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|November 13, 2012 08:43 AM EST
FALLS CHURCH, Va., Nov. 13, 2012 /PRNewswire-iReach/ -- Preparing for the New Electronic Submission Mandates:
Mastering the Tools and Strategies
**Presented by FDAnews and e-SubmissionsSolutions.com**
Dec. 6-7, 2012 – Raleigh, NC
(Photo: http://photos.prnewswire.com/prnh/20121113/CG11278)
Electronic submissions are going global, and the FDA is leading the way.
If you understand the FDA's requirements, you can satisfy any regulator worldwide. This two-day interactive workshop will bring you fully up to speed.
President Obama signed the FDA Innovation and Safety Act that, beginning October 1, 2012, mandates electronic submissions for INDs, NDAs, BLAs, ANDAs, DMFs, and all CDRH pre- and postapproval submissions. Every day regulatory authorities across the globe are turning to electronic submissions as their new preferred format ... and the FDA is leading the way.
If you don't yet have your electronic submission process perfected, there's no time to lose.
Many drug, biologic and device companies can already measure the difference in dollars — through increased first-time acceptance rates, shorter FDA review times, and yes, speed to market.
Your colleagues and competitors have already found the key.
You can, too, in the hands-on workshop that gives you the eCTD tools and tactics to satisfy any regulator worldwide.
Don't delay. Register now and mark your calendar for Preparing for the New Electronic Submission Mandate on December 6-7, 2012, in Raleigh, NC.
Space Is Limited — Register Today
Attend Preparing for the New Electronic Submission Mandate and you will:
- Discover the top 10 reasons sponsors receive a refuse-to-file from the FDA on their eCTD submissions and steps you should take to avoid these conditions in your source documents and eCTD compilation process
- Gain clarity on the acronyms and jargon of eCTD and electronic submissions
- Effectively budget for all scenarios of eCTD production — outsourcing, in-house publishing or a combination
- Develop project plans for eCTD submissions
- Understand why and how to start producing eCTD submissions at the IND phase
- Compare the similarities and differences between the eCTD format and CDRH's Electronic Copy format.
- Target skill requirements for MS Office and Adobe Acrobat that apply across all electronic submission standards.
- Master the documentation requirements for electronic datasets for nonclinical and clinical studies and better communicate these requirements to colleagues early in the drug development cycle
- Understand how to impact the deliverables from outside suppliers — including contract writers, CROs and CMOs — to assure your company is receiving submission-ready documents and datasets
- Assure the output of your outsource vendor or in-house eCTD system is valid for FDA review
- Learn about the eCTD pilot — what it does, why you need it, how it works and how to make it work for you
- Learn about the FDA's Electronic Submissions Gateway (ESG) and how to submit your eCTDs electronically, including unique requirements the ESG imposes on your eCTD publishing process
- Create quality control checklists for documents and data to be included in your eCTD application
- Develop a cost justification for outsourcing and know how to control your budget and avoid out-of-scope charges when outsourcing your eCTD
- Develop a business case for purchasing an eCTD system and electronic document management system (EDMS) as part of your total solution for eCTD submissions
- Analyze cost and timelines for selection, implementation and validation of eCTD publishing systems and understand who the vendors are and their products' distinguishing characteristics
- Understand the interdependencies of submission life cycle and document management systems in combination with eCTD publishing systems and the importance of submission life cycle management
- Participate in breakout sessions where you'll develop an eCTD strategy for your company
Click here to see the full agenda
Your Workshop Instructor
This workshop's expert instructor, Antoinette Azevedo, founded eâ€'SubmissionsSolutions.com to advise all sizes of biotechnology and pharmaceutical companies on the use of technology to manage regulatory documents and publish electronic submissions.
She was director of West Coast Operations for Liquent from 1997 to 2000. She was principal consultant in the CSC Consulting life sciences practice as technical lead for regulatory submission publishing from 1994 to 1997, working with pharmaceutical clients both large and small in North America and Western Europe.
You Get Complete Presentation Slides & CD of Invaluable Documents
Plus, you'll walk away from this interactive workshop with presentation slides and a valuable CD you can put to use immediately that includes:
- QC checklists for MS Word files and PDF files
- MS Project plan for eCTD and study reports
- Document inventory for eCTD RFI/RFP
- Sample eCTD RFP and requirements matrix
- ICH and FDA and global health authority guidances
- List of EDMS vendors, including a matrix that cross-references
integration between eCTD and EDMS systems
- MS Word template example for creating submission-ready PDF files
- Software
- Sample submissions for eCTD and CDRH Electronic Copy
- White papers
- And much, much more!
Preparing for the New Electronic Submission Mandates:
Mastering the Tools and Strategies
**Presented by FDAnews and e-SubmissionsSolutions.com**
Dec. 6-7, 2012 – Raleigh, NC
TUITION: $1,797 per attendee
4 Easy Ways to Register
Online: http://www.fdanews.com/ectd
By phone: 888-838-5578 or 703-538-7600
Fax: 703-538-7676
Mail to: FDAnews
300 N Washington St
Ste 200
Falls Church VA USA 22046-3431
Media Contact: Jeff Grizzel FDAnews, 703-538-7668, [email protected]
News distributed by PR Newswire iReach: https://ireach.prnewswire.com
SOURCE New Electronic Submission Mandate
Join us at Cloud Expo | @ThingsExpo 2016 – June 7-9 at the Javits Center in New York City and November 1-3 at the Santa Clara Convention Center in Santa Clara, CA – and deliver your unique message in a way that is striking and unforgettable by taking advantage of SYS-CON's unmatched high-impact, result-driven event / media packages.
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SYS-CON Events announced today that Commvault, a global leader in enterprise data protection and information management, has been named "Bronze Sponsor" of SYS-CON's 18th International Cloud Expo, which will take place on June 7–9, 2016, at the Javits Center in New York City, NY, and the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Commvault is a leading provider of data protection and information management...
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The essence of data analysis involves setting up data pipelines that consist of several operations that are chained together – starting from data collection, data quality checks, data integration, data analysis and data visualization (including the setting up of interaction paths in that visualization). In our opinion, the challenges stem from the technology diversity at each stage of the data pipeline as well as the lack of process around the analysis.
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What a difference a year makes. Organizations aren't just talking about IoT possibilities, it is now baked into their core business strategy. With IoT, billions of devices generating data from different companies on different networks around the globe need to interact. From efficiency to better customer insights to completely new business models, IoT will turn traditional business models upside down. In the new customer-centric age, the key to success is delivering critical services and apps wit...
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In his keynote at 18th Cloud Expo, Andrew Keys, Co-Founder of ConsenSys Enterprise, will provide an overview of the evolution of the Internet and the Database and the future of their combination – the Blockchain. Andrew Keys is Co-Founder of ConsenSys Enterprise. He comes to ConsenSys Enterprise with capital markets, technology and entrepreneurial experience. Previously, he worked for UBS investment bank in equities analysis. Later, he was responsible for the creation and distribution of life ...
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18th Cloud Expo, taking place June 7-9, 2016, at the Javits Center in New York City, NY, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterprises are using some...
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SoftLayer operates a global cloud infrastructure platform built for Internet scale. With a global footprint of data centers and network points of presence, SoftLayer provides infrastructure as a service to leading-edge customers ranging from Web startups to global enterprises. SoftLayer's modular architecture, full-featured API, and sophisticated automation provide unparalleled performance and control. Its flexible unified platform seamlessly spans physical and virtual devices linked via a world...
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SYS-CON Events announced today that BMC Software has been named "Siver Sponsor" of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2015 at the Javits Center in New York, New York. BMC is a global leader in innovative software solutions that help businesses transform into digital enterprises for the ultimate competitive advantage. BMC Digital Enterprise Management is a set of innovative IT solutions designed to make digital business fast, seamless, and optimized from mainframe to mo...
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SYS-CON Events announced today that Tintri Inc., a leading producer of VM-aware storage (VAS) for virtualization and cloud environments, will exhibit at the 18th International CloudExpo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, New York, and the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
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- Hello (again), Dolly!
- 'Hello, Dolly!' opens Thursday at EPAC
- 'Somewhereville Station' revisits the 50s and 60s
- St. Patty's musical at Ephrata Main
- Dance, concert will benefit Jamaica missions
- Happy Anniver5ary, St. Boniface!
- Downtown diversity
- Travelogue will explore Colorado River this Saturday
- Cool lineup!
- Everyone wins at the Souper Bowl
Matthew Weaver, printer,outdoorsman, tied flies
Matthew L. Weaver, age 51, passed away suddenly Monday, March 12, 2012 at home.
Born in Lancaster, Matt was the son of Alice Faye (Weaver) Roney and Lee Weaver.
Until his health declined, Matt had translated a lifelong passion for printing into employment at A&W Printing and Mt Bethany Printing. He was an avid fly fisherman, tying his own flies. He enjoyed the shooting sports including trap, skeet and hunting. He was a member of the NRA as well as a member of the Ducks Unlimited Feather Society. He also loved to travel and experience new places, often through the mechanism of hunting. Matthew will be remembered by many for his kind and generous heart and his willingness to lend a helping hand.
Matt is survived by his mother: Alice Faye, wife of C. Michael Roney, of Narvon; his father: Lee Weaver, husband of Mary Weaver, of Lititz; and four brothers: Mark, husband of Trina Weaver, of Denver; Michael, husband of Lisa Weaver, of New Holland; David Weaver, of Lititz; and Ivan Roney, of Odenton, Md.; a sister: Trina Roney, of Waldorf, Md.; 11 nieces and nephews; one great-niece; and a paternal grandmother: Anna Weaver, of New Holland.
Funeral services were held March 17 at the Roseboro Stradling Funeral Home, Denver, with Pastor Mike Roney officiating.
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Home > News > Nanoscale parts get binding aid
August 23rd, 2004
Nanoscale parts get binding aid
Nanoscale particles that are easy to manufacture piecemeal - but hard to assemble - may benefit from a new "sticky patch" technology that researchers at the University of Michigan say enables nanoscale self-assembly.
"By mimicking biological assembly, we are exploring ways to nanoengineer materials that are self-assembling, self-sensing, self-healing and self-regulating," said Sharon Glotzer, an associate professor of chemical engineering on the Ann Arbor campus. (more on earleir article)
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Gigantic ultrafast spin currents: Scientists from TU Wien (Vienna) are proposing a new method for creating extremely strong spin currents. They are essential for spintronics, a technology that could replace today's electronics May 25th, 2016
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iHerb Customer Reviews
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text: AdChoices Terms of Use Privacy Policy Hide GROOMING Appearance Grooming Perfectionist's Guide Share Tweet 0 Shares 8. The Art of Travelling for Him by Elemis Elemis This is a durable black zip carrying case containing a selection of six male-specific essentials for the jet-setter. Purchased individually, the set of hero products would cost $120, making this a great introduction to one of the most reliable men's brands out there. Buy Now Next Page TOP 10 9 8 7 6 5 4 3 2 1 Comments Share your opinion Your name More Like This Appearance Here Are The Best Tools For The Ultimate At-Home Shaving Experience Read More Appearance Here's How To Prevent And Treat Post-Shave Irritation Read More Appearance Here's How To Make The Most Of Cartridge Razors Read More Appearance Chances Are You Aren't Shaving With The Right Type Of Razor Read More Appearance Suncare 101: The Real Science Behind Your Painful-As-Hell Sunburn Read More Appearance Summer-Proof Your Hair With These 10 Styling Products Read More Around the Web Special Features Gift Guide Top 25 Father's Day Gifts Read More Dating Tips A Guide To Hooking-Up Online Read More


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Filter housing for closed fluid circulating system
October 7, 1986
A fluid containing system, as in a filter, for toxic or hazardous fluids is provided with rotatable base seals that can be alternatively positioned to permit the flow of fluids from the filter supply line, passing through the filter or, alternatively, the filter supply line can be sealed
Toy puzzle
December 24, 1985
In a tubular toy puzzle, the object is to manipulate indicia on rotatable rings to achieve a desired arrangement of the indicia. Manipulation occurs by rotating a drive mechanism connected with a combination of the rings. Axial repositioning of a drive shaft in the drive mechanism change
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TE CONNECTIVITY / BUCHANAN 1-1437381-7 Connector Accessory, End Section, 200 Series Terminal Blocks
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Chemical address tags can be defined as specific structural features shared by a set of bioimaging probes having a predictable influence on cell-associated visual signals obtained from these probes. Here, using a large image dataset acquired with a high content screening instrument, machine vision and cheminformatics analysis have been applied to reveal chemical address tags. With a combinatorial library of fluorescent molecules, fluorescence signal intensity, spectral, and spatial features characterizing each one of the probes' visual signals were extracted from images acquired with the three different excitation and emission channels of the imaging instrument. With multivariate regression, the additive contribution from each one of the different building blocks of the bioimaging probes towards each measured, cell-associated image-based feature was calculated. In this manner, variations in the chemical features of the molecules were associated with the resulting staining patterns, facilitating quantitative, objective analysis of chemical address tags. Hierarchical clustering and paired image-cheminformatics analysis revealed key structure-property relationships amongst many building blocks of the fluorescent molecules. The results point to different chemical modifications of the bioimaging probes that can exert similar (or different) effects on the probes' visual signals. Inspection of the clustered structures suggests intramolecular charge migration or partial charge distribution as potential mechanistic determinants of chemical address tag behavior.
Microscopic imaging studies examining the interaction of small fluorescent molecules with cells are challenging because cells are complex three-dimensional objects that may exist in many different structural and functional states(1–3). From highly branched neuronal cells to multinucleated myocytes, the morphological features of any particular cell type can be quite varied, and for any growing cell population, there is cell-to-cell variation in the structure, function and spatial relationships between the different cellular organelles. In addition, the quantum yield and spectral properties of fluorescent molecules can be affected by local microenvironments within cells, and by interaction with specific cellular components.
Nevertheless, to optimize the signal of a bioimaging probe for specific applications, the interactions between molecules and cells are generally studied directly based on the fluorescence staining phenotype apparent in images of cells incubated with the probes (4–6). These fluorescence staining phenotypes can be visualized using automated microscopes equipped with specialized optics and filter sets to excite the molecules with light and capture images recording the fluorescence emission patterns at specific wavelengths (7–10). Development of fluorescent, organelle-targeted probes has been driven by an interest in discovering new probes that excite and emit in the visible spectrum, and that possess specific subcellular localization features so they can be used as organelle markers or physiological biosensors (9,11–14).
Today, high content screening instruments can generate large image data sets with combinatorial libraries of fluorescent probes(15–18). Although bioimaging probe development has traditionally relied on visual inspection by human experts, new analysis strategies are being pursued to quantitatively assess relationships between the chemical structures of fluorescent small molecules and cell-associated visual signals (16,18,19). These strategies combine basic image feature extraction algorithms (20,21), machine vision techniques derived from the study of location proteomics (22–28) and multivariate analysis and cheminformatics techniques used to study the activity of compounds across multiple different assays (1,2,29–32). Ultimately, probe optimization studies could benefit from objective analysis of how the chemical features of a fluorescent probe are related to cell-associated, quantitative image features.
In the case of styryl molecules, their simple bipartite structure lends itself to analysis in terms of differential contribution of the two basic building blocks of the molecule to the spectral and subcellular localization properties of the molecules' fluorescence (17–19). Using a high content screening dataset, we previously determined that many styryl molecules exhibit idiosyncratic interactions with cells, leading to very different staining phenotypes even amongst closely related isomers (18). In spite of these idiosyncratic interactions, visualization of the images strongly suggested that much of the variation in localization could be related to the molecule's chemical structure. Thus, we hypothesized that the building blocks of the molecules could behave as "chemical address tags", and proceeded to determine the extent to which cell-associated image-based features derived from the images could be linked to additive contributions of the chemical building blocks of the molecules.
Synthesis and screening of the styryl library, and image data acquisition and preprocessing steps have been previously described(6,18). Briefly, each styryl molecule was synthesized from a conjugation reaction between 168 aldehyde building blocks with 8 methyl pyridinium/quinolinium building blocks. For notation purposes, each aldehyde building block is referred to as a number from 1 to 168, and the each pyridinium/quinolinium building block is referred to as a letter (from A to H) (6, 18). To facilitate data acquisition and analysis, an orthogonal fluorescent dye (Hoechst™ 33342) was used to label the cell nucleus. After incubation of Hela cells with the individual probes in 96 well plates, images were a acquired at 20× magnification with a Cellomics™ Kineticscan high content screening instrument, using the standard XF93 filter set's Hoechst™, FITC, TRITC, Cy5 acquisition channels(18). Analysis of the styryl molecules' fluorescence signal was based on 1 sec exposure images acquired from the FITC, TRITC and Cy5 channels. Each set of images was computationally and manually filtered to remove images with saturation or showing extensive dye precipitates or crystals. Using the Hoechst™ channel image, nuclear pixels were automatically identified using a thresholding algorithm, and images were background subtracted, by subtracting the median of pixel intensities of the noncellular region (pixels more than 10 pixels distant from any nuclear pixel). All analyses were based on whole field image features (described below), calculated for the cellular region or total nuclear region in each image. The cellular region was defined as a 5 pixel dilation of the nuclear region so as to sample the signal from the cytoplasm.
From the images, we measured a set of image-based features capturing the intensity level and distribution of probe fluorescence in cells, within and across fluorescence channels. The "integrated intensity" over a region is defined as the sum of pixel intensities of every pixel encompassing that region. In turn, dividing the integrated intensity by the number of pixels in a region corresponds to the mean (or average) pixel intensity over that region. In this manner, the average pixel intensity for all pixels within the cellular region was calculated in FITC, TRITC and Cy5 channels (excluding the Hoechst™ channel). With a control set of background-subtracted images acquired from unlabeled cells, we determined that < 1% of the images showed mean cellular autofluorescence > 100 units/pixel, so this value was chosen as a threshold for distinguishing those styryl molecules that yielded a cell-associated fluorescence signal. The average pixel intensity for all pixels within the cellular regions of FITC, TRITC and Cy5 was then summed to create a total cellular intensity (TCI) feature image. In addition, the cellular intensities for the three fluorescence channels were normalized by their sum to produce three "channel proportion intensity" (CPI) features. These values were not computed for compounds where the sum of mean pixel intensities was < 100 units/pixel. Coefficient of variation (CV) of the cellular regions was calculated as the standard deviation of pixel intensities for pixels within cells divided by the mean pixel intensity. The CV value was not computed when the mean intensity in a given image was < 100 units/pixel. "Cytoplasm to nucleus ratio" (CNR) was calculated as the ratio of the mean intensity in the cytoring region (the cellular region excluding the nuclear region) to the mean intensity in the nuclear region for a given image. The CNR was not computed when the mean intensity in the nucleus was < 100 units/pixel. To quantify the partitioning of probe fluorescence inside the cell in relation to the background fluorescence intensity, a "cell associated fluorescence" feature was computed as the ratio of mean cellular fluorescence (after background subtraction) to the median background intensity (corresponding to the probes' fluorescence in solution, before background subtraction). The CV, CNR and cell associated fluorescence features were computed for each channel, and also for the sum of the pixel intensities from all channels.
Several image features were also computed as controls or reference features: The size and number of cells in an image, quantified as the total number of pixels in either cell nuclei, or in the cellular region. The background intensity (BM) of each of the images acquired corresponds to the median background pixel intensity as used in background subtraction. The distribution of cells in an image was described in terms of the proportion of nuclear pixels in each of the four image quadrants (NQ1–NQ4). We also considered three features that represent the orientations and shapes of the cell nuclei in an image. These features were computed by first identifying all connected regions in the nuclear region consisting of more than 100 pixels in area. The x,y coordinates of the pixels in each connected region were used to construct a 2 × 2 covariance matrix of the x,y coordinates. This covariance matrix was then decomposed according to its eigenvectors to identify the principal axis (the dominant eigenvector) and the reciprocal aspect ratio (the ratio of the larger to the smaller eigenvalue). The median of the reciprocal aspect ratios across all regions in the cell (AR) was used to describe the aspect ratios of nuclei in the image. The angle of the principal axis for each nuclear region was also computed. This angle was measured relative to the increasing horizonal axis, using an origin placed at the center of mass of each cell. Angles greater than π radians were converted to lie in the range (0, π) by subtracting π radians, since the principal axis has no specific orientation. We then calculated the angular mean (AM) of these angles over all nuclei in an image. The AM was calculated by considering the angles for all cells in the image as points on a common unit circle (scaling the angles by 2 to cover the full unit circle). The arithmetic centroid of these points was then calculated, and scaled to a unit vector. The angle of this vector relative to the increasing horizontal axis divided by 2 to yield an angle between 0 and π that we used as the AM. An AM of π /2 radians corresponds to no favored orientation of the cell nuclei. In addition, the distance from the centroid to the origin (which is the centroid of all pixels in a nucleus) was also computed and used as a measure of variability, called "angular variance."
Regression methods were used to assess the extent to which additive contributions associated with the aldehyde and pyridinium/quinolinium building blocks could be used to describe the variation in image features. We first asked whether image features were predictable from additive contributions of the aldehyde and pyridinium/quinolinium building blocks. Ridge regression with a nominal ridging parameter of 1, with additive factorial main effects for the aldehyde and pyridinium/quinolinium moieties, was used for prediction. Ridge regression was chosen over ordinary least squares due to its lower prediction variance when correlated variables are used for prediction (although the combinatorial library leads to a full factorial structure, a fraction of the images were excluded from analysis as noted in the Methods, so substantial correlation between the predictor variables was expected in the data). For analysis, the image features were centered by plate, subtracting the mean feature value for each plate while retaining the original scale. A ridge regression model was fit using indicator (dummy) variables for each aldehyde and pyridinium/quinolinium group. To assess predictive accuracy without bias, 100 rounds of cross-validation were performed, holding out 10% of the data for testing. The correlation between fitted and observed image features was used to assess predictivity. Next, we used partial R2 values to quantify the additive contributions of aldehyde and pyridinium/quinolinium groups to each feature. All models included an additive effect for plate to remove plate-associated effects (due to any differences in cell preparation or instrument operation from one plate to the other). For example, the pyridinium/quinolinium group contribution was quantified in terms of the fit of the model with aldehyde, pyridinium/quinolinium, and plate effects compared to the model with pyridinium/quinolinium and plate effects. Adjusted R2 estimates (first-order unbiased estimates of the population R2) were used in calculating the partial R2 values. Bootstrapping was used to estimate standard errors of the R2 values, and confidence intervals calculated as the point estimate +/− two standard errors.
To compare variations in chemical structure and image features, we considered every pair of compounds with image feature data. For each image-compound pair, we compared the Tanimoto similarity T between the two compounds' structures to the absolute difference D between the image feature values. The Pearson correlation between T and D was used to quantify the relationship between chemical structure and image features, with a negative correlation reflecting the strongest consistency.
Isomeric pairs of pyridinium/quinolinium groups and of aldehyde building blocks as identified in our previous study(18) were used to assess whether the image feature values were more sensitive to isomeric changes in the position of functional groups in the pyridinium/quinolinium moiety or in the aldehyde moiety. First, relative difference of image-based feature values X (measured for styryl molecule A(i)) and Y(measured for styryl molecule B(i)) was defined as 2|X−Y|/(|X|+|Y|), to assess the lack of conformity between feature values X and Y. Then, for every isomeric pair of pyridinium/quinolinium building blocks (pairs A:B, C:G and D:E; see (18)), we considered each one of them conjugated to the same aldehyde group "i" (where i corresponds to aldehydes 1 through 168), and calculated the relative difference in each image-based feature for each styryl pair A(i) vs B(i); C(i) vs. G (i); and, D(i) vs. E(i). Conversely, the relative difference of feature values X and Y was determined for each isomeric pair of aldehyde building blocks conjugated to the same pyridinium/quinolinium groups.
As in the case of isomer variants, the relative difference of the calculated image-based features between of styryl molecules containing a pyridinium (A, B, C, G and H) vs quinolinium (D, E, F) group conjugated to every possible aldehyde building block was compared to the difference in image-based features between all pairs of styryl molecules containing a phenyl (aldehyde building blocks 1, 11, 85, 90, 126) vs. naphthalene (aldehyde building blocks 3, 6, 18, 20, 26, 34, 51, 67, 118, 141, 143) conjugated to every possible pyridinium/quinolinium building block. Conversely, the relative difference of feature values X and Y was determined for aldehyde moieties containing a phenyl vs. a naphthalene group conjugated to the same pyridinium/quinolinium groups. The relative difference of feature values X (measured for styryl molecule A(i)) and Y(measured for styryl molecule B(i)) was defined as 2|X−Y|/(|X|+|Y|), to assess the lack of conformity between feature values X and Y.
The additive contributions of each aldehyde group and each pyridinium/quinolinium group as estimated in the fitted regression model were concatenated over all image features into a vector. Using these vectors, we calculated the L1 norm (sum of absolute differences) between the features for any two chemical groups (either A groups or P groups). These L1 dissimilarities were used to perform an average linkage hierarchical cluster analysis of the chemical groups. The regression coefficients (scaled to (0,1)) were then displayed in a heat map.
The styryl library is a 168 × 8 combinatorial library, so there are 1344 styryl structures. Excluding images with artifacts, extensive pixel saturation, dye precipitates, a total of 1291 images were used for chemical address tag analysis (including images lacking detectable styryl signal in the cellular region). A total of 23 specific probe-associated image-based features and 9 general control image-based features were extracted from the images (Table I). To address the extent to which global trends in probe behavior -apparent in the fluorescence images acquired in the FITC, TRITC and Cy5 acquisition channels of the imaging instrument- can be traced back to additive contributions from aldehyde and pyridinium/quinolinium building blocks of the styryl molecules, multivariate ridge regressions were performed, using each image feature as a response variable, and additive factorial effects for the two building blocks of the styryl molecule as predictors. The correlation coefficients between the observed and predicted image features were calculated, using cross-validation to provide unbiased estimates of the extent to which the image features can be predicted from additive contributions of the different building blocks (Figure 1).
This quantitative analysis indicated that for many fluorescence intensity-related features, the correlation coefficient between predicted and measured values was strong and significant (ranging from 0.6 to 0.8) (Figure 1, features 1–11). In contrast, control features showed little correlation (correlation coefficient < 0.1) between predicted and measured values irrespective of wavelength (Figure 1, features 24–32). Visual inspection of arrays of images sorted according to the sign and magnitude of the regressed coefficients of the total intensity contribution from each aldehyde and pyridinium/quinolinium building blocks confirmed the expected trend: dark images in the top left of the array, with image brightness increasing towards the right and bottom (Figure 2). Furthermore, it is apparent that total intensity is linked with increased fluorescence in the TRITC channel, with the brightest images being the ones having most intense staining in the red (TRITC) channel, and images of intermediate brightness having most intense staining in the green (FITC) channel.
For the spatial features, the relative accumulation of the fluorescence signal intensity in the cells relative to the background was moderately predictable from the regressed, additive contributions of the aldehyde and pyridinium/quinolinium building blocks (Figure 1, features 12–15). Based on the total intensity of the probe, the correlation coefficient for the CV (Figure 1, feature 16) and CNR (Figure 1, feature 20) of probe signal were 0.3 and 0.6 respectively However, in the individual wavelength acquisition channels, only the correlations of CV in the FITC and TRITC channel were as large (Figure 1, features 17, 18), and the correlation coefficient for the CNR feature was close to zero for each separate wavelength channel (it was positive only for the TRITC channel). To summarize, the total probe signals, several channel specific probe signals, the cellular accumulation of total probe signal relative to the background (for each separate acquisition channels and for the sum of the signal acquired in FITC, TRITC and Cy5 channels) were strongly predictable from additive effects of the molecules' basic building blocks (Figure 1). The CV and CNR features were moderately predictable based on the total sum of the signals acquired from FITC, TRITC and Cy5 channels, although they were not predictable based on the signal from the individual acquisition channels.
Next, based on the regression coefficients, the extent to which the different aldehyde and pyridinium/quinolinium building blocks differentially contributed to variations in the observed phenotype was established (Figure 3). The contribution of the aldehyde and pyridinium/quinolinium building blocks to signal in the total intensity and FITC channel tended to be equally strong (Figure 3, features 1, 2, 5, 6, 9, 11, 12, 13, 16, 18 and 20), indicating that the different building blocks both contributed as chemical address tags to determine the probes' visual signals in the FITC wavelength. Nevertheless, in the TRITC and Cy5 channel, the pyridinium/quinolinium group generally behaved as the determining chemical address tag relative to the aldehyde group, by showing substantially greater contribution to the image features (Figure 3, features 3, 4, 7, 8, 14, 15).
By relating the chemical features of the pyridinium/quinolinium building block to the variations spectral and localization properties, we established the extent to which chemical variations in the building blocks influenced spectral and localization features (Figure 4). For the pyridinium building block, variation in the chemical structure of the pyridinium/quinolinium group showed good correlation with variations in the image-based features (Figure 4A). In contrast in the case of the aldehyde building block, the relationship between the variation in chemical structure of the building block and variation in the image-based features was minimal (Figure 4B).
Probing how chemical variations in the pyridinium/quinolinium group affected the visual signal of the styryl molecules relative to similar variations in the aldehyde group, the results revealed that changing from a pyridinium to quinolinium exerted a major effect in relation to a phenyl-to-napthalene change in the aldehyde building block (Figure 5, features 1, 3, 4, 5, 7, 8, 12, 14, 15, 18). In comparison, isomers of pyridinium/quinolinium and aldehyde building blocks exerted comparable effects on the probe's visual signal (Figure 6). For the aldehyde building blocks, the magnitude of the effect of isomer variants (Figure 6) was similar to the magnitude of the effect of phenyl vs. naphthalene substitutions (Figure 5). For the pyridinium/quinolinium building blocks, the isomer effect (Figure 6) was generally less than the effect of substituting a quinolinium for pyridinium (Figure 5).
Based on hierarchical clustering (Figure 7), we analyzed how the quinolinium/pyridinium groups contributed to the image-based features of styryl molecules, in relation to the contribution of the aldehyde groups. A dendrogram (Figure 7A) revealed that the pyridinium/quinolinium groups formed distinct clusters with the different aldehyde groups (I, II, III, and IV). Note that the dendrogram divided the building blocks into two major clusters: one formed by group IV and the other one associated with groups I, II and III. Most aldehyde groups clustered with pyridinium/quinolinium groups A, B, C, F, G and H (Figure 7A, groups I, II and III). Nevertheless, a significant number of aldehydes formed a separate cluster with quinolinium groups D or E (Figure 7A, group IV). Visualizing the global pattern of regressed coefficients in a heat map (Figure 7A), group I and II appeared most similar to each other in terms of their contribution towards the staining patterns, with group IV being distinctively different.
Visual inspection of the building blocks in clusters I, II, III and IV (Figure 7B) indicated that half of the aldehyde building blocks that appeared closely related to pyridinium/quinolinium groups D or E in terms of their contribution to the styryl molecule's visual signals possessed a nitrogen as part of the conjugated structure (Figure 7B, group IV). As part of the conjugated structure, a nitrogen atom in the aldehyde building block can facilitate the migration of the molecule's positive charge across the central methine bridge of the styryl molecule, through resonance structures that would delocalize the positive charge normally associated with the imminium nitrogen on the pyridinium/quinolinium group.
In terms of the aldehyde groups that were most like pyridinium groups A, B, C, G, or H, many of them contained one or more hydroxyl, methoxy, or ether substituents (Figure 7B, groups I, II). For the aldheyde groups that were most like quinolinium group F (Figure7B, group III), two out of three were bromobenzene derivatives. Cluster IV also contained two aldehyde building blocks with bromine atoms, while clusters I and II contained none. These chemical functionalities that were prominent in several of the aldehyde groups in each of these clusters while being less represented in other clusters suggest that specific mechanisms can strongly influence image-based features across a large number of probes.
With a combinatorial library of bioimaging probes (6, 17–19), chemical address tags can be defined as a specific part of a molecule that contributes in an additive manner to a specific, quantitative image-based feature. Applying a statistical regression approach to a combinatorial library of styryl molecules (6), we demonstrated how the building blocks of the styryl library can be analyzed as chemical address tags with respect to cell-associated image-based features. Based on the results obtained, the behavior of chemical address tags is wavelength-dependent: chemical address tags were most prominent across all noncontrol features after summing the signals from the various acquisition channels, as compared to the individual FITC, TRITC or Cy5 acquisition channels.
Our results indicate that in the styryl library, building block isomers tend to behave similarly as chemical address tags, although isomer-specific phenotypic effects underlie many idiosyncratic interactions observed between cells and styryl molecules (18). In this study, we observed that isomer variants of the pyridinium/quinolinium or aldehyde building blocks were associated with relatively small variations in image-based features. Also, the results indicate that chemical variation in the pyridinium/quinolinium building block generally had the greatest effect on the probes' cell-associated image-based features.
A key additional finding explaining the behavior of chemical address tags comes from hierarchical cluster analysis: specific chemical variations in the aldehyde building blocks associated with the presence of a conjugated nitrogen atom can lead to a major effect on the image-based features, mimicking the behavior of quinolinium group D or E as chemical address tags. Notably, every styryl molecule in this library contains a positive charge because of the quaternary, imminium nitrogen in every pyridinium/quinolinium building block (6, 17, 19). Therefore electrostatics alone cannot explain chemical address tag behavior. Instead, our observations are consistent with chemical modifications affecting charge migration or the partial charge distribution of the styryl molecules being the major determinant of chemical address tag behavior. When the aldehyde building blocks contains a conjugated nitrogen atom, the free electrons of the nitrogen atom can pi-bond with the rest of the aromatic system, and the positive charge associated with the imminium nitrogen an become delocalized across the conjugated system, resonating with the nitrogen atom on the aldehyde group. Because of resonance effects, the positive charge of the molecule can shift from the pyridinium/quinolinium group to the nitrogen atom on the aldehyde group.
Demonstrably, in spite of complex interactions between individual styryl molecules and cellular components, quantitative analysis of the probes' visual signals can be used to study the effect of chemical structure on fluorescent probe behavior. For optimizing a probes' fluorescence and intracellular accumulation properties, elucidation and quantitative analysis of chemical address tags using simple linear regressions can be useful. For future work, the apparent association between different building blocks, as revealed by hierarchical clustering analysis of the regressed coefficients, points to specific mechanisms through which different chemical variations may lead to similar effects on the probes' phenotypic, image-based features. The importance of the nitrogen atom in the aromatic structure of the aldehyde group coupled to resonance effects constitutes a testable hypothesis, in terms of determining the behavior of chemical address tags through effects on charge migration or partial charge distribution.
To conclude, the development of organelle-targeting bioimaging probes has traditionally relied on qualitative, subjective criteria (i.e. visual inspection by experts). Therefore, the ability to apply automated, objective machine vision techniques and rigorous statistical analysis to biomaging probe development constitutes an important advance. Because the molecules of the styryl library differ in their fluorescence properties (17, 19), it is practically impossible to screen this library with filter sets tailored to the specific excitation and emission properties of each molecule. Nevertheless, the results of this study indicate that it is feasible to identify chemical address tags and analyze their behavior using the sum of the signals from the FITC, TRITC and Cy5 channels of the standard XF93 multipass filter set. Indeed, although the magnification of the image dataset analyzed in this study does not resolve specific organelles, the observed structure-property relationships reveal a potential mechanism underlying chemical address tag behavior. Paralleling advances in location proteomics (22–28), we envision using higher magnification 3D image data sets, together with orthogonal, organelle-specific markers and a more elaborate set of image features, to analyze chemical address tags responsible for fluorescence signal localization to specific organelles.
This work was funded by NIH grant RO1GM078200 to G.R.R. The authors thank Andrew Parth for assistance with the figures.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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About Cherry Creek Grill - Denver
Located in the heart of Cherry Creek, the Cherry Creek Grill offers scratch-made American cuisine and prompt, friendly service. With fresh Skillet Cornbread, the colorful Macho Salad, or a slice of Banana Pie, our unique and Southwestern inspired flavors are not to be missed. We look forward to welcoming you soon.
Dining Style:
Casual Dining
American, Southwest
Hours of Operation:
Lunch: Daily: 11:00am - 5:00pm
Dinner: Monday - Thursday: 5:00pm - 10:00pm, Friday & Saturday: 5:00pm - 10:30pm, Sunday: 5:00pm - 9:30pm
Cross Street:
2nd and Steele St
Dress Code:
Business Casual
Price Range:
$31 to $50
Payment Options
AMEX, MasterCard, Visa
Phone Number:
(303) 322-3524
Parking Details:
Our private parking lot is located in the rear of the restaurant off of 2nd, between Steele St and Adams.
Executive Chef:
Mark Hunter
Bar Dining, Beer, Counter Seating, Full Bar, Non-Smoking Restaurant, Patio/Outdoor Dining, Takeout, Wheelchair Access, Wine
Cherry Creek Grill - Denver Ratings and Reviews
Macho Salad Fan
The Macho Salad is a staple of CC Grill; however, I believe the portions have decreased. When you pay almost $20 for a salad, it should be over the top and a worthy portion.
Great for busiess lunches
Consistently good meals and service. This is a busy place so reservations always a smart idea. I do many business lunches here as although crowded many times, it is also private and you can hear your associate.
requested an outdoor table and even though one was available and we asked several time the outdoor table sat empty. Salmon was cold as was the broccoli, Macho salad was excellent! The first server seemed confused and i'm not really sure who ended up being our waiter as it seemed to be a revolving door. We had reservations and were early to arrive. Despite having several tables open we still had to wait past our reservation time. The artichoke appetizer special was awful. I have been to Cherry Creek Grill many times. This was a disappointment.
This is my second time eating here and b ...
This is my second time eating here and both times were great! The service was good as was the food. This is a great place for me to have business meetings. Thank you again for the great experience.
Great wait staff, attention to detail an ...
Great wait staff, attention to detail and prep and the best appetizers in Cherry Creek.
Always great
Always great
Great service!
Great night out. Hostess over heard us talking about it being our anniversary and Restaurant gave us small bottle of champagne. Food deals delicious!
This is a regular go-to place for a nice ...
This is a regular go-to place for a nice business lunch, or any time I want to enjoy good food and conversation. They have a killer artichoke appetizer, and my butternut squash enchilada platter was heavenly. Great sauces!
Neighborhood Jewel
Cherry Creek Grill is 100% consistent, you can always count on it. Excellent food, service and atmosphere.
Good food and service but too loud
I had lunch for the first time at the Cherry Creek Grill this week, meeting two other people for business. While the food and service were very good, the "background" music was much too loud, making it difficult to hear and be heard. I know that every restaurant, coffee shop, etc. feels it must play music, even if no one is there to listen to it, but it should truly be "background" music, not so loud that diners cannot hear each other.
Bummed out
My dad used to take me here in high school. We loved the macho salad. I was bummed that when I ordered my same salad I only had two croutons, no goat cheese, and the avocado wasn't ripe.
Consistently great
We're fortunate to have this eatery in our neighborhood. The food is always consistently great and the specials are always really good. The barbecue salmon is my personal favorite.
Always a treat to dine at CCG!!!!
Always a treat to dine at CCG!!!!
This place never disappoints
The food is exceptional and the service is even better.
Been here before. Remembered it to be better than it was. Had the Rotisserie Chicken which I remembered to be better than it was. Not much to it ... be careful of tiny bones which made up 90% of the meal! I told my wife that the rotisserie chicken from Costo's is infinitely better. Sat at the bar and the bartender was great. Would I go back?? If I were single and over 30 ... maybe. Lot's of heat, if you know what I mean. Wife had the Veggie Burger which she loved.
Great food, service ok
We came for my wife's birthday lunch and the staff didn't even mention it to us/her. Server was ok, seemed to rush through the lunch time to get new customers. Wouldn't recommend for a special occasion, was too loud to chat.
Another great experience at Cherry Creek ...
Another great experience at Cherry Creek a grill. Stephanie greeted me at the front and always remembers me. She's such an incredible asset to this place... She always makes me feel so welcome here.
great food and drink
we had a great evening as always. food was good and drinks were delicious. great pours.
Par Excellence
Cherry Creek Grill has not failed to deliver excellence in quality, well prepared, variety, and presentation of each item on the menu.
Can't find anything bad
This is one of my favorite places to go when I am in Cherry Creek. The Macho salad is always a nice flavor and tasty. My wife had their awesome french dip. I have been here many times and just haven't found anything that wasn't great. The staff is always polite and on top of it. Don't miss this place, you have to try it.
Delicious but pricey
It's pricey for what it is, though the food is delicious. The skillet cornbread was excellent. Wine is so-so.
Great place
This is one of our favorite restaurants for lunch in Denver. My wife and I always order the excellent beef filet and salad. It's as good as any high end steak house and a much better value. We always get great service too.
Had lunch with a friend. Macho salad wo ...
Had lunch with a friend. Macho salad wonderful as always. Friend had French dip and said it was delicious
Never Disappoints!
Every time we dine at The Cherry Creek Grill we are amazed at the well prepared soups, salads, and entrees. It is rare to find a restaurant in which every item is well prepared and tantalizing to the palate....leaving the diner wanting more....
Weekend Dinner
Met our son and his girlfriend for dinner last Saturday. DU students, this was close to campus but a world apart in terms of sophistication and chic. Our son has food allergies and he has confidence the kitchen is careful to not cross contaminate and he will have a good experience. Cool spot without pretentions in Cherry Creek.
Cherry Creek Grill's eclectic cuisine is ...
Cherry Creek Grill's eclectic cuisine is served with unique flavors and textures that delight the most discriminating of palates.
Best in Cherry Creek!
I find the Cherry Creek Grill to be consistently OUTSTANDING! I use them for business and my wife and I frequent there often. There is always something to satisfy our taste buds. I have never had anything there I do not like therefore I find it difficult to specifically mention any one item. Their wait staff is very efficient and friendly. The front hostess is always welcoming. They are all very detailed oriented.
All around great place to eat
Great Food, Great Service, Great Atmosphere! Busy place - recommend reservations. Every time I'm in Denver, I eat dinner here - every couple of months. Good lunch place also.
We always go to CC Grill when we are in Denver, we're from here and have frequented this establishment from the very beginning. It's always consistent, has great quality food and good service. Their standards are excellent and the management is always on top of everything!! The French Dip/ Prime Rib sandwich is to die for and shouldn't be missed. There is something for everyone and a really good/great value wine list as well. I would recommend this to anyone!! 5-stars
Excellent food and service
Our server was Samantha and her pacing of our meal was perfect. Friendly, but not overbearing, we never had to wait to receive our drinks, place our order, and have the meals arrive. But we were not hurried in any way either. The menu is not extensive. Seems like what they do, they do very well. I had the trout which was excellent, including the sides. Amount of food was just right. Wife had steak and enchilada - she thought it was great.
Consistent and perfect - been coming for many years.
Keep going back -- don't know why...
Actually, I do... a friend with whom I eat with likes it. It is priced as though it is gourmet or fine/dining food, when it is just good food of average quality/creativity (overall). I used to go there only because they had the best grilled artichokes in town, but they don't even have them any more. The menu is just a little off somehow, not enough veggies. There are 2-3 items on the menu worth the money, but it is way overpriced. It is so loud (their sound system) in there you can't hear your companion or even think. Although, if you ask they will turn down the music a bit. The service is great and always has been. I gave the ambience 2 stars only because of the noise. It is beyond "energetic", it just gives you the jitters because of the noise.
Good dinner menu
The food and service was great, but the noise level was a bit greater than I expected, including the music over the speakers.
Long Wait Times With Reservation
The wait time for our table was a bit excessive even with a reservation. We arrived exactly at our reservation time, and were seated 30 minutes later. The wait staff accommodated the inconvenience with complimentary appetizers, which was a welcomed response. Once we were seated, the food was delicious, the ambiance was electric, and the service was superb.
Pricey but good
I can't afford a $30 salad and ice tea for lunch often, but it was tasty and nice atmosphere.
One of our favorite restaurants.
Comfort food kicked up a notch! Consistently great service
Not suitable for large groups
Always a perfect time for a client meeting or catching up with a friend at lunch. However, I wouldn't recommend it for groups over 4. I completely understood my party of 8 would be seated at 2 tables (since the tables are fixed, they can't be put together) however they can not guarantee they will be 'next' to each other, so I reserved a 5:30 spot thinking my chances would be better early in the evening. The main disappointment was that the 2 tables we were given, were the first 2 by the door, so all night long every person/waiter/staff is constantly walking through, so it was tough at times to visit across the tables. And since it was a birthday celebration, mingling was to be expected. They also don't recognize the 'birthday guest' like most places do - no little special dessert or anything. :( So while I will continue to enjoy the grill for a lunch - I most likely wouldn't return with a group.
The macho salad seems to be greatly diminished.
I've been a fan and regular patron of Cherry Creek Grill for many years but my last two experiences were less than terrific which is what I've come to expect. The macho salad did not have very much chicken in it and seemed smaller and disppointing. On my previous visit I had a Cesar salad that hardly had any dressing on it. It was terrible.
A local treasure
A favorite place for lunch or dinner- visited many times and have not been disappointed. Highly recommend!
CC Favorite
My friends and I choose CCG as our favorite Friday night place to dine. We love the black bean soup, the chicken kale salad, cocktails made to perfection, fresh brewed coffee, banana cream pie, and exceptional waitstaff! Actually, we have ordered other items from the menu and all are prepared with fresh tasty ingredients.
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District Announcements
FY17 Budget Update
May 10, 2016
Click here to view the FY17 BSD Budget Estimated Expenditures Details.
Burlington Free Press Opinion: Fact-finding delay worrisome (5/15/16)
Click here to view the Negotiations page.
Burlington School District Announcements
Special Education and Student Support Services Parent Night
May 26, 2016
Wednesday, June 1st 6-7:30 p.m.
Sustainability Academy, 123 North Street
Join Superintendent Yaw Obeng and Student Support Director Laura Nugent,
for an opportuntity to share your experiences, thoughts and concerns.
TONIGHT, 5:30PM: BSD New American Community Forum
May 24, 2016
The Burlington School District is inviting you to attend a New American Community Forum. You are asked to collaborate and provide ideas about the District mission and values, as well as priorities for Multi-Year Strategic Planning. Please consider participating in this process of improvement, which will guide us to the type of educational system we can all be proud of.
Tuesday, May 24th, 5:30-7:30, Burlington High School Cafeteria
Childcare, transportation and interpreters will be available.
For more information please contact:
Miriam Ehtesham-Cating: (802) 343-3775 or Nijaza Semic: (802) 288-6048
TONIGHT, 6PM: BHS Make a Change Community Night
May 23, 2016
This spring, BHS ninth grade Humanities students participated in a semester-long community action project, conducting research and attempting to make a change in their community. This evening, all are invited to an evening of conversation and student changemaker presentations and projects.Curious about what this event has looked like in the past? Watch this 2013 video.
TONIGHT, 7PM: BHS Spring Concert
May 19, 2016Can't make it in person? Today is your lucky day! Electronic Recording Arts at Burlington Technical Center and the BHS Music Department have made this concert easier than ever to enjoy. If you are home and have cable in Chittenden County, just turn your TV to Channel 16, RETN, and enjoy the concert LIVE!
An opportunity to come out and support the hard-working and talented BHS musicians.
Just click that link, and save it to your preferred browsing device.
Electronic Recording Arts - offering great programming at an amazing price....FREE!
Mayor Bernie Sanders Talks with EMS Paradise Project Students...in 1987
May 13, 2016


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Login | Sign Up!
... --- If you enjoy arts and crafts, pop-up, scrapbooking and origami, you will enjoy these craft projects too. Like Origami, Jianzhi and Kirigami are the craft of paper, with the added technique of paper cutting. Jianzhi and Kiri
by judowodo
by patioelf
by thefrugalcrafter Lindsay Weirich
by bumperclapent
by The Frugal Chef
by ArtzieRush
by CrochetMD


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Kim's Leaves Liberty
Martial arts store moves to Oak Park
From the October, 2012 issue
Kim's Martial Arts Supply was a family business for forty years. When founder Chong Kim retired, it passed through a daughter and then a cousin. When the cousin wanted to sell it, Orande Burrell, longtime customer and fifth-degree Tae Kwon Do black belt, bought and moved it to Oak Park, near Detroit. He says the store is essentially the same, but he now offers same-day delivery. He also sells online: www.ksmas.com.
What's happening in local stores and eateries, and restaurant reviews.>> Blogs
Mayonnaise Sandwich
Foraging in Cuba
Achatz Closes
The pie shop is gone, but wholesaling continues
A bistro/cigar bar on Main and a global eatery in Plymouth Mall
True North
The Laundry in Fenton
Clean Clothes, Clear Conscience
When Jinhan Jun bought Eureka Cleaners five years ago, he had headaches all the time.
What's New at Mark's Carts
Falafel and seafood chowder--and maybe lobster rolls


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Terms of use, Legal, Copyright © 2005 KBAuthority.com. All Rights Reserved.
Kraus KPF-2110 Single Lever Stainless Steel Pull Out Kitchen Faucet
Product Description
- Update the look of your kitchen with this multi-functional Kraus pull-out faucet
- Kraus kitchen faucet blends quality and durability with elegance and style
- Faucet features 100-percent solid stainless steel Lead-Free construction
- Satin stainless steel finish
- Discoloration and corrosion resistant
- Features dual stainless steel pull-out spray head with an aerated flow or a powerful spray
- Spout swivels 180-degrees for greater reach
- Spring-tensioned retractable hose
- Features drip-free ceramic cartridge
- Single-lever water and temperature control
- Single-hole installation
- Flow Rate 2.2 GPM @ 60 PSI
- All mounting hardware and hot/cold waterlines are included
- Standard US plumbing installation
- Faucet height: 10.75 inches (12.25 inches w/lever open)
- Aerator clearance: 7.5 inches
- Spout reach: 8.5 inches
- Hose reach measures 28 inches long
- ADA compliant
- Certified and Listed by UPC, cUPC, CSA, IAPMO, ANSI, SCC and NSF
- AB 1953 - California, S152 - Vermont, Lead-Free compliant
- Manufactured by Kraus
- Limited Lifetime Warranty
- Windisch 89101 Accessories Contemporary, Round, Brass Floor Standing Waste Basket
- Top Knobs TK35PC Sanctuary Sloped Pull 3-7/8 Inch Center to Center Polished Chrome
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- Wyndham Collection WCVW00924SESGGD2BM24 Centra 24 Inch Single Bathroom Vanity in Espresso, Green Glass Countertop, Pyra Bone Porcelain Sink, and 24 Inch Mirror
There have been no reviews for this product.


text:
Attempted robbery in Carlisle
Police are investigating an attempted robbery at a bookmakers in Carlisle
Police are investigating an attempted robbery at a bookmakers in Carlisle
Cumbria Police have released an image of a man they would like to speak to in connection with the attempted robbery at Ladbrokes, Scotch Street, Carlisle on Wednesday afternoon.
The man is described as being white, aged between 35 and 45-years-old with a bald head. He is said to be between 5ft 8" to 5ft 10" and described as wearing a black jacket with a white polo type shirt, dark trousers and trainers.
If you know who this man is, or you believe it is you, please contact Cumbria Police on 101 and ask for Carlisle CID, or call Crimestoppers anonymously on 0800 555 111.
A look ahead at the forecast for the Border region.
ITV Border's John Ballard, author of '10 Greatest Ships of the Royal Navy', provides the context and background of the Battle of Jutland
After her mother was ran over by a car, Peter and Iona Pennington saved the life of 'Twiggy' the fawn, who they've now adopted...


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Powwow finds new home at Expo New Mexico
The Gathering of Nations Powwow will remain in Albuquerque, moving to a new home at Expo New Mexico. ...
Continue Reading »
The Gathering of Nations Powwow will remain in Albuquerque, moving to a new home at Expo New Mexico. ...
Continue Reading »
Tue, May 31, at 7:38 pm
Tue, May 31, at 10:43 pm
From the paper
The reductions in funding will result in layoffs and reduced operations
From the paper
Superintendent says COO was hardworking, explored La Luz Trail almost every dayRead More »
Ray Birmingham looked up in the stands Saturday night at Santa Ana Star Field and…Read More »
Lovelace Health System and University of New Mexico Health System have signed off on a…Read More »
CINCINNATI (AP) — The Cincinnati Zoo, where a gorilla was shot and killed over the weekend after a 3-year-old boy…Read More »
HOUSTON -- An Army veteran of two Afghanistan tours who killed one person and wounded…Read More »
Event's founder says details of deal will be announced todayRead More »
Once prominent Santa Fe lobbyist and lawyer, he served prison time for 2008 hit-and-run accident that killed pedestrianRead More »
Both movies were panned by criticsRead More »
The doctor who attended the premature birth of Jean Johnson predicted she wouldn't make it through t ...Read More »
It's not an overstatement to say there is a local crisis of opioid addiction and deaths from drug ov ...Read More »
These are the Journal's recommendations for contested races in the June 7 New Mexico primary election for Public Regulation Commission…Read More »
The University of New Mexico recently had to relocate cats that called the campus home.…Read More »


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Written on: 02/04/2014 by morganslocksmith (1 review written)
our website build was a little different to what creare were expecting, the initial design was floored for our business in many ways. However with the website design team we created a site that not only showcases what we do and what we are good at also with a very professional design and feel.
the design team were exceptional in the way they have worked with us to create the website that was right for us, even though they have had to spend longer than expected completing the work.
with this professional design and feel i hope it will drive more customers to the phone and through our door.
As rated by our community of reviewers
" Fantastic work and great communication " Read More
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" Efficient after care service " Read More
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" Highly Recommend " Read More
" I was sold a website a year ago under a new 'government initiative'... " Read More
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text:
Amazing service! User friendly website! Great communication with constant updates as to the order status! Huge array of products. So easy and saved us time. Didn't have to go out to the store and we were able to stay enjoying our vacation right away! Wonderful experience! Would highly recommend!
This is by far the best way to go if you are going to Disney and you want to stay healthy and hydrated under budget! They deliver straight to your hotel and text you when it has been delivered. All you need to do is pick it up from bell services (if you can ) or have bell services delivery it to your room. Easy as pie. Whatever you can't pack, order from Garden Grocer. Fantastic!
I wish I knew about you on my other trips, you guys are awesome. Thank you.


text:
Now pay into the nanny's pension: Middle-class parents face £600 bill a year under new rules
- New Government scheme sees employees auto-enrolled on pension
- This includes home-help such as nannies, gardeners and cleaners
- Parent groups attack scheme saying it 'targets the squeezed middle'
Middle-class parents are to be forced to pay hundreds of pounds a year into pensions for their nannies.
Tens of thousands of families will see the cost of their childcare rise by as much as £600 a year from 2015, it has emerged.
Under the Government scheme, they will also have to fund pension contributions for cleaners, gardeners and home helps whose pay exceeds £9,440 a year.
Squeezed middle: The cost of childcare could rise by as much as £600 a year for a family paying for a nanny as they are auto-enrolled in the new scheme
Parent groups say this will add to the burden on the already-squeezed middle, with mothers accusing the Government of treating parents 'like a profitable business'.
There are an estimated 111,484 nannies working in the UK, according to the National Careers Service. And soaring numbers of families employ domestic help, including cleaners and gardeners.
More than six million people were employing domestic help in 2011, a rise of a million compared with a decade earlier.
Now, under the Government's auto-enrolment scheme – the biggest shake-up to pensions for a century – every employer will have the responsibility of enrolling their staff into a pension scheme.
The rules, which came into force for big businesses last October and are gradually being extended to smaller firms, will see more than 11million workers enrolled into a company pension for the first time, with both employee and employer paying contributions, initially at 1 per cent.
Empty pram: Parent groups such as Mumsnet say the enforced pension-enrollment will mean families will not be able to afford childcare
From as early as June 2015 it will be rolled out to those who might not consider themselves employers, such as families who take on help with cleaning, childcare or gardening.
They will be legally bound to offer a pension to anyone aged over 22 but below the state pension age who they pay above the tax threshold – currently £9,440 a year.
By the time the rules are fully implemented by 2018, contributions will rise to 3 per cent.
For someone who employs a full-time nanny earning £25,000 a year, this would push up their childcare bill by £48 a month.
Mumsnet website founder Justine Roberts said childcare issues were an 'enormous problem' and a rise in costs could prevent parents going back to work.
'The high cost of childcare is one of the most frequent concerns of Mumsnet users,' she said.
Parents have been told by the head of Revenue and Customs to 'get off their backsides' and register for tax self-assessment.
Lin Homer said hundreds of thousands of people could be caught out by the changes to child benefit. Families receiving the benefit where one person earns £50,000 or more are meant to register by today.
Households where one person earns more than £60,000 will have to pay back all their child benefit in income tax if they have not already opted out of receiving it.
Mrs Homer told Radio 5 Live: 'We think there's about 200,000 people who need to get off their backsides and do something.'
People who do not register could face fines of between 10 per cent and 100 per cent of the child benefit paid. However, it is unlikely that anyone who registers and pays the tax by January 31 will be penalised.
'HMRC is committed to helping people pay the right amount of tax and urges parents who have been affected by the changes to child benefit to register for self-assessment,' said Mrs Homer.
She advised anyone unsure whether they are affected by the change to go to the HMRC website, adding: 'We know that lots of people leave it until the last minute.'
Many of those affected had already opted out, she said.
Anita Monteith, of the Institute of Chartered Accountants, said: 'This adds considerable complication to the tax system for ordinary people, particularly for those brought into the self-assessment system for the first time.'
TUC General Secretary Frances O'Grady said some parents who are not affected had still received letters from HMRC telling them to register. 'The changes to child benefit are a mess,' she said.
'The coming requirement to contribute towards pension as well as to cover tax and National Insurance will only make it harder for parents.
'On Mumsnet people often cite the cost as a barrier to returning to work – for many once you've paid tax and contributed to a pension it will simply not be worth it.'
There are also fears that many families will try to duck the extra payments by paying their nannies 'under the table' or making them self-employed.
Dawn Kirenli, director of the Association of Professional Nannies, said: 'We are already seeing a growing problem of parents trying to cut costs by paying nannies cash in hand or illegally forcing them to become self-employed.
'It is highly likely we will see those same people trying to get round the pensions changes as well.'
On Mumsnet, mothers attacked the new pension scheme. One wrote: 'It will tip me over the edge and put one nanny out of work.
'People will put their nanny on the books for some £500 per month, call her an au pair and then pay the rest in cash. Proper on-the-books nannies will become a privilege of the rich. Treating parents like a profitable business is outrageous.'
Tory MP Mark Field said: '£600 may not seem like a lot of money to some people but in hard-pressed families it could well be the straw that breaks the camel's back. They may be forced to take on full-time childcare themselves.'
Colleague Jacob Rees-Mogg, who has paid into a pension for his family's nanny for years, said: 'I imagine very few people are aware of the scheme.'
Some families could be forced to sack their nannies, he said. 'It is a question of balancing between the need to provide for people in retirement and the need to provide now.'
As well as a financial strain, setting up a pension is likely to prove a time-consuming and laborious process for families with domestic help.
First they must register with the Pensions Regulator and find out what date they need to comply with the rules by. Then they must find a scheme, open an account and write to their employee telling them they are going to be signed up.
Failure to stick to the rules can result in penalties of up to £50 a day or even prosecution.
Families who have employed their nanny prior to April 2012 will have to pay into the pension scheme from as early as June 2015. Those who have enlisted a nanny since then will not have to pay until 2017.
Elaine Clarke, of tax consultancy Cheapaccounting, said: 'I know it really sticks in people's throats. We've got a pensions time-bomb ticking away and somebody has to pay for it.'
'Automatic enrolment is the biggest change to the pensions system in a century - aimed at addressing a culture of serious under-saving for later life,' Department for Work and Pensions spokesperson said.
'Over the next five years more than 1 million employers will provide their staff with the chance to save for their retirement, many for the first time.
'Nannies, as employees, will also be able to benefit from the reforms, and we would encourage families hiring them to look into how to prepare.
'Reliable and affordable childcare is vital for parents who want to stay in or return to work, which is why from 2015 the Government will introduce new tax free childcare which will be worth up to £1,200 per child annually.'
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