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Comparing Costs of Siding | Remodeling Library
There are lots of ways to calculate the cost of siding materials. You should consider the cost of the life of the siding, the initial investment in materials and labor, maintenance costs down the road, as well as the impact a specific material will have on the resale value of your home. Is it a type that most buyers will find attractive? All aspects deserve consideration.
While siding costs vary widely from product to product, including grades of product (high-end to low-end), you'll find a rough price comparison on siding material costs below.
To get pricing on a siding project in your area.
In general, the life of cedar siding, for instance, is shorter than those of aluminum and vinyl siding, as well as brick or stone, which outlast all other materials by many, many years. So, even though the initial expense of cedar siding might look great compared to the price of vinyl, the upkeep it requires will make it more expensive in the long run. On the other hand, cedar siding is a better insulator than vinyl or aluminum, and will keep your utility bills down in the summer and winter months. As you can see, there's more to 'cost' than meets the eye.
Of all the siding
available in today's market, vinyl leads the way; installed, it
remains the least expensive siding material. Warranties are another
key point; most vinyl manufacturers offer a lifetime warranty that
can also be transferred to the next owner, thus creating a great
value and a great investment. Estimate costs run from $2 to $3 per
square foot.
Fiber Cement
Competitively priced,
generally costing slightly more than vinyl siding. Estimate costs run
to per square foot.
Cedar runs between .5
Plywood siding
Paint grade wood siding
can run between to less per square foot than hardwood
Aluminum siding
Aluminum siding runs
between to $5 per foot.
Brick and stone veneer
siding will run between $11 to $15 per square foot.
Real brick runs between
$6 to $12 per square foot however; replacing brick is much
more expensive and runs around $18 + per square foot.
Stone siding
Natural stone is priced
between $15 to $30 per square foot.
Stucco siding
Stucco pricing falls
between $4 to $9 per square foot. Sand and cement stucco is
less expensive, latex stucco is more expensive.
Wood Shingles and shake siding
Pricing for shingles
and shake siding run between $5.12 and $7.40 per square foot.
Slate shingles have a
long life span of 75+ years, they defy extreme heat and cold, and the
Source: www.calfinder.com
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Question re installation of kitchen window
We have a 40"x24" window in our kitchen and as part of a kitchen remodel, are planning on replacing it with a 48" wide window.
What are some of the factors that should be considered when it comes to the selection of the window? The exterior is siding.Also, any thoughts on what it would cost?
Shown below are some images of the existing window.
Related posts:
- Installing Wood Siding on Brick
- Installing metal siding trim
- Installing wood siding Video
- Installation of Vinyl siding
- Cedar Impressions Siding cost
I have 30 yr. old shiplap on my detached garage and would like to try to replace it with hardiplank....but I don't have much carpentry experience.
As a professional it is not difficult however, it is very dusty and definitely not a one person job. Start with installing your 5/4 boards on the corners of the house. Then make sure your bottom board (the first one you …edge of the first board. I would make it 7" long and that will let you maintain the same space between each row. Set the next course on the top (the bottom of the "T") and nail. Keep going until your done.
The beam supports one side of a patio roof (17x17) that is made of shiplap sheathing covered with fiberglass shingles.
You need to go to a steel beam supplier and take the following information with you. They can determine the size you'd need. First take a picture of it underside and outside of the porch. They will need to know how long …br />
The 1st responder suggested talking to an architectural engineer. No such thing. There are architecs that design and engineers that calculate loads.
Hope this helps and isn't too confusing.
Anyone know how to or know of a website that explains how to make a board-on-board fence. I want to avoid having those 1-2 inch spaces between the fences after the boards shrink in a normal fence
Use 'shiplap' boards (they have a half inch rabbit on both sides).
When you place them, they will overlap a half inch on both sides and the overlap will accommodate shrinkage.
paint or stain …ge does not show a raw wood seam.
Do not fasten at each edge, as shrinkage will then tend to split a board.
If you use 6 inch boards, use 2 fasteners about an inch and a half from each edge.


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Hello. My name is Ed Goodwin
I am a professional male Holistic Therapist, based in Weston-super-Mare. All you have to do is sit back and relax!
I am a fully trained and qualified practitioner with the following Holistic Therapy and body treatment qualifications:
I am fully insured and am a Member of the Guild of Beauty Therapists, Member of the Guild of Holistic Therapists and a Member of the Federation of Holistic Therapists.
I take a holistic approach to my treatments, i.e., I try to take the whole person into consideration, such as the lifestyle and the emotional well-being of my client, as there can be many factors that contribute to physical discomfort.
When treating a client I feel it is very important that they feel comfortable to communicate what they want from the session as this is their time. For example, the client may need a meditative deeply relaxing massage, wishing for silence throughout. It is important for me to receive feedback throughout and I try to create a comfortable environment so that the client will get the most out of the treatment.
Ready to find out more?
You can contact me using the contact form and I'll get back to you as soon as I can.

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Introducing the Developers
by Jairus Elarbee, Matthew Hall, Gordon Purcell on July 11th, 2016
So from time to time, I'm going to feature the writings and works of my fellow developers on the Endless project here on the blog, so I thought it time we presented the full team. With each person is a quick bio written by the person in question.
Jairus Elarbee is an Athens based game developer with B. S. in Physics from Georgia College and State University. He enjoys tinkering with systems, learning about the world, and fixing sources of inefficiency. For these reasons Jairus seeks to study engineering as a profession to put these characteristics to use improving the world. Among his hobbies are ballroom and swing dancing, as well as playing and designing strategy and role playing games.
The second is one of my closest friends, Matthew Hall, who has had the core ideas around which our game is based. He's been making games his whole life, but our time working together goes back to high school.
Matthew Hall is a writer and game developer with a B.A. in English from the University of Georgia. All of his fiction and games take place in the same universe, called the Worldring, which has expanded slowly with time to include a vast host of colorful characters and dynamic settings. Matthew is married to his high school sweetheart, and together he and his wife founded the Inklings of Athens, a group of fantasy and science fiction writers. Matthew is pursuing law as a vocation, and has an interest in logic puzzles, balance of power, and geopolitics. Making games is his way of bringing the two sides of his interests together. In the world of Endless, his flagship game, the fantastical factions of the Worldring are pitted against each other in a battle of wits, magic and occasionally, all out cosmic war.
The final one the introduce Gordon Purcell, another of my good friends. He's been a valuable partner towards the completion of the project, offering valuable input and motivation. Below is his bio in his own words.
Gordon Purcell is a graduate student studying modern Italian history at the University of Georgia. A newcomer to the Worldring mythos and Endless, he was captured shortly after meeting Matthew by the story and has helped Matthew and Jairus where he could ever since. Approaching tabletops and world building from a historical perspective, he injects a note of real-world flavor into the game. His favorite factions to play are Athens, The Awakeners, and Unitas.
So look forward to some contributions from them in the future. You can check the author on a post to find out who wrote any given article.
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Skiing / Snowboarding – Current conditions
Klínovec ski resort resort is the largest ski centre in the Ore Mountains, with a lift capacity of 9 450 people per hour. It is located just 120 km northwest of Prague in close proximity to the border with Germany and the Oberwiesenthal resort. It usually has exceptional snow conditions throughout the season on 12 km of various difficulty pistes of 35 ha area, 80% covered by snow guns.
Source: http://zima.klinovec.cz
The ski centre has undergone significant modernisation and many new features await skiers and snowboarders. Last season, a modern four-seater CineStar Express chairlift with an orange bubble cover went into operation. This is followed this year by the SUZUKI cable car, which replaces the T-bar on the Přemostěná piste. It is a four-seater chairlift with magic carpet which can carry up to 2400 people per hour. Our snowmaking system has also been boosted.
Our successful cross-border co-operation with Oberwiesenthal ski resort continues to operate this year. The Fichtelberg – Klínovec ski region provides 27 km of pistes at every level of difficulty, with passes available from two days up.
You can find 4 chairlifts and 6 surface lifts at Klínovec. There is also a snowpark with many jumps and obstacles, plus 30 km of prepared cross-country skiing trails. And we haven't left out the kids, who can have fun and are looked after in the children's ski park with free ski lift. Families will appreciate our wide selection of family tickets.
A car park for 900 vehicles is provided free of charge.
New for season 2014/2015
Buy you all season ski pass and you can use it in 14 ski areas in the CZECH REPUBLIC!
NEW 3 km long trail - JÁCHYMOVSKÁ
Already this season!
|Opening hours
|Snow type
|750 -1244 m
|GPS co-ordinates
|50.4061, 12.9710
Source: http://www.holidayinfo.cz
Apartment Elan
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Terraced house Dynafit
size: 2 stocks


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March 20, 2018
Ask the Doctors – Could marijuana ease my chronic back pain?
Dear Doctor: I try not to use opioids for my chronic back pain, but I'm finding myself turning to them more often. Could marijuana help? Dear Reader: Pain is one of most difficult aspects of medicine to understand. No one can actually feel the pain of another person, but we can see the suffering that […]
Tags: anti inflamatory, cbd, Chronic Pain, codeine, decrease inflammation, Dr. Robert Ashley, hydrocodone, immune system, marijuana, morphine, muscle spasms, opioids


text: BioMichelle has been drawing since she was a small child with her artist father, Tommy Thompson, as her favorite teacher. She has worked with many mediums over the years, but oil is her favorite. At the encouragement of her father she took a plein air workshop with Jason Saunders. Since that first workshop she attended she has had the honor of attending classes and workshops with Roger Dale Brown, Jeremy Doss, Casey Baugh, Linda St. Clair, Calvin Liang, Qiang Huang, Jim Himsworth, Kevin Menck, Dawn Whitelaw, Dennis Perrin, and Erin Martin. Michelle has a B.S. in graphic design from The University of North Alabama.


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With the latest campus goings-on, local news and global current affairs, Concourse has got you covered.
What are students from across campus saying on the latest news and current affairs.
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From BUCS to Varsity we have all the latest on how Team Keele are doing
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Concourse is Keele University's independent student-run publication and has a long history of promoting student journalism. Having been established in 1964, Concourse has become an important part of the university and has been read by generations of Keelites.


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He's been a massive difference to how we approach games.Just shows how important it is to have a centre half who's comfortable on the ball in there.With jags and Williams everything comes back to Pickford and the midfield is bypassed.
When we beat Liverpool next week it'll be the biggest turnaround in opinion on one of our managers ever.
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SCHOOL OF ROCK! - Tickets are NOW on sale!
Posted by SEJ - Monday 19 November 2018
The Drama and Music Department are excited to announce that tickets for 'School of Rock' are now on sale at reception.
Running from Wednesday 12th December until Friday 14th December 2018. Tickets are priced at £3.00 for students/concessions and £5.00 for adults.
We appreciate your support and hope to see you there!


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Mutation and overexpression of receptor tyrosine kinases or the proteins they regulate serve as oncogenic drivers in diverse cancers. To better understand receptor tyrosine kinase signaling and its link to oncogenesis, we used protein microarrays to systematically and quantitatively measure interactions between virtually every SH2 or PTB domain encoded in the human genome and all known sites of tyrosine phosphorylation on 40 receptor tyrosine kinases and on most of the SH2 and PTB domain-containing adaptor proteins. We found that adaptor proteins, like RTKs, have many high affinity bindings sites for other adaptor proteins. In addition, proteins that drive cancer, including both receptors and adaptor proteins, tend to be much more highly interconnected via networks of SH2 and PTB domain-mediated interactions than nononcogenic proteins. Our results suggest that network topological properties such as connectivity can be used to prioritize new drug targets in this well-studied family of signaling proteins.
Receptor Tyrosine Kinase (RTK)1 signaling networks evolved in Metazoans to process extracellular cues and elicit cellular responses such as differentiation, proliferation or migration. Canonical RTK signaling is initiated when a ligand binds to the extracellular domain of its cognate receptor, inducing receptor dimerization, activation of the intracellular tyrosine kinase domain, and auto-phosphorylation of intracellular tyrosine residues (1). These phosphotyrosine (pTyr) residues then serve as recruitment sites for one or more of the ∼120 SH2 domains (2) and 44 PTB domains (3) encoded in the human genome. Upon recruitment, many adaptor proteins bearing SH2 and PTB domains themselves become phosphorylated on tyrosine residues by active receptor or cytosolic tyrosine kinases. This second set of phosphorylation events leads to the recruitment of additional SH2 and PTB domain-containing proteins (1). For example, the binding of GRB2 to pTyr427 of SHC1 (or pTyr317 in the p52 SHC1 isoform) induces activation of the RAS/MAPK kinase cascade (4). Similarly, binding of phosphatidylinositol 3-kinase (PI3KR1, p85) to pTyr612 of IRS1 initiates signaling through the PI3K/AKT cascade in cells exposed to insulin or insulin-like growth factors (5).
RTKs share a similar set of interactors and activate many of the same response pathways, including RAS/MAPK and PI3K/AKT cascades (1). They do not, however, necessarily elicit the same phenotypes. For example, both EGFR and NTRK1 induce MAPK signaling in PC12 cells, but EGFR triggers proliferation whereas NTRK1 promotes differentiation. Both of these phenotypes are dependent on ERK activity (6). This phenomenon is also observed clinically, where only a subset of RTKs have been shown to drive cancer despite sharing many downstream pathways (7). Current qualitative representations of signaling networks as linear cascades are inadequate to explain the diverse phenotypes that arise downstream of different RTKs.
Aberrant signal processing by RTK networks has been causally linked to cancer development, maintenance, and progression in many human tissues. Well-studied examples include overexpression of ERBB2 in breast cancer (8), KIT in testicular germ cell tumors (9), and MET in gastric cancer (10). Constitutive activating mutations of RTKs, such as those observed in the RET kinase (11, 12) in multiple endocrine neoplasia type 2 or KIT in gastrointestinal stromal tumors (13) are also capable of driving oncogenesis. Similarly, mutation or overexpression of SH2 domain-containing cytosolic proteins such as ABL kinase (14) or the PI3K p85 regulatory subunit (15) can also drive cancer, in these cases by inducing constitutive enzymatic activity that is decoupled from upstream signaling events.
Recently, Barabási and colleagues advanced a mathematical argument that network driver nodes, the nodes that control information flow in a network, should not be highly interconnected (16). If this notion is extended to cancer, in which signaling networks are substantially altered or rewired, we would expect that proteins driving oncogenesis would not be highly interconnected. We sought to determine experimentally if there is indeed a link between network connectivity and the propensity of a protein to drive cancer. In making this determination, we cannot rely solely on literature-derived interaction networks (17, 18) as they are confounded by study bias (19, 20). Specifically, oncogenic proteins are more intensively studied than nononcogenic proteins, potentially resulting in a bias in terms of number of binding partners. As a means to collect systematic pTyr-mediated interaction data, in vivo methods like the yeast two-hybrid system are not suitable as they do not allow for control over post-translational modification events (21). Systematic co-immunoprecipitation coupled with mass spectrometry is also problematic, as many interactions mediated by tyrosine phosphorylation are transient, with half lives on the order of seconds, and any particular cell type expresses only a subset of the proteome (22). Previous systematic research on the binding specificity of SH2/PTB domains has therefore been performed using phosphorylated peptides and in vitro binding assays. For example, pioneering studies of this type involving peptide libraries uncovered consensus binding motifs for a variety of SH2 and PTB domains (23⇓–25). It is now apparent, however, that these motifs are simplified views of in vivo selectivity and that specificity is also defined by "anti-motifs" representing excluded contacts for SH2 domains (26), SH3 domains (27), and probably other modular interaction domains as well. As a consequence, it is very difficult to predict accurately whether an SH2 or PTB domain will bind to a particular sequence known to be phosphorylated in vivo.
To overcome these limitations, it is necessary to test interactions between binding domains and peptides bearing physiological sequences one at a time and in a noncompetitive setting. To perform such assays in an unbiased, high-throughput, and quantitative manner, we used protein domain microarrays (28). In brief, 134 purified recombinant SH2 and PTB domains were printed as microarrays in individual wells of 96-well microtiter plates. The arrays were then probed with fluorescently labeled phosphopeptides derived from known sites of tyrosine phosphorylation on human proteins. By probing the arrays with eight different concentrations of each peptide, full saturation binding curves were obtained, providing an estimate of the equilibrium dissociation constant for each biochemical interaction. Our previous work using this assay focused on nine RTKs: FGFR1, IGF1R, MET, NTRK2, PDGFRβ (29) and the four ErbB receptors (3, 30). In these studies, we found that the arrays correctly identify most previously reported interactions (3). In addition, they invariably highlight new interactions, many of which we validated biologically: they occur in nonengineered cells and play important roles in signal transduction (3, 30), (31⇓–33). We now use this approach to systematically quantify, on a nearly proteome-wide level, interactions between SH2 or PTB domains and known sites of tyrosine phosphorylation on both human RTKs and the adaptor proteins themselves. We find a very high degree of connectivity that challenges conventional, linear views of receptor-adapter interaction. Moreover, RTKs and adaptor proteins that have been shown to play a causal role in cancer tend to mediate substantially more interactions than those that do not. This suggests that these connectivity profiles may provide insight into how networks are rewired and may help prioritize new targets for anti-cancer drug discovery.
A detailed protocol for preparing protein domain microarrays has been described previously (28).
Determining Interaction Affinity
Following peptide binding, arrays were scanned at multiple PMT voltages on a Tecan LS400 microarray scanner on both Cy5 and Cy3 channels. Spots with saturated pixels were eliminated. The remaining spots were fit to a line that allows for the conversion of all the Cy3 values measured at different PMT voltages to the same scale. The fold-over-background value of a titration was determined by taking the trimmed mean of the Cy3 values for each domain-peptide titration divided by the Cy3 values of the Thioredoxin control spots. The mean Cy3 value of the Thioredoxin control spots was then subtracted from the Cy3 value of the domain spot and the spots were normalized by the Cy5 value.
Each domain was printed in quadruplicate in each well and the arrays were probed using eight different concentrations of each peptide, ranging from 5 μm down to 10 nm. These 32 data points were then fit to the following equation using MATLAB®'s robust fit function with bisquare weights: where Fobs is the mean fluorescence of replicate spots, Fmax is the fluorescence at saturation, [Peptide] is the total concentration of phosphopeptide, and KD is the equilibrium dissociation constant. Robust fitting procedures are more resistant to the presence of outlier data resulting from missed spots, fluorescent debris or other aberrations (34). Only titrations with fold-over-background values in the top 10% of the data and R2 values over 0.9 were kept. Replicate affinities were then averaged in log space. The MATLAB® code used to perform the analysis is supplied in supplementary information.
Determining Oncogene Status
Oncogene status for RTKs was determined using the Sanger Institute Cancer Gene Census (7, 35). The Sanger list contains only those genes for which a strong causal link to cancer has been established. Because many SH2/PTB domain-containing proteins have no catalytic activity of their own, they serve principally to amplify and propagate signals from upstream proteins. For this reason, adaptors were assigned as having a role in cancer by their presence in a union of the Sanger list and other cancer gene lists (36⇓–38) compiled by the Bushman lab (http://microb230.med.upenn.edu/links/genelist).
Statistical Tests for Enrichment of Binding
To test against the null hypothesis that the distribution of connectivity is equivalent for both Oncogene and non-Oncogene classes, we performed the nonparametric Mann-Whitney U test in MATLAB® R2011a (The MathWorks, Inc., Natick, MA). Only those interactions with dissociation constants below 1 μm were considered.
RTK and Adaptor Expression in Tumor Samples
cBio Cancer Genomics Data Server Matlab Toolbox v1.04 was used to retrieve mRNA sequencing data corresponding to 1437 tumors from breast cancer, colon, and rectal adenocarcinoma (39) and clear cell kidney cancer collected by The Cancer Genome Atlas Network. We used a 1 read per kilobase of exon model per million mapped reads (RPKM) threshold to separate genes which are expressed. This threshold has been shown to correspond to 1 transcript per C2C12 cell (40) and optimizes overlap with mass spectrometry results in HeLa cells (41). We consider this to be an upper bound estimate to the total number of potential interaction partners.
Data Collection
We started by compiling a list of known sites of tyrosine phosphorylation on human RTKs and on all SH2 and PTB domain-containing proteins listed in the PhosphoSitePlus database (42). We restricted our studies to experimentally verified sites of tyrosine phosphorylation as nonphysiologically relevant sites, when artificially phosphorylated, may also bind SH2/PTB domains (43) and thereby confound any systems level conclusions drawn from the resulting data. We focused on 40 of the 53 Uniprot-annotated RTKs that had more than three phosphorylation sites to include only those receptors whose biology is sufficiently understood to enable systematic comparison. This resulted in a total of 729 unique phosphopeptides that we successfully synthesized, fluorescently labeled, and purified using high performance liquid chromatography (supplemental Table S1). We then used each of the peptides to probe microarrays comprising virtually every human SH2 and PTB domain (supplemental Table S2). The arrays were probed at eight concentrations of each peptide, ranging from 10 nm to 5 μm (see, for example, Fig. 1A). By repeating this process for each phosphopeptide we were able to generate a quantitative interaction map for the receptor (Fig. 1B). This process was repeated for all of the remaining RTKs to generate, for the first time, a global, systematic, and unbiased view of RTK recruitment (Fig. 1C). Larger versions of the connectivity diagrams for each RTK are available in supplemental Fig. S1. Only interactions with KD < 1 μm are included in these diagrams. SH2 domain-mediated interactions of lower affinity have been shown to be physiologically relevant intramolecularly, but it is generally accepted that most bona fide intermolecular interactions exhibit dissociation constants below 1 μm (44⇓–46).
As with any assay, one invariably encounters false positives and false negatives. With protein domain microarrays, the most frequent source of false positives is nonspecific binding between peptide and domain, whereas false negatives likely arise from low surface activity of the domains, presumably because some domains denature on the slide surface or are preferentially immobilized in a way that blocks access to the binding site. To estimate the stochastic false positive rate, we conservatively assumed that domains having the lowest frequency of binding were actually inactive in our assay and exhibited no true-positive interactions (any interactions identified for these domains are by definition false positives). We observed that domains in the bottom 20% of the binding frequency spectrum accounted for 20 interactions out of the 37,490 titrations performed on the domains, corresponding to a stochastic false positive rate of 5.33 × 10−4. If we extend this rate to all the titrations performed (195,546), we estimate that 104 of the 2808 interactions we identified are liable to be stochastic false positives (false discovery rate of 3.72%). As there is no reason to believe that false positive errors are observed preferentially with phosphopeptides derived from cancer-causing proteins, the primary conclusions of this study are not affected.
Another potential limitation of our approach is that the current list of physiological sites of tyrosine phosphorylation in PhosphoSitePlus may be incomplete. This would be particularly problematic if nononcogenic RTKs were less well annotated than oncogenic ones. To investigate this possibility, we used phosphotyrosine-directed mass spectrometry (30) to study six nononcogenic members of the Ephrin class of RTKs - EphA2, EphA3, EphA4, EphB2, EphB3, and EphB4. We overexpressed each receptor in HEK293T cells, a procedure that induced receptor auto-activation and phosphorylation in all six cases. Receptors were then immunoprecipitated using an anti-pTyr antibody and subjected to targeted and untargeted μLC-MS/MS. Using this approach, we were able to identify 32 out of the 38 known sites of intracellular tyrosine phosphorylation (84% sensitivity). Remarkably, we did not identify any sites of tyrosine phosphorylation beyond those already reported in the PhosphoSitePlus database (supplemental Table S4). This suggests that the many high throughput, pTyr-directed mass spectrometric studies that have been used to populate PhosphoSitePlus are not biased against nononcogenic receptors and that the existing list of tyrosine phosphorylation events, at least on RTKs, is nearly complete.
Oncogenic RTKs are Highly Connected
By examining the connectivity profile of the 40 RTKs at various affinity thresholds (Fig. 2A), we sought to identify whether a link exists between connectivity and oncogenicity. We determined whether or not an RTK is an oncogene based on its inclusion in the Sanger Institute's Cancer Gene Census (7) (http://www.sanger.ac.uk/genetics/CGP/Census/), which seeks to determine a strict causal (and not merely correlative) relationship between cancer development and mutation and/or overexpression of a given gene. Based on these assignments, we found that oncogenic RTKs have a significantly higher median connectivity in our interaction data set than nononcogenic RTKs. At an affinity threshold of 1 μm, for example, the median number of binding partners is 21 for nononcogenic RTKs and 56 for oncogenic receptors, corresponding to a ∼2.5-fold difference in the number of interactions (Mann-Whitney U test p = 2.77 × 10−5). Nononcogenic RTKs also have a median of six phosphorylation sites, whereas oncogenic RTKs have nine phosphorylation sites (Mann-Whitney U test p = 0.007), corresponding to a 50% increase. This indicates that the primary reason for the increased connectivity of oncogenic RTKs is the presence of more promiscuous pTyr docking sites and only secondarily an increase in the number of docking sites. For instance, the nononcogenic receptor CSF1R, although it has twice as many phosphorylation sites as NTRK3 (8 versus 4), has far fewer high-affinity (KD<1 μm) binding partners (6 versus 58). In addition, the RTK with the greatest number of phosphorylation sites in our study is the nononcogenic ERBB4 with 16. ERBB4 has only 18 binding partners, however, which places it in the bottom 25% of the RTKs we studied.
Many interactions annotated here may be of too low affinity to bind at appreciable levels to a receptor that is present at low surface density or at a low level of activation. When a cell becomes malignant, however, gene amplification or overexpression may make phosphorylated receptors (or adaptors) sufficiently abundant that low affinity interactions are enabled and downstream signaling activated. This notion is supported by the observation, in PC12 cells, that EGFR mediates proliferation when present at normal levels but differentiation when overexpressed (6). These phenomena cannot be captured in qualitative diagrams of signaling and highlight the need to think of these interactions as being contextually conditional and existing on a quantitative spectrum without a single fixed threshold.
Adaptor-Adaptor Binding
Focusing only on the initial recruitment of adaptors to RTKs provides an incomplete view of the full complexity of early RTK signaling. Adaptors can themselves become tyrosine phosphorylated and interact with each other, forming multi-protein complexes at the receptor. By systematically probing our SH2/PTB domain microarrays with phosphopeptides derived from 334 known pTyr sites on adaptor proteins, we identified a dense network of interactions among the adaptor proteins themselves (Fig. 3A). For example, the well-studied tyrosine kinase ABL1, which is responsible for driving the development of chronic myeloid leukemia when fused with the protein BCR, is currently annotated to mediate 15 interactions through its SH2 domain (47). In our study, we identified 53 biochemical binding partners, including known interactions with DAB1, ERBB2, PTK2, and SHC1 (47). Our data may also resolve some outstanding questions in the field. For example, it has previously been reported that the Vav1 SH2 domain binds to a phosphorylation site on BCR/ABL and that this interaction is critical for activation of Rac-1 and BCR/ABL-mediated leukemogenesis. Previous attempts to identify the site of binding by constructing a series of Tyr to Phe mutants, focusing in particular on the Vav1 consensus binding motif, were unsuccessful (48). Our data reveal an interaction between Vav1 and pTyr917 of BCR/ABL (Uniprot id: A9UF07), which was not included in the earlier mutagenesis experiments.
RTK-mediated activation of the MAPK pathway is well studied (49, 50), but we nevertheless find many new interactions that impinge on this pathway. RTKs vary in their ability to recruit early signaling proteins in this pathway, such as SHC1, GRB2, and PTPN11. Here, we find that these adaptors have the potential to interact with many other signaling proteins as well, increasing the complexity of MAPK pathway activation (Fig. 3D). This view aligns well with the idea that RTKs function not as discrete molecular machines, as typically depicted, but as pleomorphic ensembles that are highly complex and dynamic with many rapidly interchanging states (22, 51).
Oncogenic Adaptors are Highly Connected
To probe the relationship between connectivity and oncogenicity in the adaptor-adaptor layer of binding, we organized domains by sequence similarity (Fig. 4A) (52). The blue bars indicate how many peptides bind to each domain (in-links) and the green bars show how many binding partners interact with phosphorylation sites on the corresponding protein (out-links). Simple inspection reveals a wide range of binding promiscuity within the SH2 and PTB domain families. For example, proteins in the SRC, HCK, and PI3K N-terminal families of domains have relatively high numbers of binding partners and are frequently annotated as oncogenes. When we sort the domains by the number of in-links and out-links, from least to most connected, it is clear that oncogenic proteins (red) are preferentially enriched among proteins with high in-connectivity (median 20 versus 8 in-links, Mann-Whitney U test p = 3.4 × 10−3), high out-connectivity (median 9 versus 1 out-links, Mann-Whitney U test p = 1.0 × 10−4), or both (Fig. 4B). Because the adaptors are likely to amplify signals downstream of RTKs, especially those without intrinsic catalytic activity themselves, we used an expanded definition of oncogene that incorporates additional cancer gene lists as well as the Sanger list (see Methods).
The quantitative interaction data generated in this study (supplemental Table S3) should prove generally useful in the fields of network modeling (53) and interaction prediction (54). With the caveat that our data necessarily include false positives and false negatives, we also hope that the novel interactions identified in these studies will aid efforts to uncover signaling pathways downstream of RTKs. To facilitate the use of our data, the supplementary information for this paper contains the annotated interaction list (supplemental Table S3) and raw microarray image intensities as well as the MATLAB® scripts used to fit the titration curves, perform statistical analyses, and generate figures (Supplementary Code).
Our work shows that the genes whose mutation or overexpression drives cancer tend to be highly connected hubs. Moreover, the most highly connected proteins in our networks are the primary targets of new anticancer drugs (e.g. erlotonib for EGFR (55), lapatanib for ERBB2 (56), vandetanib for RET (57), sunitinib for KIT (58), and imatanib for ABL1 (14)). Analogously, viral proteins preferentially target hub proteins during infection (59, 60). This combined evidence suggests that disease states arise preferentially from the perturbation of network hubs and drugs should target these same hub proteins.
In conclusion, we have generated a systematic map covering a substantial fraction of the potential interactions between SH2 or PTB domains and sites of tyrosine phosphorylation on RTKs and adaptor proteins. These interactions are very poorly represented in existing unbiased human interactomes (61, 62) despite extensive evidence they play essential roles in signal transduction. We observe a high degree of connectivity among RTKs and adaptor proteins, and among adaptor proteins themselves. This is in contrast to the usual depiction of receptor-proximal signaling as a series of linear pathways connecting sites of tyrosine phosphorylation on RTKs to a few adaptor proteins and then to a few core signaling molecules such as ERK and AKT. Of course, the actual complexity of the resulting network in any particular cell type depends not only on the affinities of the interactions (as determined here) but also on the relative abundance of RTKs and SH2/PTB-containing proteins. mRNA sequencing data of 1430 diverse tumor types collected by the TCGA consortium shows that they express a median of 78% of the phosphotyrosine signaling proteins analyzed in this study. In fact, over half of these proteins are expressed ubiquitously (in >95% of the tumor samples; supplemental Fig. S2). Thus, it is highly likely that receptor and adaptor proteins combine to form a highly interconnected mesh with the potential to perform complex signal processing functions.
We thank Jeffrey Knott, Susan Rogers, and Colleen Hunter (Cell Signaling Technology Inc.) for peptide synthesis, Bogdan A. Budnick and William S. Lane (FAS Center for Systems Biology) for mass spectrometry, Vijay Warrier for Ephrin receptor cloning, Bryan H. Chang for STAT protein cloning and expression, Ethan S. Karp for help with MATLAB® scripting, Zeba Wunderlich for helpful discussions and Taran S. Gujral (Harvard Medical School) for commenting on the manuscript.
↵* This work was supported by an award from the W. M. Keck Foundation and by grants from the National Institutes of Health (R33 CA128726 and R01 GM072872). G.K. was the recipient of the AstraZeneca Graduate Fellowship and the Max Tishler Graduate Fellowship. A.K. was supported in part by the NIH Molecular, Cellular, and Chemical Biology Training Grant (5 T32 GM07598).
↵ This article contains supplemental Figs. S1 and S2 and Tables S1 to S4.
↵1 The abbreviations used are:
- receptor tyrosine kinase.
- Received November 19, 2012.
- © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
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Helios Eingya
Published Aug 01, 2006You put this album on, it ends. You put it on again, and it ends again. Where does it go? It just drifts by so effortlessly its easy to miss, gently pulsing in the background. Not to put it down, though this instrumental array of acoustic guitars and pianos on top of subtle, slight drum machines has some of the best melodies heard in these parts in some time. A one-man-band composed of Boston-based Keith Kenniff, seen elsewhere on Type as Goldmund, this has none of the self-indulgent staleness that plagues many solo productions. The reviewer concept of having to find something to slag falls short here the album is faultless. Since its "backgroundiness is inherently limiting in terms of commercial sales, hopefully somebody, anybody, will put this in a movie so it can get the exposure it deserves. (Productions Virage)


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West Valley Pediatrics
10750 W McDowell Rd Ste G700
Avondale, AZ 85392
Phone: (623) 873-0321
Fax: 623-849-9623
An online resource center providing you with additional helpful information.
View the KidsDoc Symptom Checker from HealthyChildren.org
At West Valley Pediatrics we and our friendly staff offer all aspects of pediatrics medical services:
What is a Pediatrician?
A pediatrician is a physician whose specific specialty is caring for children from birth to 18 years of age. Pediatricians address acute and chronic illnesses, learning disabilities, behavioral issues and the growth and development of children. Our goal is to help ensure that children grow into mentally and physical healthy, productive and happy adults.
Web Resources
West Valley Pediatrics
10750 W McDowell Rd. Ste G700
Avondale, AZ 85392
Questions or Comments?
We encourage you to contact us at
(623) 873-0321 for any questions.


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Are you taking care of yourself this season? Self-care doesn't mean selfish! Cozy sweaters and pumpkin spice lattes are fantastic, don't get us wrong, but wellness is where it's at. Here are some tips and tricks from the wellness experts in our spa to get you started:
1. Taste the season! From apples to squash to beets, fall is delicious – you can't go wrong with fresh and local fare…
2. Treat yourself! Take yourself to the spa, to the movies or anywhere else you want – bask in some well-deserved me time.
3. Clean out your closets, it's not just for spring! Organize your clothes, clean out your junk drawer, wash your windows or get your garden ready for spring. Accomplishing a task you've been meaning to do will feel great and motivate you to do even more.
4. Move it! Go on a bike ride with your family, join a new class or renew that expired gym membership and get your move on…
5. Wake up refreshed and ready to conquer the rest of the week! How? Try an early night: relax with a bath, put on your coziest jammies and get ready to feel fantastic in the morning.
6. Get grateful! Be thankful, give back and remember what's important in your life. Pick a charity, help a friend or start a gratitude journal: sometimes self-care is about your place in the world and how you can make a difference.
7. Give yourself a goal (or two)! Pick something that's a challenge but that's attainable and gets you fired up. Working for it will make achieving that goal so much sweeter.
For more wellness tips and tricks, visit our blog at: https://www.hockley.com/blog/


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We may look alike, but we sure don't think alike.2 Aug
5 Responses to "We may look alike, but we sure don't think alike."
Lifestormer August 2, 2011 at 6:46 pm #
I mostly agree what you say here. Let me start by saying that I am just waking up, so there is absolutely no thought going into what I'm about to say. In fact, this is a topic where I usually try to remain politic and keep my mouth shut. People are morons. What? Did I say that? It is very unlike me to make such a mean sounding generalizing statement like that. I guess I've just become jaded in my old age. I my old age, I have noticed a sad trend that, much to my dismay, people, as a group, are idiots. Politicians work in the best interest of corporations, so in order to maintain the position (and their kickbacks) and stay in office they have to make us, their constituents, be afraid of something or someone and they do that by creating an "out group" for us to fear. The keep split the classes getting rid of the middle class, they keep the lower class stupid and pregnant by cutting education, the arts and planned parenthood, and social services. They feed this growing group of fat stupid people McDonnalds and sugar, guns and Nascar, and a steady diet of hate spewed at them my Fox News. Then they say if the other side gets voted into office, they will take away there right to eat crap, tell them who they can have sex with, and take away their right to protect themselves with automatic weapons.Whoa! Sorry. Social political tirades are not my style. I'm annoyed at the state of our politics these days and frustrated at what is happening to the country I love so dearly. Maybe I'm just getting stodgy and stubborn now that I'm in my forties. Maybe this is the way that it has always been. Maybe misinformed political posturing is the way things are supposed to happen here in America, but I hope not.
Thank you for your feedback. To me it goes wat beyond politics. This way of thinking gets into peoples personal lives like at work or at the store. I wish people would have polite ways about themselves, but all these radio and "news" stations on T.V. do not help at all. Plus the " parents " of the furture adults teach this at home. Well Lifestormer. Thanks for reading my thoughts, and have a good day. 😉
Mojo Writin' August 2, 2011 at 9:09 pm #
People are people, the world over. Maybe, one perfect day, we'll all learn to get along, accept each other as we are. Until then we have to keep plugging away. One of the most important things to remember is that children learn by example. If we want the next generation to be more understanding, more accepting than ours, then we need to show our children the way by behaving how we would like the world to behave.Interesting post,Chad.


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Slingshot Kiteboarding
The Ultimate All-Around Boat Foilboarding Package
- Wakefoiler package
- Condition:
- New
The Ultimate All-Around Boat Foilboarding Package
Wakefoil WF2 / Futura FWake
- Board and Mounting Hardware
- Complete foil - 24" Mast, H2 front wing, 42cm rear wing, 610 fuselage, plate mount, Hardware, and wing covers
- Straps or half straps Optional
2019 Slingshot WF2 Foilboard
This board includes fin boxes for FCS II or FCS fins but when purchased a la carte does NOT include fins.
The Slingshot Wakefoiler WF.2 board is a welcome addition to our wakefoil board lineup. It has ample surface area for any rider to getup behind the boat while not being too large for performance maneuvers. It also happens to fit in most wakeboard boat racks, which makes leaves plenty of room on the boat for your admirers or "human ballast". For 2019, this is a new board and basically a soft top adaptation of the WF1 board that we love so much. That nice soft top is perfect for new riders, easy maintenance, and boat protection.
We have also found this board to be a popular choice for kiteboarders. Due to it's thin design, it board starts in a way more similar to twin-tip designs that most kiteboarders are familiar with. It also allows for easier strapless board starts since it sits lower in the water. This board has enough plane-ability to get novice riders foiling and perform in light winds with ease. The full length deck pad is also a nice touch for performing tricks in a variety of lift situations.
Board Dimensions: 4'10" x 20.5" x 1.45"
2018 Ride Engine Futura Foil (2019 FWake design)
Featured with the Gamma (H2) front wing which is now part of the 2019 Slingshot Fwake foil at a fraction of the price. This complete foil gives you a forgiving foil for taking your first flights and dropping the rope as well as making wake transfers, riding second/ third wake back, as well as adventure into surf foiling. Comes complete with a 24" mast to aid in your progression and safety. The H2 wing has exceptional stability, speed range, and ease of use making it one of our most versatile wings. Feel free to add a wing to adapt to any riding style, wake height, or rider weight.
Add a wing and totally change how your foil rides
H4 Originally $549 - Save $300 - Also known as the batwing, the H4 is a true joy to ride. It offers loads of stability and lift, as well as a smooth and agile attitude for pumping a wake or a wave.
Infinity 76 - Designed for surf hydrofoiling, the Infinity 76cm wing has great low speed lift for small waves, enough maneuverability to remain fun, and great top speed to keep your glide and beat the fastest sections with ease.
Infinity 84 - The Infinity 84cm front wing is a welcome wing to the Slingshot family for heavy surfers and downwind SUP riders. Featured with the larger 48cm rear wing in the Slingshot FSUP foil package, this wing packs a whopping 2066 square centimeters of surface area for maximum lift at low speeds and effortless glide.
Let's Chat: Learning How to Hydrofoil Surf
So you want to learn to hydrofoil surf? Congratulations! We too have caught the foil bug for all of our board sports. Surf foiling is truly a one of a kind experience that makes even the most marginal days into magical sessions. Aside from the silent, smooth, and effortless glide, surf hydrofoils tap into the most powerful part of the wave just beneath the surface. Read more...
1 Review
Best foilboard combo package
Followed Mack's recommendation on intro foilboarding package. This was awesome. Great price and in 3 sessions already riding on foil without any issues. Foil is easy to us and learn on. Just move your feet more forward than usual. The board is also covered with soft material to reduce any impact risk. Strongly recommend it.


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Torta de laranja
2 Table spoons fine Maize flour (Maizena corn flour)
5 Large free range eggs
2 Sweet juicy medium oranges
200g Granulated sugar
Butter for roulade tin
Icing sugar for decoration
1 lemon
1. Turn oven at 200 degrees Celsius.
2. Have a rectangle roulade tin (20 x 30cm) ready with greased bottom, add grease proof paper on top also greased with butter.
3. Blend eggs and sugar until smooth.
4. Add zest of 2 oranges, zest of 1 lemon, juice of 1 orange and Maize flour.
5. Blend all ingredients well then pour contents into a roulade tin.
6. Bake in the oven for 16 minutes at 200 degrees.
7. Remove from the oven and rest for 2 minutes.
8. Turn over roulade onto a sheet of grease proof paper dusted with sugar.
9. Pour juice of 1 orange evenly over the sponge rectangle.
10. Roll gently into a roulade shape.
11. Carefully place into a serving plate
12. Lightly dust with icing sugar.
13. Serve cold.
Pastéis de nata
(Custard Tarts)
7 egg yolks
250g caster sugar
4 tablespoons of corn flour
500ml cream
300ml milk
750 g ready rolled puff pastry
20 g Cinnamon
Lemon peel
1. Put the egg yolks, sugar and corn flour in a saucepan and whisk together.
2. Gradually whisk in the milk and the cream until smooth with cinnamon stick and lemon peel.
3. Place the pan over medium heat.
4. keep stirring until the mixture thickens and comes to the boil.
5. Remove from the heat and transfer the custard to a bowl to cool down.
6. Preheat the oven to 200degrees/gas 5.
7. Lightly grease a 24 holes 80ml muffin tin.
8. Cut the pastry sheet in half.
9. Sprinkle cinnamon powder on top and put one half on top of the other.
10. Roll up the pastry tightly from the short end and cut he pastry log into twelve 1 cm rounds.
11. Roll out each pastry until they're 10cm in diameter.
12. Press the pastry rounds into the muffin tin.
13. Remove the cinnamon stick and lemon from the custard.
14. Spoon the cooled custard into the pastry cases and bake for 25 minutes until the pastry and custard are golden.
15. Leave the tarts in the tins for 5 minutes then transfer to a wire rack to cool completely.
16. Sprinkle cinnamon powder on top for those who like it.
Bolo de Arroz
(Rice muffin)
Serves 8-10
Butter (softened), 100 gr
Sugar, 200 gr
Eggs, 2
Egg yolk, 1
Milk, 200 ml
Flour 200 gr
Rice flour, 200 gr
Baking powder, 1 envelope
Baking soda, a pinch of
Salt, a pinch of
Lemon zest (finely grated), from 1 lemon
Lemon juice, from 1/2 a lemon
Powder sugar, for dusting
For the self-made paper molds:
Baking paper
1. In a large bowl, mix the butter with the sugar until well blended.
2. In another bowl, mix the eggs and the egg yolk with the milk.
3. Mix all together (both previously prepared mixture). In another bowl sift together the flour, rice flour, baking powder, baking soda and salt.
4. Add to the liquid mixture the lemon zest and the lemon juice.
5. Mix the flour in the liquid mixture whisking until well blended. Pour the batter until half way the molds.
6. Let it rest for 10 minutes. In a previously preheated oven at 180°C bake the Bolo de Arroz for 20 to 25 minutes or until when pushing on the top them the bread feels sponge texture.
7. Dust with powder sugar.
For the molds:
1. First cut circles with the diameter of a peeled tomatoes tin (around), (18 circles in total).
2. Cover the complete tin with baking paper (enough for leaving an extra border on the side of 3cm (for the glue). Cut 9 from them.
3. Wrap the paper around the tin and glue it together with the mixture of flour and water (enough for making it sticky but not to hard for being a dough).
4. Set them aside and let it dry for around 1 hour.
5. Lift the paper mold up around 3cm and make for cuts in it so that it can be fold to the inside.
6. Lay one of the circles on top of the tin and add some glue on it, then fold the sides of the mold (previously cut) on top of the circle.
7. Brush this with some glue and cover it with another circle and let it dry for 1 hour.
8. After this time the molds are ready to be used.
(Sponge Cake)
9 large eggs (room temperature)
1 pinch salt
1 1/2 cups granulated sugar
1 2/3 cups all-purpose flour
1/4 teaspoon baking powder
icing sugar
1. Preheat the oven to 350°F Grease and parchment paper line a 10 inch tube pan, set aside.
2. Beat the eggs with the salt until light. Gradually beat in the sugar at medium speed and beat for at least 20 minutes, or until mixture is very thick.
3. In a separate bowl, stir the flour and baking powder together. At low speed, add the flour mixture to the eggs one heaping tablespoon at a time, blending well after each addition, and scraping down the sides of the bowl when necessary.
4. Pour the batter into the pan and bake for 40 minutes, or until a cake tester inserted comes out clean (cake will spring back to a light touch).
5. Let the cake cool in the pan for 10 minutes, then remove from pan and peel off parchment paper. Let cool completely on rack. Dust with icing sugar before serving if desired.
(Sweet Angel Hair)
250 g angel hair pasta
1 lemon (just the peeling)
1 1/2 liters milk
150 g sugar
1/2 cup water
100 g butter
1 1/2 teaspoons salt
2 cinnamon sticks
4 egg yolks
1. Boil the water, milk, salt, sugar, cinnamon stick, butter and the lemon peel.
2. Remove 1/2 cup of the above liquid, so you can very slowly beat in egg yolks, and set aside.
3. Add in your Angel Hair Pasta and bring to a boil, reduce heat and keep stirring at all times. If it looks like its getting to dry add in some mor hot milk.
4. Half way through your cooking add in the 1/2 cup of milk with the yolks that you had put aside, and stir untill it is cooked.
5. Pour everything into a platter and don't forget to remove the lemon peel and cinnamon stick.
6. Let it cool, then decorate with cinnamon powder to your liken before serving.
Arroz Doce
(Portuguese Sweet Rice)
2 cups water
1 cup white rice
2 cups hot milk (whole works best)
1 cup sugar
1 fresh lemon rind (use a vegetable peeler for big pieces for easier removal)
1. Bring water to a boil in medium saucepan.
2. Add rice and cover, simmering for 20 minutes.
3. Add milk, sugar and lemon rind, stirring constantly until thickened to oatmeal consistency, about 15-20 minutes.
4. It will also thicken some while cooling.
5. Pour into one large serving plate and remove lemon rind.
6. Spread flat and allow to cool on wire rack.
7. You can be decorative with cinnamon by pinching a bit between your fingers and place while your hand is no more than an inch away from the rice (criss cross patterns are traditional), or you can just dust the entire top with the cinnamon.
8. Serve at room temperature, but refrigerate uneaten portions.
Pudim caseiro
(Caramel Custard)
Serves 6
6 teaspoons soft brown sugar
1/2 cup sugar
6 eggs
3 3/4 cups milk
1 1/2 tablespoons coffee extract or 1 1/2 tablespoons strong coffee
1. Put a heaped teaspoon of brown sugar into 6 individual ramekins.
2. In a large bowl, beat sugar and eggs together until yellow and frothy.
3. Bring milk to boil, gradually add it to the egg mixture, beating constantly.
4. Add coffee essence.
5. Pour this mixture into ramekins, place in roasting pan.
6. Add enough water to come half way up the sides of the ramekins.
7. Bake in a moderate oven, 350 degrees until just set, about 45 minutes.
8. To test, stick a skewer into the custard, if it comes out clean, the custard is done.
9. Remove from oven and allow to cool
Salame de chocolate
(Chocolate salami)
200g butter cookies
100g powder chocolate
100g sugar
100g butter
1 egg
2 soup spoons of milk
Aluminum foil
1. Break all the cookies in very small pieces.
2. Mix very well the chocolate with the sugar, the egg, the melted butter and the milk. Add the cookies and mix until all the ingredients are very well mixed.
3. Cut 60cm of aluminum foil and straining it over a table.
4. Place the ingredients mixture on top of the aluminum foil in a way to make a coil in the center of the foil. Roll over the foil until it acquires cylindrical form. Press it very well with your hands.
5. To achieve a solid result put it 4 to 5 hours in the refrigerator.
6. Before serve cut it in slices with more or less 1,5cm width.


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At Saturday's IWAI Carrick-on-Shannon Branch AGM, it was announced that Denise Byrne will step forward as Commodore for the 2019 Shannon Boat Rally! Denise will be ably assisted from the Carrick side by Oisin Morgan as Vice-commodore.
Congratulations to the both of you – the 2019 SBR will not be one to be missed!


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Chief Winemaker - Chris Thomas
Chris Thomas has been involved with Dowie Doole since 2008 but officially became Chief Winemaker in 2011. Chris graduated in Oenology from the University of Adelaide in 2003 and has a wealth of experience working for top wineries including Fox Creek and Serafino Wines in McLaren Vale and also abroad with Domaine Changarnier in Burgundy, France.
As Chief and sole winemaker, Chris has worked closely with our founders to produce wines that encapsulate the spirit of McLaren Vale and nearby regions.
In 2015 Chris, along with other investors, bought the DOWIE DOOLE wine label and took on the role of Managing Director in addition to his Winemaking responsibilities. When he isn't crafting wines of exceptional quality, he travels the world spreading the DOWIE DOOLE story.
DOWIE DOOLE wines capture the essence of the vineyards in which they were grown and the vintage in which they have been produced - and in the case of the single vineyard wines - an expression of each vineyards individuality.
It is this sense of place – encapsulated in a bottle that has earned DOWIE DOOLE a reputation for crafting regionally distinctive wines. Put simply… our winemaking starts in the vineyard.
Chief Winemaker Chris Thomas works closely with the viticultural team to ensure the consistent quality of the fruit that goes into each and every bottle of DOWIE DOOLE wine. Once harvested, the grapes are hand crafted into premium wines with minimal intervention.


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Discoverorg CONNECTOR – MICROSOFT™ DYNAMICS EDITION
Get to decision makers faster with DiscoverOrg Connector – Microsoft Dynamics Edition. Let data drive your outreach and prioritize your day by pulling in the most accurate, robust B2B intelligence available right into Microsoft Dynamics. This powerful connector eliminates data entry — giving you more time to sell and market effectively using fresher, deeper data from DiscoverOrg.


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Please join us for the 2019 Blue & Gold Banquet.
Friday, February 22, 2019
Time: 6:30 PM – Dinner followed by the ceremony.
Cost: There is no charge to attend, but please RSVP so that we have an appropriate count for dinner.
Please RVSP by February 18, 2019.
Registration is now CLOSED


text: Here comes the official trailer of the upcoming tamil film titled Jagajaala Killadi, a rural comedy film with Vishnu Vishal and Nivetha Pethuraj in the lead roles directed by Ezhil and with music composed by D. Imman. Star-cast : Vishnu Vishal, Nivetha Pethuraj , Radha Ravi, Yogi Babu, Mottai Rajendran, R.Sundararajan, Singam Puli, Manobala, Vaiyapuri, Ravi Mariya, Nalini Music : D. Imman DOP : K.G. Venkatesh Art : M. Prabhakaran Edit : Gopi Krishna Choreography : Brindha, Dinesh, Dina Lyrics : Yugabharathi Stunts : Fire Karthik Story & Dialogues : Murugan – Jothi Producer : R.G. Dushyanth , Abhirami Dushyanth PRO : Diamond Babu Banner : Eshan Productions.


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Recent Posts
Tag Archives: cayenne
Mexican Hot Chocolate Snickerdoodles (Vegan)
Posted on April 27, 2011 by melbelle13
I'm telling you, this whole vegan baking thing has had me quite enraptured. Everyone expects a vegan label to automatically imply "faux something" or lacking of flavor. I have tried a handleful of vegan baked goods, and while they are different … Continue reading →
Posted in Cookies, Vegan | Tagged cayenne, chewy cookie, chocolate, cookies, snickerdoodles, vegan


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Dangerous Ecstasy Alert
A recent alert from Avon and Somerset Police warns of ecstasy tablets which have been found to contain a substance called n-ethylpentylone. This is a "novel psychoactive substance" (or "designer drug") from the cathinone family, which also includes "bath salts". It is known to cause circulation problems, lethal heart palpitations and hallucinations, and has been linked to a number of overdose deaths and mass-casualty incidents in Australia and New Zealand. It is also significantly more potent than MDMA which increases the risk of overdose.
The tablets that were tested on this occasion were brown with the Mitsubishi symbol, but it would be reasonable to expect that these are not the only pills cut with n-ethylpentylone. If you choose to use ecstasy or MDMA, please be cautious – start at a very low dose, and monitor how it is affecting you before considering taking more. Ideally, stay with someone who has not taken drugs so they can seek help if you need it. If you start experiencing adverse effects seek medical attention immediately.
Deaths linked to Xanax
There has been recent media coverage of the risks associated with using Xanax (the brand name for the benzodiazepine medication, alprazolam).
Xanax linked to more than 200 deaths
Please note that these figures refer to deaths related to Xanax rather than deaths by Xanax overdose (i.e. Xanax may be one of several drugs used in a death by overdose, or may have contributed to mental health problems that led to self-harm or suicide).
- If you are a regular user of Xanax (or any other benzodiazepine, such as Valium) please seek medical advice, particularly if you are planning to reduce or stop.
- Suddenly stopping benzodiazepines following an period of use can result in withdrawal symptoms, which can be very dangerous and fatal.
- Where possible, avoid mixing it with other drugs/alcohol as the effects can be dangerous and unpredictable.
- If you are struggling with your emotional health, please be aware that Xanax use is likely to contribute to any feelings of low mood or anxiety you may be having. Seek support from your GP or mental health service, and if you feel unable to keep yourself safe please remember that you are within your rights to access emergency treatment via 999 or A&E. You may also wish to consider speaking to the Samaritans.
Information for Cocaine and Crack users:
Over 90% of recently tested Cocaine and Crack now contain Levamisole.
What is it?
Most current commercial preparations of Levamisole are intended for veterinary use as a dewormer in cattle, pigs, and sheep. Its also used by aquarists as an effective treatment for Camallanus roundworm infestations in freshwater tropical fish.
What is the potential harm?
One of the more serious side effects of levamisole is agranulocytosis, or the depletion of the white blood cells. In particular, neutrophils appear to be affected the most.
There have also been reports of levamisole induced necrosis syndrome in which erythematous painful papules can appear almost anywhere on skin.
This adverse effect has been observed in several cocaine users in the South Gloucestershire area. It appears some people are more susceptible to it than others, but the mechanism behind this is unclear.
Why is it used?
- Something about the chemical structure of levamisole retains the iridescent fish-scale sheen of pure cocaine, according to a chemist with ties to the cocaine trade, giving cocaine cut with levamisole the same appearance as pure cocaine.
- Levamisole is a bulking agent for crack. The process of making crack involves "washing" cocaine and filtering out impurities and cutting agents. Levamisole slips through this process, meaning you can produce more volume of crack with less pure cocaine.
- Levamisole passes the "bleach test," a simple street test used to detect impurities in cocaine.
- Levasmisole also adds a 'speedy' effect to cocaine – making it appear to be better quality.


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This image was scanned from my private collection
(I borrowed the translated table from the Lacis reprint)
Title: Do It Yourself Tatting 13
Author/Designer: Teiko Fujito
Format/Publication Date: TPB:1978
Publisher: Nihon Vogue, Ltd., Japan
Page Count: 100
Book Dimensions(ht. x w.): 10" x 8 1/4"
SUMMARY- I bought this book used off e-bay. It was described as a crochet book - but it was the same cover as one of the Teiko Fujito books, so I took a chance. It is the original Japanese book that later got translated and republished by Lacis Publications under the title Tatted Fashion. There are a wealth of very original motifs, some gorgeous doilies - and did I mention all the really striking motifs? - oh! And edgings, tons of lovely edgings! She gives motifs to use covering evening bags and to make elegant stoles. She uses the doilies as pillow covers. The color photography is stunning. Her illustrations are crystal clear - and useful. Her patterns are diagrammed. The reprint is still available from Lacis.
Note from Leigh: The copyright mark is succeeded with the name "T. Seto" on the back of the book. I didn't know if this was a pen name, her maiden name, or the publisher. So I did what any intelligent person who doesn't have contacts in Japan would do. I asked Georgia! Georgia Seitz had a friend in Japan who was able to do some sleuthing. "T. Seto" is Mr. Tadanobu Seto, the former president of NihonVogue. I bought what I thought was a cro-tatting book from the same time period with the same copyright mark, and wasn't sure if that book wasn't also a Fujito book I had not been aware of. This turned out not to be the case. (It was one of Toshiko Takashima's hook tatting books). Thank you, Georgia and Mr. Tazaki, for clearing up the mystery!
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Re-mastered 25th anniversary double vinyl LP edition of the debut album from cult 80's band The Bible. Contains 5 bonus tracks.
Full sleeve notes included.
Track Listing:
- Graceland
- Mahalia
- Walking The Ghost Back Home
- Kid Galahad and the Chrome Kinema
- (Talk to Me) Like Jackie Kennedy
- King Chicago
- She's My Bible
- Red Flag
Bonus Tracks:
- Sweetness
- Spend, Spend, Spend
- High Wide and Handsome
- Glorybound
- She's My Bible (demo version)


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Conference Programme
PRS Europe 2020 will feature an informative and inspiring conference programme which will address the latest opportunities and challenges that face the plastics recycling industry. With key industry figures in attendance and a number of big name speakers, this really is a must attend event for those looking to evolve their business and generate new revenue streams.
The Conference is FREE to attend and forms part of the FREE to attend exhibition where you can not only benefit from the content, but also from quality networking, meeting top suppliers, seeing the most innovative products & services as well as see new launches.
The full conference programme will be announced in January 2020. To be the first to see the conference programme when it is announced, please register your interest