The gastrointestinal peptide hormones cholecystokinin and gastrin exert their biological functions via cholecystokinin receptors CCK1R and CCK2R respectively. Gastrin, a central regulator of gastric acid secretion, is involved in growth and differentiation of gastric and colonic mucosa, and there is evidence that it is pro-carcinogenic. Cholecystokinin is implicated in digestion, appetite control and body weight regulation, and may play a role in several digestive disorders.
We performed a detailed analysis of the literature reporting experimental evidence on signaling pathways triggered by CCK1R and CCK2R, in order to create a comprehensive map of gastrin and cholecystokinin-mediated intracellular signaling cascades. The resulting signaling map captures 413 reactions involving 530 molecular species, and incorporates the currently available knowledge into one integrated signaling network. The decomposition of the signaling map into sub-networks revealed 18 modules that represent higher-level structures of the signaling map. These modules allow a more compact mapping of intracellular signaling reactions to known cell behavioral outcomes such as proliferation, migration and apoptosis. The integration of large-scale protein-protein interaction data to this literature-based signaling map in combination with topological analyses allowed us to identify 70 proteins able to increase the compactness of the map. These proteins represent experimentally testable hypotheses for gaining new knowledge on gastrin- and cholecystokinin receptor signaling. The CCKR map is freely available both in a downloadable, machine-readable SBML-compatible format and as a web resource through PAYAO (http://sblab.celldesigner.org:18080/Payao11/bin/).
We have demonstrated how a literature-based CCKR signaling map together with its protein interaction extensions can be analyzed to generate new hypotheses on molecular mechanisms involved in gastrin- and cholecystokinin-mediated regulation of cellular processes.
Gastrin and cholecystokinin (CCK) are gastrointestinal peptide hormones that share a common C-terminal pentapeptide amide . Gastrin, produced in G-cells of the gastric antrum, is the central regulator of gastric acid secretion but also regulates growth and differentiation of gastric and colonic mucosa . CCK, produced primarily in I-cells of the small intestine, is involved in physiological processes such as digestion, appetite control and body weight regulation . The scientific interest in these hormones is further strengthened by their roles in several diseases. Indeed, CCK has been implicated in acute pancreatitis [4–6], obesity [7, 8], irritable bowel syndrome  and gall bladder disease [10, 11]. Gastrin is known to be pro-carcinogenic, affecting proliferation, angiogenesis and apoptosis , and is a risk co-factor for gastric carcinogenesis and atrophy upon Helicobacter pylori infection [12, 13]. In order to efficiently study and understand the molecular mechanisms triggered by gastrin and cholecystokinin, detailed knowledge concerning the signaling pathways they regulate is paramount.
Information concerning intracellular signaling is commonly retrieved from databases such as Reactome  and KEGG . However, none of these resources currently specify which specific molecular events are known to take place in response to gastrin or CCK. Researchers in need of such knowledge therefore must spend significant time reviewing current literature in order to gain an exhaustive and up-to-date understanding of the signaling network. A comprehensive map of gastrin and CCK intracellular signaling pathways would significantly assist in the study of normal or aberrant cholecystokinin receptor (CCKR) signaling.
In the past decade, several manually constructed maps of signaling events have been published [16–25], each providing solid foundations for a systems understanding of the signaling mechanisms. The present work extends this approach to the domain of CCKR signaling by providing a comprehensive literature-based CCKR signaling map that comprises 530 molecular species and 431 reactions, considerably extending previously compiled knowledge on CCK2R signaling [10, 26] including CCK1R downstream events.
Partitioning the total CCKR signaling map into sub-networks using the BiNoM tool  resulted in 18 modules that coordinate with each other to elicit the diverse intracellular signaling responses to gastrin and/or CCK. Finally, we used the CCKR map as a scaffold for protein-protein interaction (PPI) data integration assisted by PathExpand , in order to predict novel components of the signaling network. This resulted in the identification of 70 new proteins tightly connected to the CCKR signaling map, making them prime candidates for future experimental work aimed at further extending knowledge on regulation of CCKR mediated signaling mechanisms.
The CCKR map was constructed using CellDesigner 4.2, a structured diagram editor for drawing gene-regulatory and biochemical networks, following the Systems Biology Graphical Notation (SBGN) standard for process diagrams  and the Systems Biology Mark-up Language (SBML) for model representation . The MIRIAM (Minimum Information Requested In the Annotation of Models) guidelines were followed to characterize each species in the map .
evidence that the reported signaling event is mediated by the specific interaction of CCK or gastrin (G-17) with their receptors CCK1R and CCK2R.
signaling information to allow for linkage of a new CCKR map component to its upstream and/or downstream regulators in CCKR signaling.
CellDesigner species and reaction "note" features were used to record PubMed IDs (PMID), cell-type specific information for each reaction, and the interacting components in the CCKR map.
Final curation and quality control was done in a collaborative effort involving five different research group members who collectively used the community curation platform PAYAO (http://www.payaologue.org) , enabling efficient exchange of comments and tags. Consensus and critical comments from each annotator about the precise representation of reactions, components, and their cellular localization were discussed and implemented (Fig. 1). Finally, the CCKR map was published with an open source license for the whole scientific community through PAYAO  (map available at: http://sblab.celldesigner.org:18080/Payao11/bin/). The CCKR map is also available in the SBML data exchange format (Additional file 1), and we are also in the process of submitting this map to the PANTHER database .
We welcome comments and tags from a community of curators to continue increasing the quality of this CCKR signaling map and will keep it up to date with our growing biological understanding.
Network topology studies were performed by importing the CellDesigner-generated SBML file of the CCKR map to Cytoscape version 2.8  using the BiNoM plugin , after removing connections downstream of the transcription factor layer. BiNoM considers both 'reaction' and 'species' of a CellDesigner map as a node. The Cytoscape version of the CCKR map consisted of 807 nodes (475 species and 332 reactions) with 963 edges. Node degree and closeness centrality were calculated using the 'Network Analysis' plugin  in Cytoscape, assuming the network to be undirected. The number of nodes connected directly to a particular node defines its node degree k, and the node degrees of all nodes in the network represent the 'degree distribution' of the network. Nodes with degree k > 5 were termed 'hubs'.
We used the 'prune the graph' function of BiNoM to automatically separate the strongly connected component (SCC), i.e. the central cyclic motif of the map, from more loosely connected upstream and downstream species. The SCC was further decomposed into smallest sub-networks with the function 'extract material components'. Next, some manual curation work was performed: sub-networks with 50 % or more overlapping nodes were clustered together while the large sub-networks were decomposed further until each sub-network contained a unique central cyclic motif. Any unconnected nodes were removed from the sub-networks, yielding a total of 18 sub-networks or modules. Next, these 18 modules were merged together and the resulting network was compared with the initial map to check for completeness in terms of any missing interactions or nodes. The complete map and its 18 decomposed modules are available as a Cytoscape session file (Additional file 2).
PPI data were downloaded using PSICQUIC (all databases, version June 2012), and filtered for binary physical interactions based on PSI-MI controlled vocabulary experimental method descriptions, following the procedure in  (Charles E. Chapple, personal communication). We then tested each of the 4119 proteins found to interact with CCKR signaling map proteins with the PathExpand method  to seek for tightly linked protein interactors that enhance the network compactness of the CCKR map by leading to higher node degree, betweenness and average local clustering as well as decreasing the shortest path lengths (for details see ) .
CCK and gastrin impinge on cellular functioning by binding to two different G protein-coupled receptors, CCK1R and CCK2R, respectively, located at the surface of multiple cell types in peripheral organs such as the gastrointestinal tract, the pancreas, and the gall bladder . Today, no comprehensive resource exists that compiles current knowledge on CCKR activated signaling pathways. Gastrin has a strong preference for CCK2R, while CCK can activate both receptors with similar affinities . Most cell types responsive to one or both peptide hormones express only one CCK-receptor variant. However, a range of normal and cancer cells in whole organisms as well as model cell lines (for instance the rat pancreatic acinar cell derived cell-line AR42J ) express both CCK1R and CCK2R.
We present a CCKR signaling map built with biological inferences from more than 250 scientific publications (including original articles and reviews), and based on experiments performed in 37 different cell lines representing a wide array of cell types (Fig. 2, Methods).
The CCKR map encompasses 199 unique proteins and their relationships to complexes, genes, and small molecules (including some inhibitors, e.g. rapamycin, wortmannin), describing a total of 530 molecular species and 431 reactions experimentally documented to play a role in CCKR signaling. The reactions include molecular state transitions (e.g. activation, phosphorylation), transport, heterodimer associations/dissociations as well as transcriptional regulation of target genes by transcription factors, which are reported to be associated with the regulation of gastrointestinal hormone responsive biological processes (Table 1).
Figure 2a displays a detailed view of the map depicting the two ligands gastrin and CCK, their biogenesis and processing, their binding to the two G protein coupled receptors CCK1R and CCK2R and the ensuing signal transduction pathways including activation of transcription factors and downstream target genes reported to be triggered in response to gastrin and/or CCK. Moreover, a number of cellular processes influenced by specific CCKR signaling events are indicated, including proliferation, migration, differentiation, anti-apoptosis and inflammation. Figure 2b is an aid for the reader to navigate in Fig. 2a, as it indicates the position of major pathways involved, including protein kinase C (PKC)-dependent activation of MAPK cascades, PI3K-mTOR signaling, protein kinase A (PKA)-dependent pathway, β-catenin, and Rho-GTPase-Bcl cascades.
Network topology analysis of the CCKR map indicated scale-free characteristics, with the majority of the proteins connected to only few other network proteins (Fig. 3). The 6 most highly connected proteins include four protein kinases AKT1, SRC, PKC and PAK1, and the small GTPase HRAS (Fig. 3, inserted table).
Downstream signaling mechanisms shared by CCK1R and CCK2R include the trimeric guanine nucleotide binding alpha q protein (G-protein αq), PKC dependent phosphorylation of adaptor protein SHC - transforming protein C, and its association with GRB2/SOS1 leading to activation of the HRAS/RAF/MAPK1/3 cascade [10, 41, 42]. Other shared pathways involve MAP3K11-mediated regulation of MAPK8, −9 and −10 and p38MAPK (MAPK14), PRKD1 (in PKC signaling), PI3K, AKT1, FAK1, JAK2-STAT3 and Rho GTPase [10, 41–44]. Both receptors activate PKC isoforms PKCα, −δ, −ε, −θ and −ζ [10, 45–47]. Transcription factors reported downstream of both CCK1R and CCK2R receptors include NFκB, CREB1, ELK1 and AP1.
Two trimeric G-proteins appear to be regulated only by CCK1R. One is G alpha S (Gαs) , which leads to Protein kinase A activation via adenylate cyclase catalyzed cAMP production, and the other is G alpha 13 (Gα13) , involved in downstream activation of RHOA . The NOS1 signal transduction pathway downstream of CCK1R [50, 51] regulates Ca2+ signaling pathways by opening ryanodine receptors and two-pore channels that release calcium from the endoplasmic reticulum and endolysosomes, respectively [52–54]. Other signaling cascades, so far only reported for CCK1R, include the Ca2+/calmodulin (CaM) dependent activation of CaMKIV and calcineurin (CaN) – NFAT1 signaling pathways [55–57].
CCK2R activates EGFR via PKC activated MMP3, which cleaves membrane-attached pro-HBEGF into mature HBEGF [58, 59]. PKC isoforms PKC-β and PKC-η have been reported only downstream of CCK2R signaling [60, 61]. CCKR2 specific activation of β-catenin and E-cadherin is mediated by PAK1 [62, 63], and CCK2R specific modulation of BCL-protein family signaling regulates mitochondrial cytochrome C release [64, 65]. CCK2R, but not CCK1R, is reported to activate MAPK7 , an upstream regulator of transcription factors MEF-B,-C and D, and the PKC-η target PRKD2 , which enhances nuclear export of HDAC7 thereby relieving transcriptional repression of target genes such as NR4A1 .
The complete CCKR signaling map (Fig. 2) is very large. We therefore set out to identify structural and functional subdomains of this map. We used the BiNoM software to import the CCKR map in Cytoscape and built a modular view of the CCKR map similar to what has been previously reported for the E2F-Retinoblastoma signaling pathway [27, 68]. The resulting 18 modules (Methods, Table 2, Fig. 4a, Additional file 2) are fully based on the underlying detailed map and help to comprehend higher order map structure, navigate through the map and work on functional modules. Each of the modules represents a structural and functional signaling subunit, combining a set of closely coordinated molecular events concerning a particular protein or a protein complex (see e.g. the Rho GTPase module in Fig. 5a). Furthermore, the regulatory relations (activating/repressing) connecting the modules (Fig. 4a, black and red arrows) are directly derived from the relations encoded in the underlying detailed map (Fig. 2) and the modular view thus represents central decision-making aspects of CCKR signaling. Additional file 3 gives details for each module including the complete list of components and a discussion of their roles in the signaling mechanisms.
Depending on cell type and the state of cells, gastrin can induce different cellular outcomes, such as proliferation, migration and apoptosis. In order to investigate what is known about the involvement of each of the signaling pathway modules in these processes, we checked the scientific literature that we have used to build the CCKR map. We chose to focus on gastrin-mediated effects, because molecular mechanism studies of gastrin-regulated cellular responses are more abundantly reported in literature. Specifically, we recorded all instances where experimental evidence was reported indicating that the function of a specific signaling component had an effect on the cellular outcome in response to gastrin treatment. Based on this literature survey, involvement in cellular outcomes was indicated in Fig. 4a. While central modules such as PKC, AKT1, Rho GTPase, MAP3K11, MAPK1/3 and AP1 are reportedly involved in all three cellular outcomes, other signaling mechanisms are more specific in their effect, e.g. the BCL-module signaling is only observed to be involved in apoptosis (Fig. 4a). Below, we provide a brief description of signaling modules and components involved in each of the cellular outcomes to gastrin treatment.
Molecular mechanisms underlying gastrin-mediated proliferation involve regulation of protein synthesis and cell cycle. Protein synthesis is stimulated via the AKT1-module component mTOR triggering p70 S6 kinase [69, 70]. Gastrin-induced transcription of Cyclin D1, a central regulator of cell cycle progression, is mediated by JUN, FOS, CREB1, and TCF7L2 [71–75], which are components of the modules: AP1, ATF2 and β-catenin. The modular representation (Fig. 4a) shows that EGFR-associated signaling enhances gastrin-induced proliferation by feed-forward mechanisms involving SRC module components. The modular map (Fig. 4a) shows that the AKT1 module inhibits RAF1 and consequently MAPK1/3-module pathways. The molecular mechanism for this is AKT1 kinase-mediated phosphorylation of RAF1 . The modular map thus allows us to hypothesize that the activating role of AP1- and ATF2-submodule signaling in proliferation is more likely to proceed via SRC-MAP3K11 pathways, since these are not inhibited by AKT1.
Gastrin promotes cell migration by activating transcription of MMP7 and MMP9 [77, 78] via transcription factors SNAI1, β-catenin and JUN  represented in the β-catenin- (SNAI1, β-catenin)- and AP1-(JUN) modules. Cell adhesion, tightly linked to cell migration, is regulated through components in the FAK1/2 module (FAK1 and FAK2; Paxillin, CAS, and CRK [79, 80]), which is controlled via both PKC and SRC-modules. The module representation (Fig. 4a) indicates that PKC- and SRC-modules exert a positive feedback regulation on the FAK1/2 module.
Apoptosis is inhibited by gastrin via several mechanisms including BCL-mediated repression of pro-apoptotic caspases and AP1-activated expression of Clusterin [64, 65, 81, 82]. The modular representation reveals that these cellular responses are regulated both by PKC independent and PKC dependent mechanisms. This applies to NFκB and its downstream anti-apoptotic BIRC2 and BIRC3 target genes, which can be activated either directly by PKC or independently of PKC through the Rho GTPase module. Likewise, the AKT1-involvement in regulation of the BCL-module can be mediated by PKC-dependent mechanisms or independently of PKC by the CCK2R - Rho GTPase pathway. Activation of AP1, on the other hand, seems to be strictly dependent on PKC that mediates its effect via either RAF1-MAPK1/3 or SRC-MAP3K11 cascades.
We note that the AKT1-module both inhibits the RAF1-MAPK1/3-route to AP1-activation and enhances Rho GTPase activation of the BCL-module. Thus, AKT1 can potentially promote BCL-module apoptosis-regulating mechanisms and at the same time block MAPK1/3-mediated AP1-activation. In the latter configuration the cell would rely on MAP3K11 to bypass the inhibitory effect of AKT1 on AP1-mediated regulation of gene expression.
The comprehensive CCKR signaling map (Fig. 2) has been constructed with a knowledge-driven approach based on molecular reactions and interactions that are well-documented by scientific evidence in the literature. This thereby inevitably leaves significant gaps concerning signaling events and mechanisms that have not yet been studied and evidenced. We have therefore exploited large-scale PPI data to assess how it can complement the CCKR signaling map by a data-driven strategy.
We identified 4119 proteins interacting with at least one CCKR signaling protein (Methods, Additional file 4). Among 199 unique proteins present in our CCKR signal transduction map, 146 were part of this large protein-protein interaction network. We then set out to identify protein interactors that could be of high interest as potential interactors or modulators of the complete CCKR signaling map (Fig. 4a). For this, we analyzed each of the 4119 proteins interacting with the CCKR map proteins using the PathExpand approach . PathExpand checks each interactor to see if it satisfies a number of topological criteria leading to increased compactness of the complete CCKR map. We identified a total of 102 proteins that qualified as PathExpand interactors, 32 of them being components of the original CCKR map. The 70 PathExpand interactors not present in the original CCKR map are listed in Table 3. Interestingly, the set of 70 new CCKR map candidates include 30 proteins that are not known to participate in any signaling pathways listed in the pathway databases KEGG, Reactome, PANTHER and Biocarta (Table 3). A GO term overrepresentation analysis  showed that the set of map candidates is enriched in molecular functions relating to protein kinases, protein phosphatases and GTPase-regulators, indicating that many of them could potentially regulate the CCKR pathway via phosphorylation-dephosphorylation mechanisms and by interfering with small GTPase signaling. Among these are the protein kinases STK4, CSK21, CSK22, ITPKA, FLT4, DDR2, KS6KA4 and MAPK15 and a high number of Dual specificity phosphatases (DUSP1, 2, 4, 5, 7, 9, 22) in addition to phosphatases PHLPP1 and PTPRR.
Inspection of the expanded networks resulting from the combination of PathExpand protein interactors with 7 CCKR modules (Fig. 4b, transcription factor centered modules excluded) shows that 11 of the protein interactors are linked to more than one CCKR module and can contribute both to PKC-independent (e.g. ARHGEF25, ARHGAP31, TBC1D3F) and PKC dependent (e.g. ICMT) signaling routes. In contrast, 21 protein interactors are linked to only one module, suggesting that they may act as preferential regulators of this module. For instance, the Mitogen activated kinase 15 (MAPK15) is a compactness increasing protein only for the SRC module, where it interacts with the two kinases SRC and CSK.
By taking a closer look at the gastrin regulated Rho GTPase module and its identified PPI extensions, we here discuss putative novel signaling mechanisms involved in gastrin-mediated regulation of the Rho GTPase signaling.
Central to the Rho GTPase module (Fig. 5a) is the activation of small GTPases, RHOA, RAC1, and CDC42 by guanine exchange factor proteins (GEFs), which trigger conversion of the inactive GDP-bound form of small GTPases to the active GTP-bound form. The GEFs in gastrin-mediated Rho GTPase signaling are Leukemia-associated Rho guanine-nucleotide exchange factor (LARG) and the trimeric receptor-associated G-protein complexes Gαq and Gα13. In addition, HRAS may also act to activate RHOA and CDC42. The small GTPases RHOA, RAC1, and CDC42 are documented to activate kinases ROCK1 and PAK1, which are both part of the gastrin-regulated Rho GTPase module, and of kinase AKT1, part of the gastrin-regulated AKT1 signaling module. The inactive form of the small GTPases is restored by GTPase-activating proteins (GAPs) that enhance hydrolyzation of the bound GTP. In gastrin-mediated signaling deactivation of RHOA and RAC1 is effectuated by GAPs, ARHGAP4 and RGS2, respectively.
Eight of the ten PathExpand protein interactors (Fig. 5b, Additional file 5) of Rho GTPase module components interact with one or more of the small GTPases RHOA, RAC1, and CDC42. All of these protein interactors are annotated with GO-terms indicating a known role in regulation of small GTPases, and four of them (IQGAP2, TBC1D3F, ARHGAP31, OPHN1) are known as GTPase activators. We suggest that these eight proteins are strong candidates for potentially novel modulators of gastrin-mediated Rho GTPase module signaling. Three of the proteins (TBC1D3F, ARHGAP25, and ICMT) are not yet present in any of the common pathway databases (see Table 3). The evidence presented here, indicating that the three proteins have tight interaction with multiple proteins involved in gastrin signaling, demonstrates that our approach is well suited to identify testable hypotheses, even for candidates for which knowledge in public databases is still sparse.
The PathExpand interactor BNIP1 (BCL2/adenovirus E1B 19 kDa interacting protein 1) interacts with two downstream BCL module components BCL2L1 and BCL2, both involved in effectuating the gastrin anti-apoptotic signal. Since BNIP1 is known to be involved in SNARE vesicular transport, our findings indicate that it may be an interesting candidate to follow up with investigating a potential role of vesicular transport in modulating BCL-linked signaling mechanisms in the gastrin signaling pathway. The PathExpand interactor programmed cell death 11 (PDCD11) interacting with the two subunits of NFκB transcription factor (NFκB1 and TF65) is known to be involved in maturation of ribosomal RNA but may also play a role in mRNA processing. Our results identify PDCD11 as a potential candidate to follow up in experimental analysis of molecular mechanisms involved in NFKB-mediated gene regulation in cellular responses to gastrin.
In the work presented here, we set out to build a comprehensive and well-annotated molecular interaction map to aid future studies involving gastrin or CCK. A mechanistic understanding of CCK1R and CCK2R signaling networks is essential for experiment design and data interpretation in biological systems involving gastrin- and CCK-regulated processes. Moreover, it may enhance the identification of therapeutic chemicals able to target disease, by using the map as a functional interaction diagram with components that modeling indicates as prime targets for perturbation, as described by Lee et al. , who successful designed a drug-induced rewiring of the 'state' of oncogenic signaling networks to maximize the susceptibility to anticancer drugs. The current map depicting molecular signaling mechanisms underlying CCK1R and CCK2R triggered cellular responses may provide a tool to guide further investigations into normo- and pathophysiological processes such as gastrin-regulated stomach mucosa homeostatis and gastrin-linked carcinogenesis [59, 64, 85, 86], and cholecystokinin-induced hypoplasia, cell regeneration and digestive enzyme secretion  as well as to identify potential intervention strategies for associated disease states.
Some pathway proteins and reactions of the CCKR signaling map are also described in the Reactome  and KEGG  databases. However, the CCKR map constitutes a vastly more comprehensive and integrated model, providing detailed signaling reactions linking the receptors CCK1R and CCK2R all the way to regulated genes and cellular responses. For comparison, the recently published gastrin signaling map  comprises approximately half of the molecules and only a quarter of the reactions presented in our CCKR map. Similarly, knowledge currently in Reactome covers less than 5 % of the pathway details presented here. The CCKR map therefore represents a significant increase in curated signaling information. The provided SBML version of the CCKR map can serve as a starting point to generate quantitative mathematical models  for simulation and prediction of cellular outcomes in response to perturbations of the network.
We enhance the applicability of the map for hypothesis generation by two central strategies. First, we provide a computationally modularized version of topologically and functionally connected meta-nodes. This modular view simplifies the complete CCKR map and provides for an improved, higher level comprehension of pathway regulatory aspects concerning cell fate decisions related to proliferation, migration and apoptosis. Secondly, we take advantage of public large scale PPI knowledge to predict new potential regulators of CCKR signaling, including 70 interactors that significantly enhance the compactness of the CCKR map , through tight direct and indirect interactions with map proteins. Although experimental validations are needed to confirm these new CCKR signaling mechanisms, they represent an important source of high quality hypotheses that may be taken as a first step to develop a better comprehension of CCKR pathway functionality.
Compared to other recently published computational approaches for high-throughput hypothesis generation [20, 89, 90], the advantage of our strategy is the combination of i) biological background knowledge encoded in the signaling map, including the modules, manually curated from literature reporting detailed experimental analyses of gastrin- and CCK-signaling, and ii) large-scale PPI information downloaded from available databases of interactions, filtered for binary physical interaction based on selected experimental detection methods.
Our work demonstrates how publicly available tools can aid in the manual curation of an extensive network topology, in order to build a foundation for a systems understanding of CCKR-mediated cellular responses. Furthermore, the integration of a comprehensive model of complex biological networks with genome scale data can provide new knowledge and hypotheses on molecular mechanisms underlying cellular processes. Further development of the resources presented here should be of high interest in translational research aimed at identifying new targets and biomarkers for treatment and diagnostics of gastrin- and/or cholecystokinin-related disease, including cancer.
We thank Charles E. Chapple for sharing his protein-protein interaction network and Enrico Glaab for "a la carte" PathExpand analyses. This work was supported by The Norwegian Cancer Society, The Liaison Committee between the Central Norway Regional Health Authority (RHA), the Norwegian University of Science and Technology (NTNU) and Sør-Trøndelag University College (HiST).
Additional file 1: The file is the SBML version of the complete CCKR map.
Additional file 2: This file is an original Cytoscape session file containing the BiNoM generated modules of the CCKR map.
Additional file 3: The file contains a description of individual modules of the comprehensive CCKR map constructed using the BiNoM plugin in Cytoscape.
Additional file 4: The file contains a list of CCKR model protein interactors identified from the large scale protein-protein interaction network.
Additional file 5: The file contains the PathExpand analysis of BiNoM modules and their protein interactors.
ST conceived the idea of the CCKR map, participated in map construction, curation and modular decomposition, interpretation of PPI- analyses and manuscript writing. ÅF participated in map construction and curation, and manuscript writing. KC participated in modular decomposition with BiNoM analysis, carried out network topology studies and helped in manuscript writing. AB provided protein-protein interaction network analysis data and manuscript writing. TB participated in pathways curation and manuscript writing. LT raised funding, participated in pathway curation and helped to draft the manuscript, MK raised funding, participated in interpretation of PPI- analyses and helped to draft the manuscript. AL raised funding, participated in pathway curation, interpretation of PPI- and helped to draft the manuscript. All authors read and approved the final manuscript.


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unique bedside table lamp with vintage touches.
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unique kids bunk beds with lazy sofa.
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SEM (PPC and Social Advertising)
Search engine marketing (SEM) is a form of Internet marketing that involves the promotion of websites by increasing their visibility in search engine results pages (SERPs) primarily through paid advertising.[1] SEM may incorporate search engine optimization (SEO), which adjusts or rewrites website content and site architecture to achieve a higher ranking in search engine results pages to enhance pay per click (PPC) listings.
SEM is the wider discipline that incorporates SEO. SEM includes both paid search results (using tools like Google Adwords or Bing Ads, formerly known as Microsoft adCenter) and organic search results (SEO). SEM uses paid advertising with AdWords or Bing Ads, pay per click (particularly beneficial for local providers as it enables potential consumers to contact a company directly with one click), article submissions, advertising and making sure SEO has been done. A keyword analysis is performed for both SEO and SEM, but not necessarily at the same time. SEM and SEO both need to be monitored and updated frequently to reflect evolving best practices.
Filter Filter Back Linking Basic Content Creation Content Marketing Digital Marketing Content Creation Email Marketing Engaging Content Facebook Google Products Google Search Google+ Inbound Marketing Indexing Instagram Internet marketing Keywords Link Building LinkedIN Local Search Mobile Search Monthly Marketing Online Presence Online Reviews Organic Search Result Premier Reputation Management Search Engine Optimization Search Ranking SEO SMM Social Media Social Media Content Social Media Marketing Standard Subscription Twitter Website Architecture Website Design Website Development Youtube

redpajama_set_name: RedPajamaCommonCrawl


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Perrona perron é uma espécie de gastrópode do gênero Perrona, pertencente a família Clavatulidae.

Clavatulidae
Moluscos descritos em 1791

redpajama_set_name: RedPajamaWikipedia


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Will MH17 be our 9/11? (28) Why the one tenacious critic of the Dutch government was silenced
This article is a translation of "Wordt MH17 ons 9/11? (28) Waarom de enige criticus van de Nederlandse regering tot zwijgen werd gebracht"
Mid November the Dutch parliamentarian, Pieter Omtzigt (Christian Democrat), came under fire for allegedly having stage-managed, at a meeting at the Free University in Amsterdam, the statement of a witness contradicting the official explanation of the downing of Flight MH17. A text message in which Omtzigt made a helpful suggestion to the witness how to summarise his story given that he would get one minute at best, was passed on to the Dutch daily, NRC Handelsblad, which raised the issue of the MP's credibility and called for his resignation.
This was not only a way of getting rid of the one parliamentarian who has consistently demanded of the Dutch government that it live up to the Prime Minister's vow to get to the bottom of the MH17 affair. Omtzigt was also his party's spokesman on tax matters, pensions, and the euro and there he was an even greater liability to the powers that be. This is why after half a year, his courtesy towards an Ukrainian man was suddenly turned into something close to treason.
When the MH17 meeting at the Free University happened in May last, the Dutch general election results were only two months old and no new government had yet been formed. The video of the witness making his statement (he was primarily interested in obtaining asylum in the Netherlands, or so it seemed) was circulated without causing any concern. The claim that one or more jet fighters had been spotted near MH17 had been made many times before and by far more reliable witnesses; in this case it was not even the man himself but has wife who had seen the planes.
Now fast-forward to November, when NRC Handelsblad came with its 'scoop', six months after the fact. After a tortuous cabinet formation taking all summer and comfortably interrupted by full holidays taken, there now was a government of mainstream Liberals, neoliberals, Christian Democrats and Christian fundamentalists (who actually held up the negotiations for another week because their leader had to attend a rock concert in Germany). This coalition only had 76 seats, a majority of one. It also surprised the nation with an announcement that it would scrap the dividend tax, a gift to business of 1.4 billion euros per year—although none of the coalition partners had proposed this in their election manifestoes.
However, as Marx famously put it in the Communist Manifesto, the government is only a committee for handling the day-to-day affairs of the capitalist class; and in their plans, scrapping the dividend tax had long been on the agenda.
In 2009, the head of the Dutch employers' organisation VNO-NCW presented a report to the then-prime minister (a Christian Democrat) about the importance of having head offices located here and the need to abolish the dividend tax in addition to the many already existing tax advantages the country offers. These have made the Netherlands the single most important transit point of money seeking refuge in tax havens.
At any rate the Ministry of Finance advised against scrapping the tax, as recently revealed in a report by the investigative group SOMO.
In 2014 it was the American Chamber of Commerce in the Netherlands that asked the Dutch state secretary of finance to abolish the dividend tax, but again the Ministry advised against it, warning it would cost even 1.6 billion euros and mainly benefit foreign owners. However, continuing revelations about tax evasion and public concern led the EU and the OECD to prepare measures against it, which might affect the Dutch role as a fiscal transit point. Prime minister Rutte (Liberal) on 19 May 2015 at a high level dinner in his residence discussed how the Netherlands might tackle the expected obstacles. Then in April 2016, Shell expressly called for scrapping the dividend tax again if further exploitation of Dutch gas reserves was to take place in a favourable business climate.
After the Dutch elections, in which as noted, the dividend tax was not mentioned, the American Chamber of Commerce (in which many Dutch companies, including Shell, are also represented) again raised the issue of the dividend tax. In an investors' report in May, whilst cabinet formation negotiations were going on, it praised the Dutch tax regime but warned that the Netherlands began to lag behind in lowering corporate taxes. A new government should therefore give a clear signal to foreign investors that it was moving the goalposts further.. Then came the announcement of the new Rutte III government that it would scrap the dividend tax per January 2019. Widespread public debate followed.
This takes us back to Pieter Omtzigt, his party's spokesman on MH17 and on tax matters. In the Second Chamber's debate on public finances on 8 November, Omtzigt was besieged by other MP's after he announced that he would speak out as critically about the government's 'interesting plans' as he had done as an opposition MP. He expressly stated that in this respect the Constitution makes no difference between an MP of the governing coalition or an opposition member. This promptly brought him under fire from the spokeswoman of the opposition Socialist Party (the largest Left formation after the decimation of the mainstream Social Democrats) with the express invitation to reinforce the opposition's 74 members on the issue of the dividend tax. After she led the attack, other MP's joined in, all focusing on Omtzigt as if he on his own represented the new government.
After Omtzigt deflected the dividend tax issue as a cabinet matter, he shifted to the 'Paradise Papers' tax evasion issue. On page 39 of the official transcript of the proceedings he says that the half-yearly report on tax evasion by Dutch residents, which should have been deposited in the central database per 1 January 2017 (under the old government), had been missed and that he keenl awaits further steps under the treaty which prescribes exchange of tax evasion data. In other words, he announces he will not shrink from attacking the government's policy on tax evasion should it fail to tackle the issue.
Was this was the drop that made the bucket overflow? For within days, NRC Handelsblad, the mouthpiece of the Liberal party, began what can only be considered a character assassination of this, one of our finest parliamentarians. By unearthing a half-year-old issue of no consequence they also got rid of an MH17 critic who had been stubbornly following the government in its obvious attempt to kick the issue into the long grass. Meanwhile his own Christian Democratic fraction leader, instead of defending Omtzigt, chose to stoke the flames of paranoia about 'Russian meddling' in Dutch affairs, thus heightening the climate of suspicion in which the campaign against Omtzigt had been made possible in the first place. The victim could do little else but officially declare he would no longer be the spokesman on the MH17 portfolio.
But let one think this means the case is closed. More will follow.
Kees van der Pijl (with thanks to Babette U.)


All security devices are essentially the same inside their standard operation so the generally asked inquiries are often equivalent Alarms Dublin . The next is usually a list of by far the most requested issues about dwelling security units.
How does my household alarm process work?
There are actually three modes of procedure of any property alarm program. They are really disarmed, armed away and armed in remain manner. During the disarmed manner the sole capabilities that do the job will probably be stress alarms, medical alarms as well as hearth alarms. These features will perform a similar in almost any of the usual modes of operation. These are termed as 24 hour variety of alarms. They could usually be induced manually from the control panel or from the distant location including a essential fob if the technique is setup to acquire a person. Should your residence alarm procedure is disarmed then you definately will even now begin to see the announcement of doorways or windows which can be opened. This will be by an audible announcement with the control panel or even a zone gentle that could also light-weight within the alarm panel.
Whenever your household alarm is in the stay mode of operation it means just how it appears. You are staying house and this suggests that any of the within gadgets like movement detectors are shut off. They're going to still detect motion but they will likely not bring about your alarm. In this manner you may shift regarding your household and nonetheless hold the perimeter guarded.
You need to watch out once you use this mode simply because it truly is assumed by many that they are safe and sound and safe at night once they retire to bed which will not be the situation. In several techniques the home owner continues to be certain once they obtained the process that all they needed was the no cost process that includes a entrance door, back doorway and an inside of movement sensor. If this can be the kind of protection that your procedure has then you certainly are certainly not guarded once your technique is in keep mode. You see as a way to suit your needs to be capable to move close to your individual house the within movement in most cases is disabled by becoming armed in keep manner. When you drop by mattress once the process is still in remain method you then no longer have the defense of the movement sensor. The only real method to prevail over this is to get the control panel positioned someplace in your house where you is not going to trip the program if you stand up each morning to disarm it. When employing the process in this manner you could arm the technique in absent method while you are still in the home and preserve the within movement sensor on whilst you are asleep.
Whenever you have set your alarm in away method it means that every one of your respective zones are armed and if any of them are violated your alarm will cause. The entry/exit doorway is frequently established by using a hold off so you have the ability to enter the house and disarm the program in advance of it transmits an alarm to the central station monitoring company.
If the alarm is induced a sign is transmitted into the central checking station. This sign is received and also the monitoring station is familiar with specifically where the alarm was transmitted from and what zone is in alarm. The checking station will get in touch with you with the number that you choose to supplied to verify an true alarm. You are going to provide the possibility at that time whenever they access you to definitely cancel the alarm or maybe the law enforcement are going to be dispatched.


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ToC Day FOUR : Asal ends Gaultier run
12th Jan 20 stevecubbins 2020, NEWS, PSA, PSA PLATINUM, ToC, USA
Day FOUR : Asal ends Gaultier run
The ToC continued on Day Four with another nine matches on the Glass Court plus three at River Club for Women's Round Two (bottom) and Men's Round Three (top).
Tournament of Champions : Men's Round Three (top)
[1] Ali Farag (Egy) 3-0 Youssef Soliman (Egy) 11-9, 11-9, 11-7 (44m)
[5] Paul Coll (Nzl) 3-0 Tom Richards (Eng) 11-5, 12-10, 11-1 (38m)
Mostafa Asal (Egy) 3-2 Gregory Gaultier (Fra) 5-11, 13-11, 12-10, 10-12, 11-5 (75m)
[4] Tarek Momen (Egy) 3-1 Eain Yow Ng (Mas) 11-9, 11-4, 3-11, 11-9 (42m)
Full ToC Coverage ToC Draws & Results Live Scores
Asal halts Gaultier to reach Quarter-Finals
18-year-old Egyptian Mostafa Asal is into his first ever PSA World Tour Platinum quarter-final after he overcame former World No.1 and World Champion Gregory Gaultier in a breathtaking five-game encounter earlier today at the J.P. Morgan Tournament of Champions held at New York's famous Grand Central Terminal.
World No.21 Asal upset World No.9 Mohamed Abouelghar in the previous round, while 37-year-old Gaultier made a sensational return from 15 months out injured as he defeated former World No.3 Omar Mosaad 3-2 in a repeat of the 2015 World Championship final.
It was a match which saw youth come up against experience in an extremely high-quality affair, with both players taking two games apiece as three tie-breaks delighted spectators inside Grand Central's picturesque Vanderbilt Hall.
It was all about the teenager in the fifth game as he raced into the lead, before a contentious call with regards to a possible double bounce was called good in Asal's favour. The 8-4 advantage was too much of a gap for the war-weary Gaultier, who picked up just one more point as Asal closed out a 5-11, 13-11, 12-10, 10-12, 11-5 victory in 75 minutes to mark the biggest PSA Tour win of his career.
"Gaultier is such a legend, and I can't describe the feeling of sharing a court with him," said Asal afterwards.
"I remember when I was 13 years old, I went on court to practice with him, every single day after his matches in El Gouna, so I want to thank him for the opportunity to play with him. He really is a legend and I can't describe my feelings to him.
"I was a child and I texted him to ask if I could play with him in El Gouna and he said yes. I know if he hadn't have been injured then he would have finished me in about five minutes. It's unbelievable to play here, it's my second home, and it's the best tournament that I have ever played on the PSA."
Asal, the reigning World Junior Champion, will now clash with senior World Champion Tarek Momen for a place in the semi-finals, with Momen dispatching Malaysia's Eain Yow Ng by a 3-1 margin.
Meanwhile, defending champion Ali Farag is also through to the quarter-finals where he will take on World Championship runner-up Paul Coll in a mouthwatering fixture after they beat Egypt's Youssef Soliman and England's Tom Richards.
Farag, the World No.1, completed an 11-9, 11-9, 11-7 victory over Soliman and will now look to extend his 10-match winning run over the Kiwi, with Coll's only victory over him coming here in New York back in 2017.
"He didn't make it easy for me," Farag said.
"I was listening during the pre-match introductions and Youssef has had an amazing year, he's been beating a lot of top players and he has shown on this court that he has been playing really solidly, so I had to be on my metal from the beginning. He didn't make it easy but I think a bit of experience at the end of the games made the difference."
Tournament of Champions : Women's Round Two (bottom)
[4] Nour El Tayeb (Egy) 3-0 Donna Lobban (Aus) 11-8, 11-9, 11-6 (22m)
[14] Salma Hany (Egy) 3-0 Nadine Shahin (Egy) 11-4, 11-8, 11-8 (26m)
[12] Joshna Chinappa (Ind) 3-0 Tinne Gilis (Bel) 11-7, 11-6, 11-9 (33m)
[6] Joelle King (Nzl) 3-0 Julianne Courtice (Eng) 11-9, 11-2, 11-4 (25m)
[8] Sarah-Jane Perry (Eng) 3-0 Nele Gilis (Bel) 16-14, 11-7, 11-7 (39m)
Sabrina Sobhy (Usa) 3-1 [15] Victoria Lust (Ebg) 10-12, 11-6, 11-9, 12-10 (42m)
Olivia Blatchford Clyne (Usa) 3-0 [9] Tesni Evans (Wal) 7-4 rtd (17m)
[2] Nour El Sherbini (Egy) 3-0 Milou van der Heijden (Ned) 11-4, 11-8, 11-4 (24m)
The second round of the women's event continued today as two American players – Olivia Blatchford Clyne and Sabrina Sobhy – booked their round three berths courtesy of wins over World No.9 Tesni Evans and World No.15 Victoria Lust.
Blatchford Clyne's clash with Evans was cut short after the Welsh player rolled her ankle early on in the opening game, and the US No.2 will now take on reigning champion Nour El Sherbini after the Egyptian defeated Dutch player Milou van der Heijden in straight games to kickstart only her second tournament of the season.
"It's awful, I'm very blessed that I've never had that happen to me," Blatchford Clyne said.
"I'm sure she's heartbroken and I'm heartbroken for her. I'm also gutted I didn't get to do it, but I just hope that she's able to recover as quickly as possible. She's a really tough, entertaining cookie and I'm sure she will be back soon."
World No.39 Sobhy continued her fine tournament so far as she followed up an opening day win over Hong Kong's Joey Chan to beat the higher-ranked Lust to become the only member of the Sobhy family to reach the last 16 after older sister Amanda bowed out in a shock loss to World No.27 Emily Whitlock yesterday.
"She made it incredibly challenging for me," said Sobhy.
"I needed to focus point by point and on my game and not let the crowd or my emotions get involved. It's big to be able to see my family and friends supporting me here and makes these matches more memorable. My goal was actually just to get past the first round, so it's going to be really cool playing on the glass."
Sobhy will play England's Sarah-Jane Perry for a place in the last eight, with Perry beating Belgium's Nele Gilis in a match which saw a 16-14 win for Perry in a nail-biting first game prove crucial.
Meanwhile Australia's Donna Lobban donated $1 from every point won in her clash with Egypt's Nour El Tayeb to go towards the aid in Australia helping to stop the devastating bushfires that are affecting the country at the moment. The World No.47 tested El Tayeb, but the World No.4 pulled through to book her last 16 spot against compatriot Salma Hany.
New Zealand's Joelle King and India's Joshna Chinappa also claimed wins and will contest the other third round fixture on the bottom half of the women's draw.
Eurosport Player (Europe) SquashTV (RoW) PSA Facebook (not EU/Jpn
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ToC FINALS : Serme and Shorbagy are the Champions
ToC Semis : Five game upsets from Serme and Momen
ToC Day SEVEN : the semi-finals are set
ToC Day SIX : Serme ends losing run to oust Welily
ToC Day FIVE : Makin makes the quarters as Serme survives again
ToC Day THREE : Whitlock comeback stops Sobhy
ToC Day TWO : Gaultier makes triumphant return
ToC Day ONE : US men's hopes dashed
9th Jan 20


Welcome!! My name is Mrs. Bostic and I teach fifth grade in room C3. I am so excited to be your child's teacher! I have a BA in Liberal Studies with an emphasis in Teledramatic Arts in Theater from CSUMB and a multiple subject teaching credential from SJSU. I have three children, all boys, ages 1, 2, and 5. My oldest son, Trevor, attends kndergarten at Valle Vista. I enjoy reading, movies, animals, and spending time with my family.


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Chrzemce – wieś w Polsce położona w województwie łódzkim, w powiecie tomaszowskim, w gminie Lubochnia.

W latach 1975–1998 miejscowość administracyjnie należała do województwa piotrkowskiego.

W miejscowości są tylko 2 numery domów.

Przypisy

Lubochnia (gmina)


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How to Calculate Your RMD: a Uniform, Inherited, and Joint Divisor Calculator
by Megan Russell on April 12, 2017 with No Comments
After you reach the age of 70 1/2, the IRS requires you to begin taking minimum distributions from your traditional retirement accounts. The amount the government mandates you take out of your account each year is called a Required Minimum Distribution (RMD).
The amount which you are required to take as a distribution is based on the value of your traditional retirement account on December 31 of the previous year. That value is divided by a number (hereafter called the divisor) provided by IRS based on your age.
There are different tables and formulas used to calculate your RMD divisor based on your particular circumstances. The simplest RMD divisor is for individuals who are older than 70 1/2 and is called the Uniform Divisor. Then, the Joint Divisor is an alternate and more favorable RMD calculation for married couples with more than 10 years difference in their ages.
For Inherited IRAs, all the rules are complicated but the simplest divisor is the Inherited Divisor. If you are the spouse of the previous owner, you also have the option of doing a Spousal Rollover with the inherited assets, which counts as though it were your own money and uses the Uniform Divisor.
If a non-person (Trust, charity, estate) inherits an IRA or an IRA is inherited by a non-spouse without the aid of beneficiary designations, their RMDs do not have a divisor but instead are subject to the 5-Year Rule.
The below calculator calculates divisors for the Uniform divisor (uses your birthday), Joint divisor (you and your spouse's birthdays), and Inherited divisor (your birthday and the previous owner's date of death). It cannot advise you on if you are permitted to use the divisor it calculates. Please familiarize yourself with the requirements of each before proceeding.
Photo used here under Flickr Creative Commons.
An Updated RMD Calculator (New Divisors for 2022)
RMD Mistake: Not Using the Joint Divisor
What You Need to Know to Inherit an Inherited IRA
Q&A: How Do I Calculate My RMD from a Complicated 401(k)-to-IRA Rollover?
Inherited Required Minimum Distributions: Your Custodian May Mislead You
Best Of, Required Minimum Distributions, Tools
Follow Megan Russell:
Megan Russell
Chief Operating Officer, APMA®
Megan Russell has worked with Marotta Wealth Management most of her life. She loves to find ways to make the complexities of financial planning accessible to everyone. She is the author of over 700 financial articles. Her most popular post is "The Complete Guide to Your Washing Machine" while one of her favorites is "Funding a 3-Year-Old's Roth IRA."
Latest posts from Megan Russell
At 65, Does the 5-Year Roth Rule Matter? - January 24, 2023
#BestOf2022 How to Change a 529 Plan Account Owner - January 20, 2023
Q&A: What is Your Strategy's Expense Ratio? (2022 Analysis) - January 17, 2023


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Michael Köckritz
The Pure Elegance of Freedom
"Coolness" - on the one hand today a fashion word devoid of content, on the other a self-confidently lived, late-modern individual attitude and behavioral strategy with rebellious roots against a twisted and unjust world.
But what does the word "cool" actually mean and what does it mean "to be cool"? How does "coolness" become tangible? What makes coolness so appealing? Where do the terms come from? How has the matter evolved?
Which facets do we encounter when we take a closer look?
Michael Köckritz gets to the bottom of these questions with a holistic view, researches and collages history and stories, talks to interdisciplinary experts about backgrounds and developments, characteristics and criteria, identifies with you the icons and personalities that so strikingly shape our modern image of coolness. The result is an entertainingly stimulating as well as creative journey of discovery approaching the facets of a timelessly fascinating phenomenon of longing.
This reflected, precise look at the concepts of cool and coolness becomes an impressive plea for coolness as a timelessly modern, emotional experience and self-confident "attitude" that lives attractively from a refusal of bourgeois norms and not fitting in, and at the same time fascinates with a distinctly aesthetic dimension.
Journalist & Author
202 graphics, color and b/w photographs
23,5 x 30 cm | 9 1/4 x 11 4/5 in.
Lifestyle, Preview Spring 2023
As a journalist, author, artist, and media maker, Michael Köckritz always succeeds in delivering attentiongrabbing inspiration with good-natured ease when it comes to contemporary and visionary topics and the realms of lifestyle and luxury. As publisher and editor-in-chief, he has produced numerous book and lifestyle magazine publications that have long been regular recipients of national and international awards. The car and culture magazine "ramp," the men's lifestyle magazine "rampstyle," and the design magazine "ramp.design" are published internationally and widely regarded as influential in the world of style.


This luxurious bag is perfect for carrying all those baby and child essentials when out and about. It's fully lined and double interfaced for extra strength and durability. It has four interior pockets and a padded outer pocket, ideal for keeping your phone protected and close at hand. The adjustable shoulder strap allows you to wear the bag on the shoulder or cross-body, as well as placing over the handle bars of a buggy.
Fabrics used in example: Petite Street fabrics by Wendy Kendall for Dashwood Studio.


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Tag Archive: Edition
Punting the Pundits: Sunday Preview Edition
News, Opinion
"Punting the Pundits" is an Open Thread. It is a selection of editorials and opinions from around the news medium and the internet blogs. The intent is to provide a forum for your reactions and opinions, not just to the opinions presented, but to what ever you find important. Follow us on Twitter @StarsHollowGz The …
Tags: Edition, Open Thread, Opinion, Politics, Punting the Pundits, Punting the Pundits: Sunday Preview, TMC Opinion, TMC Politics
"Punting the Pundits" is an Open Thread. It is a selection of editorials and opinions from around the news medium and the internet blogs. The intent is to provide a forum for your reactions and opinions, not just to the opinions presented, but to what ever you find important.
Thanks to ek hornbeck, click on the link and you can access all the past "Punting the Pundits".
This Week with George Stephanopolis: The guests on "This Week" are: Rep. Jason Chaffetz (R-UT); and Republican presidential candidate Gov. Bobby Jindal (R-LA).
The roundtable guests are: Reihan Salam, "National Review"; LZ Granderson, ESPN; ABC News' Cokie Roberts; and Mark Halperin, Bloomberg Politics.
Face the Nation: Host John Dickerson's guests are; Republican presidential candidates Donald Trump and Dr. Ben Carson; Rep. Mick Mulvaney (R-SC) and National Security Adviser Tom Donilon and Washington Post's David Ignatius.
His panel guests are; Washington Post columnist Ruth Marcus; National Journal's Ron Fournier; The Federalist's Ben Domenech; and the Washington Post's Robert Costa.
Meet the Press with Chuck Todd: This Sunday's guests on "MTP" are; Democratic presidential candidate Sen. Bernie Sanders (I-VT); Rep. David Bratt (R-VA); and Rep. Charles Dent (R-PA).
The panel guests are: Eugene Robinson, Washington Post; Katleen Parker, Washington Post; Nathan Gonzales, The Rothenberg & Gonzales Political Report; and Hugh Hewitt, talk show host.
State of the Union with Jake Tapper: Mr. Tapper's guests are: Democratic presidentaate former Gov. Martin O'Malley (D-MD); and former House Benghazi Committee investigator Air Force Reserve Maj. Bradley Podliska.
Tags: Edition, Open Thread, Opinion, Politics, Punting the Pundits, Punting the Pundits: Sunday Preview, TMC Politics
This Week with George Stephanopolis: The guests on "This Week" are: Republican presidential candidates Donald Trump and New Jersey Gov. Chris Christie; and Fox News host Bill O'Reilly.
The roundtable guests are: Rep. Keith Ellison (D-MN); Rep. Tom Cole (R-OK); Greta Van Susteren, Fox News; and Matt Bai, Yahoo News.
Face the Nation: Face the Nation is preempted for an NFL game from London.
Meet the Press with Chuck Todd: The guests on today;s "MTP" are: Republican presidential candidate Donald Trump; National Security adviser Stephen Hadley; and former Ambassador Michael McFaul.
The panel guests are: Amy Holmes; Mark Leibovich; Rich Lowry; and Ruth Marcus.
State of the Union with Jake Tapper: Mr. Tapper sits down with Sen. Elizabeth Warren (D-MA) and Sen. John McCain (R-AZ).
This Week with George Stephanopolis: The guests on Sunday's "This Week" are: Republican presidential candidate Dr. Ben Carson; U.S. Ambassador Samantha Power; Rep. Devin Nunes (R-CA); and former House Speaker Newt Gingrich (R-GA).
The roundtable guests are: ABC News contributor Matthew Dowd; Bill Kristol, Weekly Standard; Democratic strategist Donna Brazile; and Robert Costa, The Washington Post.
Face the Nation: Host John Dickerson's guests are: House Speaker John Boehner (R-OH); Republican presidential candidate Gov. John Kasich (R-OH); and Democratic presidential candidate Sen. Bernie Sanders, (I-VT).
His panel guests are: CBS News Congressional Correspondent Nancy Cordes; Kim Strassel, Wall Street Journal; Ed O'Keefe, The Washington Post; and Susan Page, USA Today.
Meet the Press with Chuck Todd: The guests on Sunday's "MTP" are: Democratic presidential candidate Hillery Clinton; Republican presidential candidate Carly Fiorina; and author George Weigel.
The discussion guests are: David Brooks, The New York Times; Andrea Mitchell, NBC contributor; Eugene Robinson, The Washington Post; and Andrew Ross Sorkin, The New York Times.
State of the Union with Jake Tapper: Mr. Tapper's guests are: House Minority Leader Nancy Pelosi (D-CA); Democratic presidential candidate former Gov. Martin O'Malley (D-MD); and Republican presidential candidate Dr. Ben Carson.
This Week with George Stephanopolis:The guests on Sunday's "This Week" are: New York City's Mayor Bill de Blasio; GOP presidential candidates Donald Trump and Florida Sen. Marco Rubio.
The roundtable guests are; ABC News contributor Matthew Dowd; Republican strategist Ana Navarro; ABC News' Cokie Roberts; and Democratic strategist Donna Brazile.
Face the Nation: Host John Dickerson's guests are: Democratic presidential candidate Hillary Clinton; and GOP presidential candidate Sen. Rand Paul (R-KY).
His panel guests are: Peggy Noonan, Wall Street Journal; Jamelle Bouie, slate; Ron Brownstein, National Journal; and Michael Gerson, Washington Post.
Meet the Press with Chuck Todd: This Sunday's "MTP" guests are: JPMorgan Chase CEO Jamie Dimon; GOP presidential candidates Gov. John Kasich (R-OH) and Dr. Ben Carson.
The roundtable guests are: Molly Ball; Hugh Hewitt; David Maraniss; and Maris Shriver.
State of the Union with Jake Tapper: Mr. Tapper's guests are: GOP presidential candidates Gov.John Kasich (R-OH) and Gov. Chris Christie (R-NJ).
This Week with George Stephanopolis: The guests on Sunday's "This Week" are: Republican presidential candidate Ben Carson; Gen. John Allen, Special Envoy for the Global Coalition to Counter ISIS; and Rep. Michael McCaul (R-TX).
The roundtable guests are: NPR's Morning Edition, Steve Inskeep; Washington Post national political reporter Robert Costa; Republican strategist Kristen Soltis Anderson; and Democratic strategist Maria Cardona.
Face the Nation: Host John Dickerson's guests are: Republican presidential candidates Ben Carson and Donald Trump.
His panel guests are: Democratic strategist David Axelrod; Peter Baker, The New York Times; Wall Street Journal contributor, Peggy Noonan; John Heilemann, Bloomberg Politics; and Gwen Ifill, PBS Newshour and Washington Week.
Meet the Press with Chuck Todd: The guests on this Sunday's "MTP" are: Democratic presidential candidate Sen. Bernie Sanders (I_VT); Republican presidential candidate Gov. Chris Christie (R-NJ); Rep. Tom Cole (R-OK); former Sen. Jim DeMint (R-SC); and former ambassador to Syria, Robert Ford.
The roundtable gusts are: David Brooks; Maria Hinljosa; Ron Fournier; and Sarah Fagen.
State of the Union with Jake Tapper: Mr. Tappers guests are: GOP presidential candidate Gov. Scott Walker (R-WI); and RNC Chair Reince Priebus.
This Week with George Stephanopolis: The guests on Sunday's "This Week" are: Republican presidential candidates: former Gov. Mike Huckabee (R-AR) and Ohio Governor John Kasich (R-OH); David Miliband, President and CEO of the International Rescue Committee; and Gen. Martin Dempsey, chairman of the Joint Chiefs of Staff.
The roundtable guests are: ABC News analyst Matthew Dowd; Democratic strategist Donna Brazile; editor of the Weekly Standard Bill Kristol; and editor and publisher of The Nation Katrina vanden Heuvel.
Face the Nation with John Dickerson: Mr. Dickerson's guests are: Republican presidential candidate Carly Fiorina; and former Speaker of the House Newt Gingrich (R-GA).
Meet the Press with Chuck Todd: This Sunday's "MTP" guests are: Former Secretary of State Colin Powell; and ALF-CIO President Richard Trumka.
State of the Union with Jake Tapper: Mr. Tapper's guests are: Rep. Debbie Wasserman Schultz (D-Fla.), the chairwoman of the Democratic National Committee (DNC); and Alaska Gov. Sarah Palin (R).
This Week with George Stephanopolis: The guests on Sunday's "This Week" are: Democratic presidential candidate Sen. Bernie Sanders (I-VT); Republican presidential candidate Gov. Bobby Jindal {R-LA); and Sen. Amy Klobuchar {D-MI).
The panel guests are: ABC News' Cokie Roberts; Associated Press Chief White House correspondent Julie Pace; ESPN senior writer LZ Granderson; former House Speaker Newt Gingrich (R-GA).
Face the Nation: John Dickerson's guests are: Gov. Bobby Jindal (R-LA); New Orleans Mayor Mitch Landrieu (D); American historian Douglas Brinkley; Getty photojournalist Mario Tama; pollster Ann Selzer; and Chief Economist of Moody's Analytics Mark Zandi.
His panel guests are: The Atlantic's Jeffrey Goldberg; Washington Post's Ed O'Keefe; The New York Times Magazine's ; Mark Leibovich, and CBS News Correspondent Julianna Goldman;
Meet the Press with Chuck Todd: Then guests on today's "MTP" are: Gov. Scott Walker (R-WI); Trymaine Lee, MSNBC national correspondent; and author Malcolm Gladwell.
At the roundtable, the gursets are: Matt Bai, Yahoo! News; Helene Cooper, New York Times; Melissa Harris-Perry, Host, MSNBC's "Melissa-Harris Perry"; Steve Schmidt, Republican strategist.
State of the Union with Jake Tapper: Mr. Tapper has an exclusive interview with Democratic presidential candidate Sen. Bernie Sanders (I-VT).
His panel guests are: Rep. Marsh Blackburn (R-TN); S. E. Cupp, New York Daily News; Dan Pfeiffer, CNN; and Democratic political strategist Donna Brazile.
This Week with George Stephanopolis: The guests o Sunday's "This Week" are: GOP presidential candidates Donald Trump and Wisconsin Gov. Scott Walker and Democratic presidential candidate Martin O'Malley.
The roundtable guests are: TIME editor Nancy Gibbs; National Review editor Rich Lowry; Yahoo News national political columnist Matt Bai; Republican strategist Ana Navarro; and former New Mexico Gov. Bill Richardson.
Face the Nation: Host John Dickerson's guests are: GOP presidential candidates Sen. Ted Cruz (R-TX) and Gov. Chris Christie (R-NJ).
His panel guests are: TIME's Michael Scherer; Politico's Manu Raju; Ruth Marcus and Anne Gearan, both of the Washington Post.
Meet the Press with Chuck Todd: The guests on this Sunday's "MTP" are: Republican presidential candidate Carly Fiorina; and California Gov. Jerry Brown (D).
The political panel guests are: Alfonso Aguilar, Executive Director, American Principles Project's Latino Partnership; Susan Page, USA TODAY; Jon Ralston, Reno-Gazette Journal; and Amy Walter, The Cook Political Report.
State of the Union with Jake Tapper: Mr. Tapper will have an exclusive interview with GOP presidential candidate Dr. Ben Carson and Democratic presidential candidate former Sen. Jim Webb (VA).
His panel guests are: Neera Tanden, President of the Center for American Progress; Kevin Madden; former Rep. Bakari Sellers (D-SC); and S.E. Cupp, CNN contributor.
This Week with George Stephanopolis: The guests on Sunday's "This Week" are: Rep. Trey Gowdy (R-SC): Republican presidential candidates Carly Fiorina and Ben Carson.
The roundtable guests are: ABC News analyst Matthew Dowd; Democratic strategist Donna Brazile; and Hugh Hewitt, host of the "The Hugh Hewitt Show."
Face the Nation: Host John Dickerson guess are: Gov. John Kasich (R-OH); Sen. Lindsay Graham (R-SC); former Gov. Martin O'Malley (D-MD).
His panel guests are: The National Journal's Ron Fournier; Washington Post's Robert Costa; Wall Street Journal's Peggy Noonan; Bloomberg's Mark Halperin; and Slate's Jamelle Bouie.(
Meet the Press with Chuck Todd: The guests on Sunday's "MTP" are: GOP presidential contender Donald Trump; and Democratic presidential contender Sen. Bernie Sanders (I-VT).
Roundtable guest are a puzzlement once again.
State of the Union with Jake Tapper: Mr. Tapper's guests are: Gov. John Kasich (R-OH); former Gov. Mike Huckabee (R-AR); and senior adviser to Draft Biden 2016, Joshua Alcorn.
One of his panel guests is former Gov. Brian Schweitzer (D-MT).
We should be more outraged. 01/10/2020
The Breakfast Club (Excuses) 01/10/2020
Got Golden Fingers 01/09/2020


WASHINGTON – The Senate has confirmed two nominations to the Federal Communications Commission, ending the Democrats brief 2-1 majority at the agency.
By voice vote, the Senate approved late Wednesday the nomination of Republican Deborah Tate, an attorney and state regulator from Tennessee, to fill one empty seat at the five-member commission. Lawmakers also approved the nomination of Democrat Michael Copps to serve a second term at the commission.
Tate's confirmation means Republican Chairman Kevin Martin will no longer be outnumbered by the two Democrats on the panel — Copps and Jonathan Adelstein. Martin found himself in the minority when fellow Republican Kathleen Abernathy left the commission on Dec 9.
Even with Tate on board, the commission still has one empty seat and remains split between two Republicans and two Democrats.
The White House has yet to nominate anyone to fill Abernathy's seat.
Tate will fill the remainder of the term of former Chairman Michael Powell, who left the agency in March. Her term expires in June 2007.
Tate is a director on the Tennessee Regulatory Authority and previously served as chairman of the authority from 2003-04.
Copps, a strong advocate of tougher indecency enforcement and critic of increasing media consolidation, was first nominated by President Bush in May 2001. He has also served as assistant secretary of commerce for trade development. Before that, he spent 15 years working for Sen. Ernest Hollings, D-S.C.
Copps' term expires in June of 2010.


I'm going to keep this blog short, because I'm absolutely exausted from the day. My legs hurt entirely, and my head was pulsing until Mom gave me some medicine.
Our day mainly consisted of touring the uptown of the city, and we started by going to my favorite place we have gone on this whole trip so far. B&H, for those who don't know, is the second largest online retail behind Amazon. It is designed to cater to professionals, consumers and anyone in between when it comes to electronics and production equipment.
I had the opportunity to try on some high end headphones and I was not disappointed in the slightest. The first set I tried on were the LCD 3 cans by Audeze. (pronounced odd-i-z) These are definitely a stay at home set. You would put these in your listening room with your setup and probably never take them out of the house. They are around $2,000.00 and have the looks to back it up. On the downside, the sound quality and clamp force just didn't do it for me. I already own a pair of Monolith M1060's which retail for about $300. I have these with my setup using a Schiit Magni 2 amp to power them, and they sound almost as good, if not more enjoyable, compared to the LCD 3's. In addition, my m1060s are much more relaxed and don't have the same clamp power. I actually prefer this in a luxury headphone, as I don't really move around much when listening. I like having a cloud like fit, and with a head as large as mine, I often find that to be a make or break deal for me. Finally, at the end of the day, these are so rediculous in the price range that for quality sound I can simply stick with my 1060s.
Next on my list of to-listens were the great set of HD-800s by Sennheiser. I went into these betting on them being a hypebeast of a headphone, but I wasn't let down at all. These were incredibly detailed, had great mids and highs, and felt very comfortable. I could have worn these for hours. At the end of the day, they just didn't have the fun I would look for in a listening pair of cans. I love the bass and character associated with my m1060s and LCD 3s. If I were to want to get into actual editing of music, or any other audio work that features very precise imaging, this has to be the headphone to get. I can honestly say these are the workhorse you need to edit your work in the audio world. At a $1,200 price range, it is settled in the realm of professionals, but not so far off that they are unjustified in their price.
If you can't already tell, I would call myself an audiophile. If you don't care that much about tech or audio equipment, I will eventually catalogue this blog into different categories. I would love to have a photography thread, travel thread, and tech thread. This way, all of my blog posts are on one site, but can be selected to the desires of those reading.
After B&H we had a small lunch, went to Grand Central Station and passed through a few popular buildings. John was getting a bit carried away, and kept running. My feet were beginning to hurt at this time. After a few more blocks, I really began to slow down. Walking became more of a chore.
It took us a while to find Rockefeller Plaza, but it was really beautiful there. Sadly, NBC tours were full, so I didn't get to try that out. The big tree being put up, so that was cool to watch. It looked pretty big, but it's not the ludicrously large tree you may think of from movies.
We ended our afternoon in Central Park, taking a carriage ride, and walking around. Dad, Mom and John ice skated in the park while I sat inside watching our stuff. My feet were so sore at this point, skates would have just killed me.
I do need to go to sleep now. We are going to be up very early, trying to go to the parade. Good night everyone, and happy Thanksgiving.
This is a collection of posts about the New York trip my family took for Thanksgiving Break in 2017. I began working on the blog specifically for this trip, so bear with me as I try to figure this medium out.


Caviar from Acipenser Transmontanus sturgeon. This caviar surprises diners with the size of its grains and its subtle, buttery melting quality on the tongue. This is the signature caviar of Iranian craftsmen who came to Italy to pass on their unique knowledge.
This item requires next day shipping to ensure freshness.
Orders received by 10:30 AM will be shipped the same business day. Orders received after 10:30 AM will ship the following business day.


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Look Up Another Term
Definition: TPC
(Transaction Processing Performance Council, San Francisco, CA, www.tpc.org) An organization devoted to benchmarking transaction processing systems. In order to derive the number of transactions that can be processed in a given time frame, TPC benchmarks measure the total performance of the system, which includes the computer, operating system, database management system and any other related components involved in the transaction processing operation.
The TPC-C benchmark yields transactions per minutes expressed in tpmC ratings. Earlier TPC-A and TPC-B benchmarks produced tpsA and tpsB ratings, which measured transactions per second.
TPC-W is a Web benchmark, performed in a controlled Internet e-commerce scenario and reported as the number of Web interactions processed per second. Shopping, browsing and ordering are the three simulated profiles measured.
TPC-H carries an ad-hoc label and is used in environments where users do not know which queries will be executed against a database system. TPC-R analysis assumes pre-knowledge of a standard set of queries, and execution is very fast as a result. The earlier TPC-D benchmark based its results on the size of the database being queried and yielded a single-user Qppd Power metric and multiple-user QthD Throughput metric.
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text:
Travel Karnataka Tour
Bangalore - Mysore - Madikeri - Hassan - Hospet - Badami - Belgaum - Goa - Mumbai
Day 1: Arrival at Mumbai
Welcome India, You will be received by Premium India Tour representative at international airport and assisted to your hotel. In the Hotel you will have a brief description of your tour and the representative will hand over your documents regarding the tour, Overnight at Hotel.
Day 2: Bangalore / Mysore
Breakfast at Hotel, enjoy sight seeing tour of Bangalore by visiting The Lalbagh, one of the finest botanical Gardens of India, Cubbon Park laid in 1864 sprawling across 300 acres, Vidhana Soudha built in 1956 housing The State Legislature and Secretariat Drive to Mysore. This imperial city was the erstwhile capital of the Wodeyars. The legend takes its name from a famous demon called Mahishasur, a great warrior who ruled as a tyrant until he was killed by the goddess Chamundeshwar, on arrival check-in hotel. Rest of time at leisure. Overnight at Hotel.
Day 3: In Mysore
Breakfast at hotel, later enjoy city sightseeing tour of Mysore.by visiting Royal Palace with a magnificent Durbar Hall, particularly splendid during the Dussehra Festival when the Maharaja's jewellery, studded gold throne (weighing 200 kgs) is on display. Chamundeshwari temple perched on a hilltop is 2000 years old, Nandi Bull half way to the hill is a 4.8 metre monolith. 19 km north-west of Mysore is the KRS Dam and the ornamental Brindavan Gardens. The musical fountains and colourful lights transform this place into a fairly land in the evenings. Overnight at Hotel.
Day 4: Mysore / Madikeri
Breakfast at hotel, later drive to Madikeri. Muddurajakeri named after the first ruler Mudduraja from this place since 1681 later became Madikeri. It is a picturesque hill town with The enchanting fragrance of coffee.. The aroma of fresh cardamom or Black pepper and Coorg honey.. The holy river Cauvery.. The air is noticeably very cooler and this climate and hilly terrain of Coorg inspired the British to occupy the area for over 100 years and they called it as "The Scotland of India". With an austere beauty this god gifted pollution free, calm and quite land of mountains cordially invites you to enjoy and explore the land. Rest of the time at Leisure. Overnight at Hotel.
Day 5: In Madikeri
After a hassle-free breakfast in the morning, enjoy the full day sightseeing tours of the town. Including visit at Abey Falls or Abbi Falls, Raja's Seat, Madikeri Fort, Omkareshwara temple, Gaddige - Raja's Tomb, Gaddige Tomb, Rest of time is free to enjoy by your own. Overnight at Hotel.
Day 6: Madikeri / Hassan
After a relaxed breakfast in the morning, drive to Hassan. On arrival check in your hotel and In the afternoon, enjoy guided excursion to Belur and Halebid.Temples. Belur temple took over 103 years to build and is a classic example of the Hoysala style of architecture. It rises like a wedding cake in stone, from a star shaped plinth, one of the hallmarks of Hoysala building design. From the base upwards, there is an extraordinary wealth of decorative detail; every available inch is crammed with intricate carvings. In one frieze, 650 elephants jostle one another in a continuous line. Many of the figures of full blossomed women depicted at Belur are believed to be portraits of King Vishnuvardhana's queen. Halebid - 16 km east of Belur and 27 km from Hassan, the Hoysaleswara Temple dating back to 12th century, is astounding for its wealth of sculptural detail. The walls of the temple are covered with an endless variety of gods and goddesses, animals, birds and dancing girls. Yet no two facets of the temple are the same. The magnificent temple -dedicated to Lord Shiva guarded by a Nandi Bull was never completed despite 86 years of labour. In the inner sanctum, the star black lingam, the symbol of Shiva, is still worshipped. The carving at the door is ornate with small details. Overnight at Hotel. .
Day 7: Hassan / Hospet
After hearty breakfast in the morning, drive to Hospet. As has been called the gateway to Hampi, Hospet stands proud of the Tungabhadra Dam which keeps the river. There is a garden in the Japanese style at the base of the Dam which also a site to visit of this historical city of Hospet. Rest of the time at leisure. Overnight at Hotel.
Day 8: In Hospet
After hearty breakfast in the morning, enjoy full day excursion to the Hampi ruins. Hampi is the erstwshile capital of the Vijayanagar kingdom; Hampi is full of delightful surprises. Like the King's Balance where kings were weighed against grain, gold or money which was then distributed to the poor, the Queen's Bath with its arched corridors, projecting balconies, the two-storied Lotus Mahal with recessed archways, the huge Elephant Stables, the splendid Vittala Temple with its musical pillars and the Stone Chariot, the Virupaksha Temple, still used for worship, Ugra Narasimha, the 6.7 m tall monolith, the Mahanavami Dibba. Return back to hotel for overnight stay.
Days 09: Hospet / Badami
In the morning drive to Badami. on arrival check in to hotel. In the afternoon, enjoy tour of Badami. Picturesquely situated at the mouth of a ravine between two rocky hills, the exquisite sculptures and the rust red sandstone cliffs of Badami tell many a tale of yore. Climb a flight of steps to reach the four ancient rock-cut caves replete with carved pillars and bracket figures, all hewn out of red sandstone on the precipice of a hill. The largest of them is the third cave, dedicated to Lord Vishnu. The first sculptural embellishment to dazzle the eye is the 18-armed Nataraja striking 81 dance poses in the first cave. Overlooking the caves is the Agastya Theertha Tank, its banks dotted with a cluster of Bhoothanatha temples.North Fort, Rest of the time at leisure. Overnight at Hotel.
Day 10: In Badami
After a relaxed breakfast in the morning, enjoy the full day guided excursion to Aihole A tranquil village on the banks of the Malaprabha river, Aihole is acclaimed as the cradle of Hindu temple architecture. There are hundreds of temples in the villages and fields nearby. The most impressive one is the Durga Temple with its semicircular apse, elevated plinth, and the gallery encircling the sanctum. The Lad Khan Temple, which is one of the earliest temples, was originally a royal assembly hall and marriage mantapa chosen as the abode of a Muslim prince, Lad Khan. The Huchimalli Temple with a sculpture of Vishnu sitting atop a large cobra, the Ravalphadi Cave Temple celebrating the many forms of Shiva, the Konti Temple Complex, the Umamaheswari Temple, the Jain Meguti Temple, and the two-storied Buddhist Temple are other sights worth seeing. Later enjoy visiting Pattadakal.is an art historians dream. It has a set of nine temples built almost in a single file, showing the architects' desire for experimenting in various styles. Pattadakal represents the culmination of early Chalykyan art. Four of the temples here are in the south Indian Dravidian architectural style while four are in the north Indian Nagara style while Papanatha temple exhibits a hybrid style. The Virupaksha temple, he Mallikarjuna temple, The Galaganatha temple, Other temples here include those to Chandrasekhara, Sangameswara, Jambulinga, Kadasiddheswara.Come back to Badami. Overnight at Hotel.
Day 11 : Badami / Belgaum
After hearty breakfast in the morning, drive to Belgaum, (earlier known as "Venugrama" or the "Bamboo Village") is one of the oldest, strong, prominent and well cultured historical place nestling high in the Western Ghats. The old town area with cotton and silk weavers stands gloriously besides the modern, bustling, tree-lined British Cantonment. Step out of the forts and you have a wide choice of temples and churches to visit. Later in the day visit the Belgaum Fort and the natural beauty of Jamboti Falls & Gokak Falls. Overnight at Hotel.
Day 12 : Belgaum / Goa
After hearty breakfast in the morning, drive to Goa. "Rome of the East", and "Pearl of the Orient" The magnificent scenic beauty and the architectural splendors of its temples, churches and old houses have made Goa a firm favorite with travelers around the world. Goa is much more than just beaches and sea. It has a soul which goes deep into unique history, rich culture and some of the prettiest natural scenery. On arrival check in your hotel, Rest of the at leisure. Overnight at Hotel.
Day 13 & 14: Goa
In Goa your are totally free to enjoy and spend your time as per your choice. Overnight at Hotel.
Day 15: Goa / Mumbai
Breakfast at hotel. Transfer to airport for flight to Mumbai. On arrival meet and transfer to Hotel. Later enjoy sight seeing tour of Bombay, drive to Gateway of India and from here cruise by motorboats to Elephanta Caves. A flight of 100 steps takes you to the top of the hill where it is set. The caves houses large pillars that seem to hold the ceiling which is made of cross beams. The picturesque presentations of the 9 marvelous sculptured panels, set on the walls are awe-inspiring. The most famous of the panels is the Trimurthi, or triple-headed Shiva, where the God is depicted as the destroyer, the preserver and the creator. Later visit Prince of Wales Museum, Parliament House, Marine Drive, Jain Temple, Hanging Gardens, Colour ful Craford market. Overnight at Hotel.
Note: Elephanta Caves and Prince of Wales museum are closed on every Monday
Day 16: Mumbai / Depart
After hearty breakfast in the morning, Today you can enjoy the Mumbai as per your own described activities. In time your will be transfer to the International airport to board on flight back to home.


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