquirrh mountain ranges, Salt Lake provides abundant recreational opportunities. Salt Lake City is a flourishing cultural center including world class opera, dance, theater companies, art galleries and one of the nation's finest regional symphony orchestras. Ten national parks are within a day's drive of Salt Lake City.
The University of Utah values candidates who have experience working in settings with students from diverse backgrounds, and possess a strong commitment to improving access to higher education for historically underrepresented students.
The University of Utah is an Equal Opportunity/Affirmative Action employer and educator. Minorities, women, and persons with disabilities are strongly encouraged to apply. Veteran's preference. Reasonable accommodations provided. For Additional information: http://regulations.utah.edu/human-resources/5-106.php


text: Well, his minor league history surely doesnt show him being not good. An ERA under 3 and a whip under 1.20 constitutes good in my book. Yes its just minor leagues, but that is what we were talking about. He isnt the greatest prospect around, but I dont think he is projected to be anything but a #4/5 guy, but he is still young, and has shown success throughout his minor league career. As a 22 year old in AAA last year, he finished 9th in ERA in the league.


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Hai Peng Kopitiam Sdn Bhd: Great Hai Peng Coffee
One of the reasons I prefer this home made traditional coffee to the famous coffee like Coffeebean or Starbuck is that the coffee brewed wouldn't make me feel headache after drinking it. The mild coffee aroma and the right sweetener and creamer makes the coffee perfect. I addict to it after my first mouthful of the coffee.
Hai Peng Coffee @ www.gourmetsharing.com
Hai Peng: Traditional coffee
This coffee house was established since 1940. They serve very delicious home made coffee.
Favorite Dish: The specialty is coffee and toast bread spread with kaya (a sweet creamy spread made from coconut milk and eggs). There is also some other local snacks like nasi lemak (rice cooked in coconut milk), curry puff, keropok (fried fish crackers).
- Singles
Hai Peng Coffee: Best Local Coffee - Kopi
Delicious food although it was a very simple and plain stuff.. like bread, coffee...
It does give me a memory of old days sitting in a local "kopi" shop.. of cause they having a
latest packaging which showing in the pix below.. plastic cup with sealling on top... not like old days... plastic glass... but they do search "Kopi" hot one like old days... in a "Cawan"...
Favorite Dish: Definately the Coffee... and the Bun with Butter Kaya... I dont like tha "Tapai" though... taste weird... but you can try it... and the curry puff there is nice too...
- Budget Travel
Restoran Tong Juan: Stuffed Crab
Crab meat is extracted from shell and mix with some fish meat and other ingredients like spring onions and eggs. Then the mixed paste is filled back to the crab shell. The crab shell filling is quite meaty and tasty. RM6 per stuffed crab.
Beside stuffed crab, you can also order their crab meat fried rice which is quite delicious.
You can also savour their other seafood dishes, like sharkfins soup, abalone, lobster, fish, prawns and cuttlefish.
Favorite Dish: Stuffed crab & crab meat fried rice.
- Food and Dining
- Business Travel
- Road Trip
Hai Peng Kopitiam Sdn Bhd: The Famous Kemaman Coffee since 1940
This is a popular Kopitiam (coffeeshop) among the locals and was established since 1940. You can see all races enjoying the universal food here like coffee and toasts. This is a typical coffeeshop with some added touch of nostalgia as you can see some antique collections displaying in the shop.
Beside their famous traditional Hai Peng coffee, you can try their signature Vietnamese coffee which is strong and fragrant. Alternatively, you can call ice-blended coffee. If you are feeling hungry, why not try their nasi lemak (santan rice), fried meehoon, nasi dagang, etc. Your favourite half-boiled eggs are available too.
They have come up with a novelty idea of selling their own brand of coffee in sachets. 20 sachets in a box for RM19.90. However, the taste is very much different from the one brewed in the coffeeshop.
Favorite Dish: Tuna sandwich
French toast
Peanut butter & banana sandwich
Kaya bread
Apple pie ala mode
Hai Peng coffee Vietnamese style
Magnificent fruit king
Coco lava
Coffee breeze
Pina calada
- Road Trip
- Food and Dining
- Seniors
Kedai Kopi Hai Ping: For Local Coffee lovers
The best is the toast and kaya spread - but if you are lucky you get to order the apple pie and vanilla ice cream....nuff said. They also have those ice blended stuff people seems to like so much these days.
Restaurant Tong Juan: Wanna Stuff Yourself with crabs?
Their speciality is stuffed crab - everthing else is standard fair you get form a chinese seafood restaurant.
Favorite Dish: Stuffed Crab
- 1
Instant Answers: Kampong Kemaman
Get an instant answer from local experts and frequent travelers


text:
Calendar Of Events
Government & Civic / Lavallette
Council Meeting
Activities & Events / Point Pleasant
Life Chapel 2015 Vacation Bible School
Monday, Jul. 06, 2015, 06:00 PM-08:00 PM
Life Chapel would love to welcome any child from kindergarten through fifth grade to come join them for their Jungle Safari- themed Vacation Bible School.
There will be games, snacks and crafts for the children to enjoy.
To register a child, call Life Chapel at 732-295-9191, or visit www.lifechapelpoint.com.
|More info:
Government & Civic / Bay Head
Council Meeting
Activities & Events / Bay Head
Electrical Co-Op Information Session
Monday, Jul. 06, 2015, 06:00 PM / Bay Head Firehouse
Session will be conducted before the monthly council meeting by Stacia Scaduto, Vice President of Operations for Commercial Utility Consultants. All are welcome to attend.
Government & Civic / Manasquan
Borough Council Meeting
Government & Civic / Point Pleasant Beach
Non-Resident Taxpayer Meeting
Saturday, Jul. 11, 2015, 10:00 AM / G. Harold Antrim
Both residents and non-residents taxpayers are invited to hear topic and issues including dune replenishment, town budget, public safety, revised master plan, real estate matters, shop local tax credits and more. Attendees may send questions beforehand to email address.
|More info:
Activities & Events / Brielle
Coast Boating School Hosts Boating Cruise
Saturday, Jul. 11, 2015, 09:00 AM-12:30 PM / Reel Seat Tackle Shop
Coast Boating School will conduct a New Jersey mandatory safe boating course, under the New Jersey State Law. The cost is $35
|More info:
Activities & Events / Point Pleasant Beach


text:
Windows Enterprise Desktop by Ed Tittel
member Blog
The Windows Enterprise Desktop blog features topics of interest to IT professionals who work with Windows on large networks. Topics are Windows OS setup and configuration, release definition, deployment, migration, virtualization, terminal services, and security.
member Blog
Ed Wilson, the Scripting Guy, is starting a new series of posts on writing PowerShell scripts – he'll also cover what to script, when to script and when to work interactively.
First post is here http://blogs.technet.com/b/heyscriptingguy/archive/2015/07/05/weekend-scripter-when-to-write-a-po…READ MORE
Lois Lerner's IRS Email: It's Lost! It's Found! It's Lost Again!
member Blog
In case you thought the November 2014 revelation that Lois Lerner's missing IRS email messages might have been found when backup tapes had been located meant the end of the story – LOL. You haven't spent much time in politics, have you?
As you may recall, the whole thing started last June w…READ MORE
Let's innovate: Uncovering hidden powers of the smartwatch
editorial Blog
Scouring the Internet reveals a number of heated debates about devices like the Pebble smartwatch. Is it useful? Useless? Will wearables become the way of the future – or an embarassing fad of the past?
The doubt, however, has not kept famed innovators like Dan Bricklin from working to unveil t…READ MORE
Whoa! The Win10 Build "Hat Trick"
member Blog
Confounding all expectations, MS followed up the wham, bam sequence of two Windows 10 builds on June 30 (10158) and July 1 (10159) with a third build yesterday (July 2: Build 10162). I'm hopeful this will be all for a while because it's been time consuming and a bit frustrating to grind through the …READ MORE
member Blog
Hurrah! It's July! The part of the year where people in the United States start to think about fireworks, hot dogs, parades, independence, and Freedom. That has me thinking too.
Mostly we talk about extrinsic freedom – the freedom to speak, assemble, pray, or write. I do believe that free electio…READ MORE
Senior leadership success in 3 steps; the CIO's role in a platform business strategy
editorial Blog
A stellar CIO is only as good as his direct reports. To build a leadership team of that creates breakthroughs in its industry, leadership and agility expert Joseph Flahiff argues that CIOs need to build a supportive culture in which senior IT feels confident experimenting with new ideas. In this tip…READ MORE
The three UC issues to address before you deploy
editorial Blog
Before making the move to unified communications (UC), every organization must prioritize three issues: scalability, application integration and security. Failure to address these issues can have far-reaching implications for organizations when they enter a growth cycle or encounter a security threa…READ MORE
Experts: Data privacy and security status quo as consumer apathy prevails
editorial Blog
Last month, Apple chief exec Tim Cook gave an impassioned speech chiding tech companies such as Facebook and Google about their data collection and monetization practices and how they're stepping on consumers' "fundamental right to privacy."
For a recent Searchlight article on the topic, I talked…READ MORE
CCIE rescheduling policy is changed
member Blog
Cisco changes their CCIE retake policy, the new email I received from Cisco Learning states
"For a limited time, we will waive the current lab retake policy so that all lab candidates will be able to retest for their lab exam with only a 30-day wait period. We're offering this opportunity in …READ MORE
Convergence of Data Virtualization Servers and SQL-on-Hadoop Engines?
editorial Blog
Hadoop has become a popular and powerful platform for data storage and data processing. Data stored in Hadoop can be used by a wide range of applications and tools and for a wide range of use cases. The fact that SQL can be used to retrieve Hadoop data, has opened up the data to even more tools, esp…READ MORE
The top Windows Server tips and news of June 2015
editorial Blog
For our monthly feature, we look at the most popular stories on SearchWindowsServer.com from the previous month and share it with you.
In June, readers wanted to learn what tools could aid a Windows 10 deployment and what to expect from Group Policy in Windows Server 2016.
Patch Tuesday includ…READ MORE
AWS buffs up cost management tools, has more up its sleeve
editorial Blog
AWS rolled out the cost management tools hinted at several months ago in its job listings, with support for budgeting and forecasts up to three months out, according to an Amazon blog post.
The new capabilities are an update to the AWS Cost Explorer tool, which previously provided only historical…READ MORE
June in review: the most popular Exchange Server content
editorial Blog
In our monthly feature, we take a look at the pieces of content that were most popular with our readers in the previous month and recap it for you.
In June, our readers were interested in learning more about the latest version of Exchange, Exchange Server 2016, as well as the latest updates to ex…READ MORE
editorial Blog
Edging closer to the historic split of Hewlett-Packard into two formidable companies — HP Inc. and Hewlett Packard Enterprise — a couple of top executives are on their way out.
Today, HP announced that Bill Veghte, executive vice president and general manager of HP's Enterprise Group (EG), wo…READ MORE
Chromebooks for business gain steam
editorial Blog
BOSTON — Chromebooks have cornered the education market, and Google has made moves to make these devices more business friendly over the past year.
These simple, portable devices are big in education because they're designed to start up in seconds and provide basic Web-based apps. They run G…READ MORE
member Blog
When doing data warehouse loads into SQL DW you'll want to break your single large file that you extract into multiple smaller files in order to do loads into the SQL DW (via Azure Blob Storage) as fast as possible. There's a few ways that you can do this. One way would be to handle this in your E…READ MORE
MongoDB World fever - catch it!
editorial Blog
The long term prospects of MongoDB and other NoSQL databases will be judged by feature improvements for enterprises. We saw such updates when we visited this year's MongoDB World convocation. A case study from ADP is discussed in the podcast.
Storage islands leave data management plans adrift
editorial Blog
A major problem that IT professionals have dealt with over time is the creation of islands of storage. A common cause of islands is when organizations purchase and deploy new systems with their own storage for a specific purpose.
Storage islands create problems in these areas for administrators:
Containers, microservices, and DevOps, oh my… the big trends in enterprise open source
editorial Blog
Red Hat Summit / Dev Nation 2015 fell pretty well in line with the theme everything old is new again. The three main themes repeated again and again were containers, DevOps and microservices. I think each of these three important trends is building on a well-established base of solid practice and te…READ MORE
TechTarget's weekly roundup (6/22 - 6/29)
editorial Blog
Oracle image via Shutterstock
Can Oracle take on AWS in the cloud market? Tune into this week's roundup to find out.
1. Oracle's cloud plans for world domination start with AWS – Trevor Jones (SearchCloudComputing)
Oracle's cloud is now complete and in its typical bravado style, plans to ta…READ MORE


text: News http://www.ucl.ac.uk/star/star-news-viewer/rss Sonja Van Praag (WAMS) 2013-08-23T10:34:05Z In memoriam: Professor Bruce Swinyard http://www.ucl.ac.uk/phys/news/physics-news-publications/bs_220515 May 22nd 2015 News and Events Katherine A Wilson-Heyworth 2015-05-22T15:25:22Z A brand new sky from Planck http://www.ucl.ac.uk/phys/news/physics-news-publications/hp-CMB--02-2015 New maps from ESA's Planck satellite , forming the second major data release (February 2015) from the project, have unveiled the polarised light from the early Universe across the entire sky, revealing that the first stars formed much later than previously thought. News and Events Claire Jordan 2015-03-03T12:52:59Z IN MEMORIAM: DR BILL GLENCROSS http://www.ucl.ac.uk/phys/news/physics-news-publications/billglencross It is with great regret that we must announce the death of Dr William (Bill) M. Glencross. News and Events Katherine A Wilson-Heyworth Claire Jordan 2015-02-10T17:18:44Z Dark Energy Survey kicks off second season cataloguing deep space http://www.ucl.ac.uk/phys/news/physics-news-publications/des_082014 The Dark Energy Survey, which has just begun its second year of observations, is gathering data about one of the most puzzling phenomena to be discovered in the past century: that the universe is not only expanding, but is doing so at an ever faster rate. Some as yet unknown force dubbed 'dark energy' is driving this acceleration. News and Events Claire Jordan 2014-08-21T11:09:14Z UCL cosmologists weigh into the debate about neutrino mass http://www.ucl.ac.uk/phys/news/physics-news-publications/neutrino_debate_08-2014 The standard model of particle physics needs to be extended: it predicts that neutrinos have zero mass, but this does not fit with experimental data. Recent work has suggested an unexpectedly high mass for the neutrino, but UCL cosmologists say this is wrong. They argue that a low mass is more consistent with the observed properties of the universe. The Dark Energy Survey (which UCL is also involved in) will provide data that could resolve this debate in the next few years. News and Events Claire Jordan 2014-08-11T11:57:33Z All the Sky – All the Time: UK astronomers debate involvement in the Large Synoptic Survey Telescope (LSST) http://www.ucl.ac.uk/phys/news/physics-news-publications/LSST_2014 Image: A combination of two renderings, showing the telescope on the summit. March 2011 (Credit LSST Corporation) News and Events Claire Jordan 2014-06-24T16:28:30Z Dr Steve Fossey- wins UCL Communication and Culture Award http://www.ucl.ac.uk/phys/news/physics-news-publications/sf_04_04_14 Dr Steve Fossey has been awarded the UCL Communication and Culture Award for Media Communicator of the Year (news story). News and Events Katherine A Wilson-Heyworth 2014-04-04T15:05:35Z UCL open letter to Paul Dacre, Editor of the Daily Mail http://www.ucl.ac.uk/phys/news/physics-news-publications/hp_20_03_14 Professor David Price, Vice-Provost for Research at UCL, has written an open letter to Paul Dacre, editor of the Daily Mail, to raise concerns about an article commenting on the race and gender of UCL academics appearing on Newsnight. The contents of this letter are reproduced in full below. News and Events Katherine A Wilson-Heyworth 2014-03-20T15:20:54Z Dr Hiranya Peiris discusses 'Gravity waves seen for the first time. What does it prove?' on BBC Two Newsnight http://www.ucl.ac.uk/phys/news/physics-news-publications/hp_19_03_14 News and Events Katherine A Wilson-Heyworth 2014-03-20T15:09:42Z Professor David Walker wins IOP Optics and Photonics Prize http://www.ucl.ac.uk/phys/news/physics-news-publications/dw_10_03_14 Professor David Walker has been awarded the Institute of Physics (IOP) Optics and Photonics Prize for 2014. News and Events Katherine A Wilson-Heyworth 2014-03-10T09:44:58Z Supernova in Messier 82 discovered by UCL students http://www.ucl.ac.uk/phys/news/physics-news-publications/ou_23_01_14 Students and staff at UCL's teaching observatory, the University of London Observatory, have spotted one of the closest supernova to Earth in recent decades. At 19:20 GMT on 21 January, a team of students – Ben Cooke, Tom Wright, Matthew Wilde and Guy Pollack – assisted by Dr Steve Fossey, spotted the exploding star in nearby galaxy Messier 82 (the Cigar Galaxy). News and Events Katherine A Wilson-Heyworth 2014-01-23T16:57:17Z Royal Astronomical Society honours Astrophysics staff http://www.ucl.ac.uk/phys/news/physics-news-publications/ou_13_01_13 Five members of the Department have been commended by the Royal Astronomical Society in their 2014 awards: News and Events Katherine A Wilson-Heyworth 2014-01-13T11:12:03Z ALMA spots supernova dust factory 160,000 light years away http://www.ucl.ac.uk/phys/news/physics-news-publications/mm_16_01_14 News and Events Katherine A Wilson-Heyworth 2014-01-09T15:05:50Z Physics World Top 10 Breakthrough of the Year awarded to Planck space telescope http://www.ucl.ac.uk/phys/news/physics-news-publications/hp_06_01_13 A Physics World Top 10 Breakthrough of the Year has been awarded to the scientists working on the European Space Agency's Planck space telescope "To scientists working on the European Space Agency's Planck space telescope for making the most precise measurement ever of the cosmic microwave background (CMB) radiation." News and Events Katherine A Wilson-Heyworth 2014-01-07T10:00:35Z Astronomers discover first noble gas molecule in space http://www.ucl.ac.uk/phys/news/physics-news-publications/mb_12_12_13 Noble gas molecules have been detected in space for the first time in the Crab Nebula, a supernova remnant, by astronomers at UCL News and Events Katherine A Wilson-Heyworth 2013-12-13T12:25:52Z Dr Hiranya Peiris selected as one of ten "rising stars" by Astronomy Magazine http://www.ucl.ac.uk/phys/news/physics-news-publications/hp_04_11_13 Astronomy Magazine (July 2013 issue) selected Dr Hiranya Peiris as one of their 10 Astronomy's Rising Stars. News and Events Katherine A Wilson-Heyworth 2013-11-05T15:10:34Z Raman Prinja commended for children's science book http://www.ucl.ac.uk/phys/news/physics-news-publications/rp_04_10_13 Prof Raman Prinja has been awarded the School Library Association Information Book Award (age 7-12 category). His book, Science Crazy , co-authored with Steve Parker, explores science, with facts and activities covering physics, chemistry, astronomy and biology. The award was decided by a public vote of children around the country. News and Events Katherine A Wilson-Heyworth 2013-10-04T10:14:38Z UK scientists begin 5 year quest to solve cosmic detective puzzle http://www.ucl.ac.uk/phys/news/physics-news-publications/ol_12_09_13 A five year quest is underway to solve the cosmic detective puzzle of why the expansion of the universe is speeding up. News and Events Katherine A Wilson-Heyworth 2013-09-12T10:52:17Z Listen: Scientists aim to lift the veil on so called dark matter and energy http://www.ucl.ac.uk/phys/news/physics-news-publications/ol_04_09_13 News and Events Katherine A Wilson-Heyworth 2013-09-04T11:16:29Z Festival of the Planets comes to London http://www.ucl.ac.uk/phys/news/physics-news-publications/sm_16_08_13 From 8-13 September hundreds of astronomers from all over the world will arrive in the capital, bringing with them a huge variety of different public events to get Londoners involved in astronomy. News and Events Katherine A Wilson-Heyworth 2013-08-23T15:39:13Z National Astronomy Meeting Press Release http://www.ucl.ac.uk/star/astro_news/nampressrelease Surprisingly low temperatures detected in the remnant of the supernova 1987A Alexandra N D Fanghanel 2013-07-08T11:04:07Z RAS Michael Penston Thesis Prize for 2012: Runner-up prize awarded to Dr Stephen Feeney http://www.ucl.ac.uk/phys/news/physics-news-publications/sf_16_05_13 Dr Stephen Feeney has been awarded the runner-up prize for the Michael Penston Thesis Prize 2012. This Royal Astronomical Society (RAS) prize is awarded to the best doctoral thesis in Astronomy and Astrophysics; Stephen's thesis was entitled 'Novel Algorithms for Early Universe Cosmology'. News and Events Katherine A Wilson-Heyworth 2013-05-17T13:24:14Z ESA selects instruments to be flown on its icy moons mission http://www.ucl.ac.uk/phys/news/physics-news-publications/na_25_02_13 The JUpiter ICy moons Explorer mission (JUICE) will study Jupiter and its large, ice/ocean-bearing moons. JUICE is planned to launch in 2022 and arrive in 2030. Dr Nick Achilleos (Astrophysics) is part of the J-MAG Consortium, an international team of investigators who have successfully proposed one of the 11 scientific experiments to be flown on board this mission. News and Events Katherine A Wilson-Heyworth 2013-02-28T11:21:21Z Betelgeuse braces for a collision http://www.ucl.ac.uk/phys/news/physics-news-publications/mb_2_01_13 However you pronounce its name*, the star Betelgeuse is hard to miss on a clear winter's night. Representing the top left shoulder of Orion the Hunter it blazes a bright red colour. At over 600 light years away Betelgeuse is not particularly close, but it shines 100,000 times as brightly as our Sun. News and Events Katherine A Wilson-Heyworth 2013-01-23T09:54:58Z Dust Factory in the Crab Nebula revealed by the Herschel Space Observatory http://www.ucl.ac.uk/phys/news/physics-news-publications/mm_14_12_12 Herschel has produced an intricate view of the remains of a star that died in a stellar explosion a millennium ago. It has provided further proof that the interstellar dust which lies throughout our Galaxy is created when massive stars reach the end of their lives. News and Events Katherine A Wilson-Heyworth 2012-12-17T15:20:54Z


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picante in a sentence
Example sentences for picante
Think of someone who's bitter, or sour or maybe even a little picante.
Pour picante sauce over fish and simmer for five minutes.
Serve as an accompaniment to a main dish, and may be topped with grated cheese or picante sauce.
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Pork with Pineapple and Peppers
14 Mar 2011
|Pork tenderloin
|3⁄4 Pound, trimmed of all visible fat and sliced into 1/4-inch strips
|Curry powder
|2 Teaspoon
|Ground coriander
|1 Teaspoon
|Canola oil
|2 Teaspoon
|2 Clove (10 gm), minced
|Minced peeled fresh ginger
|2 Teaspoon
|Green bell pepper
|1 , seeded and chopped
|Red bell pepper
|1 , seeded and chopped
|Unsweetened pineapple chunks in juice
|8 Ounce (1 Can)
|2 Tablespoon
|1⁄2 Teaspoon
|Chopped fresh cilantro
|1 Tablespoon
1. Combine the pork, curry powder, and coriander in a large bowl; set aside.
2. Heat a large nonstick skillet over medium-high heat. Swirl in 1 teaspoon of the oil, then add the garlic and ginger. Cook 30 seconds, and then add the green and red peppers and continue cooking, stirring occasionally, until softened, 4-5 minutes.Transfer to a plate and keep warm.
3. Return the skillet to the heat and add the remaining 1 teaspoon oil. Add the pork mixture and cook, stirring occasionally, until beginning to brown, 3-4 minutes. Add the pineapple chunks and their juice, and the honey. Cook 2 minutes, stirring occasionally. Stir in the peppers and salt, and cook until hot, 2 minutes. Remove from the heat and stir in the cilantro.
Recipe Summary
Course:Main Dish
Method:Stir Fried
Cook Time:15 Minutes
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Pork With Pineapple And Peppers Recipe


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Polo Blue by Ralph Lauren
My favorite stage is actually the opening one, where in my skin, the spices are most predominant. After about 5 hours, this scent slowly turns quite sourish (probably a bit too much for my tastes) and synthetic. Anyway, this is a good daily scent, preferably for daytime wear as I can't imagine wearing this in the evening; I actually prefer Cool Water over this for the same purpose. Polo Blue lasts 7-10 hours on my skin by the way...
10th April, 2012


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Jay Cutler
Drunk Jay Cutler Used to Terrorize Vandy Campus Phones
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Jay Cutler is the Gift that Keeps on Giving!
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No One Likes Jay Cutler
Oh, so you're telling me no one likes Jay Cutler and no one wants to play with or coach Jay Cutler? Really? I have a hard time believing that. I mean, Cutty!
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Just Thrilled to Meet You, Cutty!
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Jay Feely, who kicked briefly for the Chicago Bears in 2014, has some opinions on why they were so bad. He says Jay Cutler and Marc Trestman were not leaders. We find that really hard to believe.
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Jay Cutler Takes Care of Kids Like He Plays Football
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Sep 23rd


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i just ran my first 5k and got 26min and 27secs. i came 12th overall and was the first kid 13 and under to finish!!!! wat is ur fastest 5k and wat did u get for ur first 5k???
My first and only 5k so far was 27 min. 40 sec. so nice job!


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Nook HD+ & Play Store: Old dog & new tricks?
Jun 23 2013 11:00 AM | PaulOBrien in Android
B&N recently kitted out their Nook HD+ tablet with the Google Play store as well as slashing the price to stimulate sales. Is it enough to make a forgettable tablet desirable?
When the Nook HD+ first came out, you might have spared it a passing glance. 9" 1080P screen? Very good! 16/32GB models with microSD expansion? Very good! Dual core TI OMAP CPU and 1GB RAM? Good enough. Customised Android build? Bad. Closed ecosystem with no Play Store? Very bad. £229 / £269 price point? Goodnight.
And so it was, that the Nook HD+ came to pass in November last year and it was largely overlooked by everyone but the most ardent of Nook fans. Intrigued Android enthusiasts tinkered in low numbers but a runaway success it certainly was not.
Fast-forward to May 2013 and something's changed. The future of Nook looks far from secure and a B&N fire sale has slashed the price of all their products, with the range starting at only £29 in the form of the Android equipped, e-ink Nook Simple Touch. The very top of the line Nook HD+ 32GB is now officially £199 (£189 from Currys), with the 16GB coming in at £179 and even better deals to be had if you're willing to hunt around and/or buy a refurbished unit.
What really makes a big difference though is that the walls around the Nook garden have crumbled and a new software update brings the full Google Play suite to the device. The Play Store, Chrome, Gmail etc. are all installed right off the bat giving the device far more versatility than before, although you are still subjected to Nook's custom UI to a degree (for notifications for example).
My tablet use nowadays really focuses around content consumption. Magazines primarily, but also news (via Currents), books, music, video with the odd bit of social (Twitter / G+ / Facebook). For this use the Nook HD+ seems perfect. A little smaller than the often overwhelming 10" tablets but with a no compromise 1920x1080 screen. As the price dropped (although it's still a lot more expensive than the insane US price - $149 / $179 for 16GB / 32GB respectively) I couldn't resist pulling the trigger and picking one up!
Let's start with the hardware first. Raw specs are only part of the story, but for a device that isn't brand new they're pretty respectable. The processor is a 1.5 GHz OMAP 4470 dual core item - not bleeding edge but not horrible either, 1GB RAM, that 9" / 1920 x 1280 / 256 PPI screen, microSD expansion, stereo speakers with SRS TruMedia support, 802.11 b/g/n WiFi and Bluetooth 4.0. No cameras of any description and a proprietary charging port (ugh) are the main flies in the ointment. The device weighs a not inconsiderable 515g and measures 240.3 x 162.8 x 11.4 mm. A sizeable 6,000 mAh battery is no doubt a significant contribution to the overall weight.
Holding the device in your hands it feels weighty but solid. On the front you'll find the huge screen (set back from the front of the device rather than flush fronted, unusual these days) a shiny silver physical Nook 'n' button and that strange 'cut off' corner with the hole in it for... well... I have no idea what that's for!
The colour is officially 'slate' which describes it well, dark grey. The screen is protected if you place the device face down on a surface. The back of the device has a soft touch coating which makes it very pleasant in the hand with a large embossed 'n' in the middle, more subtle 'nook' branding down the bottom and a speaker hole on the bottom left. Although the device does have stereo speakers with SRS, you're not going to get much stereo representation from the relatively small holes. The bottom of the device has an Apple-esque proprietary charging connector (a USB cable and 2 AMP charging adaptor ship in box) and a microSD slot behind a plastic cover. The power button for the device is on the top of the right edge, the 3.5mm headphone socket is on the top as are (strangely) the volume buttons, leaving the left edge completely empty. The edge of the device is a much darker grey (nearly black) and the overall look is very smart indeed.
After you fire it up and complete the setup wizard, you're presented with the customised UI showing links to your content and buttons along the bottom to open your library / apps / email etc. Down the bottom is a bar containing a search box and a task switching button and up top where you'd normally find the Android notifications is a bar with a user switcher on the left, a clock and clickable link to key shortcuts on the right and a notification indicator in the middle. So far so relatively easy to understand for anyone who is familiar with an Android device.
While the custom Nook UI is nice enough to look at, most of us will want to replace it with a 'regular launcher' and thankfully doing so is incredibly easy - just fire up the Play Store and download the launcher of your choice (I tried out both Action Launcher Pro and Nova and both worked admirably). This gives you a much more conventional Android feel although the customised top and bottom bars will always be retained.
The device's on screen keyboard is custom but once again, if you don't like it you can install another (e.g. SwiftKey tablet), straight from the Play Store. The recent release of Google Keyboard means you have another excellent, free alternative for the 'stock' look and feel.
If you use your launcher to fire up the Settings application you'll be in for a bit of a shock... there's not much in there! You can set up your WiFi and Bluetooth, toggle powersave and lock rotation, setup your keyboard and manually specify the brightness. There is no light sensor on the Nook HD+, so no auto brightness. An 'Applications' menu in Settings lets you specify preferences for the built in applications in a central place and accounts can be added and removed much like any other Android device. An option is also present to link the Nook to your UltraViolet account for playing video. Adobe Digital Editions is supported on the device. Automatic device backup / restore is provided by virtue of the new Google suite support (which, as we all know is patchy at best!), you can manage your internal storage (around 13.6GB is free on a 16GB device), network based location can be enabled / disabled and finally you can view the device information and factory reset. That is literally ALL the settings, a lot less than you would find on a regular Android tablet.
So that's a quick overview of Nook's changes to the base Ice Cream Sandwich OS... what about in real world use? After starting up the device and installing the latest OS and various app updates, I set about customising it to suit my use better. First up - installing a launcher. I opted to use Action Launcher Pro to give me a consistent user experience between my Android devices... it's actually well suited to the HD+, with it's tall, high resolution screen it's quick and easy to find what you want in the list.
Launcher done, I installed a battery monitoring widget (Battery Widget Reborn) to drop on the desktop giving me a better way of keeping an eye on battery. There is an indicator in the top right of the screen but it doesn't really tell me an awful lot and being a new device, I wanted to keep an eye on it.
Next? The reading apps. I installed everything I might think about using - Amazon Kindle, Currents, Nook (of course), Play Books, Play Magazines, Press Reader and Zinio. Amazon Kindle and Play Books are pure, simple, book readers and as you'd expect, work perfectly. Currents is actually unexpectedly awesome on the device - I've used it primarily on my phone in the past but it looks stunning on the tablet, with it's sync options too it's probably great if you commute. There's no need for me to tell you that the Nook app is very good on the HD+ is there. Play Magazines is the application I use most and boy, do magazines look fantastic on the device. It suffers from the same issue I have on every device without exception though... sometimes page turning can be a little slow in really rich publications. I can't honestly say that it's unbearable or it's obvious the 4470 processor is straining more than on my other devices here though. PressReader and Zinio, again, both flawless on the HD+. It's shaping up to be a great content consumption tool.
So, social. If you've used a tablet at all you already know that Facebook on tablet is an embarassment. Nothing's different on the Nook, although as it's designed to be used in a portrait orientation it looks a lot better than if you were to fire it up in landscape. For Twitter I use Plume which is fantastic and Google+ is well optimised for tablets nowadays so no complaints there.
The screen itself needs to be exceptional on the HD+ as it's the key selling point and thankfully, it is. The lack of automatic brightness can be a bit of a chore, but loading up my favourite magazine on the Nook alongside a Tablet Z I happen to have here and a Nexus 10, it really can hold it's own. In fact, I think the colour representation is probably better than on either of those.
The speaker on the device looks very small on the back, but it actually packs quite a punch. As you'd expect, there's not a ton of bass but it is loud! Being on the back you'll get better sound if you flip the device over but at least if you do so, the screen isn't touching the surface you're on.
Predictably, a great screen and a decent speaker combine to make a good device for video. A kickstand case is a good idea if that's going to form a significant part of your usage scenario. I loaded on TVCatchup, iPlayer, YouTube etc. and they all performed well. TVCatchup (the strangely named live-tv-not-catchup app) in particular is superb. I didn't yet install my video player of choice (Archos Video) for playing MKV files, so that might be worth checking if you plan to play a lot of 'downloaded content'.
Does the availability of the Play Store on the Nook HD+ really mean there's life in the old dog yet? I have to say, coupled with the price drop, yes - it does. There's some uncertainty about what Nook will be in the future but it doesn't matter really as there's a wealth of other ways to get content. If you're looking to drop sub £200 on a tablet then it's well worth considering. If you're in the US then at $149, it's an incredible bargain. Read through my pros and cons, maybe have a quick play in a store perhaps (John Lewis have display models) and go from there.
PS - I have also spent time with a Nook HD (the 7" model). Nice enough, but there are better options in the market.
Nook HD+ Pros
- 9" screen is an under-provided for market
- Excellent high resolution screen
- Solid build quality
- Google Play suite
- Very good value for money (especially in the US)
- No cameras
- No auto brightness
- Quite heavy
- CPU is a little old now
- Unknown future upgrade path
Nook HD+ pricing
Nook HD+ (32GB) @ Currys - £189.99
Nook HD+ (16GB) @ Argos - £179.00
Nook HD+ (32GB 'A' grade) @ CEX - £140.00
You can learn more about the Nook HD+ on the official UK site.
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6 Comments
When you say there is no auto brightness, is it because there is no sensor? Doesn't Lux or something similar work?
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No sensor!
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Can't even spoof it with a front camera either. ;-)
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I got a nook hd+ a few months ago and I love it. I couldn't stand the custom nook interface so I installed cm10.1 from xda developers. It is fully functional and obviously gives a full stock feel. It can now completely replace the default o/s
If anyone is bothered about cases, I'd recommend the poetic cases on amazon - I have one that cost £10 and it fits perfectly and meets my needs perfectly.
I would agree with all of Paula pros but because of the xda community I wouldn't count future upgrades as a con as it already has android 4.2.2. One other con for me is the proprietary power lead, if you want a replacement or an hdmi lead you need to pay over the odds and/or import from America!
If anyone is bothered about cases, I'd recommend the poetic cases on amazon - I have one that cost £10 and it fits perfectly and meets my needs perfectly.
I would agree with all of Paula pros but because of the xda community I wouldn't count future upgrades as a con as it already has android 4.2.2. One other con for me is the proprietary power lead, if you want a replacement or an hdmi lead you need to pay over the odds and/or import from America!
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Nice review. PCPro gave it a recommended award now it has Google Play as well.
I had one from CeX for £150 (just open box never been touched by the look of it) - now even better value at £140!
It is heavyish but does feel nice and balanced in the hand - especially in portrait mode - lack of camera is no issue to me as I don't use or plan to use Skype.
My only niggle is the raised bezel - but I can live with that - auto brightness would of been nice - but I do like the fact that the brightness does go down very low so ideal for reading in a dark room (something my Nexus 7 and Motorola Atrix can't do without resorting to some screen dimming apps).
Accessories are a bit few and far between - best price for some screen protectors I found were here: http://www.ebay.co.u...=item564f250e6d
I did try CM 10.1 running of an SD card (see XDA forums) but found it a bit laggy (even more so than the occasional lags on the stock experience) - but that could of been my SD card not being a super fast class card. Better to flash to internal memory if your after the full 10.1 performance.
All in all I am very happy with mine - it really does make you realise that in the end the key component of a tablet is the screen and that may sound obvious but plenty of people do make that quality sacrifice to own a budget tablet - the Nook fills both budget constraints with a great screen IMHO :-)
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Does anyone know if any of the Sky TV apps work on a stock Nook HD+?
Was tempted to get the Sky Sports app for the next football season, but it appears it won't run on my rooted GS3.
Was tempted to get the Sky Sports app for the next football season, but it appears it won't run on my rooted GS3.
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Vulvodynia, Vulvar Vestibulitis, Vulvar Dysesthesia, Vaginitis, Vaginismus, Vestibulodynia. It reads like a list of alien invaders, and for women afflicted with these conditions, it feels like it. These are words that show up as a diagnosis or diagnostic criteria with nearly 15% of all gynecological visits in the US today. That's a lot of women, and this number doesn't reflect the number of women that are mis-diagnosed or undiagnosed.
Let's break down the laborious terminology here.
· Vulva- (or vulvo-): is a root word that means "external female genitalia," which includes the inner and outer labia (lips) the clitoris, vaginal and urethral opening, and that little fold of skin-like connective tissue around the opening (the vestibule).
· Vestibul- : see above
· -dynia: pain (vuvlodynia – pain in vulva; vestibulodynia – pain in vestibule)
· -itis; inflammation – typically characterized by: redness; pain (often burning); maybe swelling; and tenderness to touch
· -mus: tightness or spasm
· Dysesthesia – (dys- impaired function; -esthesia: sensation) in this context, the sensory input from the vaginal area to the brain does not match the stimulus. Typically in painful conditions it means the nerve endings are hypersensitive, light touch should not cause searing pain, but for those with dysesthesia, it does.
Basically what we have here is a collection of symptoms that often serve as a diagnosis when no one can figure out WHY the symptoms have appeared. There are a lot of theories as to why this happens to so many women (some studies show as many as 50% of women will have these symptoms in their life-time), and there is constantly new research getting us closer and closer to the cause.
Here are some of the things we know (or suspect) that may predispose a women to having these problems:
· Genetics – a grant has recently been awarded to allow researchers to explore a link with certain genes that may cause an increase in the proliferation of nerve cells and irritant cells in the vulvar area, and genes that effect protein synthesis in these areas.
· Mast cell proliferation – these are the irritant cells mentioned above. Everybody has them, they are largely responsible for that histamine response you get from allergies, but for some reason they seem to be overly abundant in certain areas in certain people. They have proven that there is a hyperactive mast cell response in the bladder lining of interstitial cystitis (IC) sufferers.
· Chronic yeast infections – the constant irritation can cause the nerves to become hyper-sensitive, causing pain and irritation, even after the yeast is long gone. And please remember that thong underwear can carry yeast and other bacteria from anus to vagina very easily.
· Lichen planus, HPV, various bacterial and viral conditions.
· Contact dermatitis – This happens when a product irritates the area, and the nerves remain sensitized even after the irritant is gone. Soaps, perfumes, toilet paper, dyes in clothing can all be irritating. Here's the kicker: many of the products we use to relieve vaginal itching or burning are hugely implicated in contact dermatitis. Anti-yeast creams are the biggest culprits, and so are anti-itch creams. Even prescription ones are considered to be causative factors. The safest way to handle a yeast infection is to get it cultured before taking ANYTHING, use the most appropriate treatment as recommended – but only once! If you are very sure it is yeast, and you use an over the counter medication, if it doesn't work be sure your doctor knows what you tried, and the experts recommend that you not use a prescription cream if the over the counter doesn't work, you are better off to use an oral medication.
· Pelvic Floor Dysfunction – O.K.; if you read this blog even occasionally, you knew I was getting to this. Pressure on the nerves from tight muscles can irritate the already hypersensitive nerves. Trigger points within the muscles can set up pain patterns that mimic vulvodynia pain when the muscle is stretched or tightened. Guarding (tightening up the muscle in anticipation of pain) can lead to vaginismus.
So what do you do? FIRST – go to a doctor! The most important thing is to rule out conditions that can be treated medically. If all the cultures come back negative, it is time to start working on the symptoms.
As a physical therapist, I help you try to eliminate pain. We use biofeedback and visualization techniques to teach you to relax that pelvic floor, and take the pressure off the nerves. We work manually (internally and externally) to eliminate trigger points and to improve the muscular balance around the pelvis. We use electrical modalities including therapeutic ultrasound, and electrical stimulation to help relieve pain. We educate you about avoiding irritants (diet, chemical, mechanical). Once the pain level is controlled, we teach you how to stay pain free, or manage flares as they arise.
A side note on my own personal treatment philosophy: The most effective way to deal with pelvic floor muscle tightness is to work internally on trigger points and muscle spasms. Many of my vulvar pain patients cannot handle vaginal work, and are so uncomfortable with rectal palpation that the costs out-weigh the benefits. With these women, I use as many indirect techniques as possible until we have achieved a comfort level with internal work. With manual therapy, you may experience some extra soreness the next day – but several days (or even two) of agony is too much, and not (in my mind) effective. It is imperative that you talk with your physical therapist during your treatment, don't undergo weeks of "torture" because you think it might help. If you don't tell your PT how painful it is, she will assume everything is just dandy. Chances are if she is aware of the problems you are having, she will be able to modify the treatments.
All of this is in cooperation with your medical team. There are medical interventions to help relax the muscles and control the nerve pain, and depending on the acuity of your condition, sometimes the medical interventions are what make it possible for me to do my job.