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A method and system for quantifying and correcting spatial-intensity trends for each channel of a microarray data set having one or more channels. The method and system of one embodiment of the present invention selects a set of features from each channel of the microarray data set. Based on the selected set of features, a surface is used to determine the intensities for all features in each channel of the microarray data set. Spatial-intensity trends within the microarray data set are quantified, based on the surface to the intensities for each channel of the microarray data set. After the surface has been determined, the spatial-intensity trend can be removed from the microarray data set.
1. A method for quantifying and correcting spatial-intensity trends in a microarray data set having one or more channels, the method comprising:
selecting a set of features, based on intensity level, from each channel of the microarray data set;
determining surface intensities for each feature in the channel of the microarray data set from a surface calculated based on intensity levels of the selected set of features;
quantifying the spatial-intensity trends in each channel of the microarray data set based on the surface intensities; and
correcting feature intensities for each channel of the multi-channel, microarray data set based on the determined surface intensities; and
performing at least one of: outputting a result of the method to a display; outputting a result of the method to memory; outputting a result of the method to a computer on a network; or outputting a result to a human user in human-readable format.
2. The method of
3. The method of
4. The method of
5. The method of
varying the moving-window filter size;
incrementally moving the moving-window filter; and
selecting a fraction of the lowest-signal-intensity features or the highest-signal intensity features that are within the boundaries of the moving-window filter.
6. The method of
7. The method of
8. The method of
9. The method of
10. The method of
11. The method of
12. The method of
a spatial root mean square filtered feature minus fit;
a spatial root mean square fit;
a normalized area;
a spatial volume;
a mean of the selected feature signal intensities; and
a root mean square of the selected feature signal intensities.
13. The method of
14. The method of
normalizing the surface to the highest intensity value; and
dividing each feature intensity of the data set by the corresponding normalized surface intensity.
15. The method of
16. The method of
storing a spatial-intensity trend data set, produced by the method of
transferring the spatial intensity trend data set to an intercommunicating entity via electronic signals.
17. The method of
18. A method comprising communicating to a remote location a spatial-intensity trend obtained by a method of
19. A method comprising receiving data produced by using the method of
20. A physical computer readable medium carrying software to execute the method of
21. A program on physical computer readable media configured to, when executed, provide a computer user interface comprising:
a listing of each microarray data set stored in a microarray database;
an optional debug mode;
a scrollable display listing available filters;
a selection window for selecting optional moving-window filtering;
an input window for inputting a size of the optional moving-window filter;
an input window for selecting a fraction of selected filtered features;
an input window for selecting an increment of the moving window filter; and
a display window for displaying metric values for each microarray data set that allows a user to determine which surfaces are added to the database.
22. A system for determining spatial intensity trends in microarrays data, the system comprising:
a computer processor;
a communications medium by which one or more microarray data sets are received by the microarray-data processing system;
a program, stored in the one or more memory components and executed by the computer processor to perform a method that selects a set of features, based on intensity levels, from each channel of the microarray data set; determines surface intensities for each feature in the channel of the microarray data set based on the selected set of features; quantifies the spatial-intensity trends in each channel of the microarray data set based on the surface intensities; corrects feature intensities for each channel of the multi-channel, microarray data set based on the determined surface intensities; and performs at least one of: outputting a result of the method to a display; outputting a result of the method to memory; outputting a result of the method to a computer on a network; or outputting a result to a human user in human-readable format.
Embodiments of the present invention are related to microarrays, and, in particular, to a method and system for quantifying and correcting for trends present in feature signal intensities of microarray data.
The present invention is related to microarrays. In order to facilitate discussion of the present invention, a general background for particular types of microarrays is provided below. In the following discussion, the terms "microarray," "molecular array," and "array" are used interchangeably. The terms "microarray" and "molecular array" are well known and well understood in the scientific community. As discussed below, a microarray is a precisely manufactured tool which may be used in research, diagnostic testing, or various other analytical techniques to analyze complex solutions of any type of molecule that can be optically or radiometrically detected and that can bind with high specificity to complementary molecules synthesized within, or bound to, discrete features on the surface of a microarray. Because microarrays are widely used for analysis of nucleic acid samples, the following background information on microarrays is introduced in the context of analysis of nucleic acid solutions following a brief background of nucleic acid chemistry.
Deoxyribonucleic acid ("DNA") and ribonucleic acid ("RNA") are linear polymers, each synthesized from four different types of subunit molecules.
The DNA polymers that contain the organization information for living organisms occur in the nuclei of cells in pairs, forming double-stranded DNA helices. One polymer of the pair is laid out in a 5′ to 3′ direction, and the other polymer of the pair is laid out in a 3′ to 5′ direction, or, in other words, the two strands are anti-parallel. The two DNA polymers, or strands, within a double-stranded DNA helix are bound to each other through attractive forces including hydrophobic interactions between stacked purine and pyrimidine bases and hydrogen bonding between purine and pyrimidine bases, the attractive forces emphasized by conformational constraints of DNA polymers.
Double-stranded DNA may be denatured, or converted into single stranded DNA, by changing the ionic strength of the solution containing the double-stranded DNA or by raising the temperature of the solution. Single-stranded DNA polymers may be renatured, or converted back into DNA duplexes, by reversing the denaturing conditions, for example by lowering the temperature of the solution containing complementary single-stranded DNA polymers. During renaturing or hybridization, complementary bases of anti-parallel DNA strands form WC base pairs in a cooperative fashion, leading to reannealing of the DNA duplex.
Once a microarray has been prepared, the microarray may be exposed to a sample solution of target DNA or RNA molecules (410-413 in
Finally, as shown in
One, two, or more than two data subsets within a data set can be obtained from a single microarray by scanning or reading the microarray for one, two or more than two types of signals. Two or more data subsets can also be obtained by combining data from two different arrays. When optical detection is used to detect fluorescent or chemiluminescent emission from chromophore labels, a first set of signals, or data subset, may be generated by reading the microarray at a first optical wavelength, a second set of signals, or data subset, may be generated by reading the microarray at a second optical wavelength, and additional sets of signals may be generated by detection or reading the microarray at additional optical wavelengths. Different signals may be obtained from a microarray by radiometric detection of radioactive emissions at one, two, or more than two different energy levels. Target molecules may be labeled with either a first chromophore that emits light at a first wavelength, or a second chromophore that emits light at a second wavelength. Following hybridization, the microarray can be read at the first wavelength to detect target molecules, labeled with the first chromophore, hybridized to features of the microarray, and can then be read at the second wavelength to detect target molecules, labeled with the second chromophore, hybridized to the features of the microarray. In one common microarray system, the first chromophore emits light at a near infrared wavelength, and the second chromophore emits light at a yellow visible-light wavelength, although these two chromophores, and corresponding signals, are referred to as "red" and "green." The data set obtained from reading the microarray at the red wavelength is referred to as the "red signal," and the data set obtained from reading the microarray at the green wavelength is referred to as the "green signal." While it is common to use one or two different chromophores, it is possible to use one, three, four, or more than four different chromophores and to read a microarray at one, three, four, or more than four wavelengths to produce one, three, four, or more than four data sets. With the use of quantum-dot dye particles, the emission is tunable by suitable engineering of the quantum-dot dye particles, and a fairly large set of such quantum-dot dye particles can be excited with a single-color, single-laser-based excitation.
Sources of background signal can inflate the signal intensities associated with certain of the features of the microarray. The background signal of a microarray may contribute systematic feature-position-related background intensity to the measured intensity data read from the microarray and may cause inaccurate determination of gene expression levels during analysis. Therefore, experimentalist, designers, and manufacturers of microarrays and microarray data processing systems have recognized a need for a reliable and efficient method and system for quantifying and removing any systematic feature-position-related background intensities within a microarray data set.
Various embodiments of the present invention detect and remove systematic background signal from a microarray data set. One embodiment of the present invention provides a method and system for quantifying and correcting spatial-intensity trends within a microarray data set having one or more channels. The method and system of one embodiment of the present invention selects a set of features from each channel of a microarray data set. Based on the selected set or sets of features, a surface is constructed and used to determine the intensities of all features in each channel of the microarray data set. Spatial-intensity trends within the microarray data set are quantified, based on the constructed surface. Quantified spatial-intensity trends can then be removed from the microarray data set by subtracting the constructed surface value for each corresponding feature intensity.
Embodiments of the present invention are directed toward a method for quantifying and correcting spatial-intensity trends in microarray data. The following discussion includes two subsections, a first subsection including additional information about molecular arrays, and a second subsection describing embodiments of the present invention with reference to
A microarray may include any one-, two- or three-dimensional arrangement of addressable regions, or features, each bearing a particular chemical moiety or moieties, such as biopolymers, associated with that region. Any given microarray substrate may carry one, two, or four or more microarrays disposed on a front surface of the substrate. Depending upon the use, any or all of the microarrays may be the same or different from one another and each may contain multiple spots or features. A typical microarray may contain more than ten, more than one hundred, more than one thousand, more ten thousand features, or even more than one hundred thousand features, in an area of less than 20 cm2 or even less than 10 cm2. For example, square features may have widths, or round feature may have diameters, in the range from a 10 μm to 1.0 cm. In other embodiments each feature may have a width or diameter in the range of 1.0 μm to 1.0 mm, usually 5.0 μm to 500 μm, and more usually 10 μm to 200 μm. Features other than round or square may have area ranges equivalent to that of circular features with the foregoing diameter ranges. At least some, or all, of the features may be of different compositions (for example, when any repeats of each feature composition are excluded the remaining features may account for at least 5%, 10%, or 20% of the total number of features). Inter-feature areas are typically, but not necessarily, present. Inter-feature areas generally do not carry probe molecules. Such inter-feature areas typically are present where the microarrays are formed by processes involving drop deposition of reagents, but may not be present when, for example, photolithographic microarray fabrication processes are used. When present, interfeature areas can be of various sizes and configurations.
Each microarray may cover an area of less than 100 cm2, or even less than 50 cm2, 10 cm2 or 1 cm2. In many embodiments, the substrate carrying the one or more microarrays will be shaped generally as a rectangular solid having a length of more than 4 mm and less than 1 m, usually more than 4 mm and less than 600 mm, more usually less than 400 mm; a width of more than 4 mm and less than 1 m, usually less than 500 mm and more usually less than 400 mm; and a thickness of more than 0.01 mm and less than 5.0 mm, usually more than 0.1 mm and less than 2 mm and more usually more than 0.2 and less than 1 mm. Other shapes are possible, as well. With microarrays that are read by detecting fluorescence, the substrate may be of a material that emits low fluorescence upon illumination with the excitation light. Additionally in this situation, the substrate may be relatively transparent to reduce the absorption of the incident illuminating laser light and subsequent heating if the focused laser beam travels too slowly over a region. For example, a substrate may transmit at least 20%, or 50% (or even at least 70%, 90%, or 95%), of the illuminating light incident on the front as may be measured across the entire integrated spectrum of such illuminating light or alternatively at 532 nm or 633 nm.
Microarrays can be fabricated using drop deposition from pulsejets of either polynucleotide precursor units (such as monomers) in the case of in situ fabrication, or the previously obtained polynucleotide. Such methods are described in detail in, for example, U.S. Pat. No. 6,242,266, U.S. Pat. No. 6,232,072, U.S. Pat. No. 6,180,351, U.S. Pat No. 6,171,797, U.S. Pat. No. 6,323,043, U.S. patent application Ser. No. 09/302,898 filed Apr. 30, 1999 by Caren et al., and the references cited therein. Other drop deposition methods can be used for fabrication, as previously described herein. Also, instead of drop deposition methods, photolithographic microarray fabrication methods may be used. Interfeature areas need not be present particularly when the microarrays are made by photolithographic methods as described in those patents.
A microarray is typically exposed to a sample including labeled target molecules, or, as mentioned above, to a sample including unlabeled target molecules followed by exposure to labeled molecules that bind to unlabeled target molecules bound to the microarray, and the microarray is then read. Reading of the microarray may be accomplished by illuminating the microarray and reading the location and intensity of resulting fluorescence at multiple regions on each feature of the microarray. For example, a scanner may be used for this purpose, which is similar to the AGILENT MICROARRAY SCANNER manufactured by Agilent Technologies, Palo Alto, Calif. Other suitable apparatus and methods are described in published U.S. patent applications 20030160183A1, 20020160369A1, 20040023224A1, and 20040021055A, as well as U.S. Pat. No. 6,406,849. However, microarrays may be read by any other method or apparatus than the foregoing, with other reading methods including other optical techniques, such as. detecting chemiluminescent or electroluminescent labels, or electrical techniques, for where each feature is provided with an electrode to detect hybridization at that feature in a manner disclosed in U.S. Pat. No. 6,251,685, and elsewhere.
A result obtained from reading a microarray, followed by application of a method of the present invention, may be used in that form or may be further processed to generate a result such as that obtained by forming conclusions based on the pattern read from the microarray, such as whether or not a particular target sequence may have been present in the sample, or whether or not a pattern indicates a particular condition of an organism from which the sample came. A result of the reading, whether further processed or not, may be forwarded, such as by communication, to a remote location if desired, and received there for further use, such as for further processing. When one item is indicated as being remote from another, this is referenced that the two items are at least in different buildings, and may be at least one mile, ten miles, or at least one hundred miles apart. Communicating information references transmitting the data representing that information as electrical signals over a suitable communication channel, for example, over a private or public network. Forwarding an item refers to any means of getting the item from one location to the next, whether by physically tran-sporting that item or, in the case of data, physically transporting a medium carrying the data or communicating the data.
As pointed out above, microarray-based assays can involve other types of biopolymers, synthetic polymers, and other types of chemical entities. A biopolymer is a polymer of one or more types of repeating units. Biopolymers are typically found in biological systems and particularly include polysaccharides, peptides, and polynucleotides, as well as their analogs such as those compounds composed of, or containing, amino acid analogs or non-amino-acid groups, or nucleotide analogs or non-nucleotide groups. This includes polynucleotides in which the conventional backbone has been replaced with a non-naturally occurring or synthetic backbone, and nucleic acids, or synthetic or naturally occurring nucleic-acid analogs, in which one or more of the conventional bases has been replaced with a natural or synthetic group capable of participating in Watson-Crick-type hydrogen bonding interactions. Polynucleotides include single or multiple-stranded configurations, where one or more of the strands may or may not be completely aligned with another. For example, a biopolymer includes DNA, RNA, oligonucleotides, and PNA and other polynucleotides as described in U.S. Pat. No. 5,948,902 and references cited therein, regardless of the source. An oligonucleotide is a nucleotide multimer of about 10 to 100 nucleotides in length, while a polynucleotide includes a nucleotide multimer having any number of nucleotides.
As an example of a non-nucleic-acid-based microarray, protein antibodies may be attached to features of the microarray that would bind to soluble labeled antigens in a sample solution. Many other types of chemical assays may be facilitated by microarray technologies. For example, polysaccharides, glycoproteins, synthetic copolymers, including block copolymers, biopolymer-like polymers with synthetic or derivitized monomers or monomer linkages, and many other types of chemical or biochemical entities may serve as probe and target molecules for microarray-based analysis. A fundamental principle upon which microarrays are based is that of specific recognition, by probe molecules affixed to the microarray, of target molecules, whether by sequence-mediated binding affinities, binding affinities based on conformational or topological properties of probe and target molecules, or binding affinities based on spatial distribution of electrical charge on the surfaces of target and probe molecules.
Scanning of a microarray by an optical scanning device or radiometric scanning device generally produces an image comprising a rectilinear grid of pixels, with each pixel having a corresponding signal intensity. These signal intensities are processed by a microarray-data-processing program that analyzes data scanned from an microarray to produce experimental or diagnostic results which are stored in a computer-readable medium, transferred to an intercommunicating entity via electronic signals, printed in a human-readable format, or otherwise made available for further use. Microarray experiments can indicate precise gene-expression responses of organisms to drugs, other chemical and biological substances, environmental factors, and other effects. Microarray experiments can also be used to diagnose disease, for gene sequencing, and for analytical chemistry. Processing of microarray data can produce detailed chemical and biological analyses, disease diagnoses, and other information that can be stored in a computer-readable medium, transferred to an intercommunicating entity via electronic signals, printed in a human-readable format, or otherwise made available for further use.
In general, the intensity associated with a feature of a microarray is the sum of: (1) a first signal-intensity component produced by bound target molecule labels; and (2) a second signal-intensity component, referred to as the "background," which may be the product of a wide variety of background-intensity-producing sources, including noise produced by electronic and optical components of a microarray scanner, general non-specific reflection of light from the surface of the microarray during scanning, or, in the case of radio-labeled target molecules, natural sources of background radiation, and various defects and contaminants on, and damage associated with, the surface of the microarray. Background may also me the result of a contaminant bound to the probes, or to an underlying silane layer, or impurities in glass underlying the silane layer. Background signal may also be due to varying amounts of non-specific binding of labeled target.
The background may also contain signal intensities resulting from signals emitted by probes bound to a feature, which in turn, may be the result of weak intrinsic fluorescent properties of probe molecules and a stronger contribution induced by radiation used to stimulate emission from hybridized target molecule labels. The signals emitted by bound probe nucleotides may be sequence dependent. For example, in the case of the signal strengths produced by the four DNA nucleotide bases background signal emitted by individual nucleotides vary from a relatively weak signal produced by deoxy-adenosine, to intermediate signal strengths produced by deoxy-thymidine and deoxy-guanosine, in that order of respective strengths, to a relatively strongest signal-intensity produced by deoxy-cytosine. Therefore, oligonucleotide probes with a high proportion of A's produce smaller second signal intensity components, while oligonucleotide probes with a high proportion of C's produce larger second signal intensity component. The strength of the induced signal emitted by probes may also be proportional to the nucleotide sequence mass.
Ideally, randomly distributed microarray features having bound probes with identical nucleotide sequences should emit substantially identical signal intensity when measured by a microarray reader. A variation in signal or background intensities across a microarray surface is referred to as a "spatial-intensity trend." Features having signal-intensities within about 2 to 3 standard deviations of the negative control features, referred to as the "lowest-signal-intensity features," can be used to identify the presence of a spatial-intensity trend in the background.
One of many possible embodiments of the present invention is directed to a method for detecting, quantifying, and correcting spatial-intensity trends in microarray data.
In an initial step 1102, a user interface is employed to receive a multi-channel microarray data set, determine whether debugging is employed, and to receive data filters, moving window parameters, such as size, increment, and fraction of features selected, and best-fit surface parameters. The data set may comprise two data subsets corresponding to two different channels of one microarray, or may comprise one data subset corresponding to signals obtained from one channel of a microarray. The feature intensities of the data set can be provided in many forms, including raw intensities, background-subtracted intensities, and signal-intensity ratios for features generated form signals obtained from two different channels.
The microarray data is indexed to provide location coordinates for each feature.
Next, in step 1104, the outer for-loop executes steps 1106-1120 separately for each channel of the multi-channel, microarray data set. In step 1106, the background of the microarray features is subtracted according to a method described in Agilent U.S. patent application Ser. No. 10/153,345, which is incorporated by reference, and Agilent U.S. patent application entitled "Method and System for Computing and Applying a User-Defined, Global, Multi-Channel Background Correction to a Feature-Based Data Set Obtained from Reading a Molecular Array," filed the same day as the present invention, which is incorporated by reference. In addition, the features are filtered by removing features having signal intensities above a threshold value and irregularly shaped features. Note that the term "filtered" does not actually mean feature data is removed from the microarray data set. Instead, filtering involves identifying lowest-signal-intensity features from which to quantify any spatial-intensity trend that may be present.
Filters employed in step 1106 include, but are not limited to: (1) a filter that removes positive control features from consideration because these features typically emit strong signal intensities; (2) a filter that removes non-control features with intensity levels above a threshold saturation level; (3) a filter that removes features having a non-uniform intensity distribution; (4) a filter that removes all features except negative-control features; (5) a filter that leaves only features that are brighter than the mean or median signal on the microarray; (6) a filter that removes all but the brightest features, such as the bightest 1%, 5%, 10%, or 50% or more; and (7) a filter that retains only positive control features.
A filter designed to remove from consideration non-control saturated features with intensity levels above a threshold saturation level is described below. An image of a microarray may consist of a 2-dimensional array of pixel-intensity values, commonly stored in 16-bit words, and therefore ranging from 0 to 65535. A pixel having an intensity value of 65535 is considered to be saturated, because all measured intensity values equal to or greater than 65335 are encoded as the maximum value 65535. When more than a threshold percentage of the pixels within an area corresponding to a feature are saturated, the feature is considered to be saturated. In other words, the true intensity of the feature is not reflected in the intensity value integrated over the pixels within the feature area. For example, a saturation-level threshold of 5% results in the removal of features having more than 5% saturated pixels.
A filter designed to remove from consideration features having non-uniform intensity distributions over the areaa of the features is described in
Next, in optional step 1108, a moving-window filter can be employed to further filter the already filtered microarray data obtained in step 1106. The moving-window filter is employed to select lowest-signal-intensity features of the microarray data. The moving-window filter filtered selects lowest, signal-intensity features from substantially all regions of the microarray.
The moving-window filter is translated, at each step of a moving-window-filter-based filtering process of the already filtered microarray data by translating the window in a selected direction by a fixed number of inter-feature spacings in the selected direction. The increment ranges from about 1 to about 10 or more units in the feature coordinate system.
A fraction of lowest, signal-intensity features is selected from each window of the moving-window filter. Note that the moving window filter may also be employed to select highest, signal-intensity features. However, for the sake of illustration, the following discussion is related to selecting lowest, signal-intensity features. For example, assuming that the fraction of lowest-signal-intensity features with respect to all features is 1/10 then 10 of the lowest, signal-intensity features of a size-100 moving-window filter are selected at each position of the moving-window filter. Note that, typically, 1% of the lowest, signal-intensity features for each window is used. In order to avoid overlooking features near the edge of the microarray boundary during moving-window filtering, the microarray features are extended symmetrically near the boundaries. The size of the symmetric extensions are determined by the size of the moving-window filter.
Next, in optional steps 1110, 1112, and 1114, the set of filtered features obtained in step 1106 and optional step 1108 may be examined for clusters of filtered features. Regions where the filtered-feature data are clustered may distort the spatial-intensity-trend quantification described below in steps 1116-1120. If debugging mode is selected by the user in optional step 1110, then, in optional step 1112, the feature coordinates of the filtered feature are displayed.
The entire set of N filtered features determined in steps 1102-1114 is denoted by {(xi,yi),Ii,C}i=1 N, where (xi,yi) specifies the feature coordinates of filtered feature i, Ii represents the corresponding intensity of filtered feature i, and C is the channel index. A set of filtered features {(xi,yi),Ii,C}Ii=1 N can be used to determine a set of data points, referred to as the "best-fit surface" and denoted by S, that characterises the spatial-intensity trends for all feature in the channel C of microarray data set. The set of data points S is constructed by first fitting a best-fit plane, denoted by O, for all features. The general equation for a plane is given by:
The following discussion provides a general mathematical description of the Loess method with accompanying figures. For each feature, the constants p1, p2, and p3 are determined by minimizing the locally- weighted, least-squares error given by:
In general, for each feature, the Loess method utilizes a set of M nearest neighbor filtered features to fit a best-fit plane O(x, y). The number of neighboring filtered features associated with each feature is given by:
Note that, for the best-fit plane O(x, y) given by equation (1), p is equal to "1." Typically, the neighborhood size q is selected somewhere in the range from about 0.20 to about 0.5 and represents the fraction of the total number of filtered features used to determine the best-fit plane O(x, y).
One of many possible weighting functions wi used for the Loess method is the "tricube" function given by:
The minimum of equation (2) occurs when the gradient of E(p1,p2,p3) equals the zero vector, and is determined as follows:
Next, in step 1120, if there are more features, then controls returns to step 1118. In step 1120, if there are no more features for computing the best-fit function, then, in step 1122, the best-fit surface S can be smoothed by repeatedly applying the locally-weighted, least-squares regression for each feature. Rather than using the intensities Ii at the filtered features, the best-fit plane values Oi are used, and the weight function is modified. The locally-weighted, least-squares error is given by:
where Oi′=O′(xi,yi)=p1′xi+p2′yi+p3′ is the new best-fit plane; and
The updated weight function Wi is the product of the tricube weight function wi from equation (3) and a symmetric distribution function gi. One of many possible symmetric distribution gi used to reduce the weight for filtered features is given by the Gaussian distribution:
After the entire set of L best-fit function intensity values Oi, are smoothed, the best-fit surface S is constructed by assembling the best-fit function intensity values Oi to give the following:
The data points of a best-fit surface S characterizes the spatial-intensity trends for a channel of the microarray data set.
In step 1124, one or more metrics are employed to quantify the spatial intensity trend present in the set of N filtered features. The metrics employed to quantify the spatial-intensity trend include: (1) a root-mean-square ("RMS") difference between N filtered feature intensities Ii and the corresponding values Oi; (2) a standard deviation of the values Oi; (3) a normalized area; (4) a spatial volume; and (5) a spatial average intensity.
The RMS difference between the filtered features Ii and the corresponding best-fit values Oi, referred to as the "Spatial RMS Filtered minus Fit," is determined by calculating the following:
The standard deviation of the set of data points S is referred to as the "Spatial RMS Fit," and is determined by calculating the following:
The normalized area, referred to as "spatial surface area" is determining by calculating the surface area of surface 2204 divided by the surface area of the microarray 2201. In
The spatial volume is approximated by computing:
The spatial average fit of the best-fit intensities is computed according to the following expression:
The above described metrics can be used as assess the overall quality of a microarray hybridization assay, and therefore, can be used to discard any microarray data sets that cannot trusted to yield an accurate assessment of gene expression levels in a microarray hybridization assay. For example, a microarray data set having a standard deviation larger than a user defined standard-deviation threshold could be used as a criterion for discarding the entire microarray data set.
Next, in step 1126, the feature intensities for a given channel can be corrected by removing the spatial-intensity trend in order to improve the microarray data quality. As described above, a spatial-intensity trend attributed to the background adds to the signal intensities of those affected features. Therefore, for each feature of the microarray, spatial-intensity trends attributed to the background can be corrected as follows:
For high-intensity features, spatial-intensity trends are often proportional to the intensity of the signal. For example, a hypothetical feature having a signal intensity of 1,000 is increased to 1,100, while another hypothetical feature on the same microarray having a signal intensity of 10,000 is increased to 11,000. Rather than subtracting this kind of spatial-intensity trend from each feature, the spatial-intensity trend may be corrected by dividing each feature intensity by the corresponding normalized best-fit surface intensity. For example, consider a dome-shaped, spatial-intensity trend having highest signal-intensity features of 1000 in the middle of the microarray and highest signal-intensities features of 500 around the edges of the microarray. The normalized best-fit surface intensities are determined by dividing all best-fit surface intensities by 1000 to give corresponding signal intensities of 1.000 in the middle of the microarray and signal intensities of 0.500 around the edges. The microarray feature intensities are corrected by dividing each feature intensity by the corresponding normalized best-fit surface intensity.
Next, in step 1128, if the multi-channel microarray data has more channels, then steps 106-1126 are repeated. In step 1128, if there are no more channels to quantify the spatial-intensity trend, then return to the calling function.
Although the present invention has been described in terms of a particular embodiment, it is not intended that the invention be limited to this embodiment. Modifications within the spirit of the invention will be apparent to those skilled in the art. For example, an almost limitless number of different implementations of the many possible embodiments of the method of the present invention can be written in any of many different programming languages, embodied in firmware, embodied in hardware circuitry, or embodied in a combination of one or more of the firmware, hardware, or software, for inclusion in microarray data processing equipment employing a computational processing engine to execute software or firmware instructions encoding techniques of the present invention or including logic circuits that embody both a processing engine and instructions. In alternate embodiments, the best-fit function can be a quadratic function given by:
In alternate embodiments, an interpolating function can be used to approximate the filtered features. Interpolation involves construction of a function that assumes the values Ii at each (xi, yi) for each filtered features. In alternate embodiments, the shape of the moving-window filter can be adjusted to accommodate a variety of microarray feature layouts. For example, diamond, hexagonal, triangular, circular, or elliptical or any other closed boundary may be employed. In alternate embodiments, the method of the present invention can be applied to one or more microarray data sets.
The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that the specific details are not required in order to practice the invention. The foregoing description of specific embodiments of the present invention are presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Obviously many modifications and variations are possible in view of the above teachings. The embodiments are shown and described in order to best explain the of the invention and its practical applications, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the following claims and their equivalents.
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COLUMBIA CITY ŌĆö A Pierceton man pleaded guilty to a burglary charge in Whitley County Circuit Court Monday.
Jeremiah Smith, 26, pleaded guilty to burglary, a Class C felony. With his criminal history, he also was charged with being a habitual felony offender as part of a plea arrangement.
A charge of theft, a Class D felony, was dismissed as part of the agreement.
Smith admitted to breaking into the Larwill Deli, located at U.S. 30 and Ind. 5. He was accused of stealing $1,252.76 of merchandise ŌĆö 12 cartons of cigarettes.
COLUMBIA CITY ŌĆö Pocket change is needed to make positive change for Whitley County families.
B.A.B.E.ŌĆÖs annual April giving campaign is in its fifth year and baby bottles are being prepared for distribution across the county to collect monetary donations.
ŌĆ£These bottles will be in businesses all over the county,ŌĆØ said Shawn Ellis, B.A.B.E.ŌĆÖs executive director. ŌĆ£There are smaller bottles that we are handing out to churches so that their members can take them home and fill them.ŌĆØ
COLUMBIA CITY ŌĆö Honoring the past while creating the future.
That is the idea behind much of the educational practices of Northern Heights Elementary School. Jake Hoag, principal of NHES, gave a presentation to the Whitley County Consolidated Schools Board of School Trustees (WCCS) Monday about the vision in his building.
SOUTH WHITLEY ŌĆö A crushed pipe, resulting in more than $1,500 in repair work, was deemed to not be the responsibility of the town by the South Whitley Town Council last week.
When a resident brought the concern to the townŌĆÖs council, President Tony Starkey asked for more information.
After bills were submitted to Town Manager Dave Wilkinson and more questions were answered, the council members decided there was no liability on the townŌĆÖs part to cover the repair costs.
SOUTH WHITLEY ŌĆö WhitkoŌĆÖs girls track team excelled in the Three Rivers Conference last season.
For 2013, the Lady Wildcats are back for more and are hoping to take the conference championship once again.
Whitko won the Three Rivers Conference two ways last year, taking first in the conference meet, 48 points ahead of second-place Southwood, and also posting a 7-0 mark in the season, league-wise.
While the Wildcats graduated three seniors from last yearŌĆÖs team, Coach Gary Sims was excited about the talent that remains.
See Saturday's Post & Mail for an updated review of Whitley County unemployment numbers.
Betty L. Hodges, 89, a resident of rural South Whitley, died at 12:30 a.m. Thursday March 21, 2013, at the home of her daughter. She had been in failing health.
She was born May 10, 1923, in Carroll County, a daughter of the late Leo F. and Axie E. (Cross) Landis.
Her formative years were spent in north central Indiana. She graduated from Larwill High School in 1941.
On June 1, 1941, she was united in marriage to George E. Hodges. They made their home in on a farm in rural South Whitley. Mr. Hodges died Nov. 27, 1995.
COLUMBIA CITY ŌĆö Though Columbia CityŌĆÖs boys and girls swim teams didnŌĆÖt have a state-title, stand-out season ŌĆö there was much to highlight about the small squadŌĆÖs performance this year.
Eagle head coach Kristen Swonger, who is stepping down after this season, said every swimmer broke their personal record at least once, and some swam new events for the first time.
With only 11 girls and 12 boys on the team, winning many meets posed big challenge for the Eagles.
ŌĆ£We had no idea what was going to happen,ŌĆØ Swonger said.
INDIANAPOLIS ŌĆö In light of all ChurubuscoŌĆÖs football teamŌĆÖs success throughout the last three years ŌĆö including a 33-5 combined record ŌĆö only three players have received such an honor.
Offensive lineman Eric Kuznar joins former ŌĆÖBusco standouts Kyle Monk and Kyle Matthewson as recipients of a ŌĆśGriddyŌĆÖ award Sunday.
The senior was honored at the Colts Pavilion in Indianapolis ad the awards ceremony.
COLUMBIA CITY ŌĆö Bringing home a national award is cause for celebration for any team, squad or group.
But for Vanessa Bills and the Whitley County Dazzlers, winning a cheerleading national title is somewhat shocking.
ŌĆ£I didnŌĆÖt even realize we would be competing like that,ŌĆØ said Bills who is the DazzlerŌĆÖs coach.
The special needs cheerleading squad is open to any age and gender in Whitley County who has a disability.
Last week, the squad took its first cross-country trip to Myrtle Beach, S.C. to compete in Cheer Ltd.ŌĆÖs national competition.


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Learn more about Moen Kitchen Faucet Camerist 7545C:
Manufacturer: Moen
Mfg Part#: 7545C
Sku: 219597660
Package Weight: 1 lbs
See more in Plumbing & Water
|MOE4419: Features: -Pullout kitchen faucet.-One or three faucet holes.-Deck mount.-Single lever handle.-4 Spray functions.-Low arc pullout spout design for conventional styling.-Pullout spray with braided hose.-Flexible supplies with 0.375'' compression fittings.-Aerated stream; powerful rinse; light gentle veggie spray; pause function.-Conventional deck mount design.-Hydrolock quick connect system for easy installation.-Spray functions: four function.-Cartridge type: 1255.-ADA compliant.-Connection size: 0.5''.-Third party certified to CSA B 125.1, ASME A112.18.1 and NSF61/9.-Flow rate: 2.2 gpm max (8.3 L/min).-Made in USA.-Meets s152(vermont); ab1953(california) legislation. Construction: -Metal construction. Dimensions: -Supply length: 8.5''.-Hose length: 68''.-Overall dimensions: 10.875'' H x 9.125'' D. Collection: -Camerist collection. Warranty: -Limited lifetime warranty.-Moen provides lifetime limited warranty against leaks, drips and finish defects to the original consumer purchaser.-Moen provides five year warranty if used in commercial installations.


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19-year-old arrested for Forestville bank robberyComment
A 19-year-old was arrested in connection with a bank robbery in Forestville earlier this month, Prince George's County police said.
Shop Express robbed for second time in three monthsComment
A Northeast D.C. convenience store that was the target of a "flash mob" robbery in August has been robbed again, police say.
Man arrested in Popeyes robberyComment
Police have arrested an Upper Marlboro man suspected of an armed robbery of a Popeyes Restaurant in Mitchelville.
Sherman Circle robbery suspects still at largeComment
Police are searching for several suspects who they say tried to rob two people near Sherman Circle in Northwest D.C. early Friday morning.
Wheaton Giant abduction leaves residents, shoppers shakenComment
A 75-year-old man is recovering Thursday after being abducted at knife point in Wheaton on Wednesday and forced to take money out of ATMs.
Georgetown student robbed on P Street NWComment
For the second time in three days, a Georgetown University suspect was the victim of a robbery on Monday night.
Isaiah Graham arrested by UMD police for robbing studentComment
University of Maryland police have charged a man they believe robbed a student earlier this week on the College Park campus.
Georgetown student robbedComment
A Georgetown University student was robbed off-campus late Saturday, police said.
Businesses suffer through string of robberies in Congress HeightsComment
Business owners in Congress Heights are worried after a number of stores were robbed. Some call for better protection.
iPhone, electronics theft spikes throughout D.C. areaComment
A group of teenagers closed in on David Bonelli in his Northwest D.C. neighborhood. Their target: his iPhone. He's not alone - it's all part of a striking trend of cell phone theft throughout the city.
Metro cell phone theft: How to keep yourself from being a victimComment
There are some very simple things you can do to keep yourself from being a target of theft while you're using your valuable electronic devices. Check out how to prevent yourself from being a victim of crime here.
Montgomery County 7-Eleven robberies suspects still on loose, police sayComment
Police are looking for two men they believe are behind a string of 7-Eleven robberies in Montgomery Village and Gaithersburg, police said.
Police arrest 4 more suspects in Halloween-candy armed robberyComment
Police have arrested all four of the remaining suspects in the Halloween-candy armed robbery in Dale City.
Rhode Island Avenue business robbery suspect still at largeComment
The man pictured above is the suspect that D.C. Police are searching for in the robbery of a business on Halloween in Northeast D.C. near the Prince George's County line.
Woodbridge teen arrested after implying gun in candy robberyComment
A Woodbridge teenager who allegedly try to steal candy from two people on Halloween night ended up getting the trick himself.
Halloween turns truly scary for robbery victimsComment
Two armed men, dressed in Halloween costumes, pulled a big scary trick today with no treats.
Prince George's County McDonald's robberies under investigationComment
Prince George's County Police are searching for the suspects they believe are responsible for robbing two McDonald's in Camp Springs and Ft. Washington in the past week.
Fa De Zheng, Ming Gang Lu caught stealing cooking oil in ArlingtonComment
Police say that an Oxon Hill man and another man from New York City have been stealing used cooking oil, which can be coverted into clean-burning biodiesel fuel, from the Ballston mall.
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Torah: You shall love your neighbour as yourself.
If selected for publication, it will appear as soon as possible on Haaretz.com.
"Do something, write, tell the world," cries out Dr. Arieh Avidan, deputy director of the ophthalmology department at the Rebecca Sieff Hospital in Safed. He is still haunted by the image of a 15-year-old boy who arrived at the hospital in recent days with a missing hand and both eyes shattered.


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Is there any way of saving e-mail attachments to the phones storage, say for example you get an e-mail with an attached WAV ring tone you want to use? Also is there any way of adding attachments from the phone storage to an e-mail?
Saving e-mail attachments to your phone storage area
Started by Pinball_Wizard , Nov 28 2002 11:56 PM
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Zoho Corporation
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Implementation details of iCal Feed
- Views(List,Summary or Grid) which has a Date-Time field in its list of columns selected, will have an additional option "iCal Feed" under More Action.
- Once the user clicks the option, a pop-up window similar to Embedding Options will be opened
- In the popped up screen, User will first enable the iCal feed.
- Once enabled, user will get a default feed url
- Options for matching the view columns with the iCal property names will also be shown.
- User can match the fields and get the corresponding iCal Feed url.
Note :
- Option of enabling iCal feed will be available only to the owner of the application
- Shared users can get the iCal feed and get the options for matching, if iCal feed is enabled by the owner,
Will the url look like this?
That would enable a live feed to any ical complaint calendar.
We are also planning to introduce the option of enabling it first for all other feeds. Off late, due to the huge surge in traffic for these feeds, it is affecting the general performance of the system, causing slowness to majority of the users. Hence we might bring in a cap of number of feeds one can subscribe to, so that we have some balance. For this we want to first give the option of enabling the feed. Then we will monitor the number of feeds enabled and then arrive at optimal number to limit that will be sufficient to normal users.
For my purposes (not being a "normal user"), I'll be feeding about 8 icals.
Can you give us an update on the progress of our dedicated resource for instantiation of this fist community driven feature? That will be much appreciated.
We are done with the back-end implementation. We have just started on the GUI front. Will publish more details on the implementation soon.
Santa Fe, New Mexico US
As of now the situation is not that bad to be put under once-per-hour or scheduled update of feeds. It will be real time updates only, but you will have to manually enable them. We will also monitor the consumption of such feeds per user level.
Dear all,
We have planned to let users preview the ical feature by next week. Those who are interested for a trial run, can contact Zoho Creator Support with a subject "ICAL TRIAL - <Your Zoho User Name>". We will give more details on this next week.
For ex, the subject of your mail should be ICAL TRIAL - charles
We are yet to update the site with the preview version of this feature. Once updated, we will intimate to all who have signed up for trial.
Hi Charles,
It's been a week since the community got an update. Have you run into any issues that would benefit a discussion here?
It is taking longer than the anticipated time. We are not running into any issues. So here is a preview on how iCal feed feature will be in Creator.
A typical iCal feed (on enabling it) will look like http: //creator.zoho.com/<App owner
If you access the above url, you will get
PRODID:-//ZOHO Creator//iCal Feed//EN
As you can see, there will be only the default properties here. To get more properties, you need to add them as parameters to the given iCal feed url. For the value, you need to pass on the deluge field name of any of the columns in the view. Zoho Creator will take the corresponding values for those columns and will present as value for the given parameter names.
For example you can configure an iCal feed like this
http: //creator.zoho.com/<App owner name>/<app link name>/ical/<view link name>/ORGANIZER=Name&DTSTART=Starting_Time&DTEND=Ending_Time&CREATED=created_time&SUMMARY=Summary&CLASS=Class&STATUS=status
where Name, Starting_Time, Ending_Time, created_time, Summary, Class and Status are deluge field names of the columns in the view.
And you will get
PRODID:-//ZOHO Creator//iCal Feed//EN
SUMMARY:Test ICal.
DESCRIPTION:Test ICal Events.
UID:<App owner name>/<App link name>/<View link name>/<Record Link ID>/@zohocreator.com
In case, you do not want the value from view to be assigned for a parameter, you will have to write down in " ", like CLASS="public".
Parameters supported by Zoho Creator will be
DTEND (or) DURATION
Hope you all find this information useful.
I am very happy that Zoho is supporting so many ical tags. But, I wish you also had the category tag. Not a big issue.
So you are moving away form from the GUI "- Options for matching the view columns with the iCal property names will also be shown. "
Yes, we are moving away from the GUI options for matching the columns for the initial version.
Can you provide the community with an idea when this will be introduced? I'm asking because I see lots of new ideas in the forums for a Round 2. Also, I've tasked myself to help Gaev collect the ideas for voting via a Zoho Creator app. We are patiently waiting to Start Round 2...
passing the time....waiting....
Hi niskypto,
The testing phase of the scheduled build which has this feature got delayed. Will be updated in a day or two.
Dear all,
We have enabled iCal feature for all those who have requested. In case anyone else need it, please reply to this. We will enable it for you.
@ niskypto,
There seems to be an issue when the deluge field name is kept as "DESCRIPTION" . Can you change it and try it? We will fix this in a day or two.
But in the calendar, the "Created By" value is the url above. I has thinking it would be the ORGANIZER?
Please do some testing using Google Calendar.
DTEND:20090710T025959 09-Jul-2009 23:59:59
DESCRIPTION:yadd yadda
SUMMARY:A Sample Event
DTSTART:20090709T103000 09-Jul-2009 07:30:00
I think it's due to the feed part saying "CALSCALE:GREGORIAN X-WR-TIMEZONE:US/Eastern"???
I hope this helps!
Hi niskypt,
We will be ironing out these issues in the next update.
- Timezone issue
- DESCRIPTION issue
- If there is an empty value, it is not generating
Right now, it is a generic ical feed. We are also analyzing on including the google specifics into it.
Looking forward to the update,
Please implement a fix for this. We are starting Round 2 for the community driven features and it would be prudent to follow-through with this task.
I made a new ical feed:
And it's not displaying in my g-calendar, although if you past it into a browser, it does generate a page with a text stream.
Hi niskypt,
I have tested the ICal url given in your post with browser and also imported in g-calendar. It works fine. (please refer the attached screenshot).
It would be easier to assist you if you could explain the issue that you faced while importing.
The timezone issue has been resolved in our local environment, which will be available for the users in the next update.
ICalevent_GCalendar.JPGSize : 81.69 KB Download : 936
I'm in New York, but have to set my G-cal time zone to Pacific for the events to show at the correct time. Is that the fix your will provide in the next update?
What Google Uses: X-WR-TIMEZONE:America/New_York
What Zoho Uses: X-WR-TIMEZONE:US/Eastern
That's the problem.
I've begun to use the iCal Feed and am excited by the possibilities but encountered some immediate questions.
I have a lookup field to display available dates but that lookup field is not available as a parameter for the iCal feed. How do I work around that? Additionally, I have a drop down menu to display times since I have only preset times available. How can I concatenate this time to the date (taken from the lookup) into one Date-Time field?
Hi niskypt,
Yes, we have fixed the timezone issue. You can get it from our next update(within a week).
What Zoho Uses: X-WR-TIMEZONE:US/Eastern That's the problem.
G_cal takes the imported calendar in GMT Timezone by default and then changes it to user's timezone settings. In the to-be-updated fix, we are going to convert the time to GMT timezone - which will solve the issue.
What Zoho Uses: X-WR-TIMEZONE:US/Eastern
That's the problem.
@ Mike:
Yes, now the ICal feed does not work with lookup(Date_Time) field. Thanks for pointing this issue. We are working on it and roll out the fix in next update(within a week).
Thank You. Please let us know when this the fix is made live.
PS: To all following this feed. If you generate a DESCRIPTION that is an html string, Google Calendar will render it! This is fanatic, and could solve the issue of not having a built-in rich text editor for Google Calendar event descriptions.
We need to have better support for "all day" events in the ical feed. Basically, the ical standard for all day events is to simply list the date without any time information
SUMMARY:Independence Day
Since we can only select one DTSTART and DTEND, this causes less flexibility in the feed since these two value will typically be date-time fields in Zoho. Accordingly, I'd like to see some logic on Zoho's side to recognize that if a date-time field is 16-Jul-2009 00:00:00, then Zoho was only pass along 16-Jul-2009. In this way calendar systems like Google, Outlook, etc will immediately render the event in the all day display area.
We have completed the update. Both timezone and lookup field(Date_Time) issues are fixed in this update.
@ niskypto
Now even the Date field is formatted as Date-Time. We will change it to just Date format in our next update. That will solve your issue.
Thank you for the updates
Muthuraj: If you change it to just date, will any time information be ignored? For example will 16-Jul-2009 07:00:00 be fed as 16-Jul-2009 or as 16-Jul-2009 07:00:00? I do not want to lose the time information if it's in there, I just want support of all day events (aka "banner" events), which are always reported as two dates without any time information.
May be the reply was not that explicit. It is going to be like this. If the field type is "Date", you will get it in Date Format(16-Jul-2009) and if the field type is "Date-Time", you will get it in Date-Time format(16-Jul-2009 00:00:00 ). So for a field with Date-time type, we will not change 16-Jul-2009 07:00:00 as 16-Jul-2009. That's because, a person for whom an event should begin at mid-night will not get as he intends to.
Please understand this is not a big issue, more cosmetic. It is only apparent for events like holidays, which will be represented like "Tue Jul 21 12am – Wed Jul 22 12am" if we are feeding a date-time field, when it would look better as "Tue Jul 21 – Wed Jul 22". Typically, my calendar data will contain a mixture of all day events and events with starting and ending times. As I am forced to select one field for both DTSTART and DTEND, the result is that all events will have time value attached, like I described. Unfortunately, there's no ical value to specify that an event is all day, or multiple days. This is why I was looking for some logic on the zoho server to recognize that if an event starts and ends on midnight, the time value 00:00:00 will be stripped-out so that the feed only contains date info, and thus rendered in the banner as "Tue Jul 21 – Wed Jul 22" or "Tue Jul 21 – Wed Jul 28", for example.
Implementation details of iCal Feed
In that case, I will go for another solution. You decide on the format through the url. We will let you specify how you want the format by adding parameters like DTSTART_TYPE=DATE or DTSTART_TYPE=DATE_TIME . And we will override the actual type with the type specified in the url. I believe that would solve the problem
[Upodate:] And I read through your reply again and found that the above solution would not solve your problem since you will not know in advance what kind of data will be there . Instead we will allow some generic preference like ZC_TRIM_DATE_TIME=true and then trim the 00:00::00 value of the Date-Time. This, I believe, would solve your problem.
I really appreciate your effort in working this out!
Ah-ha! So in my forms, I can have some script to analyze my date-time data for a particular entry. If it finds the text string 00:00:00, then it will set the ZC_TRIM_DATE_TIME=true. Zoho will then only feed date data for that particular entry. That would be very, very cool, Charles! Thank You. Let me know and I'll test it out.
You need not have any additional field and you need not do the check. You just need to add this parameter ZC_TRIM_DATE_TIME=true in the url. We will then check if any of the date-time data has 00:00:00 and then trim them and then give the feed.
Let me know when it's ready to test.
By the way, for those following this thread, if you do have an event starting at exactly midnight (which is unlikely except for vampires, werewolves, and the New York state congress), you can script the date-time field to one second after midnight so Charles' invention will not impact your calendar feed.
Due to the date-time bug http://forums.zoho.com?ftid=2266000000354227
I'll never get ZC_TRIM_DATE_TIME to work until the bugs are fixed. Is there a workaround?
I'd like to propose the idea of a Zoho Creator variable in the ical feed, could be ZC_TRIM_DATE_TIME, that if "1" will trim the time (for both start and end date-times), and if "0", will not trim the time regardless what the time sub-string is. The 1 and 0 would be set by the admin's script. This will provide a workaround that is imune to the 00:00:00 and 24:00:00 date-time bugs.
I imagine this should be no more difficult to implement on your side than the original proposal, and gives greater flexibility to the admin.
I've built some icals files from scratch to see how Google Calendar renders them. It turns out that time information is ignored by modification of the DTSTART and DTEND as so:
This effect is reproducible and reliable. For example, to make a "banner" event for one day (July 22), you can use:
...the 08:00:00 and 11:00:00 time parts are ignored in the rendering.
Thus, using the VALUE=DATE: string is the way to go to make banner events appear properly. My proposal in the comment above now even makes more sense rather than Charles' idea. There is no need to clip the time part off, just substitute VALUE=DATE: if the admin specifies a true/false ZOHO variable (like ZC_TRIM_DATE_TIME) in the database for that entry.
ZC Team: Please let me know if this is workable.
We already support VALUE=DATE string. You just need to pass a Date field value for DTSTART and DTEND. That would solve your problem. So for a full day event, you will have to use Date field type and not Date-Time field type.
Charles, I thought this was clear to you. I'll explain again and also quote you:
I read through your reply again and found that the above
solution would not solve your problem since you will not know in
advance what kind of data will be there . Instead we will allow some
generic preference like ZC_TRIM_DATE_TIME=true and then trim the
00:00::00 value of the Date-Time. Please understand that a typical ical "file" will contain a mixture of full-day and finite duration events. Please also recall that I have to pick one variable for DTSTART and one variable for DTEND. With these limitations, how can I possibly differentiate between full-day and finite duration events using your proposal and have it all render properly? Also, since your system does not currently support (bug free) date-times with 00:00:00, I am proposing that your ical parsing routine recognize a new Zoho Creator variable that will tell the routine to pass-thru or cut the time portion of any date-time information prior to generating the ical text file.
Updated: Not cut! I wanted to say, ' insert the "VALUE=DATE:" string'. For example, if this new Zoho variable is true:
If it is false:
I wanted to illustrate the "rendering issue" I have described. Here are some picts when the VALUE=DATE is missing from the ical stream, and why Zoho ical users need control over when this parameter is employed:
Let me know if this will work out for you.
In the url, you will pass ZC_FULL_DAY_EVENT_VAR=<field_name> where field_name is the deluge field name of the field in which you will set true or false. So in the runtime, we will see if there is a parameter named ZC_FULL_DAY_EVENT_VAR and get the field name from which we have to check. We will get the the value of the specified field name from the corresponding row in the view. If it is true, we will append VALUE=DATE . If not, we will not append.
This is the most flexible implementation and the community will be grateful. Please let us know when this is ready for testing.
Will it be ready this week?
Cycle 2 voting will commence after this first community feature is done. Right Gave?
Will be available before this weekend.
I have extended the Suggestions Phase by one week in order to ...
a) have Cycle 1 development completed before Cycle 2 candidate is selected (one week after end of Suggestions Phase)
b) allow for mre suggestions to be made (in case people were on vacation)
c) provide an opportunity to have Voting Application be completed
As Charles mentioned above, Full day event feature is available now on.
Will be available before this weekend
It works as advertised!
I'll test it some more for a few more days before officially calling this completed. In the mean time, Zoho Support should update the wiki entry on this and provide some more details and pictures.
Last night I had a number of my users post events to my web-calendar application, which syncs via Zoho iCal to various Google calendars. Although the sync time from Zoho to Google is not instant, the submissions did show up after a few hours. With this test, I am happy to announce that...
The Zoho Creator iCal Feed Feature is Ready for Prime-time!
This concludes Cycle 1 for the community driven features.
Thank you Zoho Team for turning this idea into an awesome reality!
I have spent a few hours and still cannot import an iCal link from Zoho into Google Calandar.
My test link looks like the above.
The only successful imports I have made are when I only use 1 parameter. As soon as I add a second parameter, I get an error from GCal.
I appreciate any thoughtys.
I'm going to take a guess that the issue is the private link (very long private ID). Under the share tab, make this view public. Then, edit your ical string to remove the private ID part. Add some more ical tags, and then report back.
I have made special public views for all my ical feeds. While updates can take a few hours to propagate, all is working quite well.
Send me an email at webmaster at niskypto dot org for more extensive discussions.
Thank you niskypto. I should have realized a character length issue myself.
I've imported a calendar and am waiting to see when all the details show up.
Additionally, the iCal Feed help page suggest that
I do not think you can have quotes in your ical url string. It will not import.
Also, once my calendar imports to GCal and I click on the event, then click on "more details", the page infinitely loads. Do you just have to wait until the ical feed fully loads?
The CLASS tag is something I am not calibrated on. I'd just use the built-in gcal private/public options.
I have not seen this loading issue. Can you send me a link to your Cal?
Here's one of mine for reference LINK
This morning the "more details" link works. I think there must be a lag time between the initial load of the calendar and all the info showing up?
Yes, it seems Google refreshed the ical feed at least once every 8 hours, but it could be less or more. I have tried to find some documentation on this, but failed.
It sure would be nice of ZOHO Calendar did some of this...you know to keep it close to home. I suspect this is way down the road from now.
I have an events database in Zoho Creator. I want a front-end widget to display the db with a calendar. This process seems super complicated and convoluted. Is there simply a way to attach my creator db with the the zoho calendar widget?
(there should be)
Hoping somebody here can help me!
Thanks much,
For a simple calendar, you can user Zoho Creator's in-built calendar . You just need to select the Date component from your form. Click "Create View" and then select "Calendar View", then select the form and then select the date field, based on which you need to create the calendar.
If you want to hook to an external calendar like Google Calendar (Integration with Zoho Calendar is on the way), you have to construct the iCal Feed in Zoho Creator and add it to Google's calendar . Steps for constructing iCal Feed in Creator is given here .
Please help!
I'm trying to write this url - but I have NO IDEA how to get the deluge names for my columns....is this correct?
I need a Zoho Calendar widget to show the events from my creator database....when will I be able to do this? What's the point of the widget if it doesn't attach to your databases?
Hi Andrea,
The widget that you are referring is for Zoho Calendar Service. As of now, there is no integration between the two. Hence you will not be able to see Creator's form information in that widget.
Integration of ZOHO Calendar and Creator's iCal feed service may be happening soon!
See my post over the the ZOHO Calendar forum: http://forums.zoho.com/topic/zoho-calendar-reloaded
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Traditional design and the latest optical and manufacturing technology (to ISO 9001) are combined to produce a telescope that performs flawlessly in the most difficult conditions and will last for decades.
The lenses are multicoated to maximise light capture and all tubes are anodised to protect against corrosion.
With a magnification of 25x, the Gray telescope enables detailed subject viewing at distances of over a mile, where binoculars are simply not powerful enough, and yet still focuses down to just 15 yards.
The 50mm objective lens, with built in sun and rain shield, gathers ample light to provide crisp, clear images.


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Finnan Haddie Nileta
30 Aug 2010
|Finnan haddie
|1⁄4 Pound
|Macaroni bow ties
|5 Ounce (1/2 Package)
|Grated sharp cheddar cheese
|1 1⁄2 Cup (24 tbs)
|1 Large, sliced
|1⁄2 Cup (8 tbs), sliced
|Green pepper
|1⁄2 Cup (8 tbs), sliced
|4 Clove (20 gm), minced
|2 Cup (32 tbs)
|1⁄2 Cup (8 tbs)
|1⁄4 Cup (4 tbs)
1.' Place finnan haddie in pan and cover with boiling water.Let sit while you are preparing sauce.
2.Saute' onion, celery, green pepper in the butter until soft but not brown.
3.Add garlic and saute' 14 minute more.
4.Add flour and mix thoroughly.
5.Add milk gradually to make a thick sauce.
6.Add cheese and remove from heat.
7.Cook and drain the macaroni.
8.Break fish into bite-size pieces, removing any bones; discard liquid.
9.Combine the sauce, macaroni, fish in 3-quart casserole. Sprinkle with additional grated cheese. Bake in 350 degree oven for 20 minutes to 14 hour, until bubbly.
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Finnan Haddie Nileta Recipe


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Necklace with Malachite Heart Pendant
The necklace is 24.5" long. It is gold plated with a lobster claw clasp.
The Malachite heart pendant is 7/8" x 7/8". The necklace shows normal signs of wear but is in good condition. The heart is absolutely beautiful!
Please note that pictures may have darker or lighter colors on different monitors.
CARE: Clean with soft fabric, or non-abrasive polishing cloth. Avoid direct contact with perfumes, hairspray, and deodorants. Jewelry should be worn after application of cosmetics. Store wrapped in soft fabric or the gift box.
Your purchase will be packed with the utmost care to ensure its safe arrival in a gift box. Open, admire and, if giving a gift, then wrap it the way you like.
If you have any questions just contact me.
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If you intend to buy multiple items from me, please let me know and I will combine shipping. For US buyers...Buy 3 items, receive FREE SHIPPING.
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1882 $20 MS60 PCGS. Ex: Dr. Barry Southerland Collection. Last offered (but not sold) at public auction in our August, 2000...
2007 January Orlando, FL (FUN) Signature Coin Auction #422
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|Printable auction results for all items in the 2007 January Orlando, FL (FUN) Signature Coin Auction.
Extremely Rare Uncirculated 1882 Double Eagle1882 $20 MS60 PCGS. Ex: Dr. Barry Southerland Collection. Last offered (but not sold) at public auction in our August, 2000 Philadelphia Sale as lot 7471. We quote in part from that description, updating where necessary: "First introduced in 1849, Longacre's Liberty motif would grace the double eagle through 1907. This long-lived series has numerous scarce deliveries and several legendary rarities among its business strike issues. The latter include the 1854-O, 1856-O, 1861 Paquet, 1870-CC, 1881, 1885, and 1886. With a total original mintage of only 630 pieces, the 1882 not also belongs in the same category as these other issues, but it surpasses all of them in terms of rarity with the exception of the 1861 Paquet. Unlike the 1881, the 1882 is more difficult to locate in business strike format. There are perhaps 13-15 extant proofs from an original delivery of 59 specimens, but Akers places the total number of business strike survivors at no more than 12 coins....
According to Breen (1977 and 1988), the Philadelphia Mint used a single pair of dies to produce its 571 business strike and 59 proof 1882 double eagles. Since most, if not all of the business strikes are fully prooflike and some of the proofs have been impaired from either circulation or mishandling, the line between the two deliveries can become blurry. For example, Akers (1982) states: "There is also one known [Uncirculated 1882 double eagle] and that coin is really something. By the most conservative grading standards it is a true Gem...or possibly even a bit better." Since we are confident that Akers could not have been referring to the present example, he may have mistaken a well preserved proof for a Gem BU survivor. Still, we must also allow for the possibility that Akers was referring to a coin that has since remained uncertified, perhaps tucked away in the collection of a little known specialist.
The potential confusion that surrounds this issue notwithstanding, we are confident that this Uncirculated example will garner all of the accolades that its low mintage and poor rate of survival deserve. This is a fully prooflike example whose devices are as sharply defined as one could expect for on a business striking. The noticeably abraded, scuffy appearance accounts for the grade, but the thickly frosted devices, fully mirrored fields, and rich orange-rose patina provide relatively pleasing eye appeal. A moderate abrasion in the obverse field between stars 4 and 5 should be useful as a pedigree marker." A great rarity among Liberty double eagles with real potential to reach six figures. Population: 1 in 60, 2 finer (11/06).
From The Kutasi Collection.(Registry values: N10218) (NGC ID# 26BE, PCGS# 8996)
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After completing undergraduate work in Biopsychology at Wesleyan University in Middletown, CT, Diana Wetzel received her Ph.D. in Neuroscience from the University of Pennsylvania in 1989. Following a postdoctoral fellowship at the University of Washington, she moved to The University of Montana as an Assistant Professor in 1995.
Research in the Lurie laboratory focuses on the glial response to central nervous system (CNS) injury and disease. Specifically, Lurie and her co-workers are interested in those cellular cascades which control the proliferation and migration of glial cells following damage, as well as those processes which regulate both the production of, and the glial response to, various growth factors. Recent work has centered on elucidating the role that tyrosine phosphorylation plays in these signal transduction events during CNS injury. These studies utilize a wide variety of model systems including the avian auditory system, rat hippocampus, mouse CNS, and several different tissue culture preparations. Techniques employed in the laboratory include non-radioactive enzyme activity assays, cell proliferation assays, polyclonal antibody development, tissue histology and immunocytochemistry, and image analysis.
Glial cells, particularly astrocytes, play a key role in CNS regeneration following damage. Individual responses of astrocytes are complex, varied, and are not well defined. Some subsets of astrocytes respond to injury by increased proliferation and other activities which are thought to inhibit neuronal regeneration. Other subsets may aid in regeneration by phagocytosis of cellular debris, reconstitution of the extracellular matrix, and secretion of growth factors. To date, it has been difficult to identify which population of astrocytes are involved in these various cellular activities. However, modulation of proliferation and other related cellular functions by external cues is often mediated by phosphorylation/dephosphorylation of intracellular proteins. This process is controlled by the competing activities of specific kinases and phosphatases, and protein tyrosine phosphorylation has been implicated in both the proliferation and differentiation of astrocytes.
Recent work in the Lurie laboratory has identified a subset of astrocytes in the chick auditory brainstem that show strongly increased immunostaining for the tyrosine phosphatase, SHP-1, following injury. This increase correlates with an increase in glial proliferation. Interestingly, the SHP-1 positive astrocytes appear to be those cells which do not enter the cell cycle, even though they are among the population which divide following injury. Similar responses have been found in the rat hippocampus following excitotoxic or metabolic-induced injury. These observations suggest that SHP-1 plays an important role in the regulation of cellular proliferation following CNS damage.
Other research in the group involves elucidating the role of SHP-1 during manipulation of both the cell cycle and growth factor-mediated signal transduction cascades in vitro, as well as the role this enzyme may play during the oncogenic transformation of astrocytes into malignant glial brain tumors. The Lurie lab maintains active collaborations with other research groups at the University of Washington, the University of Kansas Medical Center, and the Institute of Psychiatry, London.
Decreased expression of the voltage-dependent anion channel in differentiated pc-12 and SH-SY5Y cells following low-level Pb exposure.Prins JM, Park S, Lurie DI.Toxicol Sci. 2010 Jan;113(1):169-76. Epub 2009 Oct 12. PMCID: PMC2794334
Chronic low-level lead exposure affects the monoaminergic system in the mouse superior olivary complex.Tyler T and Lurie DIJ. Comp. Neurol. 513(542-58). (2009) PMCID: PMC2677089.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.Harris JA, Iguchi F, Seidl AH, Lurie DI, Rubel EWJ. Neurosci. 28(43):10990-11002. (2008) PMCID: PMC2585504.
Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading, and temporal processing deficits within the murine auditory brainstem.Jones LG, Prins J, Park S, Walton JP, Leubke AE, Lurie DIJournal of Comparative Neurology, 506(6): 1003-1017. (2008) PMID: 18085597.
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37 year old man | Murrieta, CA, USA | Seeking women 25-37 within 75 miles
Willing to Lie About How We Met......
I'm pretty much a what you see is what you get kind of deal, lucky for you I'm pretty hot looking. My pictures are really kind of crappy but they are the only ones I have. Well, I have more, but I refuse to put a "no shirt" picture on the Internet because I don't want them plastered all around my work, no matter how rad my side abs look. I did P90X. Don't be jealous. Here are some fun facts about me: I would never put a personalized license plate on my car. If you take drugs, we will not get along at all. I don't wear hats. If I see someone mistreat an animal I wish I could turn into a bear and eat that person. I appreciate poetic justice. I don't understand the motivation to grow a beard. They are creepy. I can rip a telephone book in half. I think girls who smoke are sexy. I am from Queens, NY. I believe in God, not organized religion. I am a member of Mensa. I have a filthy mouth when I'm angry. I don't get angry often. I have a moderately filthy mouth when I'm not angry. I like to learn new things all the time. I can do a flip. I think the best sex always involves someone being tied up. If I decide to do something, I try to do it better than everyone else, and usually do. I have a titanium plate in my neck that sets off metal detectors. I like to wear flip flops whenever I can. I have a peculiar work schedule but I always make time for people who are important to me. I like to be on the right when walking with a girl. In case of Ninjas. I often find humor where other people don't. I think a few tattoos on a girl looks sexy. I do not follow sports. I didn't realize I was 6'1" until like six months ago. I always thought I was 6'. Don't know how that happened. I'm not sure if I believe in ghosts or not. I don't like country, rap, or hip hop but I like techno. I always try to do the right thing even if I don't do it right. I'm better in bed than your ex. I'm looking for someone who is sexy, smart, and who has a sense of humor. Doesn't sound like too much to ask, right?
Coffee and conversation , Dining out , Movies/Videos , Museums and art , Music and concerts , Exploring new areas , Performing arts , Playing sports , Shopping/Antiques , Travel/Sightseeing , Watching sports , Wine tasting
Other types of exercise, Running, Weights / Machines
I exercise 3-4 times per week.
I have Dogs
I found both of my dogs hurt down by the Mexican Border. One is part pit bull and the other is just yellow. Might be part coyote. Don't know, don't care. They're awesome.
Some other viewpoint
My armpits and my groin.
I have lots of favorite things. My dogs. I love those f*cking dogs. Music: lately, Black Label Society, Pantera, COC, typical white guy music. TV: anything on the History Channel. Color: green.
I read, work out a few times a week, play guitar, play with my dogs, go out with friends, watch TV, research/follow up with work projects, and just relax. Nothing too crazy.
What Every Body is Saying. It's about reading body language. It points out behaviors and gives kind of a key for figuring out what they mean depending on the context. Jedi shit. It was good.
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What he is looking for
|6'1" (185cms)
|3'0" (91cms) to 5'11" (180cms)
|Body type:
|Athletic and toned
|Slender, About average, Curvy, Athletic and toned
|No preference
|Dark brown
|No preference
|Occasionally, Daily, Yes, but trying to quit
|Social Drinker
|No preference
|Other profession
|No preference
Not at Liberty to Discuss.
|No preference
|No preference
|Have kids:
|No preference
|Wants kids:
|No preference
|White / Caucasian
|Asian, Black / African descent, Latino / Hispanic, Pacific Islander, White / Caucasian, Other
If I was any more Irish I would be able to grant wishes.
|I'll tell you later
|No preference
|English, Spanish
|Bachelors degree
|No preference


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|Pictured: Mark Zuckerberg and Priscilla Chan look miserable on their honeymoon ... - Daily Mail
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|The Official Site - Q&A Forum
|Jack Russell Terrier Club of America
Forum Main Menu
Post Response (Restricted)
Head with protruding bonePosted by: Natalie
Category: Medical
Posted on: September 27, 2001 at 15:02:41
Hi, I was noticing that my dog has a hard, nontender area rising on top of his between his ears. I was wondering if Reena who had posed a similiar question ever found out why her dog had the same symptom. Thanks Natalie


text:
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Bay County, Mich.
Manager: Gib Garcia is coaching here for the fourth time. Bay County also participated in the CWS in 2002, 2003, 2005 and 2006.
North Zone: Defeated Mt. Pleasant, Mich. in the championshiup game. Bay County was 5-0 in the zone and 4-1 in the region.
Facts of interest: This team is comprised of players from four high schools, including eight juniors from Bay City Central. Ace pitcher Lennon Gwizdala's father, Jim, played in the Colt World Series during the early 1980s.
Top pitchers: Gwizdala and Tyler Wiechec.
Top hitters: Gwizdala, Wiechec, Kegan Cottick (C), Zach Booty (SS), Derek Lambert (OF/1B), Calyb Shaw (2B).
Style of play: Bay County's top six hitters in the lineup are difficult outs and usually produce lots of scoring opportunities. Plus, Gwizdala and Wiechec have kept Bay County in every game as the 1-2 punch on the mound.
Manager: Sven Huhnholz is coaching in the Colt World Series for the fifth time.
European Zone: Defeated Israel 15-1 in the championship game. Beat Czech Republic 7-6 in the semifinals.
Facts of interest: In preparation for the Colt World Series, the Germans spent five days in Pittsburgh participating in a tournament. Several of Germany's top pitchers did not make the trip because they are participating in an instructional camp in Germany staged by former big league pitcher Bruce Hurst. Several MLB scouts are expected to watch ace pitcher Julius Reitemeier, who has been clocked at 91 miles per hour.
Top pitchers: Reitemeier, Benjamin Thaqi, Nadir Ljatifi.
Top hitters: Elias Von Garfsen (C), Lucas Dickman (SS), Sean Cowan (OF).
Style of play: Germany will feature solid pitching, and the defense is strong, although the hitting is average. Plus, there is no home run power in the lineup.
Greensboro, N.C.
Manager: Reid Holmes is coaching in the Colt World Series for a second consecutive year.
East Zone: Defeated Mooresville, N.C. 22-0, Youngstown, Ohio 8-0 and New Hampshire 8-3 to advance to the winner's bracket finals. Lost to Youngstown 2-1, then defeated Youngstown 8-1 to advance to Lafayette.
Facts of interest: Three of the top four hitters attend Jamestown, N.C. Ragsdale High School. This is the 21st time Greensboro has sent a team to the Colt World Series, winning in 1965.
Top pitchers: Taylor Sugg, Reed Jenkins.
Top hitters: Niko Orfanedes (2B), Sugg (3B), Ben Fischer (CF), Cesar Trejo-Ziri (SS/DH).
Style of play: Greensboro will feature strong front-line pitching and good defense. Holmes said his team must be opportunistic at the plate. Greensboro hit only two home runs in the East Zone playing in a park that is smaller than Loeb Stadium.
Manager: Gilberto Sayogo.
Asia-Pacific Zone: Defeated Rajawali 6-3 in the championship game of the tournament staged in Jakarta. The Asia-Pacific Zone champions were 5-0 in the tourney.
Facts of interest: Assistant coach Donny Trisnadi graduated from Ohio State in 2004 with a degree in finance.
Top pitchers: Muhammad Rizqi Fauzan, Ahmad Abda'oe.
Top hitters: Azfarhan Munaf, Rizky Moehammad Adjhari, Yeremia Prabhaswara.
Style of play: Indonesia will feature bunting, the fake bunt swing and the hit-and-run play, but with the bunt instead of a full swing. They also will try to steal lots of bases.
Los Noches, Mexico
Manager: Roberto Garcia
Mexico Zone: Los Noches defeated Mededa, Yucatan 8-2 in the championship game.
Facts of interest: The team from Mexico drove 60 hours by bus to reach Lafayette, including a delay at the United States border. Manager Garcia also coached here in 2009 and 2010.
Top pitcher: Carlow Pico, who was the winner in the zone title game.
Top hitter: Armando Dominguez was unable to accompany the team to Lafayette because he could not get a visa.
Style of play: Garcia says his team relies on balance in its pitching, hitting and defense.
Pasadena, Texas
Manager: Brock Mayo
South Zone: Defeated Austin, Texas 9-4 in the championship game to cap a 4-0 tourney run. Pasadena scored 49 runs in its four South Zone victories.
Facts of interest: Center fielder Juan Adame was 8 for 11 in the South Zone, including a key two-run double in the top of the seventh inning of a 12-11 semifinal victory against Austin, a game Pasadena trailed, 11-4. Pasadena is a southern suburb of Houston. Pasadena won the 1973 Colt World Series staged in Loeb Stadium.
Top pitchers: Jiovanni Alatorre, Cody Corbell, Robert Loza, Juan Aguilar, Matthew Buennostro.
Top hitters: Adame (CF), Reynaldo Rodriguez (C), Aguilar (3B), Christopher Martinez (SS).
Style of play: Mayo says Pasadena advanced to the Colt World Series because of its pitching. Defense is a concern.
- Jeff email@example.com


text:
Audio Samples
Album Summary
- Franco Bonisolli (Tenor)
- Gino Sinimberghi (Tenor)
- Pietro Bottazzo (Tenor)
- Julia Hamari (Voice)
- Paolo Washington (Bass)
- Anna Balboni (Voice)
- Montserrat Caball� (Voice)
Notes & Reviews:
The Lady of the Lake, based on the narrative poem by Sir Walter Scott, has been one of the most successful of Rossini's "serious" operas to be revived in recent years. Overflowing with thrilling melodies and exciting ensembles, it gets a stellar performance here with Caballe in her prime in 1970.
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Also Purchased
Works DetailsRossini, Gioachino : La donna del lago (The Lady of the Lake), opera
- Performers: Gino Sinimberghi (Tenor); Pietro Bottazzo (Tenor); Montserrat Caballé (Voice); Julia Hamari (Voice); Paolo Washington (Bass); Anna Balboni (Voice); Franco Bonisolli (Tenor)
- Conductor: Piero Bellugi
- Running Time: 101 min. 6 sec.
- Period Time: Romantic
- Form: Opera/Operetta
- Written: 1819
- Studio/Live: Live