text:
|Publication number
|Publication type
|Application number
|Publication date
|Mar 24, 1998
|Filing date
|Jun 6, 1995
|Priority date
|Oct 20, 1989
|Fee status
|Also published as
|Publication number
|Knud Erik Mogensen, Gilles Uze, Georges Lutfalla, Ion Gresser
|Original Assignee
|Societe Leb-Tech
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (1), Non-Patent Citations (33), Referenced by (20), Classifications (15), Legal Events (7)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a Divisional of application Ser. No. 08/453,090, filed May 30, 1995; which is a Continuation of Ser. No. 07/900,642, filed Jun. 15, 1992, now abandoned; which is a continuation of international application PCT/FR90/00758, filed Oct. 19, 1990.
The present invention relates to the sequence, in particular to a cDNA sequence, coding for the gene for the alpha interferon receptor.
Interferon is a generic term specifying three antigenic classes: alpha, beta and gamma, of proteins capable of inducing, among other things, an antiviral state and of inhibiting the multiplication of sensitive cells.
Between the alpha and beta interferons, which are produced as a consequence of vital infection, there exists a sufficiently extensive structural homology for these two types of interferon to be able to react via the same cell receptor.
Human alpha interferon is itself a mixture of a dozen proteins with very extensive homology, encoded by different structural genes. These subtypes have an identical functional spectrum but their specific activities are different.
Gamma interferon, which is produced by activated lymphocytes, does not possess any homology with the alpha/beta interferons and it does not react with their receptor.
At present, the structures of the interferons (which possess about 165 amino acids) are quite well known as regards their amino acid sequences and several studies have been directed towards the analysis of the functional domains of these proteins. Hybrid molecules, constructed between the interferons of high and low affinity by using restriction sites on the DNA coding for these interferons, have been used to show that the N-terminal part of the molecule determines the affinity of binding to its cell receptor and, consequently, the specific activity of the alpha interferons.
Respiratory diseases of vital origin pose considerable economic problems for public health. Clinical trials have shown that alpha interferon provides 100% protection to volunteers infected with different rhinoviruses. Similarly, it has been demonstrated that among volunteers treated with alpha interferon and infected with a coronavirus, 6% develop the symptoms of a cold compared with 37% of the volunteers treated with placebo.
Nonetheless, although human alpha interferon was found to be efficacious in these trials, the toxicity that it exerts on the nasal mucosa poses a major problem.
Interferon also possesses an antitumoral activity in man and at present it has become the treatment of choice for some cancers. However, interferon injected by the systemic route also exerts toxicity on the nervous system which limits the possibilities of treatment.
In fact, at present, there is no means of determining which interferon should be used to obtain therapeutic activity and reduced toxicity. Several laboratories have made considerable efforts to construct modified interferons which might have pronounced activity associated with low toxicity. This approach has been shown to be disappointing.
It is now obvious that the possible success of such a project requires knowledge of the structure of the receptor of the interferons in order to devise the structure of an agonist. An agonist having a high activity and low toxicity for the nasal mucosa would find a very large market for the treatment of respiratory diseases of vital origin.
That is why the present invention relates more particularly to the production of a protein having the structure of the alpha interferon receptor and its expression, in particular at the surface of cells as well as the DNA sequences coding for the said protein.
Hence, the present invention relates, in the first instance, to the human alpha interferon receptor characterized in that it corresponds to the sequence shown in FIG. 4 or to one of its allelic variants which does not differ from it by more than 3 amino acids.
These allelic variants may include the sequence shown in FIG. 4 in which the threonine at position 164 is replaced by an arginine and an aspartic acid is inserted between the aspartic acid at position 479 and the glutamic acid at position 480.
The present invention also relates to a DNA sequence coding for the receptor for human alpha interferon.
This DNA sequence will preferably correspond to the sequence shown in FIG. 4 or to a sequence allelic with the latter.
The structure of the DNA sequence coding for the receptor for human alpha interferon is analysed in the examples. In particular, it bears a signal peptide. In some cases, it will be possible to delete or replace this signal peptide by another signal peptide but in most cases it will be preferable to retain this signal peptide shown in FIG. 4 and hence the corresponding coding sequence.
This sequence is preferably inserted into a system which ensures its cellular expression in a suitable host cell, in particular at a transmembrane site.
In particular, the present invention relates to the DNA fragment, in particular the cDNA fragment, characterized in that it codes for the gene of the alpha interferon receptor. In particular, it will correspond to the sequence shown in FIG. 4 or to a sequence allelic with the latter.
It may thus be the DNA sequence shown in FIG. 4 in which the cytosine at position 569 is replaced by guanine and a TGA codon inserted between the adenine situated at position 1514 and the thymine at position 1515.
The present invention also relates to non-human cells characterized in that they express the said receptor for human alpha interferon and to a process for the production of the said cells.
According to this process, compatible host cells are transfected or infected with an element of DNA bearing a DNA sequence coding for the said receptor, as well as the elements capable of ensuring the expression of this sequence in the said cell.
The examples given hereafter demonstrate how it has been possible to express this sequence coding for the receptor for human alpha interferon (IFN-alpha h) in non-human mammalian cells, in particular mouse cells. The procedures which make possible the cell expression of exogenous DNA sequences are known. Depending on the host cells, it may be a question of using self-replicating vectors such as plasmids or integrating vectors, DNA sequences or viral vectors for example. In the case in which it is desired to produce a cell line expressing the human IFN-alpha receptor, the procedure used may be a low yield procedure since only one line is sought. On the other hand, when the production of the protein alone is desired, it is preferable to use vectors ensuring amplification, in particular plasmid vectors comprising an origin of replication or multicopy system of integration.
In addition, the present invention relates to a process for the preparation of human alpha IFN receptors.
Thus, when it is desired to produce the protein cells transformed, transfected or infected by an expression vector for the said proteins comprising a DNA sequence coding for the said receptor under the control of a promoter of transcription of this sequence in the host as well as the elements ensuring the translation of the protein, will be cultivated in a suitable culture medium and then the protein obtained will be separated by any appropriate means.
This protein will be used to prepare antibodies, in particular monoclonal antibodies directed against the receptor; the appropriate technology will not be described in detail since it is a known procedure.
The invention thus makes it possible to produce:
the receptor for human alpha interferon,
antibodies directed against this receptor, and
cells expressing the said receptor.
The applications of these elements are very varied. First, the receptor in isolation or expressed on the surface of a cell may enable analogues of human alpha interferon to be tested in order to define the best agonists.
This type of test may also be performed by means of the corresponding protein attached to a solid support such as plates, beads, etc. These procedures have already been used for other receptors or for antigen-antibody assays.
The receptor agonist assays may be performed by measuring direct binding or by measuring displacements which make it possible to estimate the affinity of the agonist in relation to a reference substance, for example the human alpha IFN.
The antibodies will be used for the assay of the receptors or for their visualization in the case of imaging. These are procedures which make it possible to evaluate certain pathological conditions justifying, for example, treatment with alpha interferon or which make it possible to evaluate certain conditions in which the level of these receptors varies.
Hence, the invention also relates to diagnostic kits containing one or more of the preceding elements as a diagnostic or imaging agent, or as a pharmacological model to test the compounds derived from human alpha interferon.
The receptor protein or the corresponding antibodies may also be used as a pharmacological agent when it is desired to block the human alpha IFN receptors or when the protein is used as an inhibitor to block human alpha IFN in certain states in which the over-expression of human alpha interferon may be harmful.
Finally, the antibodies may be used as targetting agent for the insertion of an active principle coupled to this antibody in the vicinity of a receptor for the human alpha IFN.
The examples and figures given hereafter are non-limiting and will make it possible to demonstrate other advantages and characteristics of the present invention.
FIG. 1 shows the binding curves of human alpha interferon B (black symbols) or the hybrid BDBB (white symbols) to the primary transfectant 10BH7 (A) or to the parental cells BTG 9A (B).
FIGS. 2A and 2B represent the "Southern blot" analysis of the genomic DNA of the primary and secondary transfectants. FIG. 2A:
Well No. 1: EcoRI digestion of the DNA of the primary clone 10BH7 hybridized with a Alu probe.
Well No. 2: same DNA hybridized with a Lambda probe. FIG. 2B:
Wells No. 1 and 3: BamHI digestion of the DNA of the two secondary transfectants 1B4D10 and 2A415 hybridized with a Alu probe.
Well No. 2 and 4: BamHI digestion of the DNA of two negative secondary transfectants hybridized with a Alu probe.
Well No. 5: BamHI digestion of the DNA of the parental cells BTG 9A hybridized with a Alu probe.
FIG. 3 shows the "Northern blot" analysis of the RNA polyA+ of the two secondary transfectants (wells No. 1 and 3) and of the parental cells (well No. 2) hybridized with the probe EcoRI 5 kb.
FIG. 4(a-f) shows the nucleotide sequence of the cDNA of the receptor for human alpha interferon (SEQ ID NO:1) as well as its amino acid sequence (SEQ ID NO:2). The signal peptide and the transmembrane region are shown in boxes. The glycosylation sites linked to nitrogen are underlined by dashes. The two polyadenylation sites and the Sma I restriction site are underlined.
Selection of transfected BTG mouse cells sensitive to human alpha B interferon.
Mouse BTG 9A cells are co-transfected with a human cDNA bank cloned in a mammalian lambda phage expression vector also containing the bacterial gene neo and the genomic DNA Daudi of high molecular weight in a ratio 1:1. This system of co-transfection in which the expression of a human interferon receptor may result from the genomic human DNA and/or the human cDNA is used to increase the chances of isolating useful transfectants.
Clones of stable transfectants are selected in a G418 medium at a frequency of 10-2 -10-3. In order to detect cell clones sensitive to human alpha interferon, transfected clones are treated with 30 000 units/ml of human B interferon and infected with VSV. At this concentration, mouse BTG cells are insensitive to alpha B interferon but a transfectant clone expressing the receptor gene for human alpha interferon ought to be in an antiviral phase.
In view of the fact that the interferon titer is inversely proportional to the multiplicity of infection, this viral selection makes it possible to neutralize the large quantity of VSV produced by the majority of the clones of the unsuitable cells which would abolish the antiviral state of the clone of the cell of interest. This method implies a rapid absorption of the virus by the cells followed by a treatment with rabbit anti-VSV antiserum to neutralize the excess of the virus, and development of the cytopathic effect in a rabbit anti-VSV antiserum containing a semi-solid gelose medium. Surviving cellular clones are isolated individually. In order to avoid a chronic VSV infection, the cell clones are subjected to a treatment with mouse alpha/beta interferon and the anti-VSV antiserum is maintained in a G-418 medium for one week. They are then retested for their sensitivity to human alpha B interferon in relation to the VSV or EMC infections. Most of these transferred clones are insensitive to human alpha B interferon. Nonetheless, one clone showed an interesting sensitivity to human alpha B interferon. It was then subcloned and designated 10B H7.
The sensitivity of the 10B H7 cells to numerous mouse and human alpha interferons was determined, then the behaviour of these cells was compared with that of the parental mouse BTG cells.
Table I shows the activity of mouse alpha/beta interferon, human alpha B interferon, human beta interferon and human gamma interferon tested on mouse parental BTG cells of the transfected 10B H7 clone and of human Wish cells using both the VSV and the EMC viruses.
With respect to mouse interferon, the 10B H7 cells are as sensitive as the parental BTG cells. Moreover, the 10B H7 cells show a sensitivity at least 64 000 times greater to human alpha B interferon than the parental cells. The activity of human beta interferon on the 10B H7 cells is also observed to be increased 8-fold but no antiviral activity of human gamma interferon is detected since it is recognized by a different receptor on both the parental BTG cells and on the transfected 10B H7 clone. The specific antiviral activity of alpha B interferon (4.7�106 units/mg) on the 10B H7 cells is of the order of the specific activities of the human alpha interferons on human cells.
TABLE I______________________________________ Antiviral activities of interferon preparations tested on: (units/ml) RATIO BTG 10BH7 WISH 10BH7/BTG______________________________________Mouse alpha/ 12.8 � 10.sup.6 12.8 � 10.sup.6 240 1beta IFNHuman alpha B <20 1.27 � 10.sup.6 54 � 10.sup.6 >64,000IFNHuman beta 200 1.6 � 10.sup.3 2.7 � 10.sup.6 8IFNHuman gamma <1 � 10.sup.3 <1 � 10.sup.3 20 � 10.sup.6 --IFN______________________________________
Transfectants of a mouse BTG cell sensitive to interferon which express, the receptor for human interferon.
Human alpha B interferon behaves towards 10B H7 cells like alpha D interferon on human cells, with similar specific activity and similar apparent binding affinity. Like alpha D interferon on human cells, the binding of human alpha B interferon to 10B H7 cells may be measured only at 37� C.
Several binding experiments were performed with iodinated alpha B interferon used as probe for the human receptor and a iodinated hybrid interferon designated BDBB which is active on both the parental mouse lines and on the clone 10B H7, as positive control. This hybrid interferon which has a specific activity on mouse cells close to that of human alpha B interferon on the 10B H7 cells, could be a probe for the mouse and human receptors on both the parental BTG cells and the transfected 10B H7 cells.
FIG. 1 shows that the binding of BDBB is similar to the BTG and 10B H7 cells. Conversely, the 10B H7 cells bind alpha B interferon specifically whereas the BTG cells do not. The binding parameters calculated from the Scatchard data show that the 10B H7 cells express about 500 binding sites per cell for alpha B interferon with an apparent Kd of 2.10-10 M. This is similar to the values for the BDBB interferon (1,500 binding sites per cell; apparent ED 5.10-10 M), which is active on both the parental mouse lines and on the clone 10B H7.
In conclusion these results, supplemented with other studies, indicate that human alpha B interferon binds to a specific receptor on the 10B H7 cells but not to the parental mouse cells.
Cloning of a probe covering the gene for the human alpha interferon receptor in clones of a secondary transfected cell.
Starting from the hypothesis that the 10B H7 cells express a transfected human gene necessary for conferring binding sites and an antiviral activity of alpha B interferon on a mouse cell, the distribution of the human DNA in the transfected 10B H7 genome was investigated.
FIG. 2A is a "Southern blot" with the DNA of the 10B H7 clone using either a human Alu sequence which detects human genomic DNA or a probe with lambda DNA in order to detect the integrated cDNA.
Thus it was shown that the transfectants had integrated more than one part par 1000 of human Daudi DNA and 100 copies of the human cDNA of the mammalian library. In view of the considerable amount of human DNA in this clone, it was necessary to isolate secondary transfectants in order to clone the DNA sequence responsible for the expression of the receptor in the initial 10B H7 clone. For this purpose, mouse BTG cells were co-transfected with genomic DNA from the 10B H7 clone and from neopSV2. Cells sensitive to human interferon were isolated. The stable secondary transfectants were subjected to 4 cycles of treatment with alpha B interferon and to VSV infection. After subcloning, two independent secondary clones 1B4D10 and 2A415 were obtained. These two secondary clones are independent but are derived from the same initial clone. They have the same characteristics as those of the initial clone 10B H7, i.e. sensitivity to human alpha interferon and expression of the receptor at their surface. These two secondary clones have not retained the sequences associated with the lambda phages in their genome and, consequently, the expression of the receptors for human alpha interferon is due to the genomic DNA of the Daudi cells which had been transfected initially into the BTG cells. They have, in fact, conserved the human genomic sequences. FIG. 2B shows a BamHI digestion of the secondary DNA clones hybridized with a Alu probe which detects the repetitive Alu sequences. The two positive secondary clones 1B4D10 and 2A415 have in common a main band of 18 kb.
A Alu probe was used to screen fragments of size 20-15 kb of a genomic library after complete digestion of the DNA of the secondary clone 1B4D10 by BamHI cloned in a lambda phage EMBL 3. The repeated Alu sequences containing the BamHI fragment of 18 kb were isolated and then subcloned in a plasmid vector pUC.
This fragment contains two EcoRI sites giving end fragments of 11 kb and 2 kb and a central fragment of 5 kb. There are human Alu repetitive sequences in these three fragments and thus the central 5 kb fragment must be deleted from the DNA sequences of the mouse, The central 5 kb EcoRI fragment is present in a EcoRI digestion of the DNA of the two secondary clones 1B4D10 and 2A415, obtained independently from the same initial clone.
Cloning and nucleotide sequence of the cDNA of the receptor for human alpha interferon.
FIG. 3 shows that the 5 kb EcoRI probe detects a transcript of equal size in the secondary clones which is absent from the RNA poly A+ of the parental BTG cells.
A cDNA library prepared in a lambda ZapII phage vector from the RNA of the secondary clone 1B4D10 is screened and the cDNA hybridizing with the 5 kb EcoRI probe is isolated. Eight independent cDNA clones, all bearing the same 3' end, are analysed by sequencing. The longest (1900 bp) have at their 5' end a HindIII restriction fragment of 400 bp covering only the coding sequences and lack the repetitive elements. Used as a probe, this fragment detects the 2.5 kb transcript present in both the secondary clones and in the Daudi human cells but which is absent from the mouse BTG. In view of the fact that point mutations may arise in transfected genes, this HindIII probe of 400 bp has been used to study a lambda ZapII cDNA library starting from Daudi human cells in order to isolate complete cDNA clones corresponding to the human transcript.
Overlapping cDNAs isolated from human Daudi cDNA libraries were preserved in "pBluescript" plasmids starting from the in vivo excision of ZapII lambda by f1 helper phages. The single-stranded DNA recovered in the presence of the M13 intermediate phage from bacteria containing "pBluescript" plasmids is sequenced at one end of the cDNA by the chain termination method (Sanger et al. 1977) and the sequences of the other end of the cDNA are obtained from the sequence of the double strand in the plasmid. Oligonucleotides were synthesized and used in particular for sequencing the DNA when "gaps" appeared in the sequence.
The two strands of the longest cDNAs described in FIG. 4 were completely sequenced.
The sequence of cDNA is of the order of 2784 bp and contains an untranslated region of 1035 bp at the 3' end which includes two polyadenylation sequences ATTAAA. The sequence of the open reading frame is complete since it is terminated at the 5' end by a STOP codon. Two ATG codons are found side by side at positions 79 and 82.
In addition to the hydrophobic region of the amino terminus, a second hydrophobic region (amino acids 456 to 476) was identified. There are 15 potential glycosylation sites linked to nitrogen, 12 in the putative extracellular domain and 3 in the putative intracellular domain.
The molecular weight of the sequence suggested as receptor (including the signal peptide) is 63,485 Dalton, and glycosylation may give rise to a value of the order of 95,000-100,000 Dalton for the protein of the naturally occurring receptor.
The receptor for human alpha interferon appears to be a single protein. Its sequence nonetheless exhibits a certain allelic variation. Such variation is found, for example, in the Daudi heterozygote cells which express two alleles of the receptor, the one corresponding to the sequence described in FIG. 4, the other exhibiting a substitution of a cytosine by a guanine at position 569 and the insertion of three bases T, G and A after the adenine situated at position 1514. At the level of the protein, this results in a substitution of the threonine 164 by an arginine, and by the insertion of an aspartic acid after the aspartic acid 479.
__________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 2(2) INFORMATION FOR SEQ ID NO:1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 2784 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: DNA (genomic)(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:TTAGGACGGGGCGATGGCGGCTGAGAGGAGCTGCGCGTGCGCGAACATGTAACTGGTGGG60ATCTGCGGCGGCTCCCAGATGATGGTCGTCCTCCTGGGCGCGACGACCCTAGTGCTCGTC120GCCGTGGGCCCATGGGTGTTGTCCGCAGCCGCAGGTGGAAAAAATCTAAAATCTCCTCAA180AAAGTAGAGGTCGACATCATAGATGACAACTTTATCCTGAGGTGGAACAGGAGCGATGAG240TCTGTCGGGAATGTGACTTTTTCATTCGATTATCAAAAAACTGGGATGGATAATTGGATA300AAATTGTCTGGGTGTCAGAATATTACTAGTACCAAATGCAACTTTTCTTCACTCAAGCTG360AATGTTTATGAAGAAATTAAATTGCGTATAAGAGCAGAAAAAGAAAACACTTCTTCATGG420TATGAGGTTGACTCATTTACACCATTTCGCAAAGCTCAGATTGGTCCTCCAGAAGTACAT480TTAGAAGCTGAAGATAAGGCAATAGTGATACACATCTCTCCTGGAACAAAAGATAGTGTT540ATGTGGGCTTTGGATGGTTTAAGCTTTACATATAGCTTACTTATCTGGAAAAACTCTTCA600GGTGTAGAAGAAAGGATTGAAAATATTTATTCCAGACATAAAATTTATAAACTCTCACCA660GAGACTACTTATTGTCTAAAAGTTAAAGCAGCACTACTTACGTCATGGAAAATTGGTGTC720TATAGTCCAGTACATTGTATAAAGACCACAGTTGAAAATGAACTACCTCCACCAGAAAAT780ATAGAAGTCAGTGTCCAAAATCAGAACTATGTTCTTAAATGGGATTATACATATGCAAAC840ATGACCTTTCAAGTTCAGTGGCTCCACGCCTTTTTAAAAAGGAATCCTGGAAACCATTTG900TATAAATGGAAACAAATACCTGACTGTGAAAATGTCAAAACTACCCAGTGTGTCTTTCCT960CAAAACGTTTTCCAAAAAGGAATTTACCTTCTCCGCGTACAAGCATCTGATGGAAATAAC1020ACATCTTTTTGGTCTGAAGAGATAAAGTTTGATACTGAAATACAAGCTTTCCTACTTCCT1080CCAGTCTTTAACATTAGATCCCTTAGTGATTCATTCCATATCTATATCGGTGCTCCAAAA1140CAGTCTGGAAACACGCCTGTGATCCAGGATTATCCACTGATTTATGAAATTATTTTTTGG1200GAAAACACTTCAAATGCTGAGAGAAAAATTATCGAGAAAAAAACTGATGTTACAGTTCCT1260AATTTGAAACCACTGACTGTATATTGTGTGAAAGCCAGAGCACACACCATGGATGAAAAG1320CTGAATAAAAGCAGTGTTTTTAGTGACGCTGTATGTGAGAAAACAAAACCAGGAAATACC1380TCTAAAATTTGGCTTATAGTTGGAATTTGTATTGCATTATTTGCTCTCCCGTTTGTCATT1440TATGCTGCGAAAGTCTTCTTGAGATGCATCAATTATGTCTTCTTTCCATCACTTAAACCT1500TCTTCCAGTATAGATGAGTATTTCTCTGAACAGCCATTGAAGAATCTTCTGCTTTCAACT1560TCTGAGGAACAAATCGAAAAATGTTTCATAATTGAAAATATAAGCACAATTGCTACAGTA1620GAAGAAACTAATCAAACTGATGAAGATCATAAAAAATACAGTTCCCAAACTAGCCAAGAT1680TCAGGAAATTATTCTAATGAAGATGAAAGCGAAAGTAAAACAAGTGAAGAACTACAGCAG1740GACTTTGTATGACCAGAAATGAACTGTGTCAAGTATAAGGTTTTTCAGCAGGAGTTACAC1800TGGGAGCCTGAGGTCCTCACCTTCCTCTCAGTAACTACAGAGAGGACGTTTCCTGTTTAG1860GGAAAGAAAAAACATCTTCAGATCATAGGTCCTAAAAATACGGGCAAGCTCTTAACTATT1920TAAAAATGAAATTACAGGCCCGGGCACGGTGGCTCACACCTGTAATCCCAGCACTTTGGG1980AGGCTGAGGCAGGCAGATCATGAGGTCAAGAGATCGAGACCAGCCTGGCCAACGTGGTGA2040AACCCCATCTCTACTAAAAATACAAAAATTAGCCGGGTAGTAGGTAGGCGCGCGCCTGTT2100GTCTTAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAAAACAGGAGGTGGAGGTTG2160CAGTGAGCCGAGATCACGCCACTGCACTCCAGCCTGGTGACAGCGTGAGACTCTTTAAAA2220AAAGAAATTAAAAGAGTTGAGACAAACGTTTCCTACATTCTTTTCCATGTGTAAAATCAT2280GAAAAAGCCTGTCACCGGACTTGCATTGGATGAGATGAGTCAGACCAAAACAGTGGCCAC2340CCGTCTTCCTCCTGTGAGCCTAAGTGCAGCCGTGCTAGCTGCGCACCGTGGCTAAGGATG2400ACGTCTGTGTTCCTGTCCATCACTGATGCTGCTGGCTACTGCATGTGCCACACCTGTCTG2460TTCGCCATTCCTAACATTCTGTTTCATTCTTCCTCGGGAGATATTTCAAACATTTGGTCT2520TTTCTTTTAACACTGAGGGTAGGCCCTTAGGAAATTTATTTAGGAAAGTCTGAACACGTT2580ATCACTTGGTTTTCTGGAAAGTAGCTTACCCTAGAAAACAGCTGCAAATGCCAGAAAGAT2640GATCCCTAAAAATGTTGAGGGACTTCTGTTCATTCATCCCGAGAACATTGGCTTCCACAT2700CACAGTATCTACCCTTACATGGTTTAGGATTAAAGCCAGGCAATCTTTTACTATGAAAAA2760AAAAAAAAAAAAAAAAAAAAAAAA2784(2) INFORMATION FOR SEQ ID NO:2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 557 amino acids(B) TYPE: amino acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: protein(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:MetMetValValLeuLeuGlyAlaThrThrLeuValLeuValAlaVal151015GlyProTrpValLeuSerAlaAlaAlaGlyGlyLysAsnLeuLysSer202530ProGlnLysValGluValAspIleIleAspAspAsnPheIleLeuArg354045TrpAsnArgSerAspGluSerValGlyAsnValThrPheSerPheAsp505560TyrGlnLysThrGlyMetAspAsnTrpIleLysLeuSerGlyCysGln65707580AsnIleThrSerThrLysCysAsnPheSerSerLeuLysLeuAsnVal859095TyrGluGluIleLysLeuArgIleArgAlaGluLysGluAsnThrSer100105110SerTrpTyrGluValAspSerPheThrProPheArgLysAlaGlnIle115120125GlyProProGluValHisLeuGluAlaGluAspLysAlaIleValIle130135140HisIleSerProGlyThrLysAspSerValMetTrpAlaLeuAspGly145150155160LeuSerPheThrTyrSerLeuLeuIleTrpLysAsnSerSerGlyVal165170175GluGluArgIleGluAsnIleTyrSerArgHisLysIleTyrLysLeu180185190SerProGluThrThrTyrCysLeuLysValLysAlaAlaLeuLeuThr195200205SerTrpLysIleGlyValTyrSerProValHisCysIleLysThrThr210215220ValGluAsnGluLeuProProProGluAsnIleGluValSerValGln225230235240AsnGlnAsnTyrValLeuLysTrpAspTyrThrTyrAlaAsnMetThr245250255PheGlnValGlnTrpLeuHisAlaPheLeuLysArgAsnProGlyAsn260265270HisLeuTyrLysTrpLysGlnIleProAspCysGluAsnValLysThr275280285ThrGlnCysValPheProGlnAsnValPheGlnLysGlyIleTyrLeu290295300LeuArgValGlnAlaSerAspGlyAsnAsnThrSerPheTrpSerGlu305310315320GluIleLysPheAspThrGluIleGlnAlaPheLeuLeuProProVal325330335PheAsnIleArgSerLeuSerAspSerPheHisIleTyrIleGlyAla340345350ProLysGlnSerGlyAsnThrProValIleGlnAspTyrProLeuIle355360365TyrGluIleIlePheTrpGluAsnThrSerAsnAlaGluArgLysIle370375380IleGluLysLysThrAspValThrValProAsnLeuLysProLeuThr385390395400ValTyrCysValLysAlaArgAlaHisThrMetAspGluLysLeuAsn405410415LysSerSerValPheSerAspAlaValCysGluLysThrLysProGly420425430AsnThrSerLysIleTrpLeuIleValGlyIleCysIleAlaLeuPhe435440445AlaLeuProPheValIleTyrAlaAlaLysValPheLeuArgCysIle450455460AsnTyrValPhePheProSerLeuLysProSerSerSerIleAspGlu465470475480TyrPheSerGluGlnProLeuLysAsnLeuLeuLeuSerThrSerGlu485490495GluGlnIleGluLysCysPheIleIleGluAsnIleSerThrIleAla500505510ThrValGluGluThrAsnGlnThrAspGluAspHisLysLysTyrSer515520525SerGlnThrSerGlnAspSerGlyAsnTyrSerAsnGluAspGluSer530535540GluSerLysThrSerGluGluLeuGlnGlnAspPheVal545550555__________________________________________________________________________
|Cited Patent
|Filing date
|Publication date
|Oct 19, 1990
|May 2, 1991
|Centre National De La Recherche Scientifique (Cnrs)
|cDNA FRAGMENT CODING THE ALPHA INTERFERON RECEPTOR GENE AND PROCESS FOR THE PREPARATION OF A CORRESPONDING PROTEIN
|Branca, J. Interferon Res. 7(1):77 85 (1987).
|Branca, J. Interferon Res. 7(1):77-85 (1987).
|Colamonici et al, Proc. Natl. Acad. Sci USA 87(18):7230 34 (1990).
|Colamonici et al, Proc. Natl. Acad. Sci USA 87(18):7230-34 (1990).
|Eid et al, Biochem. Biophys. Acta 1034(1):114 117 (1990).
|Eid et al, Biochem. Biophys. Acta 1034(1):114-117 (1990).
|Eid et al, J. Interferon Res. 7(6):762 (1987).
|Epstein et al, Biochemical and Biophysical Research Communications, 107(3):1060 1066 (Aug. 16, 1982), Academic Press, Inc. (New York, US) Direct evidence that the gene product of the human chromosome 21 locus, IFRC, is the interferon alpha receptor .
|Epstein et al, Biochemical and Biophysical Research Communications, 107(3):1060-1066 (Aug. 16, 1982), Academic Press, Inc. (New York, US) "Direct evidence that the gene product of the human chromosome 21 locus, IFRC, is the interferon-alpha receptor".
|Gaboriaud et al, FEBS 269(1):1 3 (1990).
|Gaboriaud et al, FEBS 269(1):1-3 (1990).
|Langer et al, BBRC 157(3):1264 1270 (1988).
|Langer et al, BBRC 157(3):1264-1270 (1988).
|Langer et al, Somatic Cell & Molecular Genetics 16(3):231 240 (1990).
|Langer et al, Somatic Cell & Molecular Genetics 16(3):231-240 (1990).
|Lutfalla et al, J. Biol. Chem. 267(4):2802 09 (1992).
|Lutfalla et al, J. Biol. Chem. 267(4):2802-09 (1992).
|Meadows et al, J. Interferon Res. 10(Suppl. 1):5159 (1990).
|Meadows et al, Proc. Am. Assoc. Cancer Res. 31:55 (1990).
|Mouchel Vielh et al, FEBS 313(3):255 259 (1992).
|Mouchel-Vielh et al, FEBS 313(3):255-259 (1992).
|Raziuddin et al, Proceedings National Academy Science, vol. 81, Sep. 1984, "Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21", pp. 5504-5508.
|Raziuddin et al, Proceedings National Academy Science, vol. 81, Sep. 1984, Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21 , pp. 5504 5508.
|Revel et al, ICSU Short Reports, vol. 4, 1986 "Interferon receptor and interferon-activated genes", pp. 362-365.
|Revel et al, ICSU Short Reports, vol. 4, 1986 Interferon receptor and interferon activated genes , pp. 362 365.
|Shearer et al, J. Cell. Biochem. Supple. (12 Part A):216 (1988).
|Shulman e tal, J. Interferon Res. 8(1) (1988) "Molecular cloning of the human IFN-alpha, beta receptor cDNA", p. S16, abstract No. 3-9.
|Shulman e tal, J. Interferon Res. 8(1) (1988) Molecular cloning of the human IFN alpha, beta receptor cDNA , p. S16, abstract No. 3 9.
|Siemens, Pro. Am. Assoc. Cancer Res. 31:238 (1990).
|Traub et al, J. Biol. Chem. 259(22):13872 77 (1984).
|Traub et al, J. Biol. Chem. 259(22):13872-77 (1984).
|Uze et al, Cell 60:225 234 (1990).
|Uze et al, Cell 60:225-234 (1990).
|Citing Patent
|Filing date
|Publication date
|Jun 6, 1995
|Jan 19, 1999
|Societe Leb-Tech
|Use of the alpha interferon receptor and cells which express the receptor, for identification of alpha interferon agonists
|May 30, 1995
|Mar 30, 1999
|Societe Leb-Tech
|Purified human alpha interferon receptor
|Apr 17, 1991
|Nov 5, 2002
|Medisup International N.V.
|Water-soluble polypeptides having a high affinity for α and β interferons
|Jun 20, 2005
|Feb 16, 2010
|Medarex, Inc.
|Interferon alpha receptor 1 antibodies and their uses
|Apr 23, 2004
|May 10, 2011
|Medarex, Inc.
|Methods for the therapy of Inflammatory Bowel Disease using a type-1 interferon antagonist
|Oct 19, 2007
|Jan 17, 2012
|Ambrx, Inc.
|Modified human interferon polypeptides with at least one non-naturally encoded amino acid and their uses
|Apr 30, 2008
|Feb 14, 2012
|Ambrx, Inc.
|Modified interferon beta polypeptides and their uses
|Jan 28, 2005
|Feb 21, 2012
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
|Dec 8, 2011
|Jul 31, 2012
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
|Feb 12, 2010
|Jun 11, 2013
|Medarex, Inc.
|Interferon alpha receptor I antibodies and their use
|Mar 17, 2011
|Sep 9, 2014
|Medarex, L.L.C.
|Methods for the therapy of inflammatory bowel disease using a type-1 interferon antagonist
|May 9, 2013
|Sep 27, 2016
|E. R. Squibb & Sons, L.L.C.
|Interferon receptor 1 antibodies and their uses
|Jan 17, 2002
|Jan 23, 2003
|Genentech, Inc.
|Monoclonal antibodies to IFNAR2
|Apr 23, 2004
|Jul 14, 2005
|Pickford Lesley B.
|Compositions and methods for the therapy of Inflammatory Bowel Disease
|Jan 28, 2005
|Oct 6, 2005
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
|Jun 20, 2005
|Feb 9, 2006
|Medarex, Inc.
|Interferon alpha receptor 1 antibodies and their uses
|Mar 17, 2011
|Jul 7, 2011
|Medarex, Inc.
|Methods for the therapy of inflammatory bowel disease using a type-1 interferon antagonist
|Nov 16, 2006
|Jun 29, 2011
|Ambrx, Inc.
|Methods and compositions comprising non-natural amino acids
|Jan 22, 2007
|Jul 17, 2013
|Genentech, Inc.
|Method for using BOC/CDO to modulate hedgehog signaling
|May 28, 2001
|Nov 29, 2001
|Shanghai Biowindow Gene Development Inc.
|Novel polypeptide - a human alpha interferon receptor 115.62 and polynucleotide encoding it
|U.S. Classification
|435/69.1, 435/320.1, 536/23.5, 435/361, 435/254.11, 435/325, 435/252.3
|International Classification
|Cooperative Classification
|European Classification
|Sep 10, 1999
Owner name: MEDISUP INTERNATIONAL N.V., NETHERLANDS ANTILLES
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LABORATOIRE EUROPEEN DE BIOTECHNOLOGIE;REEL/FRAME:010226/0109
Effective date: 19980925
|Feb 17, 2000
Owner name: MEDISUP INTERNATIONAL N.V., NETHERLANDS ANTILLES
Free format text: "DOCUMENT PREVIOUSLY RECORDED AT REEL 10226, FRAMES 0109-0114 CONTAINED AN ERROR IN PROPERTY NUMBER5,595,193. DOCUMENT RERECORDED TO CORRECT ERROR ON STATED REEL".;ASSIGNOR:LABORATOIRE EUROPEEN DE BIOTECHNOLOGIE;REEL/FRAME:010609/0344
Effective date: 19980925
|Sep 17, 2001
|Fee payment
Year of fee payment: 4
|Jan 25, 2005
Owner name: MEDAREX, INC., NEW JERSEY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MEDISUP INTERNATIONAL N.V.;REEL/FRAME:015612/0810
Effective date: 20040730
|Aug 26, 2005
|Fee payment
Year of fee payment: 8
|Sep 24, 2009
|Fee payment
Year of fee payment: 12
|Jun 13, 2013
Owner name: MEDAREX, L.L.C., NEW JERSEY
Free format text: MERGER;ASSIGNOR:MEDAREX, INC.;REEL/FRAME:030603/0924
Effective date: 20121231


text:
Friday, February 13, 2015
Be mine!
7 comments:
What a wonderful card. I just love that cute dragon, what a fabulous die. Will have to check out if Top Dogs dies are available in the UK. xxReplyDelete
This is such a great card. Like everything about it!!!!! TFSReplyDelete
Aw, your darling dragon stole my heart, Laurie!! Happy Valentine's Day! Have a great weekend! Hugs, DarnellReplyDelete
Awe...that is just too cute Laurie! Great take on the Just Add Ink Inspiration, thanks for joining us this week.ReplyDelete
Awesome dragon Laurie - I could do with one of those for a March 1st St Davids Day card, he definitely looks Welsh!ReplyDelete
This card makes me smile. I like how you have added stitching look around the hearts. Chantell JAIReplyDelete
I love how you've placed the sentiment, Laurie - very clever! Cute card, and the pink and red look fabulous together. Thanks for joining in the fun at Just Add Ink this week. :)ReplyDelete

subset: commoncrawl


text:
What does it mean when, at 22, no desire exists to go out for drinks or join the party; When the thought of going to the bar is appealing until the moment arrives and suddenly, going home seems to be the most beautiful thing that could possible exists on your agenda?
potential causes:
-Depression? is that not what people typically diagnose excessive introverts with?
-Been there, done that? But, at 22, how often is it that one has partied so much as to possess no desire to do so anymore.
-Desire for something more. If this was an answer, would it not be more common? Instead of every single person in one's life (with similar age ranges) finding joy in the night life, would there not be those who also don't want to go out, other than oneself?
Every time I go out, I love the people I'm with but I cannot help but to think about what I could be doing with my time. It's true, we all need to relax. I only long for moments when I am relaxing as I am working towards my success. I can no longer force myself into believing that being out is contributing to my well being in any manner. Friends make it sound so enticing to go out and blow money and time and will proceed to somehow make you feel guilty for not doing so. well, maybe THEY don't have things that they would rather be doing. At one point and a rather long span of my life, I didn't either. Now, in this moment, I am so incredibly afraid that my future will not be every last thing that I anticipate it being, I can't join the party. It's not a sacrifice, either. I don't miss it. There's no, "I wish I were there." I may not accomplish all that I wish to when I choose to stay home. I may not exercise, write, read, learn or paint each time I skip out on a night at the bar. Nonetheless, it's hard to believe that I am not doing more for my well being than spending money on a buzz I'll hardly remember.
I suppose I found my answer. I cannot allow myself to feel guilt from skipping the party, any longer. I'll buy ya a birthday card.


text:
Hectic bidding battle for prime Kilkenny ground
A strong price of €15,600/ac was paid for a 24ac parcel of grazing ground near Gowran in Co Kilkenny when it sold under the hammer last Friday for €375,000.
Located outside the village of Gowran on the Bennettsbridge road, the land is all in one field with excellent road frontage.
It is described by auctioneer Ed Donohue as the best of ground, "You could do anything with it," he said, adding "it hasn't an inch of waste, it was a pleasure to walk it."
Proceedings opened at auction when Mr Donohue accepted a bid of €225,000.
Initially there were three bidders in action and this was soon reduced to two but the price kept increasing and the farm went on the market when it reached €370,000.
The hammer fell at €375,000 and the property sold to a local buyer.
The underbidder was a solicitor acting in trust for a client.
Ed Donohue was very happy with the result and with the per acre price of €15,600. "I expected it to go well," he said, "but maybe not that well.


text:
Results 1 to 4 of 4
04-02-08, 19:27 #1Registered User
- Join Date
- Oct 2003
- Posts
- 233
Unanswered: How do I update a column to be incrementing each row by 1
I have a temp tbl and in col1 row1 i would like to have 1, col1 row2 value 2, col1 row3 value 3 and so on. how can i do this?
04-02-08, 23:39 #2SQL Consultant
- Join Date
- Apr 2002
- Location
- Toronto, Canada
- Posts
- 20,002
make sure that you declare col1 as an IDENTITY column before loading the tablerudy.ca | @rudydotca
Buy my SitePoint book: Simply SQL
04-03-08, 08:11 #3Annie's Dog Walker
Provided Answers: 6
- Join Date
- Nov 2004
- Location
- on the wrong server
- Posts
- 8,842
or the rownumber function in sql 2005.If one brings so much courage to this world the world has to kill them or break them, so of course it kills them. The world breaks every one and afterward many are strong at the broken places. But those that will not break it kills. It kills the very good and the very gentle and the very brave impartially. If you are none of these you can be sure it will kill you too but there will be no special hurry. Earnest Hemingway, A Farewell To Arms.
04-03-08, 10:12 #4Window Washer
- Join Date
- Nov 2002
- Location
- Jersey
- Posts
- 10,322
Use a cursorBrett
It's a Great Day for America everybody!
dbforums Yak CorralRadio 'Rita
dbForums Member List
I'm Good Once as I ever was
The physical order of data in a database has no meaning.


text:
Project comments (0) | Write a comment
For You Card
|Abbie Friesen
For You Card
By Abbie Friesen
Click to Enlarge
Designer's Tip: When embossing the lines of the stencil on Pergamano® paper, be careful to push hard enough on it to make a white line but not punch through the paper. Practice on a test sheet to determine the right amount of pressure needed.
- Penelope Paper Pack
- Penelope Ribbon Set
- Silver Tiny Words & Phrases Dazzles™
- White Cards & Envelopes
- 12x12 Classic Cardstock
- Butterfly Kisses Multi-Stencil
- Pergamano Papers
- Single Perforating Pen
- Paper Blossoms Paper Tool Kit & Case
- Stylus
- Craft Molding Mat
- . Sharp Point Scissors
- Stencil Tape
- Foam Tape
- Knife & Refill
- Medium Zots™
- Place the card with the fold on the top. Cover it with green cardstock. Cut 6"x4½" of black cardstock, and glue it centered on the card. Using an X-acto® pen knife, cut a 6½" strip of two Penelope scalloped paper layers, outlining the scalloped edge. Glue it on the top edge. Cut a 6 ½" strip of scalloped paper, six layers. Glue it 1" from the bottom edge.
- Using stencil tape, tape the large butterfly grid on Pergamano® paper, and place it on the embossing mat with the stencil on top of the paper. Using the stylus, emboss the stencil shapes. Reach the edges of the shapes using the Paper Blossoms 1 mm embossing tool. Emboss the stencil lines using the stylus. Flip the stencil over and place it on the perforating mat. Pierce the stencil holes using the perforating pen. Remove the stencil, and clip the outside perforated edge of the large butterfly using the sharp point scissors. Mat it on black cardstock with 1/16". Foam tape it 1/8" from the bottom-left corner of the card, and at a slight angle as shown. Place "For You" Dazzles above the butterfly antennae.
- Cut 10" of ¾" mauve sheer ribbon. Zot it on the right side of the card, ¾" from the edge. Fold over the ribbon and Zot it on top of the first layer. Emboss the butterfly/hearts small border on Pergamano® paper. Pierce the holes, and clip the perforated edge. Zot the border on the bottom of the ribbon as shown. Cut a 1½" length of ½" white grosgrain ribbon with dovetails. Zot it on the top of the mauve ribbon. Tie a bow of 1/8" pink grosgrain ribbon, and cut the left strand at 2 ¼" in length and the right strand at 5". Zot the bow on the center of the white ribbon. Curl the strands and Zot them in place.


text:
Casino name: Party City Casino
claim 14 free spins a day, every day this week on Count Spectacular Slot
As long as you've made a deposit in the past 15 days, the spins are already yours. If you haven't made a recent deposit, there's still time.
30X Wager requirement
$100 Cashout details
Valid for all players.
Exp: November 3, 2016
Post navigation


text:
Friday, October 31, 2014
Blog Email Spam, Are You Getting This One?
In other news, I started doing an elimination diet last Sunday after another week of migranes. Actually, it's the BRAT diet. I didn't have any bread when I started it, and I try to avoid yeast and sugar, so skipped that one for awhile. However, I made a stew for Hubby and then made biscuits to go with it, so I decided to toast a couple for me. The next day I had a mild headache. Bummer. But hopefully it was a coincidence. Even though I often eat paleo, I love bread and can't imagine never being able to eat anything with wheat in it again. I'll give it a few more days and try it again.
Just a few weeks ago, after cooking for hours and then facing the cleanup of lots of dishes, I whined to Hubby that it sure would be easier if there was people chow like there is dog chow and cat chow. But after being on this diet for a week, I've changed my mind. On the upside, I have lost some weight.
6 comments:
- Nancy said...
I hope you can find the culprit for your headaches and avoid the culprit who sends the emails. I would miss bread terribly: I love it!
- November 1, 2014 at 10:01 AM
- Mdm Samm said...
Hello Marti...I came across your most delightful blog and insights and concluded I LIKE YOU....I GET YOU...and you are wayyy funny.....and yes if you are feeing headaches after eating breads....especially in an elimination diet..it really is a side effect of the elimination.....I am a Registered Nutritionist ..very few people have wheat allergies..it is more the sugar in stuff they are having effects too.....and do not open those emails they are virus and trojans that affect your pc or macs... will drop by again soon
- November 2, 2014 at 12:55 AM
- Martha said...
I'm glad you decided against the people chow!!! Hope those Headaches go away. I had a daily headache for a year that started with a sinus infection., got another sinus infection, took the antiobiotics for 10 days and the headaches are completely gone!! I think I had an infection that whole time. Too weird!!!
I get some strange comments on my blog too, I just delete them.
Take care!!!
- November 2, 2014 at 11:33 AM
- Marti said...
Thank you. I wish I could say for sure it was a side effect of the diet, but I think I'm going to go for a gluten test to make sure. I know sugar causes problems for me. I think it's sugar, not money, that is the root of all evil. Then money.
- November 2, 2014 at 1:50 PM
- Marti said...
The weird thing is that they don't come through my blog at all. They go straight to my email. But yes, I have the same policy as on my blog; I just delete them.
- November 2, 2014 at 1:57 PM
- Kate said...
That seems like a really weird spam message, but I've seen a few weird ones lately.
Hope you've worked out what's causing those headaches.
- November 4, 2014 at 9:28 PM


text:
Welcome to WebmasterWorld Guest from 220.127.116.11
Forum Moderators: incrediBILL & lawman
basically this is a prelude to my absence from the system, come Thursday till Monday.
If your going add your name: and what you are looking forward too.
IMO, the day of the conference is for business. If you choose to go out at night on other nights, that is your own prerogative.
i think more than anything, i'm looking forward to putting faces to names, shaking a few hands, maybe even picking up useful info so i can blackmail search engine reps into putting my site top etc etc.
it would be nice to pick up some good tips or business, or (as topr8 says) to hook up with people that might be interested in a project or 2, but i have a brain like a sieve and when it's soaked in alcohol, i got no hope.
if i can just stick to the tea ......
oh yeah, i want a free pen too.
It might be a little bit late now, but after extensive and i say extensive searching you will find quite a few pictures of the members here, but it can take you a really long time though :)
>>One of the best parts!
yup .... i've done a lot of "meets" like this in the past ... you know, chatting on forums or in chat rooms and arrange big parties etc .... i've met hundreds of people this way .... and i don't think anyone i've met has looked how i thought they would .....
the first big meet i did like this was feb 96 ... i got caught in a compromising position that resulted in divorce .... i'll be on my bestest behaviour this time tho ......
I don't wear glasses but I admit, I'm half geek. You have to be a bit geeky to get excited about the Google Update
I'm not so sure, I have some ungeeky friends who can get a bit excited about the Google update, I think a true geek is one who gets excited at the sight of a full moon ;)
I admit to being a true geek. I even have the glasses to prove it.
Personally I have contacts but, that's just cheating
I've had LASIK done, so I'm not sure if that counts as cheating or if that part of the geek quotient is just closed to me now.
what you are looking forward too
Knowledge. Contacts. Matching up faces to names. These are the things I'm most looking forward to during the conference.
Beer. This is what I'm looking forward to as things wind down.
See you guys in a few days.


text:
Contract Manufacturing Services
Mendtronix manages the complexities of your manufacturing process to ensure raw materials, work-in-process inventory, and finished goods flow properly from point of origin to point of consumption. Established OEMs and new product innovators trust Mendtronix to manage their product assembly and ensure quality, service and on-time delivery.
Let Mendtronix' team of passionate contract manufacturing professionals and technology help you create net value, build a competitive infrastructure, and synchronize supply with demand. Simplify your business so you can focus on product innovation while Mendtronix builds and ships as you demand.
- Engineering to Assembly
- Supply Chain Management
- Quality Systems
- Quality Control
- Offshore Capabilities
Contract Manufacturing: The Benefits
- Cost Savings
- Save on your cost of capital. No need to pay for a facility and the equipment needed for production.
- Save on your labor costs such as wages, training and benefits.
- Advanced Skills – Take advantage of skills outside your company's sweet spot. Mendtronix provides top notch electronics and product assembly team. Mendtronix also has relationships with many raw material suppliers.
- Quality – Mendtronix has ISO 9001 certified quality control systems in place that helps detect counterfeit or damaged materials early and ensure an end product of the highest quality.
- Focus – Focus on your core competencies of product innovation and building client relationships while Mendtronix handles the rote tasks product assembly.
- Economies of Scale – No need to re-invent the wheel. Mendtronix can offer reduced costs in acquiring raw materials and organizing repetitive labor tasks by benefiting from the economies of scale of servicing many clients.
Tells Us About Your Project
"As a global company, we needed a full-service solution designed for scalability and continuous optimization."Luke Leininger


text:
The holidays and seasons present an opportunity to create original content that not only boosts SEO but also provides value to your audience and prospects. During various holidays and seasons it's not uncommon to find a rise in search engine traffic for holiday keywords.
Let's take a look at how you can take advantage of the seasons to create great content.
1. Holiday Articles
A simple way to capitalize on the holidays is to write articles that directly relate to them. For example, if you have an information website that promotes various computers you might write an article titled:
- "Back to School Computer Shopping Guide."
- "Christmas Computer Comparison Chart."
- "How to Find Budget Computers after Thanksgiving"
The list could go on and on but you see the point. Make your content timely by integrating it with the current holiday or season.
2. Holiday Gifts
Everyone loves gifts and you can embrace the holiday gift giving spirit by giving away content. For example, you might create a free report on how to buy a computer for your college student and give it away during the back to school shopping season. Inside the pages of your report you will ,of course, link to relevant affiliate sites so you can earn income from this free report.
Your gift doesn't have to be a report or e-book. You can also give away worksheets, blueprints and templates, free videos and checklists. For example, "The Back to School Computer Buying Checklist." These free gifts help your audience, readers and subscribers feel appreciated and it drives traffic to your website. (Not to mention it also provides an opportunity to earn affiliate income.)
3. Holiday Promotions
Finally, take advantage of the holiday to create new promotions. You may partner with others to create unique promotions or you may bundle or package your items in a new way. For example, if you offer coaching services, you might announce a "back to school" coaching package. If you have an information site about computers, you might send your email list a coupon or a special promotion from an affiliate
There are many ways to take advantage of the holidays. They provide a way to create fresh, timely and valuable content and that's what it's all about. If you can consistently provide value and interest you will grow your business.


text:
SHARE THIS PAGE View Viral Dashboard ›
Response to 74 Of The Tiniest, Most Tasteful Tattoos Ever:
So many judgmental tiny tattoo critics out there. Tattoos, temporary or permanent, big or small, are not for the pleasure of the viewer as much the wearer. Armchair tattoo "critics" commenting on how small tattoos are "pretentious" is the height of hypocrisy. Who says ALL tattoos have to be HUGE?


text:
Already a print subscriber? Get Access Already a digital subscriber? Log In
Never Miss a Story Subscribe Today
Two Wildcats earn All-America honors in indoor track
0 CommentsTwo Villanova athletes earned All-America honors at the NCAA Indoor Track and Field Championships held over the weekend in Nampa, Idaho. Sophomore... Read more
A look at South Florida, and avoiding a season sweep
0 CommentsThere may be people who feel that Villanova has a good chance Wednesday night in the second round of the Big East tournament against South... Read more
Villanova to play in 2012 season-opening 2K Sports Classic
0 CommentsVillanova has accepted an invitation to tip off its 2012-13 season at the 2K Sports Classic, a tournament that wraps up with two games at New... Read more
Villanova loses 'Cat fight
0 CommentsVideo: Villanova clawed back against Cincinnati in the Big East finale, but it still wasn't enough as the Wildcats fell, 72-68, to the Bearcats... Read more
Villanova hopes to keep momentum vs. Cincinnati
0 CommentsNow that Villanova finally has won a game after building a big first-half lead, the Wildcats appear to have heightened confidence going into... Read more
Joe Juliano has been a member of our sports staff since 1985. His current beats are Penn State football, college basketball, golf, and the Penn Relays. A graduate of Temple University, he also worked for 10 years with United Press International, the last seven as Philadelphia sports editor.


text:
Name: Dr. Clementina Salinas
Designation: Director of Transportation
Email: firstname.lastname@example.com
Dr. Clementina Salinas, has served the Cartwright School District as the Director for Transportation for the past seven years. Dr. Salinas has increased the capacity of new AC buses for the children of the district with the support of the Superintendent Dr. Chavez and Financial Assistant Superintendent Mr. Ojeh.
Dr. Salinas' education background experience is extensive as she was the first Latina Superintendent in the State of Oregon. During her seven years as superintendent, she served the seven communities in the Oregon Trail School District. She was appointed as superintendent representative for the State Revenue Committee, Department of Education Professional Advisory Team for the Office of Oregon State Superintendent, Representative for Global International Businesses in Washington D.C., Presenter at the International Women's Leadership Conference Oxford University. Her 38 years experience in education include positions as Assistant Superintendent in the Isaac School District; Multicultural Education Director and Principal in the Roosevelt School District; and Bilingual teacher in the Tempe Elementary School District.


text:
- Please select a date to see the proper prices!
- Meal can be requested on the spot
Best offer
99 € / person / night, no meal
Description of the accommodation:
Rooms, services Voi Floriana Resort Crichi is welcoming all guests in Crichi with 335 comfortable rooms to stay in. The hotel is happy to have you in the restaurant for a hearty lunch or a romantic dinner. For those arriving by car parking is available nearby. You may check the most important tourist higlights by taking a car rental service. The fans of actively spent leisure time may take the table tennis, volleyball, sailing and surfing opportunities nearby. For meetings and nice evening chats the local bar will provide an ideal location. You may secure your valuables in the safe. To learn more about the exact range of services of Voi Floriana Resort Crichi (including services for an extra fee) and the exact equipment of the rooms, please check the information sheet below.
Payment In order to finalize the reservation you may be required to provide credit card guarantee or advance payment by credit card, depending on the chosen room, date and price.
Arrival, opening hours The earliest arrival time is 16:00, the latest time to leave the rooms is 10:00. You will be able to speak with the personnel in Italian and English languages.
Voi Floriana Resort Crichi rooms Rooms
- Please select a date to see the proper prices!
Accommodation services
Relaxation: Table-tennis
Car rental nearby, Volleyball facility nearby, Sailing nearby, Surfing nearby
- Pool (Outdoor - seasonally open)
Garden, Bar, Safe deposit box
Own restaurant
Hairdryer, Desk in the room, Mini-bar


text:
Laser Hair Removal Tulsa OK
Tulsa Surgical Arts is proud to offer laser hair removal with the new LightSheer DUET by Lumenis, known throughout the world as the gold standard in laser hair removal.
The DUET system offers several innovative improvements over previous laser hair removal systems. Vacuum assisted technology combined with a dramatic increase in the laser spot size enables a greater depth of penetration, and improved absorption of energy at the hair follicle.
These improvements mean the treatment times are reduced by 75% in many cases, for instance we can treat backs and legs comfortably, without anesthetics and gels.
The number of treatments required depends on several factors including hair and skin type. Laser hair removal treats hair in an active growth phase. Since all hairs are not in this phase at the same time, 4 or more treatments may be necessary for the best results.
DUET reduces hair removal treatments up to 75% and vastly improves patient comfort, eliminating the need for topical anesthetics. Significant reduction in cost is possible with the shortened treatment times.
The LightSheer DUET system is a quick and pain free way to permanently remove unwanted hair from your legs, back, face, bikini, and other areas of your body where unwanted hair is a problem.


text:
Ford announced today that it will begin rolling out its fuel-saving start-stop system on some 2012 North American models but also light trucks powered by four-cylinder engines.
For those who don't know, the fuel-saving start-stop system which is already used by several Ford models in Europe, will be seen on vehicles such as the 2012 Fiesta and Focus models, but also on other models such as the Escape crossover, C-Max minivan and Transit Connect.
The start-stop technology will also be seen on the new concept vehicle, which Ford will show us at the 2011 Detroit Auto Show. Furthermore, Ford also said that it will offer the start-stop system on most nameplates in North America by 2015.
Since 2004, Ford sold over 170,000 gasoline-electric hybrid vehicles fitted with start-stop technology. According to the manufacturer, the technology can improve fuel consumption by 10 percent in the city and by 5 percent the overall fuel consumption. Auto Start-Stop is the latest example of Ford moving aggressively to bring affordable advanced fuel-saving technologies to all customers.
The new system promises to be much simpler than the current one. Furthermore, the system uses new key components such as a more robust starter motor and an enhanced 12-volt battery.
According to Ford vice-president of Powertrain engineering Barb Samardzich, the Ford Auto Start-Stop is fully automatic and gives the driver that needed extra fuel efficiency without any of the inconvenience. Similar to its hybrid vehicles, she continued, the air conditioner and heater work normally so comfort is never sacrificed.
Currently, the rollout of its Auto Start-Stop is ongoing in Europe. This particular system works well with either diesel or the gasoline engines. It however comes standard on the ECOnetic version of the Ford Ka and the Ford Mondeo. This same system is being launched on the C-MAX, Grand C-MAX, and Focus.
After the European market, it will then be launched by 2012 in North America after which it will be offered on all the company's markets. A number of Ford customers in North America are already familiar with this system as a similar one has been installed in gasoline-electric hybrid vehicles it has sold ever since 2004.
This accounts for more than 170,000 units ensuring that the company continues to lead the domestic market in terms of start-stop systems. For 2011, the Auto Start-Stop system created for its gasoline-electric powertrains will be equipped on the Fusion Hybrid, the Escape Hybrid, and of course, the Lincoln MKZ Hybrid.
Samardzich continued that a number of the same company engineers that designed the system on the hybrids are developing the same system for the non-hybrid vehicles that are sold worldwide. Once the Auto Start-Stop system makes its official debut in the North American market, it will be on gasoline-powered cars that are paired with either automatic or manual transmission.
It will even be on vehicles that carry the company's very own six-speed dual-clutch automatic transmission. One of the reasons that the system is able to run seamlessly, according to Samardzich, is because the company made a bold move to have the direct-injection EcoBoost engines.
With the direct-injection system, the right amount of fuel is sprayed directly on the exact location of its combustion chamber resulting in a faster engine start, Samardzich continued. While the system will initially come with the four-cylinder engines, they will later be expanded to include the V6 engine and the V8 engine.
One good thing about this system is that there is no need to have any additional vehicle maintenance. Program manager for Auto Start-Stop Birgit Sorgenfrei shared that the system utilizes an improved 12-volt auto battery with an upgraded starter motor.


text:
Monday night's raucous Beaumont Independent School District board meeting could very well be the last one for the current trustees.
Board Vice President Janice Brassard told 12News, "As for anything I know at this point, the commissioner will be taking over."
The majority of the board has been fighting a state takeover for weeks, but it appears they have reached their breaking point. Massive public pressure at board meetings has taken a toll.
That is why four of the six board members present at Monday's meeting abstained from casting a vote on a proposed list of layoffs. The measure would have left more than 100 BISD employees without a job.
Jobs were saved, but possibly not for long. The Texas Education Agency's conservator over BISD Fred Shafer said a reduction in force is necessary. But most teachers say they would trust an appointed board of managers to do the cuts more than the current board.
Brassard said that is why the burden should be the managers appointed by Commissioner Williams.
She said the cuts will probably be more severe.
"Because many of the people are only going to be business people, they are not really going to understand classroom management," she said
Trustee Woodrow Reece said he could not pass the buck. He was the only trustee to vote for the layoffs. He said without the reduction in force, BISD might not have enough money to start school next year. Even though he believes the takeover will happen, Reece thinks Commissioner Wiliams' actions are wrong.
"I mean just walking right over us and the voters cause people put me in office for a reason, not for a commissioner to take me out of my seat," said Reece.
Trustees are going ahead with a record review on July 10, which is basically an appeal to the Texas Education Agency, but they do not expect it to go their way, and since Commissioner Williams is limiting the board's authority to spend on legal fees, their options appear to be gone.
Reece said he has not ruled out contacting the U.S. Department of Justice.
State Board of Education Member David Bradley had this to say about the situation, "Given what we've seen in the last couple days, I think this board is giving up finally. They just don't know how to do it. Having lost they're just going to dynamite the train tracks and leave as big a mess as possible."
BISD trustees acknowledge state takeover is unavoidable, and take parting shots at Commissioner...
Monday night's raucous Beaumont Independent School District board meeting could very well be the last one for the current trustees.
To find out more about Facebook commenting please read the
Conversation Guidelines and FAQs
Jasper County Sheriff's deputies investigating death of Tristan Dilley
Las Vegas/Mandalay Bay shooting - What we know
Custody case of child found clinging to mother's body in flood waters postponed
Railing on the Red Cross: Help for Denied Applicants
11 new features in IOS 11
Silsbee teen's little brother discovered her fatally shot in bed Sunday evening This ad will end in 13 seconds. UP NEXT: Railing on the Red Cross: Help for Denied Applicants RANKED In Last 24H 00:48 Don't Fall For This Netflix Scam WATCHED BY of viewers like you 04:30 Port Arthur man recalls dramatic moments while gunman opens fire in Las Vegas WATCHED BY of viewers like you President Trump remarks on Las Vegas shooting IN TOP New Videos 00:38 Las Vegas/Mandalay Bay shooting - What we know W
Salvation Army contnues to provide recovery efforts a month after Harvey
Shooting survivors want more than prayers for Las Vegas
HPD: Man kills his mom, critically wounds dad
Segment One of Blitz - 9/29/17
More Stories
Travelers pass through Southeast Texas to reach…Nov 22, 2017, 10:47 p.m.
Now on Amazon.com: 44 amazing Black Friday dealsNov 18, 2017, 1:31 p.m.
Beaumont Lieutenant honored for leadership, kindness…Nov 22, 2017, 7:22 p.m.


text:
On the Health, Education, Labor and Pensions Committee, Democrats are opting to drop one Democrat (for a total of 12) instead of adding any Republicans to the current 10.
Sens. Sheldon Whitehouse (D-R.I.) and Richard Blumenthal (Conn.) are the new Democrats, taking over from Sens. Chris Dodd (Conn.), Joe Manchin (W.Va.) and Jack Reed (R.I.) Republicans are replacing Coburn and Sen. Judd Gregg (N.H.) with Sens. Rand Paul (Ky.) and Mark Kirk (Ill.).
Sen. Ben Cardin (D-Md.) will be replacing defeated Sen. Blanche Lincoln (D-Ark.) on the Senate Finance Committee, according to a list of committee assignments obtained by The Hill. Republicans, meanwhile, have added Sens. Tom Coburn (Okla.) and John Thune (S.D.) to their roster after losing Sen. Jim Bunning (Ky.).
That changes the ratio of Democrats to Republicans from 13:10 to 13:11, adding one extra Republican to the panel after the GOP picked up six seats in the midterm elections.


text:
Customized Cursor in Flash MX 2004
Visit Publisher Site
Customized Cursor in Flash MX 2004 Hosting Promo
You want to create advanced presentation or shooter game? Need a cursor in the shape of target or you simply tired of dull default cursors? No problem! With this easy tutorial you will be able to change the cursor in your flash presentations to anything you wantVisit publisher site: Customized Cursor in Flash MX 2004
Listing Details
- Filed in:
Scripts / Flash / Tutorials & Tips / Actionscript
- Submitted on:
- Last Updated:
- Mar 22, 2005
- Publisher:
- Jitender Kumar Other listings by this publisher
License & Pricing Information
- License Type:
- Freeware
- Price:
- 0.00
- Additional Info:
User ReviewsBe the first to review this listing!
Not yet reviewed by any member.... You can be the FIRST one to write a review for Customized Cursor in Flash MX 2004


text:
Going To Press
Sea Prints the book
Going To Press
Sea Prints the book
Tin Prints the book
Resting on the Shore line of a now Forgotten Bay
Art studio on Wheels
My fully faired three wheel front wheel drive trike is perfect for getting to the beach back and back again to my m studio. I can carry two sculptures and my Nikon D 80 no need for gas and I leave no carbon footprint. The sea provides me with all the art supplies I need, then I come back to the seaside to shoot my creations seems to make sense to me. The ocean side is a very peaceful place and its never the same, tide, wind and light, as well as what has washed up the night before. Always fun to visit and re- visit the seaside keeps me balanced and in check. No matter what happens in this crazy world the tide will always come in and go out, there is something very comforting in that.
Golden Fish,sneak preview into the third series
Don't you want a big car? nope! A big house, nope! , Ah your crazy, am I? .
Two books in the can one more in the works. Not Sure may be Beach Prints still in process to early to tell.
Recent Articles
Tiki Island (6)
New Sculptures (6)
Surf Beach (6)
Illustrations (5)
Studio (8)
Tnkers Toys (8)
Tin Can Art from Surf Beach (8)
Space Art (9)
Familiar Shapes and Forms (6)
Happy July 4TH
Steam Rocket
Drawger and Friends at Hartford University Campus


text:
Home » American cars , American Muscle , cars , Ford Mustang » 1965 Shelby Mustang GT350
1965 Shelby Mustang GT350
As if the production Mustang wasn't hot enough, legendary Texas tuner Carroll Shelby collaborated with Ford in 1965 on these special GT350 models. These were basically street-legal versions of Shelby's GT350R race car, powered by Ford's 289 Hi-Po small-block. The legend grew the following year when rental company Hertz snapped up some Shelbys as part of their "Rent-a-Racer" program. Some were apparently returned with their high-power engines myseriously swapped out. Huh.
Tags American cars, American Muscle, cars, Ford Mustang


text:
The Son That Former NFL Player Rae Carruth Tried To Kill Turns 18, Still Suffering From Permanent Brain Damage
The former wide receiver, who plotted the murder of his ex, Cherica Adams, is scheduled to be released from prison soon.
A 42-year-old man in Oklahoma City was shot and killed by police after performing a long string of unpredictable acts.
The day started when Miguel Chavez-Angles was seen banging his head on the floor of a church because of a potential divorce. Police were then called to the scene, where they transported him to St. Anthony's Hospital for a mental examination.
After being released from the hospital, Chavez called his wife and told her that he was roaming the streets and looking for a ride home. He ultimately ended up getting in a car with two women and instructing them to drive.
At this time, police had received reports of a kidnapping. Chavez was followed in the car until he eventually jumped out and ran into O'Reilly Auto Parts and locked the door. When the store manager told Chavez to leave, he ran to a city bus that was nearby.
Now this is when things got more disturbing.
Chavez hopped on the bus and told the bus driver to drive. "I will give you whatever you want," Chavez said to driver, while also asking him to lock the door. He then climbed on top of the luggage rack, grabbed a fire extinguisher, and took the pin out. The driver then instructed everyone to get off the bus, including Chavez.
Two officers then arrived on the scene. When Officer Heather Lane approached Chavez, he dropped the fire extinguisher and lunged for her gun. The two wrestled over the gun until one shot was fired. That was when Officer Daniel Carli gots on the bus and shot Chavez.
Chavez was pronounced dead on the bus and the officers have been placed on restricted duty while investigators determine if the shooting was justified.
You can watch the video below. Warning: it is very graphic. The video has been purposely frozen before the kill shot.
(Photo: Zodebala/Getty Images)
The former wide receiver, who plotted the murder of his ex, Cherica Adams, is scheduled to be released from prison soon.
Each of the men could be served a life sentence in prison.
Presented by


text:
O'Reilly Automotive (ORLY) Profit Margin History
Historical gross, operating and net quarterly profit margin for O'Reilly Automotive (ORLY) over the last 10 years. The current net profit margin for O'Reilly Automotive as of November 17, 2017 is 12.13%.
|Market Cap
|Retail & Wholesale Auto Parts
|O'Reilly Automotive, Inc. is a specialty retailer and supplier of automotive aftermarket parts, tools, supplies, equipment and accessories to both ``do-it-yourself`` customers and professional mechanics or service technicians. O'Reilly stores carry an extensive product line consisting of new and remanufactured automotive hard parts, such as alternators, starters, fuel pumps, water pumps, and brake shoes and pads, maintenance items, such as oil, antifreeze, fluids, engine additives and appearance products, accessories, such as floor mats and seat covers.


text:
Woman dies after being shot in Warren, suspect still on the run
WARREN, Mich. (WJBK) - A woman who was found shot in Warren Friday morning has died, according to the Warren Mayor's Office.
Police are still looking for a suspect. They questioned the woman's boyfriend earlier but have determined he is not a suspect, according to the mayor's office.
K9 units from Troy and Sterling Heights were helping police search for the suspect earlier this morning. The shooting happened at Stoneridge Heritage Village, which is off Mound Road between 12 and 13 mile roads near the GM Tech Center.
Warren police say the woman was shot multiple times in her torso and was found in the front yard of the residence. She was found next to her car.
A witness told police they saw a person running away from the area immediately after hearing the gunshots.
St. Anne Catholic School, about a mile north on Mound Road, was locked down until 10 a.m. while the investigation was active in the area. We're told police are still currently looking for a weapon.
This is a developing story. Stay with FOX 2 for updates.


text:
Moraine Valley Community College campus ministry
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Information about Moraine Valley Community College campus ministry, and registering for elective seminars and discussion sections. As a student, your first stop should be the registrar's office, where you can pick up a free copy of both the academic calendar and course catalog, in order to find available credit classes that you may be interested in taking. You may be surprised that you can enroll for a full-time course load, without having to attend any 8am classes at all. Finally, check with your major department for assistance with prerequisites, tuition payment deadlines, and Moraine Valley Community College social work degree information. Please use the form above to request admissions info for Moraine Valley Community College.
Students with a degree in psychology can find career opportunities working in schools, corporations, or in the social services sector. Many psychology grads work in the field of mental health, under the supervision of a clinical psychologist or psychiatrist. Psycho-analysis is based on changing problematic behaviors, feelings, and thoughts by discovering their unconscious meanings and motivations. By comparison, Jungian therapy focuses on the collective unconscious, dream archetypes, and symbolic representation. In dysfunctional families, children must learn to cope with unbearable situations, and often develop classical psychological symptoms. Therapists in turn will attempt to identify destructive behavior and emotions, and select suitable therapy.
In brief therapy as outlined by Milton Erickson, the therapist treats clinical and subjective conditions faster by precise observation, and direct intervention. Rather than a prolonged analysis of historical causes, the primary approach of brief therapy is to help the client become more versatile in the present, prompting successful clients to undergo spontaneous changes. Behavioral Therapy, on the other hand, addresses both normal and abnormal behaviors. Desensitizing is classical conditioning in action, where a therapist might help a client with a phobia through repeated exposure to the causal agent. Operant conditioning is more direct, relying on rewards and punishments to shape behavior. Beyond consideration for Moraine Valley Community College campus ministry, you may think about Navajo Technical College honors classes for complementary electives to your primary course of study.
Staff Assistant III
Harvard University
College degree preferred. Assist with coordination of faculty search and graduate admissions candidate visits..
4 days ago Admissions Director
Lorien Mays Chapel
College degree preferred. Conducts admission screening of potential patients, determine level of care, services required, equipment needs, insurance coverage.
5 days ago Admissions Representative
Aviation Institute of Maintenance
Prefer prior admissions experience at a private for profit college or technical school. Wynn, Campus Director of Admissions.
8 hours ago Admissions Officer
Strayer University
Enroll new students and ensure appropriate basis of admission is obtained, all prerequisites are satisfied, and previous college transcripts are ordered if..
17 hours ago Enrollment Counselor
Bethel University
Facilitate prospective students admissions process in a timely and efficient manner through the admissions funnel using recruiting best practices.
4 days ago


text:
This place has great shipping. I live on Washington and shipping was only 2 days!!!!
Read More ->
I have sent an inquiry to MJM about some item that I want to order and I was surprised how fast they have answered. But not only fast, I have sent...
Read More ->


text:
NFPA Presentations from 2017 Annual Conference Available
By Eric Lanke
NFPA President/CEO
Re-recordings of the presentations given at the Annual Business Meeting as well as during the Foundation Report at the 2017 Annual Conference in Maui, Hawaii are now available for NFPA members who were unable to attend the event. Videos and supplemental documents are below.
Annual Business Meeting
Learn more about how the association is doing financially as well as where the strategic plan is going and what networking and industry statistics programs are available.
Supplement: Membership Video
Foundation Report
Learn more about the association's workforce development and education initiatives, including the new Robotics Challenge and the rebranded Vehicle Challenge.
- 2016 Donor Impact Report
- Table of Programs and Objectives
- Pascal Donors 2016-17
- Complete Pascal Donor List


text:
The much awaited "5-day fashion frenzy" as I like to call it, began on October 6th with some very promising shows. I got to meet so many amazing people and made lovely new friends. I also did the Trend Spotting of cool footwear during the fashion week which was published in Designer Mode. For those who don't know what Designer Mode is, it's a magazine by FDCI(Fashion Design Council of India) which is published only during the fashion week and it covers all sorts of articles and pictures of everything happening at the venue of WIFW. Since, it's only available at the WIFW Venue, I tried to stream live pictures to my best as I wanted my readers to be updated with everything happening in the F Week as well ;)
The Media Accreditation I received by Wills Lifestyle allowed me to access all the shows as well as the Wills Lounge which was super cool but sadly, they did not provide an accreditation for Aman which was very unprofessional of them as I had made it very clear from the beginning that he is my blog partner and I would need him to be with me all the time! There were many more unprofessional behavior on their part but I don't think, leashing out my thoughts here is gonna help the situation. I would just be careful from the next time about who I choose to work with.
This stunning installation by Ranna Gill in the Wills Lifestyle Lounge took my breath away!! Isn't the jacket to-die-for?!!!
I like the designers who go an extra mile to add a little something to their show. I will always remember Atsu Sekhose's show because of this installation...
Few of my favorite footwear spotted on Day 1....
There were many designers and celebrities spotting also happening and I tweeted a lot of pictures of Rajesh Thakore, Pernia Qureshi, Nandini Bhalla, Nida Mahmood etc etc...
One of the most interesting and amazing show was the opening show of Payal Pratap and her cotton peplums, maxi dresses, and very unique silhouettes attracted a lot of attention.
The fabulous show by Rohit Gandhi+Rahul Khanna....dramatic as usual!
The soft flow-y silhouettes by Kiran Uttam Ghosh.
The dramatic and not-so-pret collection of Suneet Verma!
If I had to choose one show which was my favorite from Day 1, it will be Poonam Bhagat! The strong prints, dip-dye effect, long bolero jackets, all had me wanting for more...
Since Aman was not around most of the time, I could not get an outfit picture from Day 1 but as luck had it, I was featured in Designer Mode under the Trend Spotting article for Western Wear :D
You can look forward to a lot more posts from the Fashion week!


text:
My son has been a member of the Oakland Youth Chorus since 2013. I cannot stress enough how glad I am that a friend of ours suggested that he go check them out. He began in the All City Miracles with Miss Rhonda Crane. Through her instruction and gentle guidance he was able to go from being a kid who just sang around the house, to one who really began paying attention to honing his vocal skills. He moved on last year to audition for Miss La Nell Martin, and gained entry into the Concert Chorus. He loves their attention to detail and expanded
repertoire. His experience with fundraising for their tour to New Orleans in April 2016 was a invaluable. Being part of Oakland Youth Chorus has enriched my son's knowledge of music theory and performance, that I expected. It has also given him a sense that through hard work and dedication he can achieve success, not only in chorus, but in other areas of his life, and for that I am grateful.
I decided to join the board of Oakland Youth Chorus for a number of reasons—let me count the ways! I am a teacher and school administrator professionally, and OYC is serious—and seriously fun—not only about performance excellence; it also provides a hands-on musical and cultural education that students take with them as they grow up. The love for the craft of teaching and engaging kids is truly evident at each rehearsal. My own formative musical experiences—Cleveland Orchestra Children's Chorus, Yale Gospel Choir, my folk-singing uncle—also resonate with how I see OYC impacting its youth. Last but not least, I get to hear the concert chorus voices echo up the church stairway during meetings, and witness the joy in my own daughters' faces as they sing together walking home from school or at bedtime. I'm so glad OYC is here for them—and for all of our young singers—and I'm lucky to also get to play a part!
I have had the unique opportunity to experience the Oakland Youth Chorus in three very different ways, as a former funder, a board member and as a parent of two children who are singers. As a funder I was always impressed by the organization's professionalism and positive work in the community. When I began serving on the board my children were not old enough yet to sing in the chorus but I wanted to support an organization that was providing such a valuable service. Now that both my kids are chorus, my ties to the organization have become all the stronger as I see the positive affect the program has on them. I expect to be involved with OYC for many years to come!
I was introduced to OYC by my daughter who sang in the chorus throughout elementary school. She had such an outstanding experience and I was blown away by the quality of the singers at the concerts. I was happy to join the board of this organization that works hard to bring choral music to children throughout Oakland and surrounding communities. The economic downturn has hit arts nonprofits hard and I am so proud to be part of an organization that continues to fulfill its mission despite big funding challenges. Our Executive Director, Keri Lindell Butkevich, joined us in June 2012 and she is outstanding! Come to a concert and see for yourself why Oakland Youth Chorus is so special.
In spite of the dramatic drop in public funding, this agency forges ahead in its commitment to provide music education and ensemble opportunities to kids who want this option but cannot or choose not to participate in more classically oriented choruses. It boasts a corps of professional, performing artists who teach and mentor participants at school sites. The all-city middle and high-school choruses are vehicles not only for a musical education, but present an opportunity for students from all parts of Oakland to work and learn together. OYC has been around for 35 years and has been credited with providing a life changing experience for thousands of Oakland school children. It could use an infusion of new energy and vision, to bring it current with the needs of children who have limited access to this low-cost program and to cultivate the continuing, active support of chorus parents, chorus alums and the general community. OYC has the potential to make a significant difference - it needs folks to know about it and to care.
The Oakland Youth Chorus has been serving the East Bay Area since 1974 providing music education, performances, and tour opportunities for children and youth ages 5 -24. I joined OYC in 1975 and cannot express how profoundly it has affected my life. I gained choral music education, performance confidence, and, most importantly, lifelong friends with whom I still sing as a member of the OYC Alumni and various other groups. I am now a member of the Advisory Board and have served as the Alumni Association President for over a decade.
The Oakland Youth Chorus provides an incredibly educational and nurturing environment with teachers who are, themselves, professional music and dance performers and many are former OYC members. They provide an inclusive experience for elementary school children who are then able to advance through the Middle School and Concert Chorus levels. Many of the OYC choral students have become music professionals and all profess the value of this experience.
I think that an organization that can evolve over 4+ decades deserves recognition for its continuing success.
OYC rocks.


text:
Coffee has played a very significant role in many states, cities, home, and especially in offices. There are some who can't survive a day without a cup of Joe. Coffee Geeks makes coffee breakfasts' best buddy.
Why there are many coffee aficionados is simple. This is because coffee is a stimulant. It provides for that energized feeling and way of thinking. The consumption of coffee is also for pleasure.
It is undeniable that coffee is one of the best drinks in the world. There are in fact many varieties of coffee flavor. When it comes to coffee making, there is one brand you can trust – Philips Saeco RI9737/20 Vienna Plus Espresso Machine. Used to be called the 4050 until Philips appeared.
Vienna is a company which had been devoted to making excellent coffee making machines. For years, it came up remarkable coffee makers which coffee geeks die for.
Inspired by the passion in making outstanding coffee making machine, and technology, Vienna has created Saeco 4045. This machine belongs from Vienna's line of patented coffee making machine.
With this machine, you can automatically make your favorite latter, cappuccinos, espressos and other coffee flavor. This is but perfect for gourmet coffee lovers. This machine can be affordably availed for office, business or home use.
Philips Saeco RI9737/20 Vienna Plus Espresso Machine is a coffee making machine which aesthetically measures at about 14x15x15-1/2 inches. It has a Pannarello frothing device for the milk, stainless steel boiler, removable water tank, strong pump or steam at 15 bars, tamper, bean container, dreg drawer with 15 puck capacity, and conical burr grinder.
It also has a built-in water filter, steam wand, programmable brew amounts or cup sizes, and operates automatically. It also has a user-friendly control panel, steam function button, alarm light, and a knob used to adjust the amount of coffee.
Click Here For Philips Saeco RI9737/20 Vienna Plus Espresso Machine Reviews
Saeco 4045 Vienna Plus is a revolutionary machine which can be conveniently used by anyone. It can be easily operated by familiarizing with the control panel. The conical burr grinder is just fantastic. It can hold about 12 ounces of whole coffee beans.
Through technology applied in the machine, you can adjust the fineness of the ground coffee. Hence, you'll get only the most flavorful coffee in the world. The panarello makes the frothing of milk easy. Also, you can use the adjustable dose in order to determine and adjust the coffee in each cup.
Moreover, this machine allows quick rinsing, cleaning, and descaling. The highlights of this machine also include its stainless steel boiler and the machine's ability to accommodate varying cup measurements.
True enough, this new coffee making machine from Saeco Vienna is no way comparable to its predecessors. This new machine can make your coffee in a swoop and with intense flavor. You can also use its hot water for other drinks like teas, chocolate, and so on. Just like the Krups Espresso Machine too.
Indeed, this Philips Saeco RI9737/20 Vienna Plus Espresso Machine is just so perfect. With just a few press and adjusting, you can come up with the most flavorful and pleasurable coffee right in the comfort of your home. Know more about how great Saeco 4045 is, you may browse for product reviews.


text:
Interview With A Blogger: Tiffany Cruz, Fabulous Mom Blog
Good morning and happy Mother's Day, Mom Spark readers!
This is a very special Sunday for mamas everywhere, and we all know what Sunday means around these parts, eh? It's time for another Interview With A Blogger! Oh yes!
And today's guest? Why that would be the obviously fabulous Tiffany Cruz of Fabulous Mom Blog! I can't wait for you to take a peek below to learn more about this rad mama blogger — enjoy!
Welcome, Tiffany!
So, what prompted you to start blogging?
I've always kept a journal, as far back as I can remember I've written down my daily activities and I look back at those journals and it's easy to see why I easily fell in love with blogging. I started blogging back in 2007 shortly after my daughter was born. A few months after Jasmine was born I started an Etsy shop to sell all the baby headbands and bows I was making. Bloggers started approaching me to send them samples of my work in exchange for a blog post feature. I had not read a blog before being approached by bloggers. I was intrigued by blogs and knew I had to start one for my Etsy shop, and so I did.
That very first blog was lost when I accidentally let my domain expire. But that didn't bother me too much. I knew I wanted to close down my Etsy shop and dive head first into blogging full-time.
Many years of hard work, and another child later. I'm a full-time blogger, and I love it.
Tell us about your day job/educational pursuits?
I'm a full-time work at home mom. My kids keep me very busy, but I do manage to find time to blog. Blogging is a passion of mine that I haven't felt for anything else. I'm able to make a pretty good income blogging and it's nice to be able to work from home.
In the long run I would like to go back to school to get a degree in Journalism and maybe take a photography class.
Where's the farthest from home you've ever travelled? Tell us about your experience.
As a child growing up in a military household we were always moving. The first 12 years of my life were spent in California and Hawaii. In 1992 my dad and mom packed us up and we went cross-country, all the way to Virginia. I stayed in VA until I got married and decided on a whim to start my life with my husband far from home, in Louisiana.
If I were to tell you the farthest I've traveled from where I currently live, I'd have to say Pennsylvania. The trip to Pennsylvania for my cousin's wedding was the first time my husband and I went on a trip without the children. It was a nice few days, the wedding was amazing and it was nice to see family and to travel alone, without children.
What skill do you hope to master over the next year?
Over the next year I'd like to work on becoming a better writer, and photographer. I want to put my iPhone down and pick up my DSLR more. I want to learn how to use my DSLR in manual mode. My all around goal is just to keep improving my blog.
What's your current favorite song/band? And what are you reading?
I've been on a F. Scott Fitzgerald kick lately. I recently finished up The Great Gatsby and I'm currently reading The Beautiful and Damned.
I listen to all sorts of music. In my late teens and early 20s I went to concerts, mostly metal, punk, and alternative. These days I listen to a lot of modern country music. I still have 3 favorite bands, The Beatles, 311, and Sublime.
Share three blogs you adore!
I find so much inspiration from all over the interwebs, but there are three blogs that I adore more than you'll ever know.
Thank you so much for sharing a peek into your life with us, Tiffany!
Be sure to hop on over to Fabulous Mom Blog for more style inspiration, motherhood moments, and beyond! You can also find Tiffany via her fave social media sites too:
- twitter.com/tiffcruzblogs
- pinterest.com/fabulousmomblog
- instagram.com/fabulousmomblog
- fb.com/FabFindsByTiff
PS. Do you know a rad blogger we should interview? Click here!


text:
Lousee & bkro9
View Single Post
April 6th, 2010, 08:08 AM
Mega Super Mommy
Join Date: Nov 2009
Location: Houston
Posts: 1,393
I would hate her too! I am hoping the weight goes pretty fast for me. I havent gained a ton, but I can def. see and feel the weight gain now!
I thought of you last night, DH took me to dinner and we got this free appitizer and it was seared tuna on this cucumber/seaweed salad thingy... with a wasabi sauce, it was sooooo good! I was like, I just need the tuna and that is all!!!! But it made me think of you!
So do you think you are going to have him right around his due date? I have a feeling I am going to be late...
Oh and his name is finally finalized Jaxon James (James is my gpas last name), I think DH likes it because it sounds like a name an outlaw from the old west hehehe.
View Public Profile
Find all posts by LOUSEE


text:
0 items ·
Check out
is back-ordered. We will ship it separately in 10 to 15 days.
This pretty backpack by Kreative Kids, Inc, will help your little one purple ballet slippers. Padded shoulderstraps provide extra comfort. Sure to enhance your image and help pull together your wardrobe! Measures 11 x 5 x 13 inches.Exciting and educational, this backpack would make a nice gift for any child!
Copyright © 2017 Capital Books and Wellness. Ecommerce Software by Shopify.


text:
Angel, United Kingdom (PressExposure) October 13, 2008 -- Littlewoods Direct, the UK's leading online and home shopping retailer, has announced the re-launch of the Ravel footwear collection, offering a number of a variety of in-vogue styles, which will appeal to fashion minded women looking to wear the finest winter fashion trends.
The new collection captures a multitude of looks, from stylish workwear through to party styles, all of which encompass Ravelâs own unique characteristics.
Heels in all shapes and sizes have been combined with an eclectic variety of finishing touches to give the range a real point of difference. Heels, stilettos [http://www.littlewoods.com/rf/navigation/mainsearchthumbs.do?Ns=prod_in_stock|1||price_est|0||prod_min_base_price|1||scu_id|1&pageSize=12&N=151+4294484632+85+4294484755&Nu=this_product&Np=1], the ultra modern cone heel and the platform have been incorporated onto an array of styles. Detailing, such as including striking patent and suede combinations, snake skin effect applications, buckle features, covered buttons and pepper pot punching have also been incorporated into the collection.
Applying subtle twists to the Mary Jane style, Ravel offers a new interpretation to this look for the season. Almond points have been teamed with an assortment of detailing which includes brogue cut out trims, contrasting wooden stack heels and feminine fastening systems which all provide this styling with a fresh new look. Also featuring strongly in the shoe range are a number of T-bar designs, which are available across a spectrum of styles from striking daywear through to alluring sandals for the party season.
Suede shoe-boots, patent knee highs and casual options with blunted toes are featured within in the boot range. Womens fashion [http://www.littlewoods.com/rf/navigation/spreadDsbs.do?categoryId=7595685] devotees will appreciate the finishing touches that have been applied such as contrast stitching, overlay detailing, buckle features and brogue inspired touches which all add to the modernistic look of the collection.
The attention to detail which is lavished on every pair of Ravel womens shoes [http://www.littlewoods.com/rf/navigation/mainsearchthumbs.do?Ns=prod_in_stock|1||price_est|0||prod_min_base_price|1||scu_id|1&N=151+4294484632&Nu=this_product&Np=1] and boots ensures that the wearer creates the ultimate head turning statement. Plush suede and soft leather uppers are teamed with a rich colour palette of ruby reds, rich teal, moss green, luxurious mink and deep purple, together with strong metallics.