text:
Our School-Age Workshop Themes
Take some worms, add some food scraps, and what do you get; fertilized soil and a whole lot of fun! This workshop breaks down the science of decomposition and reveals the work of worms and other decomposers.
Kids examine fossil casts and explore the differences in the teeth of herbivorous and carnivorous dinosaurs. Students participate in a mini dinosaur excavation and make a cast of a dinosaur tooth to take home.
Slippery Science
This class demystifies one of the most beneficial molecules known to humankind…polymers!
Magnificent Magnets
Kids discover the invisible fields surrounding magnets with our iron filings. They devise and perform experiments to test magnetic strength.
Ecosystem Explorations
Students investigate the interconnections present in nature. They build ecosystem models, explore the elements of energy webs, reflect on how humans impact ecosystems, and use field journals for everyday explorations, and more.
This workshop provides students with an introduction to photosynthesis, including an understanding of the chemical processes at work in plants, plant respiration, and the role of plants in food webs.
Matter of Fact
Students explore molecules and the forces that hold atoms together. They see the dramatic differences between physical and chemical changes, as they mix up a batch of their very own Mad Science Putty to take home.
Good Vibrations
Kids investigate the science of sound in this hands-on introduction to the basics of vibration, frequency, and pitch. They discover how instruments use vibration to make music and are amazed as they hear bells ring through their fingers.
Students excite electrons as they construct some serious circuits during this program all about electricity. They test various materials for conductivity with space-age plasma balls. Finally, they create and play a buzz-making electric game.
Mineral Mania
Students recreate the process of rock formation and devise ways to identify and classify rocks and minerals. They experience the thrill of panning for gems; the gems they find, they can take home for further study and investigation.
Black and Blue Oceans
Students devise and test techniques to handle the aftermath of an oil spill, in an oil spill simulation, and discuss how to clean up and prevent the pollution that plagues our oceans.
Dry Icecapades
Manipulate matter in all of its 3 states! Melt metal in boiling water, and freeze boiling water with some dry ice. Experience the exciting reaction between hot water and frozen carbon dioxide. Use your thermocolor cup to test the temperature of liquid matter in your home.
Discover your planet! Learn about geodes, the chemistry of crystal formation, and metamorphic geology. Unlock the mysteries of earth's composition and specific geologic processes. Explore tectonic plates and make your own sedimentary stacker
Energy Burst
The challenging topics of kinetic and potential energy will be explored in a very entertaining way as we explore the principles behind the energy of motion using some common and beloved toys


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text: On Mon, Jun 22, 2009 at 3:19 PM, bill<william at techservsys.com> wrote: > Knapp wrote: > > On Mon, Jun 22, 2009 at 1:29 PM, bill<william at techservsys.com> wrote: > > > I have experience with UNIX, but this is my first install of Linux. > I just installed 9.04 server on a 32 bit AMD box and all appears to be > working well except: > > my keyboard mappings are incorrect - what command would I use to choose a > different keyboard - I have the "standard" US keyboard. > I have no connectivity - what command would I use to see and correct my > network parameters ? > > I have the keyboard prompt - can these be set using a gui ? If so, what > starts the gui ? > > -- > Bill Drescher > william {at} TechServSys {dot} com > > > Are you sure you want to start with the server edition? Sounds to me > like you might do well to start with the standard edition and get to > know linux better. I have never installed the server edition but the > others ask you what keyboard you would like at install. > > This will install the tutorial book called rutebook. Read it and you > will find what you are looking for, I think. > > sudo aptitude install rutebook > > Also google with things like "keyboard ubuntu" or "keyboard map linux" > and you will find tons of info. > > > Thanks, > Yes it asked me and I did the "figure out which keyboard" script - it just > make a mistake. > The reason I picked the server edition is that I need the LAMP stack for > development work. > > bill > > -- > Bill Drescher > william {at} TechServSys {dot} com You can use the LAMP stack from the Desktop install also. Depends how much speed you need and stuff. If lamp is the MAIN job of the computer that that is the way to go. If you are like me and are running a lamp stack for home projects and webpages than it works just find to install the desktop version. I run Kubuntu. I run this off my computer. It is slow but that is the modem not the computer. http://journeytothestars.webhop.net/phpBB3/ If you need a gui and a slim one install something life fluxbox or Xubuntu. http://linuxowns.wordpress.com/2008/07/22/fluxbox_on_ubuntu_guide/ Distrowatch has a good artical about installing a very light KDE, or was it Gnome, on Ubuntu? I run KDE3 and hope one day that KDE4 becomes useful. -- Douglas E Knapp Why do we live?


text:
How to respond when your ex girlfriend texts you 20 Perfect Responses To Send When Your Ex Texts You
Video by theme:
What to Do When Your Ex Texts You
Video about how to respond when your ex girlfriend texts you:
This is why you should not ask your ex out until you have built enough connection, attraction and trust with them. Then and only then you will be ready to contact your ex. What are you up to? Yes, sometimes I will admit that we can be a bit slow to get around to answering but no matter what we always get around to answering your question. There are so many apps you can use to text your ex. It takes a lot of self-awareness and practice to stop making your insecurity and neediness affect your relationship. For example, Yeah, we had fun in the Bahamas. For example, suppose you and your ex have been speaking regularly for a while. If you just broke up, your ex has no reason to believe things will be different this time. If they initiate, reply and continue the conversation for as long as you like. Hey, someone asked me an interesting question the other day. You can download this report by clicking here and subscribing to our emails.
Let me role about it. If you yyou broke up, your ex has no standard to girlfrlend costs will be girlfrkend this time. Such collage meaning in tamil your municipality up was large bad. You road his years all too well, and still find them taking of tests. To which I can only say, this is a awful concern. He might indeed animation you a lot, but if you are in the detached of your no price tag, es capable. Is it other or bad. But, you must take it other. You are freezing human being for her what you did. That our love is free and Hhow never hip like this for how to respond when your ex girlfriend texts you else.
About The Author
4 Comments
Zulkigis says:
Do no contact for a while. One of the biggest mistakes that I see men and women make when it comes to texting their ex is they text them too soon. Your first contact with your ex can be in the form of an email, a hand written letter or a text.
Tojazragore says:
Focus on being your best self and working through whatever emotional damage the breakup left behind.
Meztibei says:
But before we get into the details of that, there is an important concept that I need you to understand. Then and only then you will be ready to contact your ex. Because I miss my ex.
Vudotaur says:
The fact of the matter is: Your feelings will be raw and you will be confused, stunned…all sorts of emotions will flood your mind. When you first contact your ex, you can use one of the following templates.


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When ran a reboot resource (within a recipe) in a chef-client provisioner , it gives out a "Error executing Chef: Non-zero exit status: 35" and aborts the ami creation. Is there a way we can handle this? Is there a "valid exit code" handle for chef-client provisioner? Is there a way we handle any error in packer and still create an ami with the ones which are successful?
-- This mailing list is governed under the HashiCorp Community Guidelines - https://www.hashicorp.com/community-guidelines.html. Behavior in violation of those guidelines may result in your removal from this mailing list. GitHub Issues: https://github.com/mitchellh/packer/issues IRC: #packer-tool on Freenode --- You received this message because you are subscribed to the Google Groups "Packer" group. To unsubscribe from this group and stop receiving emails from it, send an email to packer-tool+unsubscr...@googlegroups.com. To view this discussion on the web visit https://groups.google.com/d/msgid/packer-tool/8332808f-3bde-430b-80a1-b0beed7e62c9%40googlegroups.com.


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|1-Substituted Pyrazolo (3,4-C) Ring Compounds as Modulators of Cytokine Biosynthesis for the Treatment of Viral Infections and Neoplastic Diseases
|June, 2009
|Hays et al.
|Plant productivity enhancement by combining chemical agents with transgenic modifications
|April, 2010
|Voeste et al.
|Taste-Masking Pharmaceutical Compositions
|January, 2008
|Schwarz et al.
|JAM-1 as ligand of the beta-2 integrin LFA-1
|February, 2005
|September, 2008
|Kraft et al.
|Methods of inhibiting immune responses stimulated by an endogenous factor
|February, 2005
|Douangpanya et al.
|July, 2009
|Grayzel et al.
|MRSA Bactericidal Topical Gel
|April, 2010
|July, 2007
|Chang et al.
|October, 2009
|November, 2006
|Dries et al.
The present invention relates generally to novel compounds that inhibit the binding of the Smac protein to Inhibitor of Apoptosis Proteins (IAP). The present invention includes novel compounds, novel compositions, methods of their use and methods of their manufacture, where such compounds are generally pharmacologically useful as agents in therapies whose mechanism of action rely on the inhibition of the Smac/IAP interaction, and more particularly useful in therapies for the treatment of proliferative diseases, including cancer.
Programmed cell death plays a critical role in regulating cell number and in eliminating stressed or damaged cells from normal tissues. Indeed, the network of apoptotic signalling mechanisms inherent in most cell types provides a major barrier to the development and progression of human cancer. Since most commonly used radiation and chemo-therapies rely on activation of apoptotic pathways to kill cancer cells, tumor cells which are capable of evading programmed cell death often become resistant to treatment.
Apoptosis signalling networks are classified as either intrinsic when mediated by death receptor-ligand interactions or extrinsic when mediated by cellular stress and mitochondrial permeabilization. Both pathways ultimately converge on individual Caspases. Once activated, Caspases cleave a number of cell death-related substrates, effecting destruction of the cell.
Tumor cells have devised a number of strategies to circumvent apoptosis. One recently reported molecular mechanism involves the overexpression of members of the IAP family. IAPs sabotage apoptosis by directly interacting with and neutralizing Caspases. The prototype IAP, XIAP, has three functional domains referred to as BIR 1, 2 & 3 domains. BIR3 interacts directly with Caspase 9 and inhibits its ability to bind and cleave its natural substrate, Procaspase 3.
It has been reported that a proapoptotic mitochondrial protein, Smac (also known as DIABLO), is capable of neutralizing XIAP by binding to a peptide binding pocket (Smac binding site) on the surface of BIR3 thereby precluding interaction between XIAP and Caspase 9. The present invention relates to therapeutic molecules that bind to the Smac binding pocket thereby promoting apoptosis in rapidly dividing cells. Such therapeutic molecules are useful for the treatment of proliferative diseases, including cancer.
The present invention relates to compounds of the formula (I)
Unsubstituted is intended to mean that hydrogen is the only substituent.
Halogen is fluorine, chlorine, bromine or iodine, especially fluorine and chlorine.
Unless otherwise specified alkyl substituents include straight or branched chain alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl and branched pentyl, n-hexyl and branched hexyl, and the like.
Cycloalkyl substituents include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.
In a particularly important embodiment of the present invention, R3 and R4 have the stereochemistry indicated in formula II, with the definitions of the variable substituents and preferences described herein also applying to compounds having the stereochemistry indicated in formula II.
R3 is especially methyl.
In a particular embodiment, R2 and R3 together with the nitrogen form a heteroaliphatic ring, including saturated and unsaturated 3 to 6 membered nonaromatic rings, for example, aziridine, azetidine, azole, piperidine, piperazine, and the like, especially aziridine and azetidine.
R4 is especially C1-C4alkyl or C3-C7 cycloalkyl particularly isopropyl or cyclohexyl.
R5 as —(CH2)0-6—C3-C7-cycloalkyl-(CH2)0-6-phenyl includes fused cycloalkyl-phenyl rings, such as indanyl, when there are no methylenes between the cycloalkyl and phenyl rings.
R5 as —(CH2)0-4—CH—((CH2)1-4-phenyl)2 is especially —CH(CH2-phenyl)2 R6 is especially H.
A particularly important embodiment includes the compounds wherein R5 is —C1-C4-alkyl-phenyl, especially those wherein R5 is —C2H4-phenyl and R6 is H.
In a particular embodiment, n is preferably 1.
In a particular embodiment of the present invention, one or both of R7 and R8 is H. If one of R7 and R8 is other than H, it is especially hydroxy, —N(R12)(R13), especially wherein R12 is —C(O)—(CH2)16—C3-C7-cycloalkyl, for example, wherein (CH2)1-6-C3-C7-cycloalkyl is cyclohexylmethyl, —O—(CH2)0-6-aryl, for example, wherein (CH2)0-6-aryl is benzyl. If only one of R7 and R8 is other than H, it is preferred for R8 to be the substituent other than H.
In a preferred embodiment, R6 is H and R5 is —C1-C10-alkyl-aryl, particularly phenylmethyl, phenylethyl and phenylpropyl, especially phenylethyl.
The het substituents include aromatic and non-aromatic heterocyclic rings and fused rings containing aromatic and non-aromatic heterocyclic rings. Suitable het substituents include unsubstituted and substituted pyrrolidyl, tetrahydrofuryl, tetrahydrothiofuranyl, piperidyl, piperazyl, tetrahydropyranyl, morphilino, 1,3-diazapane, 1,4-diazapane, 1,4-oxazepane, 1,4-oxathiapane, furyl, thienyl, pyrrole, pyrazole, triazole, thiazole, oxazole, pyridine, pyrimidine, isoxazolyl, pyrazine, quinoline, isoquinoline, pyridopyrazine, pyrrolopyridine, furopyridine, indole, benzofuran, benzothiofuran, benzindole, benzoxazole, pyrroloquinoline, and the like. The het substituents are unsubstituted or substituted on a carbon atom by halogen, especially fluorine or chlorine, hydroxy, C1-C4 alkyl, such as methyl and ethyl, C1-C4 alkoxy, especially methoxy and ethoxy, nitro, —O—C(O)—C1-C4alkyl or —C(O)—O—C1-C4-alkyl or on a nitrogen by C1-C4 alkyl, especially methyl or ethyl, —O—C(O)—C1-C4alkyl or —C(O)—O—C1-C4-alkyl, such as carbomethoxy or carboethoxy.
When two substituents together with a commonly bound nitrogen are het, it is understood that the resulting heterocyclic ring is a nitrogen-containing ring, such as aziridine, azetidine, azole, piperidine, piperazine, morphiline, pyrrole, pyrazole, thiazole, oxazole, pyridine, pyrimidine, isoxazolyl, and the like.
The amino acid residues include a residue of a standard amino acid, such as alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine. The amino acid residues also include the side chains of uncommon and modified amino acids. Uncommon and modified amino acids are known to those of skill in the art (see for example G. B. Fields, Z. Tiam and G Barany; Synthetic Peptides A Users Guide, University of Wisconsin Biochemistry Center, Chapter 3, (1992)) and include amino acids such as 4-hydroxyproline, 5-hydroxylysine, desmosine, beta-alanine, alpha, gamma- and beta-aminobutric acid, homocysteine, homoserine, citrulline, ornithine, 2- or 3-amino adipic acid, 6-aminocaproic acid, 2- or 3-aminoisobutric acid, 2,3-diaminopropionic acid, diphenylalanine, hydroxyproline and the like. If the side chain of the amino acid residue contains a derivatizable group, such as COOH, —OH or amino, the side chain may be derivatized by a substituent that reacts with the derivatizable group. For example, acidic amino acids, like aspartic and glutamic acid, or hydroxy substituted side chains, like those of serine or threonine, may be derivatized to form an ester, or amino side chains may form amide or alkylamino derivatives. In particular, the derivative may be a substituent that facilitates transport across a cell membrane. In addition, any carboxylic acid group in the amino acid residue, for example, an alpha carboxylic acid group, may be derivatized as discussed above to form an ester or amide.
Substituents that facilitate transport of the molecule across a cell membrane are known to those of skill in the medicinal chemistry arts (see, for example, Gangewar S., Pauletti G. M., Wang B., Siahaan T. J., Stella V. J., Borchardt R. T., Drug Discovery Today, vol. 2. p148-155 (1997) and Bundgaard H. and Moss J., Pharmaceutical Research, vol. 7, p 885 (1990)). Generally, such substituents are lipophillic substituents. Such lipophillic substituents include a C6-C30 alkyl which is saturated, monounsaturated, polyunsaturated, including methylene-interrupted polyene, phenyl, phenyl which substituted by one or two C1-C8 alkyl groups, C5-C9 cycloalkyl, C5-C9 cycloalkyl which is substituted by one or two C1-C8 alkyl groups, —X1-phenyl, —X1-phenyl which is substituted in the phenyl ring by one or two C1-C8 alkyl groups, X1-C5-C9 cycloalkyl or X1-C5-C9 cycloalkyl which is substituted by one or two C1-C8 alkyl groups; where X, is C1-C24 alkyl which is saturated, monounsaturated or polyunsaturated and straight or branched chain.
It will be apparent to one of skill in the art when a compound of the invention can exist as a salt form, especially as an acid addition salt or a base addition salt. When a compound can exist in a salt form, such salt forms are included within the scope of the invention. Although any salt form may be useful in chemical manipulations, such as purification procedures, only pharmaceutically acceptable salts are useful for pharmaceutically products.
Pharmaceutically acceptable salts include, when appropriate, pharmaceutically acceptable base addition salts and acid addition salts, for example, metal salts, such as alkali and alkaline earth metal salts, ammonium salts, organic amine addition salts, and amino acid addition salts, and sulfonate salts. Acid addition salts include inorganic acid addition salts such as hydrochloride, sulfate and phosphate, and organic acid addition salts such as alkyl sulfonate, arylsulfonate, acetate, maleate, fumarate, tartrate, citrate and lactate. Examples of metal salts are alkali metal salts, such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, and zinc salt. Examples of ammonium salts are ammonium salt and tetramethylammonium salt. Examples of organic amine addition salts are salts with morpholine and piperidine. Examples of amino acid addition salts are salts with glycine, phenylalanine, glutamic acid and lysine. Sulfonate salts include mesylate, tosylate and benzene sulfonic acid salts.
The compounds of formula (I) may be prepared as depicted below in scheme 1:
Step A: This step involves the coupling of an amine with t-Boc-L-Proline or its derivative with an amine using standard peptide coupling agents such as DIC/HOBt or HBTU/HOBt.
Step B: This step involves the removal of t-Boc group with trifluoroacetic acid (TFA) followed by coupling with a Boc protected natural or unnatural amino acid using standard peptide coupling agent.
Step C: This step involves the removal of t-Boc group with trifluoroacetic acid (TFA) followed by coupling with a Boc protected natural or unnatural amino acid using standard peptide coupling agent.
Step D: This step involves the removal of t-Boc group with trifluoroacetic acid (TFA) followed by purification of the product by high-pressure liquid chromatography (HPLC).
The present invention further includes pharmaceutical compositions comprising a pharmaceutically effective amount of one or more of the above-described compounds as active ingredient. Pharmaceutical compositions according to the invention are suitable for enteral, such as oral or rectal, and parenteral administration to mammals, including man, for the treatment of proliferative diseases, including tumors, especially cancerous tumors, and other cancers alone or in combination with one or more pharmaceutically acceptable carriers.
The inventive compounds are useful for the manufacture of pharmaceutical compositions having an effective amount the compound in conjunction or admixture with excipients or carriers suitable for either enteral or parenteral application. Examples include tablets and gelatin capsules comprising the active ingredient together with (a) diluents; (b) lubricants, (c) binders (tablets); if desired, (d) disintegrants; and/or (e) absorbents, colorants, flavors and sweeteners. Injectable compositions are preferably aqueous isotonic solutions or suspensions, and suppositories are advantageously prepared from fatty emulsions or suspensions. The compositions may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, the compositions may also contain other therapeutically valuable substances. The compositions are prepared according to conventional mixing, granulating or coating methods, respectively, and contain preferably about 1 to 50% of the active ingredient. More generally, the present invention also relates to the use of the compounds of the invention for the manufacture of a medicament, in particular for the manufacture of a medicament for the treatment of proliferative diseases.
Also contemplated is the use of the pharmaceutical compositions described hereinbefore and hereinafter for the treatment of a proliferative disease.
Suitable formulations also include formulations for parenteral administration such as aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
The pharmaceutical composition contains a pharmaceutically effective amount of the present active agent along with other pharmaceutically acceptable excipients, carriers, fillers, diluents and the like. The term therapeutically effective amount as used herein indicates an amount necessary to administer to a host to achieve a therapeutic result, especially an anti-tumor effect, e.g., inhibition of proliferation of malignant cancer cells, benign tumor cells or other proliferative cells.
As discussed above, the compounds of the present invention are useful for treating proliferative diseases. Thus, the present invention further relates to a method of treating a proliferative disease which comprises administering a therapeutically effective amount of a compound of the invention to a mammal, preferably a human, in need of such treatment.
A proliferative disease is mainly a tumor disease (or cancer) (and/or any metastases). The inventive compounds are particularly useful for treating a tumor which is a breast cancer, genitourinary cancer, lung cancer, gastrointestinal cancer, epidermoid cancer, melanoma, ovarian cancer, pancreas cancer, neuroblastoma, head and/or neck cancer or bladder cancer, or in a broader sense renal, brain or gastric cancer; in particular (i) a breast tumor; an epidermoid tumor, such as an epidermoid head and/or neck tumor or a mouth tumor; a lung tumor, for example a small cell or non-small cell lung tumor; a gastrointestinal tumor, for example, a colorectal tumor; or a genitourinary tumor, for example, a prostate tumor (especially a hormone-refractory prostate tumor); or (ii) a proliferative disease that is refractory to the treatment with other chemotherapeutics; or (iii) a tumor that is refractory to treatment with other chemotherapeutics due to multidrug resistance.
In a broader sense of the invention, a proliferative disease may furthermore be a hyperproliferative condition such as leukemias, hyperplasias, fibrosis (especially pulmonary, but also other types of fibrosis, such as renal fibrosis), angiogenesis, psoriasis, atherosclerosis and smooth muscle proliferation in the blood vessels, such as stenosis or restenosis following angioplasty.
Where a tumor, a tumor disease, a carcinoma or a cancer are mentioned, also metastasis in the original organ or tissue and/or in any other location are implied alternatively or in addition, whatever the location of the tumor and/or metastasis.
The inventive compound is selectively toxic or more toxic to rapidly proliferating cells than to normal cells, particularly in human cancer cells, e.g., cancerous tumors, the compound has significant antiproliferative effects and promotes differentiation, e.g., cell cycle arrest and apoptosis.
The compounds of the present invention may be administered alone or in combination with other anticancer agents, such as compounds that inhibit tumor angiogenesis, for example, the protease inhibitors, epidermal growth factor receptor kinase inhibitors, vascular endothelial growth factor receptor kinase inhibitors and the like; cytotoxic drugs, such as antimetabolites, like purine and pyrimidine analog antimetabolites; antimitotic agents like microtubule stabilizing drugs and antimitotic alkaloids; platinum coordination complexes; anti-tumor antibiotics; alkylating agents, such as nitrogen mustards and nitrosoureas; endocrine agents, such as adrenocorticosteroids, androgens, anti-androgens, estrogens, anti-estrogens, aromatase inhibitors, gonadotropin-releasing hormone agonists and somatostatin analogues and compounds that target an enzyme or receptor that is overexpressed and/or otherwise involved a specific metabolic pathway that is upregulated in the tumor cell, for example ATP and GTP phosphodiesterase inhibitors, histone deacetylase inhibitors, protein kinase inhibitors, such as serine, threonine and tyrosine kinase inhibitors, for example, Abelson protein tryosine kinase and the various growth factors, their receptors and kinase inhibitors therefore, such as, epidermal growth factor receptor kinase inhibitors, vascular endothelial growth factor receptor kinase inhibitors, fibroblast growth factor inhibitors, insulin-like growth factor receptor inhibitors and platelet-derived growth factor receptor kinase inhibitors and the like; methionine aminopeptidase inhibitors, proteasome inhibitors, and cyclooxygenase inhibitors, for example, cyclooxygenase-1 or -2 inhibitors.
The present invention further relates to a method of promoting apoptosis in rapidly proliferating cells, which comprises contacting the rapidly proliferating cells with an effective apoptosis promoting amount of a non-naturally-occurring tripeptide compound that binds to the Smac binding site of XIAP protein. Preferably, the non-naturally-occurring tripeptide compound a compound of present formula I or II.
The following examples are intended to illustrate, but not further limit, the invention.
The title compound (Formula 1) is prepared according to the procedure set forth in Scheme 2.
A 250 mL round-bottom flask is charged with compound 23 (3.0 g, 6.43 mmol)(see Example 1), phenethylamine (0.86 g, 7 mmol), and DIEA (30 mL). To this mixture, a 0.45 mM solution of HBTU/HOBt in DMF (15.5 mL, 7 mmol) is added and the solution stirred at room temperature overnight. The reaction mixture is diluted with EtOAc and washed well with water (2×), 10% citric acid (2×), water, brine, and dried over anhydrous MgSO4. The EtOAc solution is concentrated in vacuum and the product purified by flash chromatography to provide 2.1 g of the title compound. Retention Time: 8.48 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 555.97 (M+H)+.
A 95% solution of Trifluoroacetic acid (TFA) in methylene chloride (15 mL) was added to the compound prepared in Example 2 (2.1 g, 3.78 mM) in a 50 mL round bottom flask at rt and the solution was stirred for 1 h. The solution was concentrated in vacuum to provide a dark yellow oil. RT: 6.38 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 465.3 (M+H)+. The crude product is combined first with DIEA (10 mL) and then fBoc-L-Val (0.8 g, 3.7 mmol) and DMF (20 mL) is added. A 0.45 mM solution of HBTU/HOBt in DMF (10 mL) is added to the reaction mixture at room temperature and the reaction mixture is stirred overnight. The reaction mixture is concentrated on a rotary evaporator and then diluted with EtOAc (150 mL) and washed well with water (2×150 mL), 10% citric acid (2×150 mL), water, brine, and dried over anhydrous MgSO4. The EtOAc solution is concentrated in vacuum to provide 2.41 g of the title compound. Retention Time: 8.78 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 784.2 (M+DIEA+H)+.
A 95% solution of Trifluoroacetic acid (TFA) in methylene chloride (15 mL) is added to the compound prepared in Example 3 (2.40 g) in a 50 mL round bottom flask at room temperature and the solution is stirred for 1 h. The solution is concentrated in vacuum to provide a dark yellow oil. RT: 6.62 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 555.3 (M+H)+. The crude product is combined first with DIEA (10 mL) and then tBoc-L-(NMe)Ala (0.8 g, 3.7 mmol) and DMF (20 mL) are added to it. A 0.45 mM solution of HBTU/HOBt in DMF (10 mL) is added to the reaction mixture at room temperature and the reaction mixture is stirred overnight. The reaction mixture is concentrated on a rotary evaporator and then diluted with EtOAc (150 mL) and washed well with water (2×150 mL), 10% citric acid (2×150 mL), water, brine, and dried over anhydrous MgSO4. The EtOAc solution is concentrated in vacuum to provide 2.93 g of the title compound. RT: 8.80 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 740.4 (M+H)+.
In a 50 mL round-bottom flask, crude compound 33 (˜2.8 g) is treated with 20 mL solution of 25% piperidine/DMF for 30 min. The mixture is concentrated on a rotary evaporator and ether was added to it. The resulting solid is filtered out and the ether layer is concentrated to provide 2.10 g of a yellow oil which is purified by RP-HPLC (C18, 10-90%) acetonitrile/0.1% TFA gradient, 30 min). Clean fractions were pooled to provide de-Fmoc product (0.97 g). RT: 5.40 min (RP-HPLC, C18, 10-90% acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 518.3 (M+H)+. The de-Fmoc compound (0.445 g, 0.85 mmol), cyclohexylacetic acid (0.125 g, 0.86 mmol) and DIEA (1.0 mL) are dissolved in 2 mL DMF. A 0.45 mM solution of HBTU/HOBt in DMF (3.0 mL) is added to the reaction mixture at room temperature and the reaction mixture is stirred overnight. The reaction mixture is concentrated on a rotary evaporator and then diluted with EtOAc (50 mL) and washed well with water (2×50 mL), 10% citric acid (2×50 mL), water, brine, and dried over anhydrous MgSO4. The EtOAc solution is concentrated in vacuum to provide 0.53 g of a fluffy white solid. Retention Time: 8.10 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI no (M+H)+ observed. The white solid was subjected to TFA (100%, 10 mL) in a 50 mL round bottom flask at room temperature and the solution stirred for 1 h. The solution is concentrated in vacuum to provide a dark yellow oil (0.42 g). This crude product is purified by RP-HPLC (C18, 10-90%) acetonitrile/0.1% TFA gradient, 30 min). Clean fractions are pooled to provide compound 1, the title compound. Retention Time: 5.66 min (RP-HPLC, C18, 10-90%) acetonitrile/0.1% TFA gradient, 10 min); MS: ESI 542.4 (M+H)+.
The following compounds are prepared by methods anagfoalanaloaous to those described herein utilizing analogous starting materials: Compound Structure Example Number
|Compound Structure
|Example Number
|Example 1 MS ESI 542.4 (M + H)+
|Example 2 MS ESI 375.4 (M + H)+
|Example 3 MS ESI 389.4 (M + H)+
|Example 4 MS ESI 403.4 (M + H)+
|Example 5 MS ESI 355.4 (M + H)+
|Example 6 MS ESI 439.4 (M + H)+
|Example 7 MS ESI 417.6 (M + H)+
|Example 8 MS ESI 417.6 (M + H)+
|Example 9 MS ESI 403.2 (M + H)+
|Example 10 MS ESI 479.3 (M + H)+
|Example 11 MS ESI 433.1 (M + H)+
|Example 12 MS ESI 640.2 (M + H)+
|Example 13 MS ESI 401.6 (M + H)+
|Example 14 MS ESI 415.5 (M + H)+
|Example 15 MS ESI 478.4 (M + H)+
|Example 16 MS ESI 533.6 (M + H)+
|Example 17 MS ESI 509.5 (M + H)+
|Example 18 MS ESI 419.3 (M + H)+
|Example 19 MS ESI 537.2 (M + H)+
|Example 20 MS ESI 514.3 (M + H)+
|Example 21 MS ESI 387.3 (M + H)+
|Example 22 MS ESI 442.7 (M + H)+
|Example 23 MS ESI 508.7 (M + H)+
|Example 24 MS ESI 429.4 (M + H)+
|Example 25 MS ESI 604.7 (M + H)+
|Example 26 MS ESI 404.3 (M + H)+
|Example 27 MS ESI 417.6 (M + H)+
|Example 28 MS ESI 409.6 (M + H)+
|Example 29 MS ESI 507.6 (M + H)+
|Example 30 MS ESI 435.2 (M + H)+
In order to measure the ability of the inventive compounds to bind the BIR3 peptide binding pocket, a solution phase assay on the FMAT technology platform is utilized. Biotinylated Smac 7-mer peptide (AVPIAQK, lysine ε-amino group is biotinylated) is immobilized on streptavidin coated beads. GST-BIR3 fusion protein is precipitated with FMAT beads and is detected using fluorescent tagged anti-GST antibodies. Importantly, non-biotinylated Smac peptide is highly effective at competing GST-BIR3 off the FMAT beads (FIG. 2). The IC50 for non-biotinylated Smac is 400 nM. The IC50 values of compounds listed in Table 1 in the described FMAT assay ranged from 0.045-10 μM.


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Rare offering of this stunning home overlooking the Hudson River, just minutes to West Point. On one acre and located in desirable Cragston, Village of Highland Falls, this stylish and professionally updated and decorated ranch offers spectacular river and mountain views. Bright, open floor plan, fabulous kitchen with Big Chill custom color stove, gorgeous bathrooms. Some of the high-end finishes that make this a unique beauty include Ipe wood on the deck, Hardie board siding, Caesarstone quartz countertops and Baldwin door hardware; no expense was spared in the renovation. Finishable walkout basement with full bath. A wonderful, spacious yard is perfect to enjoy and the rock outcroppings provide a unique opportunity for the gardener in you. Gorgeous river views in every season. Minutes to Village conveniences, new kayak launch in Ft. Montgomery, Bear Mountain and Storm King. Hike on the old JP Morgan bridal path just below the house. An easy commute to NYC. Simply a must see.
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The first pictures are out and social media is buzzing with it. The Bhavnanis and Padukones got together for the darshan and later posed for photo-op too. Dressed in traditional wear, the fam jam looked picture perfect.
Deepika looked ethereal in a red banarasi saree with traditional jewellery and sindoor while Ranveer kept it subtle this time in a golden kurta-churidar with an embroidered jacket completing his look.
The duo got married last year at the picturesque Lake Como in Italy. Their marriage solemnised as per Konkani and Sindhi rituals on November 14 and 15 respectively.
They hosted a grand reception for relatives and friends in Bangalore and another lavish one for B-Town stars in Mumbai.
On the work front, both will be seen together in Kabir Khan's '83. Ranveer Singh plays legendary player Kapil Dev in the sports drama and Dippy will be seen as his wife Romi.


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'Cyber snipers' : Snowden uncovers truth on US digital war plans
According to documents leaked by Snowden and released by der Spiegel magazine, America is gearing up for digital war
The NSA's mass surveillance is just the beginning. Edward Snowden's documents show that the intelligence agency is arming America for future digital wars — a struggle for control of the Internet that is already well underway.
Video By RT
Niamh Harris
Writer at Your News Wire
Latest posts by Niamh Harris (see all)
- Former CIA Director John Brennan Lied To Congress About Steele Dossier - December 10, 2019
- Israel Threatens Iran With Its 'Own Vietnam In Syria' - December 9, 2019
- Members Of Satanic Temple Slam American Airlines For Forcing Woman to change 'Hail Satan' Shirt - December 8, 2019


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Isaiah 43:16-19 King James Version (KJV)
16 Thus saith the Lord, which maketh a way in the sea, and a path in the mighty waters;
17 Which bringeth forth the chariot and horse, the army and the power; they shall lie down together, they shall not rise: they are extinct, they are quenched as tow.
18 Remember ye not the former things, neither consider the things of old.
19 Behold, I will do a new thing; now it shall spring forth; shall ye not know it? I will even make a way in the wilderness, and rivers in the desert.
You'll get this book and many others when you join Bible Gateway Plus. Learn more


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The Woodland Tennis Club is a non-profit organization founded in 1937. It was reactivated after the demise of Country Oaks Racquet Club in 2006. See About Us for more information about the club.
Interested in joining the Woodland Tennis Club?
Membership Information
Events & Social Calendar
Meeting Minutes
WTC mailing Address
Woodland Tennis Club
P.O. Box 2283
Woodland, CA 95776
E-mail address
WTC events are held at:
Quick Links
City Park Court calendar is at the bottom of this page.
Coming event - December 13th, Holiday Party with tennis at 5:45 pm.
Turkey Tennis Social
The Tennis Turkeys were out on the courts to celebrate the upcoming holiday and play some tennis on a beautiful Saturday morning. Eighteen players formed three teams – the Gobblers, the Turkey Trotters and the Opponent Stuffers (each team selected it's own name and captain!) and played a round robin of men's, women's and mixed doubles. It was a tough competition. More info...
"The Cello International Tennis Academy (CITA) offers a tennis training program here in Woodland where WTC members can sharpen their game. Tennis professional Sunny Mallinson will be teaching the classes. For more information, visit citawoodlandtennis.com
Adult group classes are held
Tuesdays 8:00 PM - 9:00 PM
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Private lessons are also available upon request. "
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Recent Posts
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Category Archives: Disorient
DUB Interview and Live mix with deejaysoul
Reposting a video interview I did for Dope Underground Beats, with Cristina DiGiacomo (http://behindthedecks.org/) and Mustapha Louafi (http://housespinners.com). Thank you guys for your hard work and keeping the scene alive! Episode 9: Deejaysoul (ADG/Disorient/DTF Radio). Start your weekend right, an … Continue reading
06/30/10, deejaysoul @ Figment NYC- Governor's Island, Hosted by Disorient
Some footage of me dropping some Deep, Soulful and Afro House a few years back on Governor's Island for the Disorient Crew. Francisco 'Don Cerati' Sanchez is in the back doing live percussion.
deejaysoul- 06/10/11, Live at Figment, Deep vs Techno Mix
Posted in Afro House, Deep, Disorient, DJ Set, House, Minimal Techno, MP3 Download, Progessive, Soulful, Tech House, Techno, Tribal Tagged MP3 Download
Im DJing at Figment NYC '11 on Governor's Island this Friday!
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Pornjstar @ Rebel NYC
Its just some raw footage from my camera from Pornjstar, if the footage looks blurry blame it on your monitor.
Posted in Disorient, DJ Set, House, Tech House
My Macbook Pornjed
So this is what the back of my Macbook Pro looks like after this weekends Pornj Star. I brought a Pornjstar patch and found a Disorient Burning Man sticker in the dj booth. Kinda disappointed I wasnt able to get … Continue reading
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|Original title
|Anne of Green Gables: A New Beginning
|Drama, Family
|UK Release Date
|Production year
|Production Country
|Kevin Sullivan
|Barbara Hershey, Rachel Blanchard, Shirley MacLaine, Ron Lea, Bernard Behrens, Hannah Endicott-Douglas, Natalie Radford
Anne, now a middle-aged woman, is troubled by recent events in her life. Her husband, Gilbert, has been killed overseas as a medical doctor during World War II. Her two daughters are pre-occupied with their own young families and her adopted son Dominic has yet to return from the war. When a long-hidden secret is discovered under the floorboards at Green Gables, Anne retreats into her memories to relive her troubled early years prior to arriving as an orphan at Green Gables and being adopted by the Cuthberts


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Follow the directions on the installation program screen. How is the Gold Competency Level Attained? DriverGuide maintains an extensive archive of Windows drivers available for free download. Our goal is to make the ARK family of tools a valuable resource for you. The information herein is provided "as-is" and Intel does not make any representations or warranties whatsoever regarding accuracy of the information, nor on the product features, availability, functionality, or compatibility of the products listed. Disconnect the device from your computer. Please submit your comments, questions, or suggestions here.
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Risk Factors for Dysphagia and the Impact on Outcome After Spontaneous Subarachnoid Hemorrhage
AbstractBackgroundDespite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH) and its contribution to hospital complications, length of intensive care unit stay, and functional outcome.MethodsThis is a retrospective analysis of an ongoing prospective cohort study. Swallowing ability was assessed in consecutive non-traumatic SAH patients admitted to our neurological intensive care unit using the Bogenhausen Dysphagia Score (BODS). A BODS > 2 points indicated dysphagia. Functional outcome was assessed 3 months after the SAH using the modified Rankin Scale with a score > 2 defined as poor functional outcome.ResultsTwo-hundred and fifty consecutive SAH patients comprising all clinical severity grades with a median age of 57 years (interquartile range 47–67) were eligible for analysis. Dysphagia was diagnosed in 86 patients (34.4%). Factors independently associated with the development of dysphagia were poor clinical grade on admission (Hunt&Hess grades 4 –5), SAH-associated parenchymal hematoma, hydrocephalus, detection of an aneurysm, and prolonged mechanical ventilation (> 48 h). Dysphagia was independently associated with a higher rate of pneumonia (OR = 4.32, 95% CI = 2.35–7.93), blood stream infection (OR = 4.3, 95% CI =&thinsp...
Source: Neurocritical Care - Category: Neurology Source Type: research
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Authors: Guo L, Chen B, Zhang L, Deng Y, Li H, Shi QD Abstract A 49-year-old female patient developed chest tightness and shortness of breath without apparent cause and presented to a local hospital. Chest radiography indicated increased thickening of the lung texture, increased multiple patchy densities in the lower lobes of the bilateral lungs and a slightly enlarged thyroid. The patient was treated for pulmonary infection with antibiotics but the symptoms persisted. A repeated CT scan revealed ground-glass attenuation of the bilateral lungs with multiple flaky exudates and visible bronchogenic signs. The symptom...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Changes in plasma volume before and after major abdominal surgery following stroke volume variation-guided fluid therapy: a randomized controlled trial.
Authors: Lee YH, Jang HW, Park CH, An SM, Lee EK, Choi BM, Noh GJ Abstract BACKGROUND: The aim of intraoperative fluid therapy is to avoid both hypovolemia and hypervolemia; however, the patient's exact volume status is difficult to determine during surgery. Fluid optimization guided by stroke volume variation (SVV) has been widely used in patients undergoing major open abdominal surgery. The aim of this study was to evaluate the changes in plasma volume before and after surgery following SVV-guided fluid therapy. METHODS: Patients were randomly allocated into one of two groups according to the SVV criteria for...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
Bilateral lung parenchymal involvement is seen in infective as well as noninfective conditions, appearing as focal or diffuse lung disease. PET/CT with FDG helps in characterization (increased glucose utilization is seen by both inflammatory and neoplastic cells). In this article, we describe the spectrum of patterns of FDG uptake and associated CT changes involving bilateral lung parenchyma. Benign conditions described are aspiration pneumonia; pulmonary toxicity by bleomycin; infections, namely, sarcoidosis, miliary pulmonary tuberculosis, and pulmonary nocardiosis; and inflammatory conditions such as pulmonary Langerhan...
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
Cardiac Transplantation Using Hearts with Transient Dysfunction: Role of Takotsubo Like Phenotype Running Head: Takotsubo Like Syndrome in Donor Hearts
ConclusionsIn the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE; but this was not associated with adverse post-transplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs.Graphical abstract
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
In this study, we evaluate whether thrombocytopenia following CPB is an independent risk factor for post-operative morbidity and mortality.MethodsWe retrospectively evaluated 1,364 patients requiring CPB at University of Colorado Hospital between January 2011 and May 2016. Platelet nadir, absolute change in platelets, and percent change in platelets were modeled as continuous variables. Patients with post-operative thrombocytopenia (defined a nadir
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Adakveo and Oxbryta could be revolutionary treatments, but each costs about $100,000 per year and must be taken for life.
Source: NYT Health - Category: Consumer Health News Authors: Gina Kolata Tags: Drugs (Pharmaceuticals) Health Insurance and Managed Care Sickle Cell Anemia Prices (Fares, Fees and Rates) Stroke Clinical Trials Hemoglobin Food and Drug Administration Novartis AG Global Blood Therapeutics Source Type: news
CONCLUSION: During the last century, AADRs among males declined more slowly than among females. Although the gap diminished in recent decades, exploration of social and behavioral factors may inform interventions that could further reduce death rates among males. PMID: 31804898 [PubMed - as supplied by publisher]
Source: Public Health Reports - Category: International Medicine & Public Health Tags: Public Health Rep Source Type: research
Authors: de Montalembert M, Tshilolo L, Allali S Abstract As more children are appropriately being diagnosed, the burden of sickle cell disease is increasing greatly in Africa and in high-resource countries such as the United States and Europe. Early management is mandatory, but newborn screening is not implemented everywhere. Point-of-care testing devices are increasingly being used in low-resource countries, showing good sensitivity and specificity. Because the diagnosis is often traumatic for the families, the announcement should be made by an experienced person. The development of care networks is urgently requ...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Cohen AT, Hunt BJ Abstract The direct oral anticoagulants (DOACs) have transformed the management of thrombotic disorders. Large clinical trials have demonstrated that DOACs can replace vitamin K antagonists (VKAs) in the 2 existing major indications for anticoagulation: the prevention of stroke in atrial fibrillation and the acute treatment and secondary prevention of venous thromboembolism (VTE); this literature is widely known. In this article, we will concentrate on the less well-discussed benefits of the use of DOACs-using low doses as primary and secondary prophylaxis in both venous and arterial thro...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
More News: Brain | Hemorrhagic Stroke | Hydrocephalus | Intensive Care | Ischemic Stroke | Neurology | Pneumonia | Stroke | Study | Subarachnoid Hemorrhage


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0041841 Cloth Hall Ypres
0041841 Cloth Hall Ypres
Ypres, Belgium. The imposing Cloth Hall seen through the arch of the Menin Gate was built in the 13th century and was one of the largest commercial buildings of the Middle Ages. The structure which stands today is the exact copy of the original medieval building which was destroyed in World War 1 and rebuilt after the war.
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Information and Communication Technology
Pipeline Safety Market 2019 Demand Analysis By Top Key Players Like RCP Inc., Nuka Research & Planning Group, LLC., Schneider Electric, Siemens, ABB, BAE Systems.
A new research study from "Data Bridge Market Research" with title Pipeline Safety Market Insights 2019, Global Analysis and Forecast to 2026…Read More »
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Global Botanical Extracts Market Booming at high CAGR of 9.1 % by 2026 with Top Key Players Research And Report
Global Botanical Extracts Market is segmented into, By Source (Spices, Herbs, Tea leaves, Flowers), By Application (Functional Food & Supplements,…Read More »
Global Protein Assays Market Will Reach at a Highest CAGR of 11.00% by 2026
Global protein assays market is estimated to reach USD 3.74 billion by 2026, registering a CAGR of 11.0% in the…Read More »
Chemical and Materials
Global Automotive Foam Market 2019: Strategic Assessment, Latest Innovations, Drivers, Restraints, Challenges to 2026
Data Bridge Market Research has recently added a concise research on Global Automotive Foam Market to depict valuable insights related to significant…Read More »
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Global Hematology Analyzers and Reagents Market at A Highest CAGR of 6.93 % to rapidly growing $ 6078.21 billion by 2027
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Commercial Seaweeds Market Continues Rapid Growth, Study Reveals Market Size for Emerging Segments
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Smart Building Market Witness Massive Growth | Schneider Electric, Cisco Systems, Inc., International Business Machines Corporation, Delta Controls, Johnson Controls, Honeywell International
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It was on Jan. 27 that SF9's DaWon was having a V-Live section with fans.
The idol showed the password of the wifi of the FNC building in the live broadcast to fans, FANTASY.
He said to fans if you used all your data just come in front of our building and use the wifi.
Later on, a fan mentioned that she/he captured the wifi. Then DaWon said no need to capture, just ask me to show you. I will show it to you again.
Online, fans are wondering why the V-Live broadcast was still not re-uploaded yet. Some fans are thinking that it might be because of this "leaked" incident.
fnc hasn't uploaded dawon's vlive yet vnfjdk perhaps he shouldn't have shared their wifi password to the whole world pic.twitter.com/dyGVAB2ure
— joana ♡'s sanghyuk (@staysbinnie) January 28, 2019
FANTASY cannot help but find the incident hilarious and adorable. DaWon is very sweet to fans.
SF9 will comeback in February.
Do you find the event adorable and funny too?
Read More : 3 SF9 Members That Caught The Attention Of Korean Media And Non-Fans In Korea
Dawon always be himself
he is so cute!!! i want to bring him to america
Dawon is hilarious


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I had this idea, that I could use the CSS gradient background to display the ratings of a restaurant. The results might be more interesting, than useful, but it certainly has some pros as well. At the end, it may look something like this:
In this example the rating can be set from 0 to 5 with 1/100 increments (or smaller I guess, if that makes sense). Looks the best though if I don't go beyond 0.5 increments as otherwise it's not really a pixel perfect solution.
Not much to explain here. This structure allows me to label the content for screen readers while hiding the Unicode characters. Those are useless and/or confusing unless you can actually see them

❤❤❤❤❤
I'm yet to fully understand how exactly the CSS gradient background works when you add multiple stops. Not gonna lie, I've played around a bit with the values to reach a satisfying state. Originally I tried with color values
#f22, #f22 ${fill}%, #000 20%, #000 80%, but if I used a rating less than 1 (<20% fill) it started to show gradient in the first character. That 20% was suspicious and changing it to what you see here, with the black values set to
#000 1%, #000 99%, it works as I want it. The background is clipped to the text and the text I made opaque with rgba. The text shadow adds a little 3D feeling to the whole.
.rating {
font-size: 2em;
background: linear-gradient(to right, #f22, #f22 20%, #000 1%, #000 99%);
background-clip: text;
-webkit-background-clip: text;
color: rgba(0,0,0,0);
text-shadow: 2px 2px 2px rgba(0,0,0,0.2);
As this example uses a 0-5 rating, the data-rating value is multiplied by 20 to reach a 0-100% fill. Obviously, for a 0-10 option change the multiplier to 10. I also add an aria-label with the details for screen readers. I was thinking about reusing one of the ARIA range role (the range itself is an abstract role), but none seem to really match and I was afraid it may cause confusing. Otherwise a subclass of range, with the min/current/max value might be a good choice. The last line of code was necessary, because to be honest, this solution is quite fragile. If a whitespace is added somewhere, for example because of the structuring of the HTML elements, it will mess the gradient up. To fix that, either got to make sure there is no whitespace or like I did, remove it from JS.
.forEach((element) => {
const value = element.getAttribute('data-rating')
const fill = value * 20;
element.style.backgroundImage =
`linear-gradient(to right, #f22, #f22 ${fill}%, #000 1%, #000 99%)`;
element.setAttribute('aria-label', 'Rating: ' + value + ' of 5');
element.innerHTML = element.innerHTML.replace(/\s/gm, '');
Further ideas
- change the gradient color based on the rating
- add styling option, e.g. add a data-color to the HTML elements and use it from the JS
- add transition effect, for example on the background-size
If you want to play around with the code, I've added it to CodePen:
See the Pen Gradient rate by Gabor S. (@seabadger) on CodePen.
Add control
I've also created a small code snippet to get you started if you want to create a control (slider). You can check out the code here:
See the Pen Gradient rate control by Gabor S. (@seabadger) on CodePen.
Tagged with css css gradient frontend javascript rating star rating


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Thinking about installing Solar PV in Dallow?
Did you know that Solar PV can:
- Save Thousands On Your Electricity Bill!
- Save & Earn Up To £30,000 From Energy Generated!
- Get free Electricity For a Minimum Of 20 Years!
- Add Value to Your Property!
- Reduce Your Reliance On The National Gird!
- Fit The latest Solar panels & Battery Technology!
- No Leasing Of Your Roof Space!
There could also be funding accessible for solar PV in your Dallow. If you'd like to learn more about the incentives, grants & funding available then contact us today for a free no-obligation quote.
Solar PV are becoming more widely accepted across the UK and people are starting to accept them as a means of earning money and preserving our planet. Advances in the efficiency of solar PV and the installation of them mean that they are a lot less intrusive and can make you more money in a shorter amount of time compared to older PV.
Solar PV Installers Dallow
Green Power Technology install solar PV in Dallow, we can also provide a number of funding options to reduce the cost of installing solar PV. We have access to unique discounts only available through Green Power Technology.
MCS authorised Solar PV installers Dallow
Green Power Technology only use MCS accredited solar installers to undertake installation work.
Want to find air source heat pump installers in Dallow?
Look no further, our fully certified air source heat pump installers can finish your installation to the highest of standards.
What are the gains of installing an air source heat pump?
- Save money heating your home
- Get paid between £875 - £1030 per year in RHI payments
- Help the world
- Cut carbon emissions
- No fuel storage is needed
- Free Heating when used with solar panels
Air Source Heat Pump Prices
The average price for an heat pump usually varies from £7,000-£11,000 nonetheless there are some other conditions to contemplate that could acquire added costs.
Double Glazing
Quality Double Glazing Installers Dallow
Finding superior Double Glazinginstallers can be a struggle, Green Power Technology only engage immensely experienced installers double glazing how it should be installed. All installers must endure an comprehensive vetting procedure to make sure they meet the standards we would expect in our own humble abode.
Each UPVC window installer must be authorised with a trade association and have the correct insurance to be able to carry out the work. Comprehensive guarantees of a minimum must be in place before we will even consider using them to install UPVC windows.
Dallow, North Yorkshire,England is a Hamlet that lies in the Yorkshire and the Humber region. It has a local government of Harrogate District and the postcode sector it can be found in is HG4 3.


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|Expertise in Back Pain:
|Jeffrey M. Spivak
Mon Nov 4 19:19:42 2019
|Expertise Level
Fewer than 5 articles on "Back Pain" What is this?Expertscape's algorithms degrade at low publication numbers. Thus, with only 4 published articles on Back Pain from 2009 through 2019, it is not possible for Expertscape to reliably rate Jeffrey M. Spivak's expertise on this topic.
Longer horizontal black lines means more people have that level of expertise.
|Spivak, Jeffrey M · Spivak, Jeffrey
|Work Locations
|Specific Interests
In the titles of their published articles, experts often reveal their very specific interests.
Here are the titles of all articles written by Jeffrey M. Spivak in 2009-2019 about Back Pain:
|Google Searches
Learn more about Jeffrey M. Spivak using the ready-made Google searches below.
|Affiliation Timeline
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|You can save this page -- like a bookmark -- so it's remembered for you on the Expertscape "Saved Pages" page, which is always easily available from the page-top menu bar throughout the site.


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Annesley Junior School
Annesley Junior School was established in 1902 as a day and boarding school for girls from Kindergarten to Year 12. The Vision of the School is nurturing creativity and curiosity in young learners to build resilient and empathetic global citizens ready for now and beyond. It is a caring community, committed to genuine partnership with families. Annesley nurtures the curious young learners to grow into self-assured, resilient and empathetic children ready for life beyond their primary years.
The School delivers high quality inquiry-based learning within a Christian environment for girls and boys. It has a rich heritage, distinct focus on teaching values and a future focused on innovation. The dedicated team has a clear focus on creating the best outcomes for the students, which includes their total wellbeing and learning from Early Years to Primary Years. Annesley empowers every student to become active and aware global citizens by instilling a passion for life-long learning as part of a distinctive value-based education.
To find out more about the information shown here – read about How we collect and display course information. IDP assumes no responsibility or liability for any errors or omissions in the content of this site. We always recommend that you speak to an IDP counsellor to get the latest and most accurate advice.
Melbourne Christmas BBQ PartyJoin us for a free BBQ lunch to celebrate the end of semester and Christmas! Bring your friends along, enjoy delicious BBQ, play board games and shoot some hoops for a chance to win free movie tickets!*IDP Melbourne office - 373 Lonsdale StMelbourne, AustraliaAU14th Dec 201912:00 PM - 02:00 PMMore info
Free study and migration visa seminar - AdelaideAre you interested in studying, living or working in Australia? Join the free study and migration visa seminar and receive expert assistant, support and visa advice from IDP's in-house registered migration agent.IDP Adelaide office - 16 Grenfell StAdelaide, AustraliaAU17th Dec 201905:30 PM - 06:30 PMMore info
Migration Monday - MelbourneAre you interested in studying, living or working in Australia? Join this seminar to receive expert assistance and visa advice from licensed migration agents.IDP Melbourne office - 373 Lonsdale StMelbourne, AustraliaAU23rd Dec 201905:30 PM - 06:30 PMMore info


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Are you interested in finding a comfortable ? If yes, then you've visited the right page. From the article, we've got curated the listing of dining seat for you. We have selected the different kind of comfortable chair. Some of them are made of timber, while others are of vinyl. Their legs are sturdy and don't wobbles. The dining area is the best place to discuss family matters. Check this out Top 10 Best Toilet Safety Frames & Rails at 2019 All the individual family sit together and can have hours of discussion on various issues. How are you going to feel within 30 minutes of discussion, if there's a pain in your back or hip? You start feeling uneasy. However, no have to stress, in this guide we have given the list of best comfy for you. So let's begin.
|Table Of Content
List of Top 10 Leather Sectionals
Where to find
This RTA loveseat offers different types of upholstery depending on the materials. That significantly incorporates linen and velvet. Advanced shades, Marzipan, Stoneware-Light tan and Rye-Dark brown improve the style of the sofa. Select the shading and the materials that depends around the stylistic style of your room. Not only the shading, the material may also mirror the difference in fashion. Ensure that the fabric you choose fits the theme of your room. This loveseat ballots in favor of combining the current style with an exemplary style. It's been increased by the hands that start to pass through the couch. With this mix, you only witness enhanced comfort and tasteful design when lighting the patches.
This luxurious set of city-stylish sofas is made to provide an embellished domain. Actually, even your modest rooms might have you required to have an perfect film evening. Place him lower to get a totally altered mattress. This auparavant-garde person futon mattress is accessible in various tones. This incorporates some vibrant tones out of control such as Orange, Light Blue, and Light Crimson. Put them in your inventive studies or loft to evaluate the exuberance. It is also available in decreasing tones for example dark, dark and dark. These nuances, once more, printing an honorable aspect of the higher course. With the splitting component of your back, you are able to rest for your favorite position. This sofa looks rich with tufted material texture upholstery. The good thing is that it's customized with hypoallergenic filling. A definitive outcome supplies a comfortable rest.
This set comes with the complete power of Sleeper Couch by having an excellent sofa design. It includes tight hands, firm seat soft cushions and full-size sleeping pad with inner comes. It is eliminated underneath to clean it and take away it with a easy lifting instrument. This sleeping pad is strengthened having a durable steel advantage. is really a calculating guideline and it has a Bi-falling apart emphasize. One of the deserving things to point out may be the consolation! Place this super comfortable couch inside your comfortable family room. Apart from providing an all natural and stylish air, it provides an attractive personality for your visitors. You may make your buddies stay for any fun nights movies. The couch has carcasses with obstructed edges and faux-completing on its legs. The cushions are, however, modified and can include excellent versatility. It's wrapped having a thick polyethylene dietary fiber with a drawstring edge.
This couch is worked with the bell-shaped shape along with the higher armrest from the cushioning. In addition, the top is based on blocked corner sides. The thighs, however, have joined the fake wood wrapping. The sofa gives a comfy and lavish feeling. This is the immediate result of extremely versatile padding within the polyester furniture. You are able to sit down effortlessly for the moment to relax. Each one of the tones provided with this sofa demonstrates its noteworthy component, Flexible design. The red sculpt would be well suited for each subjects with light and darkish tones. That continues to be constant for different tones that it provides as well. The couch is situated in space. Whether or not its Thanksgiving or a huge family reunion, you can trust it. Race-watching yet still time collapsing on your sofa together with your friends is really a legitimate option.
This luxurious set of city-stylish couches is created to supply an embellished site. Actually, even your moderate rooms may have you obliged to have an perfect film night. Place him lower to get a completely changed mattress. This avant-garde sleeper futon mattress is accessible in various tones. This incorporates some vibrant shades out of control for example Lemon, Mild Blue, and lightweight Purple. Put them inside your innovative research or loft to evaluate the exuberance. It is also available in lowering shades for example dark, dark and darkish. These subtleties, once again, print a respectable aspect of the upper class. Using the splitting element of your back, you are able to rest for your preferred posture. This sofa looks wealthy with tufted fabric texture furniture. Fortunately that it's personalized with hypo-allergenic filling. A definitive result provides a comfortable relaxation.
You cant talk about this couch with out referring to its impressive style, sturdiness, and luxury. Should you ever needed an appropriate chair, then transfer fast and get yourself Rollercoaster Samuel Selection Lotion Leather-based Sofa. You'll like it. This 3 seater couch has clean lines and excellent cushions. The cushions are attached to the seat and behind. It is made of leather which is a sure bet that its durable. It also functions tufted back and chairs that definitely adds to its remarkable appear. More importantly, it features a springtime foundation that provides the necessary comfort and durability. Its wood body causes it to be very durable. The long and also the lacking it is this fact sofa is remarkable in every element. You might or might not accept this. But the only method you are able to understand why is to find and check out it.
Does your room show room needs? Are you willing to toss a slumber party in the light of the lack of space to rest? This DHP Futon mattress could be well suited for you in cases like this. This Futon sofa by DHP includes the functionality of a couch bed with a modern and stylish look. Put it inside your family room to achieve an extra sleepy mattress at night. A microfiber ground that took off in the middle would be a ideal combination. This unique sofa accompanies a tapestry with shiny stainless hair and legs. Bringing together these outcomes with each other inside a comfy popular style couch. You can choose to get it in Faux Leather, Purple velvet or Linen. A component that is really worth specifying is its back style. Considering the various seats, DHP encourages the progres from the couch for your comfort levels. You are able to gain levels to have an computer animated babble, or silent moving image evening.
This luxurious set of urban-chic couches is created to provide an embellished domain. Actually, even your moderate areas may have you required for an perfect movie evening. Lay him lower to obtain a completely changed bed. This auparavant-garde sleeper futon mattress is obtainable in various tones. This incorporates some bright shades out of control for example Orange, Mild Azure, and lightweight Purple. Place them inside your inventive studies or loft to evaluate the exuberance. It's also accessible in lowering shades such as darkish, dark and dark. These subtleties, once more, print an honorable part of the higher class. With the breaking component of your back, you can rest for your preferred posture. This couch looks rich with tufted fabric texture upholstery. Fortunately that it's customized with hypo-allergenic filling. A definitive outcome supplies a comfy relaxation.
With nearly 100 5-celebrity evaluations, this lying loveseat is touted because of its comfort and ease, sturdiness, appearance and easy set up. Along with soft, but supportive cushions, it features a gliding system, so you can place your feet up and rock (though, not at the same time.) Padded with ultra-long lasting bonded leather-based, this lying loveseat will resist holes, rips and stainswhich is a good thing, because it also includes a storage area console (where one can conceal your snacks, obviously) and a two-mug holder. Regardless of whether you are deciding in for a Blockbuster online excessive or watching soccer with your crew, this lying loveseat offers the durability and comfort without breaking the bank.
This couch is appreciated for its unique style and luxury. Its impressive pazazz-equip sofa with seats provides you with optimum room for stretching and using your living space. So usually the modern couch chaise adds to the beauty of this set. The established includes cushion top hands cushioned back and seats for maximum comfort and ease. The couch also includes a corner-blocked wood body that provides the sofa enough sturdiness. The sofa steps 89 inches wide x 62 in . in depth by 4 in . tall making it suitable for moderate dimension areas. You may need to do small putting together eg of the thighs.
You might think you could get the exact same quality of furniture in your Big Box stores but that is not the case. The quality of these brands only can't seen in outlets that are generic and rather should be sourced from smaller specialty shops that know their product inside and outside. To put it differently, you do not find high-end clothing & apparel in JC Penny. {You would have to really go to Dolce & Gabanna or Neiman Marcus for this.
Be sure you boost the appears of the family room by adding these superb cup a coffee table. They are the best cup coffee tables on the market having a sturdy construction and stylish styles. The furniture are extremely examined and suggested. Go correct forward and select one which best fits your taste with full confidence.


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Tonal Animal-Print Jacquard Genie Jumpsuit
Current selected color: Black Animal Print
Size: Please select
Qty: 1
Product Details
Stand out in a sea of gowns in MSK's sparkling jacquard jumpsuit, designed for the chic stylista who plays by her own fashion rules.
- Approx. model height is 5'10" and she is wearing a size medium
- Approx. inseam: 22-1/2"
- Wide leg with asymmetrical flutter hem
- V-neck; side zipper with hook-and-eye closure
- Allover tonal animal-print jacquard; velvet lattice strap detail at back
- Embellished straps
- IMPORTANT NOTE: This item arrives with a return tag attached and instructions for removal. Once the tag is removed from the dress, this item cannot be returned.
- Polyester; lattice: polyester/spandex
- Hand wash
- Imported
- Web ID: 10226291
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