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80 per cent of India Inc. foresees increase in fraud cases in next two years: Deloitte report
The survey suggested that technology can help organisations in fraud response
New Delhi [India], November 30 (ANI): The uncertainty and business disruption brought about by the pandemic has contributed to fears amongst corporate India about the rise fraudulent cases.
Releasing its biennial survey - The India Corporate Fraud Perception Survey, Edition IV - Deloitte Touche Tohmatsu India LLP (DTTILLP) said over 80 per cent people felt fraud cases would rise in the next two years, a 22 percentage point increase over the previous edition of the survey in 2018.
"Traditionally, many Indian organisations have directed a majority of their FRM (Fraud Risk Management) efforts towards fraud detection, whereas technology interventions can be primarily geared towards fraud prevention. This will require a shift in mindset from fraud detection to fraud prevention. We believe this shift can be enabled by working towards building an enterprise-wide view of fraud and making strategic technology investments," said Nikhil Bedi, Partner and Leader, Forensic, Financial Advisory, DTTILLP.
About 70 per cent respondents felt that fraud losses would rise and one-third of the respondents felt losses would be between 1 per cent and 5 per cent of revenues, the survey revealed.
According to it, these adverse sentiments are due to large-scale remote working arrangements and changes in business models, which have made it challenging to understand fraud-related vulnerabilities. The survey indicated that such adverse sentiments were further exacerbated by reliance on static data for FRM efforts.
"About 43 per cent of respondents felt their existing fraud risk management frameworks were inadequate to address future frauds. Accordingly, they indicated diverting budgets towards adopting enhanced technologies that could provide an enterprise view of fraud (22 per cent); implementing enhanced fraud risk management processes for third parties (17 per cent); and creating awareness amongst employees (17 per cent) for fraud prevention," the survey stated.
For the first time in four editions of the survey, nearly 35 per cent respondents believed that future frauds would be detected using data analytics and other technology tools (and not rely entirely on conventional approaches, such as internal audit). However, despite a growing realisation that technology would be key to future fraud risk management efforts, less than 5 per cent respondents indicated investing in anti-fraud technologies in the past six months.
The survey also suggested that technology can help organisations in fraud response, particularly if it involves responding to a regulator or seeking legal recourse. About 50 per cent respondents indicated seeking legal action against the parties involved in fraud (compared with 33 per cent in the previous edition of our survey).
"The confidence to seek legal recourse may be a result of regulatory changes that are increasingly pushing for greater disclosures, as well as increased use of technology by organisations that can help document and preserve evidence to aid in faster resolution of cases," Bedi said.
The survey also outlined the evolution of the fraud risk management ecosystem comprising third-party experts, such as law firms, forensic accountants, technology companies, and others.
"The effectiveness of fraud risk management efforts in the future will rely on building a trustworthy ecosystem of experts. While in-house fraud risk management teams will continue to grow and manage known risks, ecosystem players will be sought for strategic advice on future fraud risk management," Bedi added. (ANI)
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PRESS RELEASE-Donation to Worcester County Education Foundation from Healing Hands Chiropractic, P.C.
As a way to give back to the community, Drs. Chris and Tracy Rush of Healing Hands Chiropractic as well as their patients, were not charged for appointments on October 31st, but instead made donations to the Worcester County Education Foundation. Pictured above with the $1,796 donation check are Dr. Tracy Rush and Mr. Lou Taylor, Superintendent of Worcester County Public Schools.
For more information on the Worcester County Education Foundation, please visit our website at www.wced.foundation or call Hope Palmer at 410-632-5038.


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By freakpool / June 12, 2017
C3 AFA Bangkok Booth Report: Aniplex holds Sword Art Online popularity contest and figure display
C3 AFA Bangkok 2017 is a wrap, and one of the most popular booths during the event belonged to Aniplex….
C3 AFA Bangkok 2017 is a wrap, and one of the most popular booths during the event belonged to Aniplex. The booth held plenty of highlights, including life-size standees of Sword Art Online characters, as well as figure displays. They featured plenty of Aniplex titles, including Eromanga Sensei, Saekano, and Recreators. But of course, Sword Art Online really dominated the booth.
But one of the biggest highlights is their Sword Art Online character popularity poll. The poll asked event-goers to vote for their favorite character from Sword Art Online the Movie: Ordinal Scale. The staff gave fans a sticker, and they would then add that sticker to any character they want. After two whole days of voting, the results are in:
Sinon won the C3 AFA Bangkok popularity poll, but it was really close! She narrowly won over Asuna, who got second place. Sorry Kirito, better luck in the next one. And he actually lead at some point during the first day… until Asuna and Sinon caught of course.
Inside the booth, Aniplex displayed Kirito and Asuna's Ordinal Scale costumes, as well as their swords. They also displayed a few stills from the film, along with some line art.
Outside the Aniplex Booth, they featured Love Live! Sunshine!!, as well as a few others. But it was pretty clear that Aniplex really focused on SAO for the event. They even had life-size standees of the characters, with Asuna and Kirito sporting traditional Thai costumes.
They also featured a figure display at the back of their booth. Along with some other merchandise, the figure display featured Madoka Magica, Black Butler, and many others. Did we mention that there's also a lot of SAO merch in there too?
Well, at least there were a lot of Madoka Magica and Fate merch to rival SAO there, right?
Categories: ORIGINALS Tags: aniplex, C3AFA Bangkok, Sword Art Online
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redpajama_set_name: RedPajamaCommonCrawl


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Candidate metastasis suppressor genes uncovered by array comparative genomic hybridization in a mouse allograft model of prostate cancer
Yajun Yi1,
Srinivas Nandana2,
Thomas Case2,
Colleen Nelson3,
Tatjana Radmilovic1,
Robert J Matusik2 and
Karen D Tsuchiya4, 5Email author
© Yi et al; licensee BioMed Central Ltd. 2009
The purpose of this study was to identify candidate metastasis suppressor genes from a mouse allograft model of prostate cancer (NE-10). This allograft model originally developed metastases by twelve weeks after implantation in male athymic nude mice, but lost the ability to metastasize after a number of in vivo passages. We performed high resolution array comparative genomic hybridization on the metastasizing and non-metastasizing allografts to identify chromosome imbalances that differed between the two groups of tumors.
This analysis uncovered a deletion on chromosome 2 that differed between the metastasizing and non-metastasizing tumors. Bioinformatics filters were employed to mine this region of the genome for candidate metastasis suppressor genes. Of the 146 known genes that reside within the region of interest on mouse chromosome 2, four candidate metastasis suppressor genes (Slc27a2, Mall, Snrpb, and Rassf2) were identified. Quantitative expression analysis confirmed decreased expression of these genes in the metastasizing compared to non-metastasizing tumors.
This study presents combined genomics and bioinformatics approaches for identifying potential metastasis suppressor genes. The genes identified here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human prostate cancer.
Array Comparative Genomic Hybridization
Copy Number Alteration
Metastasis Suppressor Gene
Fred Hutchinson Cancer Research
Prostate cancer (PCa) is a heterogeneous disease and the ability to predict its clinical outcome is limited. Numerous chromosomal abnormalities and alterations in gene expression have been reported in PCa, yet identification of many of the specific genes that drive the progression of these tumors is still lacking. The finding of the TMPRSS2/ETS fusion and the overexpression of ETS transcription family members in the majority of PCa illustrates the success of utilizing a bioinformatics approach to gene discovery [1], but the consequences of many other recurrent acquired genomic alterations remain to be elucidated. Studies of human PCa are hindered by the biologic and genetic heterogeneity of this disease not only between individuals, but also within a given individual. Genetically engineered mouse models of PCa provide an in vivo experimental system in which tumors with the same underlying etiology can be sampled during the course of progression at defined time points. The LPB-Tag mouse model of prostate cancer is one such model that has been well characterized [2–4].
We have previously described the establishment of an allograft (NE-10) from a primary prostate tumor from the LPB-Tag mouse model that consistently metastasized by 12 weeks after transplantation in nude mice in early passages [4]. Conventional cytogenetic analysis of the NE-10 allograft revealed numeric and structural chromosome abnormalities, including a deletion of distal chromosome 2 that was consistently present over multiple in vivo passages of the allograft in nude mice [4]. A similar chromosome 2 deletion has also been described in a mouse model of acute promyelocytic leukemia [5]. After repeated in vivo passages, the NE-10 allograft eventually lost the ability to metastasize. In this study, we have taken advantage of the differential metastasizing behavior of the NE-10 allograft, arising from the same original tumor, to screen the genome for candidate genes that play a role in metastasis. High resolution genomic technology, combined with novel bioinformatics approaches, enabled us to identify different regions of chromosome imbalances between the two allograft lines, and to propose candidate metastasis suppressor genes within a region of chromosome 2 that was found to harbor a larger deletion in metastatic compared to non-metastatic tumors.
NE-10 allograft model
The 12T-10 line of the LPB-Tag mouse model of prostate cancer was generated using a transgene that consists of the rat probasin promoter driving the SV40 large T antigen with deletion of the small T antigen [3]. These mice develop low-grade and high-grade prostatic intraepithelial neoplasia at 2-5 month of age, with progression to invasive and metastatic, high-grade, androgen-independent carcinoma demonstrating neuroendocrine differentiation at 6-14 months of age. A primary prostate tumor from the ventral prostate of a 12T-10 transgenic mouse was used to establish an allograft model by implantation subcutaneously in male athymic nude mice [4]. After 18 weeks, the allograft was passaged to another male nude mouse and the process was repeated to establish the NE-10 line [4]. Initial passages in all mice developed grossly visible metastases to liver and micrometastases to lung by twelve weeks after implantation. All metastases from the allografts were histologically similar to the metastasis seen in the 12T-10 mice. Later allograft passages showed histologically identical features to the early passages; however, fewer allografts developed metastases. By passage 15, metastatic potential was completely lost, at least up to the point where it was no longer feasible to maintain the mice due to the size of the subcutaneous tumors. Tumors consisting of non-metastasizing subcutaneous allografts (SQnon-met), metastasizing subcutaneous allografts (SQmet), and liver metastases (LiverMet) were collected at 12 weeks post-implantation and snap-frozen for array CGH. All procedures involving mice were approved by the Vanderbilt University Medical Center and Fred Hutchinson Cancer Research Center Institutional Animal Care and Use Committees.
Array comparative genomic hybridization (CGH)
Array CGH was initially carried out using mouse bacterial artificial chromosome (BAC) arrays produced by the Genomics Shared Resource, Fred Hutchinson Cancer Research Center as described [6]. The mouse BAC clone set was obtained from A. Bradley, Wellcome Trust Sanger Institute [7] and provides an average resolution of 1 Mb. DNA was isolated using the Gentra Puregene genomic DNA purification kit (Qiagen, Valencia, CA). For the BAC arrays, three SQnon-met tumors (passage 19), three SQmet (passages 4, 9, and 12), and four LiverMet (two each from passages 9 and 12) were analyzed. One matched SQmet and LiverMet from the same nude mouse at passage 9 was included in the analysis. Pooled DNA obtained from normal kidney from four different CD-1 males was used as a reference. DNA labeling, hybridization, scanning, and data analysis was performed as described previously [6].
Array CGH was repeated on a subset of two tumors each from the SQnon-met and LiverMet groups using the Agilent mouse 105K oligonucleotide CGH arrays. These arrays were designed using UCSC mm7 (NCBI build 35, August, 2005), and have an average probe spacing of 15 Kb. One ug of RsaI/AluI digested DNA was labeled with either Cy3 or Cy5 using the BioPrime Array CGH genomic labeling system (Invitrogen Corp., Carlsbad, CA). Approximately 4 ug each of Cy5 labeled test (tumor) DNA and Cy3 labeled reference (normal female C57Bl/6 liver) DNA was combined with 25 ug of mouse Cot-1 (Invitrogen Corp.), Agilent 10× blocking agent and 2× hybridization buffer (Agilent Technologies, Santa Clara, CA) to a final volume of 260 ul. Hybridization and washes were carried out according to the Agilent oligo array-based CGH protocol v. 4.0. Scanning was performed on an Agilent scanner and data extraction was carried out using Agilent feature extraction software v.9.1, employing linear and Lowess normalization. Results were analyzed and chromosome plots generated using CGHanalytics software v. 6.0. The Z-score algorithm with the threshold set at 2.0 and a 2 Mb window was used for determining gains and losses. The LPB-Tag tumors were generated on an outbred CD-1 background, and we did not have non-neoplastic DNA available from the mouse whose tumor was used to establish the allograft. As C57Bl/6 reference DNA was used for the oligonucleotide array CGH experiments, gains and losses smaller than 2 Mb were ignored in order to avoid mistaking benign copy number variants between mouse strains from acquired copy number alterations in the tumors.
To compare array CGH profiles between the different groups of tumors, the Differential Gene locus MAPping software (DIGMAP version 2.0) was used to analyze array CGH data sets [8]. Using the default parameters specified in the program, DIGMAP displayed array CGH data as a heat map based on log2 ratio between test and reference DNA for each tumor. The chromosome regions with significantly different log2 ratios were marked as differential flagged regions (DFRs) by direct visualization and computational screening using a T-test based sliding window (TTSW) analysis. For this analysis, a window size of 40 genes was used and DFRs represent regions greater than 3 standard deviations from the whole genome average T score.
Expression arrays
Expression arrays were performed on two SQnon-met tumors (passages 11b, 18c) and four SQmet tumors (passages 2, 5, 14a, 14c). Allograft passages were labeled a, b, c, etc. when the same graft passage was implanted into more than one mouse. As a control, mouse reference RNA from two postnatal day 1 mice was pooled. RNA was isolated using the RNeasy kit (Qiagen Valencia CA), including treatment with DNase. RNA was quantified using a NanoDrop (ThermoScientific). All samples analyzed had a A260/230 ratio greater than 1.8. RNA quality was analyzed on an Agilent 2100 BioAnalyzer. All samples analyzed had a 28S peak greater than 18S peak, or an RIN number greater than 7. The 16 k mouse arrays used for the study were printed at the Vancouver Microarray Facility using Operon's 16 K 70 mer oligomers printed on aminosaline slides. Ten ug of total RNA was labeled using Genisphere's Dendrimer 350 expression array detection kit for microarrays according to the manufacturer's protocol. Samples were co-hybridized with ten ug of the above described mouse reference RNA. Arrays were pre-hybridized in 5 × SSC, 0.1% SDS and 0.2% BSA for 45 minutes. Pre-hybridization buffer was washed off with 3 × 30 second water washes and a 2 minute wash in isopropanol. Slides were spun dry at 2000 rpm for 4 minutes. The samples were applied to arrays containing 60 × 22 mm lifter slips (Erie Scientific). Slides were subsequently treated as described in the Genisphere Array 350 expression array detection kit for microarrays. Arrays were scanned on a Axon 4200AL scanner (Molecular Devices). Image intensities were extracted using ImaGene V8.0 software (BioDiscovery).
To identify chromosome regions that demonstrate differential gene expression between metastatic and non-metastatic tumors, expression array datasets were analyzed between SQnon-met and SQmet mice using DIGMAP as described above for array CGH data. A TTSW genome scan was also performed as described above.
Identification of candidate metastasis suppressor genes in chromosome 2 DFR
A total of 146 known genes in the chromosome 2 differential region of deletion (DFR) between metastatic and non-metastatic tumors (nucleotides 122,316,740-139,585,560) were retrieved from the UCSC mm7 database http://genome.ucsc.edu. Two bioinformatics filters were designed to determine which of these 146 genes might function as candidate metastasis suppressor genes. A functional filter utilized the Gene Ontology (GO) database http://www.geneontology.org, PubMed http://www.ncbi.nlm.nih.gov/PubMed/, and Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com) to evaluate the 146 genes for potential metastasis suppressor function. A parallel filter employing our recently developed human cancer expression signature database (EXALT) was used to independently validate the genes as candidate metastasis suppressors in silico [9]. A weighted score was assigned to each gene for both filters (see Additional file 1).
Quantitative reverse transcription (RT)-PCR
Total RNA was isolated using the RNeasy Mini kit (Qiagen, Valencia, CA) according to the manufacturer's protocol, including the recommended DNase treatment step. Three ug of RNA was reverse transcribed using the ReactionReady First Strand cDNA Synthesis Kit (SuperArray Bioscience Corp., Frederick, MD). Primer sets for mouse Hprt1, Slc27a2, Mal, Snrpb, and Rassf2 were purchased from SuperArray (proprietary primers, sequence not disclosed).
PCR reactions were carried out in triplicate in a 25 μL volume using SYBR Green Master Mix (SuperArray). The standard two-step amplification with an annealing temperature of 60°C was performed in an ABI 7900 PCR machine. Hprt1 was chosen as an endogenous control gene because Hprt1 expression values were stable among test samples in the microarray expression data set.
To allow for a comparison between samples and the two groups, quantities of all target genes in the test samples and a common reference RNA (Mouse XpressRef Universal Total RNA, SuperArray) were normalized to the corresponding Hprt1 levels. Relative expression levels (fold changes) were calculated using the relative standard curve method as outlined in the manufacturer's technical user manual (SuperArray). A standard curve was generated using the fluorescent data from 10-fold serial dilutions of the common reference RNA sample. Four tumors each from the metastasizing and non-metastasizing allografts were analyzed. Statistically significant differences in expression between the two groups were determined using a Student's T-Test.
Differences in copy number alterations between metastatic and non-metastatic tumors
Copy number alterations in tumors were identified by array CGH performed using BAC arrays for all tumors, and oligonucleotide arrays for a subset of tumors. Array CGH using both BAC and oligonucleotide platforms detected multiple gains and losses in both non-metastatic tumors (SQnon-met) and tumors with metastatic potential (SQmet and LiverMet). Both array platforms uncovered similar chromosome imbalances, but the oligonucleotide arrays allowed us to more precisely map regions of gain and loss. Many copy number alterations were common to both groups of tumors, including deletions involving regions of chromosomes 1, 2, 3, 4, 8, 13, 16, 17 18, 19, whole chromosome loss of 14, and gains of chromosome 8 (Figure 1 and Table 1); however, differences in copy number changes between the tumors with and without metastatic potential were also uncovered (Figure 1 and Table 1). One notable difference between the two groups of tumors was a differential region of deletion in distal chromosome 2. Both the metastatic and non-metastatic tumors shared a common 27.4 Mb interstitial deletion of distal chromosome 2, from bands F3 to H3 (139,585,560-167,088,181 bp); however, the metastatic tumors (LiverMet) showed a larger 45 Mb deletion (122,316,740-167,088,181 bp) that extended proximally to band E5 (Figure 2). The non-metastatic tumors showed clonal heterogeneity for both the larger and smaller deletions, with low-level mosaicism for the larger deletion (Figure 2 top), but the clone or clones with the larger deletion were enriched in the metastatic tumors (Figure 2 bottom).
Heat map of oligonucleotide array CGH results. Array CGH results are partitioned by chromosome number and clustered by probe location in the chromosomes. The length of each chromosome bar is based on the total number of probes for that chromosome present on the array. Within each chromosome bar, each row represents a separate NE-10 tumor, and the non-metastatic tumors (SQnon-Met) are separated from the metastatic tumors (LiverMet) by the white line (SQnon-Met above and LiverMet below the line). Black represents normal copy number in tumor compared to the normal reference; red represents increased copy number; green represents decreased copy number. A larger interstitial deletion in chromosome 2 can be visualized in the metastatic compared to the non-metastatic tumors (blue box). Relative loss of the X chromosome in the metastatic tumors, and most of the X chromosome in the non-metastatic tumors, is seen because array CGH for these tumor samples was performed using a sex-mismatched (female) reference DNA. The non-metastatic tumors also show a region of copy number gain on the X chromosome.
Chromosome 2 oligonucleotide array CGH plots. Chromosome 2 plots are shown for one representative non-metastatic (SQnon-Met) and one representative metastatic (LiverMet) tumor. The normalized log2 ratio is on the Y axis, and the chromosome bands are designated on the X axis. Copy number gains and losses are designated by the bars above or below a log2 ratio of 0, respectively. The shaded area reflects the magnitude of the gain or loss. The metastatic tumors show only the larger chromosome 2 deletion (bottom panel), whereas the non-metastatic tumors demonstrate clonal heterogeneity, with the both the smaller deletion, as well as low-level mosaicism for the larger deletion (top panel).
Summary of acquired copy number changes identified by oligonucleotide array CGH in liver metastases (LiverMet) from NE-10 allografts, and in non-metastasizing (SQnon-met) NE-10 allografts
SQnon-met
LiverMet
1 - loss
*84525268-103082423
11809017-qter
3010281-131339250
4 - gain
whole chromosome
8397754-17345126
10 - gain
10 - loss
X - gain
N.A. = not applicable
*Nucleotide sequences are from NCBI build 35
Differences in gene expression profiles between metastatic and non-metastatic tumors
To obtain differential gene expression profiles between non-metastatic and metastatic NE-10 tumors, the different groups of tumors (SQnon-met, SQmet, and LiverMet) were profiled using gene expression microarrays and analyzed by DIGMAP. A T-test sliding window whole genome scan was performed and plotted by chromosome (see Additional file 2). Based on this analysis, chromosome 2 had the greatest number of regions showing the largest difference in gene expression between metastatic (SQmet and LiverMet) and non-metastatic (SQnon-met) tumors. A detailed T-test sliding window plot of chromosome 2 revealed the highest DFR expression peak in band H4, from 179 to 181 Mb (see Additional file 2). This region is distal to the common region of deletion found in both the metastatic and non-metastatic tumors. Three other smaller peaks were also located slightly more centromeric, from 155 to 168 Mb, within the common region of deletion. Thus, regions of differential gene expression between metastatic and non-metastatic tumors were located both within and distal to the common chromosome 2 deletion; however, we were unable to detect any clusters of genes that demonstrated down-regulation in the metastatic compared to the non-metastatic tumors. There were also no significant differences in gene expression detected in the differential region of deletion on chromosome 2 between the metastatic and non-metastatic tumors.
Identification of candidate metastasis suppressor genes in chromosome 2 differentially deleted region
Metastasis suppressor genes are expected to show inactivation or decreased activity in metastatic tumors because of genetic or epigenetic changes that result in loss or down-regulation of expression. The finding of a differentially deleted region on chromosome 2, potentially resulting in loss of a metastasis suppressor gene in the metastatic tumors, led us to focus on this region for more detailed analysis. Given that only a subset of genes in the differentially deleted region was represented on the expression arrays, we employed an informatics approach to identify all potential candidate metastasis suppressor genes in the region of interest (chromosome 2 E5-F3; nucleotides 122,316,740-139,585,560). Two parallel bioinformatics filters were designed to carry out this analysis. Out of a total of 146 genes in the region of interest, 11 candidate metastasis suppressor genes were identified based on the function-based filters, while 22 candidates were identified using a filter that employed a cancer expression signature filter using the EXALT database (see Additional file 3). A final list of four candidate genes (Slc27a2, Mall, Snrpb, and Rassf2) was chosen based on having the highest total score.
Quantitative RT-PCR of 4 candidate metastasis suppressor genes in chromosome 2 differentially deleted region
Quantitative RT-PCR for the four candidate metastasis suppressor genes was performed in tumors with metastatic potential (SQMet) and tumors without metastatic potential (SQnon-Met). Metastatic liver tumors were not analyzed due to the presence of contaminating normal liver tissue in some of the tumors. All four candidate metastasis suppressor genes demonstrated decreased expression in the metastasizing tumors compared to the non-metastasizing tumors, with Slc27a2 and Snrpb showing statistically significant decreased expression in the metastasizing tumors (Figure 3).
Relative expression levels between metastatic and non-metastatic NE-10 tumors by RT-PCR. The X-axis shows four candidate metastasis suppressor genes and the Y-axis shows relative fold change (log2 based) between SQMet and SQnonMet NE-10 tumors (top panel). The relative expression levels are designated by the height of bars, and standard deviation error bars are in the direction of SQMet samples. An asterisk indicates significantly decreased expression in SQMet samples (P < 0.05). The corresponding genomic locations of the four candidate genes on mouse chromosome 2, and the regions of conserved synteny in human, are shown below.
Using high-resolution array CGH, we uncovered multiple copy number changes common to both the metastatic and non-metastatic tumors, consistent with a phenotype of genomic instability in this model. Many of the regions of loss overlap with frequent losses that have been observed by conventional CGH and array CGH performed on localized and metastatic human PCa, including human 4q22.3-q31.1, 5q21.1-q21.3, 6q15-q16.2, 8p21.1-p23.1, 10q23.1, 10q25.1-q25.3, 13q14.2-q22.1, 16q12.1-q24.3, 18q12.3-q21.1, 18q21.31-q21.32, 18q22.1-q23 [10–12]. Loss of specific tumor suppressor genes implicated in human PCa, such as Nkx3-1 and Rb1, was also present in the mouse NE-10 allograft. Other alterations that are frequently seen in human PCa, such as loss of PTEN, loss of CDKN1B, and gain of MYC, were not observed in the NE-10 model.
In addition to copy number alterations common to both the metastatic and non-metastatic tumors, we also observed differences in copy number alterations between these two groups of tumors that could be responsible for their divergent behavior. These differences included loss of chromosome 2 (122.3-139.6 Mb), gain of chromosome 4 (132.2-149.2 Mb), loss of chromosome 7, loss of chromosome 16 (36.9 Mb -qter), loss of chromosome 17 (10.8- 29.1 Mb), and loss of chromosome 18 (3.3-35.6 Mb) in the metastatic, but not the non-metastatic tumors. Our attention was drawn to a differentially deleted region of chromosome 2 for a number of reasons. First, haploinsufficiency or inactivation of metastasis suppressor genes can occur through deletion. We have also detected distal chromosome 2 deletions in approximately 35% of metastatic tumors from multiple independent mice from the original 12T-10 transgenic line (unpublished data), confirming that this is a recurring chromosome abnormality in tumors from this model. In addition, a similar deletion of chromosome 2 has previously been reported in a mouse model of acute promyelocytic leukemia [5]. Also, the larger region of deletion that is enriched in the metastatic tumors demonstrates conserved synteny with the short arm of human chromosome 20 that has been implicated in metastatic PCa [13]. In the mouse model of acute promyelocytic leukemia, loss of one copy of the Sfpi1 (Pu.1) gene due to the chromosome 2 deletion, and reduced expression of this gene, have been implicated in the progression of leukemia in these mice [14]. The Sfpi1 gene is not an obvious candidate metastasis suppressor gene in the NE-10 allograft model, as the gene maps approximately 31 Mb centromeric to the proximal chromosome 2 deletion breakpoint in the metastatic tumors. Cd82 (Kai1) and Cd44, known metastasis suppressor genes for prostate [15, 16], are also located many megabases (~29 Mb and 20 Mb, respectively) proximal to the chromosome 2 deletion. Expression array analyses that we performed also did not uncover candidate metastasis suppressor genes within this differentially deleted region; therefore, we employed a bioinformatics approach to identify potential candidate genes that may be involved in the metastatic behavior of these tumors.
The candidate metastasis suppressor genes in the differential region of deletion of chromosome 2 that we identified, based on prior evidence of metastasis suppressor function and down-regulation in cancer, consisted of Slc27a2, Mall, Snrpb, and Rassf2. All of these genes demonstrated decreased expression in the metastasizing compared to the non-metastasizing NE-10 tumors by quantitative RT-PCR. MALL (MAL, T-cell differentiation protein) is a raft-associated integral membrane protein that is involved in membrane trafficking processes. Expression of the MAL protein has been demonstrated in specific types of normal epithelial cells throughout the respiratory system, the gastrointestinal tract, and the genitourinary tract, including strong expression in the ductal and acinar cells of the prostate [17]. Loss of or decreased MALL expression, sometimes as the result of DNA methylation of the promoter region, has been found in a variety of benign and malignant epithelial tumors compared to their normal epithelial counterparts, consistent with a role for this protein in tumor suppression [17–21]. Furthermore, MAL has been shown to enhance apoptosis through the Fas pathway, and suppress tumorigenicity, invasion, and motility [21]. Although loss or decreased MALL expression has not been evaluated in human prostate cancer, the expression of this protein in normal prostate epithelium and its ability to suppress invasion and motility render it a biologically plausible metastasis suppressor gene for prostate cancer.
SLC27a2 encodes a protein that is an isozyme of the long-chain fatty-acid-coenzyme A ligase family, and as such plays a role in lipid biosynthesis and fatty acid degradation. It may also be involved in translocation of long-chain fatty acids across membranes [22]. Long-chain fatty acids participate in many cellular functions and have been implicated as modulators of carcinogenesis, partly through their ability to activate peroxisome proliferator-activated receptors (PPAR). There is evidence that PPAR gamma regulates prostatic epithelial differentiation and may restrict epithelial proliferation; therefore, it is possible that decreased expression of Slc27a2 in the NE-10 allograft model could alter the tumor suppressor activity of PPAR gamma and contribute to metastatic behavior.
With regard to RASSF2 and SNRPB, Goodzari and co-workers found evidence for a prostate cancer metastasis suppressor gene on the short arm of human chromosome 20 [13]. The differential region of chromosome 2 deletion in metastatic compared to non-metastatic tumors in the NE-10 model shows conserved synteny with a region of human 20p. RASSF2 and SNRPB also map to the short arm of human chromosome 20, although they are telomeric to the most likely metastasis suppressor region of 20p (20p11.23-p12) that was proposed [13]. SNRPB encodes a protein that is one of several nuclear proteins that are found in common among U1, U2, U4/U6, and U5 small ribonucleoprotein particles (snRNPs). These snRNPs are involved in pre-mRNA splicing. RASSF2 (RAS association domain family 2) is a negative effector of Ras and has been implicated as a tumor suppressor gene in a number of other forms of epithelial cancer, such as colon, gastric, breast, and lung carcinoma [23–25]. The mechanism of inactivation of RASSF2 described in these tumors is aberrant promoter methylation, primarily in early tumors. In addition, inactivation of the A isoform of RASSF2 by promoter methylation has been found to correlate with a higher frequency of lymph node metastases in patients with nasopharyngeal carcinoma [26].
In summary, using an approach based on bioinformatic filters applied to array CGH data on a divergent metastasizing and non-metastasizing mouse model of PCa, we have identified genes that are biologically plausible metastasis suppressor genes. Our studies have identified an association between deletion with decreased expression of these genes and the metastasizing NE-10 model, suggesting a biological role for these genes in the metastatic process. We believe the divergence in behavior of the allograft can be attributed to clonal heterogeneity, with both metastasizing and non-metastasizing clones present in early allograft passages, but with selection for a non-metastasizing clone or clones after multiple in vivo passages. This selection could be due to preferential subcutaneous growth of the non-metastasizing compared to the metastasizing component of the allograft, such that over time, a larger and larger percentage of the allograft consists of the non-metastasizing population. It is possible that the clone or clones with the larger chromosome 2 deletion are enriched in the metastatic tumors because the differentially deleted region itself is responsible for the metastatic behavior, either alone or in combination with other genetic alterations, or that the larger deletion is simply a marker for a clone that is selected for because of the presence of some other alteration that confers metastatic potential. Additional studies are needed to prove that a gene or genes within the differentially deleted region of chromosome 2 are responsible for suppression of metastatic behavior.
We have taken advantage of a mouse allograft model of PCa (NE-10) with divergent metastasizing and non-metastasizing behavior to identify regions of the genome that potentially harbor metastasis suppressor genes. Using a combination of genomics and bioinformatics approaches, we identified candidate genes from a differentially deleted region on mouse chromosome 2 between the metastasizing and non-metastasizing allograft lines. The genes presented here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human PCa.
NE-10:
mouse allograft established from a primary tumor from the LPB-Tag mouse model of prostate cancer
PCa:
SQnon-met:
non-metastasizing subcutaneous allograft
SQmet:
metastasizing subcutaneous allograft
LiverMet:
CGH:
comparative genomic hybridization
BAC:
DFRs:
differential flagged regions
TTSW:
T-test sliding window.
We thank the Genomics Resource Core at the Fred Hutchinson Cancer Research Center for assistance with array CGH. This work was supported by NIH grants NCI R01-CA76142 (R.J.M.), DOD grant DAMD17-03-1-0035 (K.D.T.), NCI Howard Temin Award CA114033 (Y.Y.), and the Frances Williams Preston Laboratories of the T.J. Martell Foundation (R.J.M.).
13039_2009_46_MOESM1_ESM.DOC Additional file 1: Weighted scoring for the selection of candidate genes in 2E5-2F3. Detailed description of the weighted scoring method that was used to select candidate suppressor genes in the differentially deleted region of chromosome 2 between metastasizing and non-metastasizing allografts. (DOC 24 KB)
13039_2009_46_MOESM2_ESM.PPT Additional file 2: T-test sliding window whole genome and chromosome 2 analysis. Comparison of expression array results between metastatic and non-metastatic allografts using a T-test sliding window analysis. (PPT 332 KB)
13039_2009_46_MOESM3_ESM.DOC Additional file 3: Complete candidate gene list. Complete list of candidate genes from the 2E5-2F3 identified from the function-based bioinformatics filter and the cancer expression signature filter. (DOC 52 KB)
13039_2009_46_MOESM4_ESM.pdf Authors' original file for figure 1
YY interpreted the expression array results, conducted the bioinformatics, directed and interpreted the RT-PCR experiments, and helped draft the manuscript. SN participated in the expression array experiments and helped revise the manuscript. TC maintained the allografts and harvested tissues. CN provided oversight of the expression array experiments. TR performed the quantitative RT-PCR experiments. RJM provided the allograft model, designed the expression array experiments, and helped draft the manuscript. KDT conducted and interpreted the array CGH experiments, and drafted the manuscript. All authors read and approved the final manuscript.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Department of Urologic Surgery and Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Department of Urologic Sciences, University of British Columbia, The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada
Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Laboratories, Seattle Children's Hospital, WA, USA
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, WA, USA
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Our Creepers, boots and MJ's are made to last. Like forever. We make them in the old school "shoey" way but this makes them fit nice and snug. So, please check our size chart to make sure of your size. If you don't like your shoes to fit too tight or you have a wide old foot, then we suggest going up one size, especially in the Point Toe styles.


If you're stuck in Operation Flashpoint: Cold War Crisis, ask your fellow GameFAQs members for help.
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text:
Keith Haring – Pop Shop Figure
TITLE: Keith Haring Pop Shop Figure
PRODUCER: Medicom VCD
MEDIUM: Vinyl
SIZE: 9 inches tall (approximate)
PRICE: SOLD OUT
Please note, this is a special order item and expects to ship within 3 weeks of purchase.
During a brief but intense career that spanned the 1980s, Keith Haring's work was featured in over 100 solo and group exhibitions. In 1986 alone, he was the subject of more than 40 newspaper and magazine articles. He was highly sought after to participate in collaborative projects ,and worked with artists and performers as diverse as Madonna, Grace Jones, Bill T. Jones, William Burroughs, Timothy Leary, Jenny Holzer, Yoko Ono and Andy Warhol. By expressing universal concepts of birth, death, love, sex and war, using a primacy of line and directness of message, Haring was able to attract a wide audience and assure the accessibility and staying power of his imagery, which has become a universally recognized visual language of the 20th century.
See all available art by: Keith Haring


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redpajama_set_name: RedPajamaGithub


A new lease for Old Navy prompted developer NewQuest Properties to begin construction on a 12,500-square-foot retail building at Brazos Town Center in Rosenberg, TX. The space, tucked between Kohl's and Gordman's in the development's first phase, is anticipated for completion in February 2019.
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The growing medical need and the lack of effective treatments for bone tumors gave rise to Atlanthera in 2011, a drug discovery company focused on bone diseases and created in collaboration with U957 INSERM laboratory.
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Before Master Chief ever set foot on the first Halo megastructure, UNSC Marines fended off the advances of the alien alliance known as the Covenant on a remote colony called Reach. Halo: Reach recounts the story of one of humanity's greatest battles against the Covenant. Noble Team may be comprised of genetically augmented Spartan super soldiers, but regular humans can rely on this IGN Guide for the locations of the Data Pads, a full Heroic difficulty walkthrough and much, much more.


text:
Financial Planning & Management
How much money do you need each year in retirement?
Asked by: Mr. Dan Rath | Last update: February 9, 2022
Most experts say your retirement income should be about 80% of your final pre-retirement annual income. 1 That means if you make $100,000 annually at retirement, you need at least $80,000 per year to have a comfortable lifestyle after leaving the workforce.
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How Much Do I Need to Retire? Retirement Planning 101
What is the 4 retirement rule?
The 4% rule essentially hypothesizes that, based on past U.S. investment returns, a retiree expecting to live 30 years in retirement should be safe (in other words will have money left over at death), if she withdraws approximately 4% of her retirement capital each year, adjusting the income annually for inflation.
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No. You can retire comfortably on a sum like $600,000 if you take the right steps (and don't confuse "comfortable" with "luxurious"). With the right financial choices, a $600,000 nest egg might be enough for an adequately funded retirement without depleting your savings at a dangerous rate.
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Yes, you can retire at 62 with four hundred thousand dollars. At age 62, an annuity will provide a guaranteed level income of $21,000 annually starting immediately, for the rest of the insured's lifetime. ... The longer you wait before starting the lifetime income payout, the higher the income amount to you will be.
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In late 2021, the Social Security Administration announced that the average benefit for a retired worker would be increasing by $93, from $1,565 to $1,658, starting in Jan. 2022. For those earning the spousal benefit, the average benefit increased from $794 to $841, or an increase of $47.
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Recommended 401k Amounts By Age
Middle age savers (35-50) should be able to become 401k millionaires around age 50 if they've been maxing out their 401k and properly investing since the age of 23.
How much money do you need to live comfortably in retirement?
Many financial professionals recommend that you account for between 70% and 80% of your pre-retirement income each year in retirement. This means that if you currently earn $60,000 per year, you should plan to spend between $42,000 to $48,000 annually once you retire.
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How far will 2 million dollars go in retirement?
Following the 4 percent rule for retirement spending, $2 million could provide about $80,000 per year, which is above average. The Bureau of Labor Statistics reports that the average 65-year-old spends roughly $3,800 per month in retirement — or $45,756 per year. Of course, these are all "back-of napkin" calculations.
How much money do I need to retire at 66?
Some advisors recommend saving 12 times your annual salary. Under this rule, a 66-year-old $100,000 earner would need $1.2 million at retirement.
31Can I take my pension at 55 and still work?
32What is the 4 retirement rule?
17What is a good rate of return for 401k?
34At what age should you have no debt?
29How much power does an executor of a will have?
22What is the downside of an irrevocable trust?
39Is it safe to keep all your money in one brokerage?
32Why should you avoid annuities in retirement?
15What happens if I retire at 65 instead of 66?
39Can I leave my money in super after I retire?
15What should I do with 500K?
42Does my 14 year old need to file taxes?
24What makes a Roth distribution qualified?
15How does Fast payday loans work?
38Are retirement accounts protected in a lawsuit?
27Can bill collectors take your Social Security?
37Is a 752 credit score good?
15What is the minimum turnover for audit?
19Is it better to pay your credit card in full or leave a balance?
26Why is the IRS reviewing my taxes?


At the west edge of Kootenay National Park, the town of Radium Hot Springs is a swift change from the natural idyll. Motels, cafés, and gas stations line Hwy-93 block after block, and apart from satisfying your fuel-and-food needs, there's not a lot here. The one good place to eat is Springs Elevation Restaurant, west of town on the golf course at family-friendly Radium Resort (250/347-6200 or 800/667-6444, C$114 and up). Standard motels here include the Alpen Motel (250/347-9823, C$79-139).
The actual hot springs from which the town takes its name are just east, inside the park boundary. Unfortunately, the water is heavily chlorinated, and there are no "natural" springs left.


18th-century depiction of the Moloch idol (Der Götze Moloch mit 7 Räumen oder Capellen. "The idol Moloch with seven chambers or chapels"), from Johann Lund's Die Alten Jüdischen Heiligthümer (1711, 1738).
Moloch[a] is the biblical name of a Canaanite god associated with child sacrifice. The name of this deity is also sometimes spelled Molech, Milcom, or Malcam.
The name Moloch results from a dysphemic vocalisation in the Second Temple period of a theonym based on the root mlk, "king". There are a number of Canaanite gods with names based on this root, which became summarily associated with Moloch, including biblical מַלְכָּם Malkam "Great King" (KJV Milcom), which appears to refer to a god of the Ammonites, as well as Tyrian Melqart and others.
Otto Eissfeldt in 1935 argued that mlk was not to be taken as a theonym at all but as a term for a type of fire sacrifice, and that *lĕmōlek "as a molk-sacrifice" had been reinterpreted as the name of a Canaanite idol following the Deuteronomic reform under Josiah (r. 640–609 BC). According to Eissfeldt, this 7th-century reform abolished the child sacrifice that had been happening.
Moloch has been used figuratively in English literature from John Milton's Paradise Lost (1667) to Allen Ginsberg's "Howl" (1955), to refer to a person or thing demanding or requiring a very costly sacrifice.
Biblical Hebrew מלך (mlk) usually stands for מֶלֶךְ melek "king" (Akkadian malku), but when vocalized as מֹלֶךְ mōlek in the Masoretic Text, it has been traditionally understood as a proper name. While the received Masoretic text dates to the Middle Ages, the existence of the form Ancient Greek: Μολοχ (Molokh, whence Vulgate Moloch) in the Septuagint establishes that the distinction dates to the Second Temple period.
Moloch has been traditionally interpreted as the name of a god, possibly a god surnamed "the king" (cf. adon "lord", baʿal "master"), but pejoratively mispronounced as Molek instead of Melek, using the vocalisation of Hebrew בּשֶׁת bosheth "shame", distinguishing it from the title of melek "king", written identically in the consonantal text, which is also frequently given to Yahweh.
Thus, in Psalm 5:3, the מלכי mlk-y ("my mlk") of the Hebrew text is vocalized מַלְכִּי malk-ī and translated ὁ βασιλεύς μου ("my king") in the Septuagint; by contrast, in Amos 5:26, מלככם mlk-km ("your (plural) mlk") is vocalized מַלְכְּכֶם malk-chem ("your king") but translated Μολοχ ὑμῶν ("your Moloch") in the Septuagint.
The name of the god of the Ammonites is also given as מַלְכָּם malkam ("great king"),) rendered as Milcom in KJV. In 1 Kings 11:7, לְמֹלֶךְ שִׁקֻּץ בְּנֵי עַמֹּֽון (KJV: "for Molech, the abomination of the children of Ammon"), the Septuagint has τῷ βασιλεῖ αὐτῶν εἰδώλῳ υἱῶν Αμμων ("for their king, idol of the sons of Ammon"), while in 1 Kings 11:33 לְמִלְכֹּם אֱלֹהֵי בְנֵֽי־עַמֹּון (KJV: "Milcom the god of the children of Ammon") is translated τῷ βασιλεῖ αὐτῶν προσοχθίσματι υἱῶν Αμμων ("for their king, the abomination of the sons of Ammon").
Leviticus 20:2: "Again, thou shalt say to the children of Israel, Whosoever he be of the children of Israel, or of the strangers that sojourn in Israel, that giveth any of his seed unto Molech; he shall surely be put to death: the people of the land shall stone him with stones."
Leviticus 20:3: "And I will set my face against that man, and will cut him off from among his people; because he hath given of his seed unto Molech, to defile my sanctuary, and to profane my holy name."
Leviticus 20:4: "And if the people of the land do any ways hide their eyes from the man, when he giveth of his seed unto Molech, and kill him not"
Leviticus 20:5: "Then I will set my face against that man, and against his family, and will cut him off, and all that go a whoring after him, to commit whoredom with Molech, from among their people."
2 Kings 23:10: "And he (King Josiah of Judah) defiled Topheth, which is in the valley of the children of Hinnom, that no man might make his son or his daughter to pass through the fire to Molech."
Jeremiah 32:35: "And they built the high places of Baal, which are in the valley of the son of Hinnom, to cause their sons and their daughters to pass through the fire unto Molech which I commanded them not, neither came it into my mind, that they should do this abomination, to cause Judah to sin."
The practice of "passing through fire" (`abar ba-'esh עָבַר בָּאֵשׁ) associated with the name Moloch in the citations above also occurs without reference to Moloch in Deuteronomy 18:10–13, 2 Kings 16:3 and 21:6 and Ezekiel 20:26,31 and 23:37.
Isaiah 30:33 has the vocalization melek ("king"), but this is widely accepted as an omission of the Masoretic correctors: "For Tophet is ordained of old; yea, for the king it is prepared; he hath made it deep and large: the pile thereof is fire and much wood; the breath of the LORD, like a stream of brimstone, doth kindle it."
On the other hand, while 1 Kings 11:7 has the vocalization Molek, in "Molech, the abomination of the children of Ammon", this is widely accepted as an error for Malkam (Milcom), the specifically Ammonite idol.
The Septuagint uses Μολοχ three times, rendered by KJV as Moloch or Molech, in 2 Kings 23:10, Jeremiah 32:35 (both verses have Masoretic molek, cited above), and Amos 5:26 (where the Masoretic text has melek "king"). In the other instances of Masoretic molek, LXX has βασιλεύς basileus "king".
The variant Malkam, rendered by KJV as Milcom, is found only three times in Kings (1 Kings 11:5, 11:33 and 2 Kings 23:13). Malkam is each time specifically mentioned as a god of the Ammonites, while Molek is generally depicted as a god worshipped by the Israelites in the context of the "passing through fire" of their children (with the exception of 1 Kings 11:7, which mentions "Molech, the abomination of the children of Ammon", widely accepted as an error for Malkam).
Canonical Christian scriptures refer once to the pagan idol, Moloch (Acts 7:43).
The figure of Mōlok appears in the Quran (43:77) as Mālik (مَالِك). Islamic tradition expanded on this enigmatic reference, portraying Malik as the guardian of Hell. In Modern Standard Arabic, the word mālik means "owner". It is used as a male given name.
Later commentators have compared these accounts with similar ones from Greek and Latin sources speaking of the offering of children by fire as sacrifices in the Punic city of Carthage, a Phoenician colony. Cleitarchus, Diodorus Siculus and Plutarch all mention burning of children as an offering to Cronus or Saturn, that is to Baal Hammon, the chief god of Carthage. It has been suggested that the practice of child sacrifice may have been exaggerated in Roman post-war propaganda in order to make their arch-enemies seem cruel and less civilized.
Freeman in The History of Sicily from the Earliest Times (1894) states that the Carthaginian nobles had acquired and raised children not of their own for the express purpose of sacrificing them to the god. The author states that during the siege, the 200 high-born children were sacrificed in addition to another 300 children who were initially saved from the fire by the sacrifice of these acquired substitutes.
... but with full knowledge and understanding they themselves offered up their own children, and those who had no children would buy little ones from poor people and cut their throats as if they were so many lambs or young birds; meanwhile the mother stood by without a tear or moan; but should she utter a single moan or let fall a single tear, she had to forfeit the money, and her child was sacrificed nevertheless; and the whole area before the statue was filled with a loud noise of flutes and drums that the cries of wailing should not reach the ears of the people.
Scholars of the 17th century received from medieval rabbinical tradition the notion that the various gods named mlk "king" in the Hebrew Bible are closely related, if not identical.
Early modern scholarship tended to accept the biblical and Greco-Roman accounts of child sacrifice at face value, although there were early suggestions that the biblical account might refer to a symbolic practice, among them an essay by John Selden of 1617 with the suggestion that the phrase h'byr b'sh lmlk "making to pass over the fire to Molek" might have entailed a februation (purification ritual) rather than human sacrifice.
Valentin Greissing in 1678 suggested that the vocalisation Molek was modelled after חֹלֵם ḥōlem "dreamer; prophet" to distinguish it from melek "king", presaging the much more influential suggestion by Abraham Geiger (1857) that the vocalisation is a dysphemism modelled after בּשֶׁת bōshet "shame". John Spenser wrote a seminal study on Molek, Lex transitum per ignem, in honorem Molechi prohibens in 1686, initiating the influential interpretation of Molek as a solar deity.
Greco-Roman authors describe the Carthaginian practice of child sacrifice as dedicated to Baal Hammon or, in interpretatio graeca, to Cronus. The explicit identification of this Punic deity with the biblical Moloch is modern, suggesting a continuity of the practice of child sacrifice from Iron Age, or possibly Late Bronze Age Canaan to 2nd-century BC Carthage. Carthaginian child sacrifice in the context of biblical Moloch is studied, still based on the authority of ancient authors rather than archaeology, by Friedrich Münter in Die Religion der Karthager (1816) and by Franz Karl Movers in Die Phönizier (1841). Both Münter and Movers concluded that Molek was identical with Baal and to be categorized as a fire god.
In 1841, both Georg Friedrich Daumer and Friedrich Wilhelm Ghillany published influential works on the topic. These authors came to the conclusion that the biblical text reflects an original identity of Molek and Yahweh, and that the cult of Yahweh grew out of that of Molek, by the abolishing of human sacrifice. The authors find numerous instances of vestigial references to human sacrifice, most notably the law that all firstborns must be "consecrated" or "given" to Yahweh (Book of Exodus 13:2, 22:28).
Abraham Geiger (1857) argued that the vocalisation molek was a secondary "dysphemic" correction due to the redactors of the Masoretic text, and argued that there were a further 25 or so instances that should be taken to refer to molek which had been missed by the correctors (and remain vocalised melek in the received text). Of these proposed instances, Isaiah 30:33 has become commonly accepted, while the others have at best found partial support.
The hypothesis of Daumer and Ghillany of the original identity of Yahweh and Molek was controversially discussed by widely accepted in mid-19th century scholarship. It was influentially rejected by Wolf Wilhelm Friedrich von Baudissin in his dissertation Jahve et Moloch: sive de ratione inter deum Israelitarum et Molochum intercedente (Leipzig, 1874). Baudissin argued that the theonym Mlk was of genuinely Phoenician (and neither Hebrew nor Assyrian) origin, reflected in Melqart of Tyre and the later reports of child sacrifice in the Tyrian colony of Carthage, and that it was only the import of the cult of the Tyrian Baal (i.e. Melqart) under king Ahab (r. ca. 885–850 BC) that gave rise to his worship among the Israelites (and the corresponding condemnation of the practice by the Yahwist faction represented in the Hebrew Bible).
In the early 20th century, scholarly opinion on the topic begins to be informed by the results of archaeological excavations in the Near East, notably those by R. A. S. Macalister at Gezer during 1902–1909. Macalister reported evidence of child sacrifice in Late Bronze Age Canaan. Consensus shifted towards the assumption of widespread child sacrifice in Canaan, although there were dissenting opinions. French-led excavations at Carthage began in 1921, and from 1923 reported finds of a large quantity of urns containing a mixture of animal and children's bones. René Dussaud identified a 4th-century BC stela found in Carthage as depicting a child sacrifice. A temple at Amman (1400–1250 BC) excavated and reported upon by J.B. Hennessy in 1966, shows the possibility of bestial and human sacrifice by fire. While evidence of child sacrifice in Canaan was the object of academic disagreement, with some scholars arguing that merely children's cemeteries had been unearthed, in Carthage, the mixture of children's with animal bones as well as associated epigraphic evidence involving mention of mlk led to a consensus that, at least in Carthage, child sacrifice was indeed common practice.
The term mlk in Punic epigraphy was given a re-interpretation by Otto Eissfeldt in 1935. Eissfeldt's suggestion was that molk was not to be taken as a theonym at all but as a term for a type of fire sacrifice. For the Hebrew Bible, he argued that seven out of the eight instances of Masoretic Molek (excising 1 Kings 11:7 as an error for Milkom) should also be regarded as the technical term for child sacrifice rather than as the name of a god, and that *lĕmōlek "as a molk-sacrifice" had been reinterpreted as the name of a Canaanite idol following the Deuteronomic reform under Josiah (r. 640–609 BC). According to Eissfeldt, this 7th-century reform abolished the child sacrifice that had hitherto been an acceptable part of the cult of Yahweh. Paul G. Mosca's Child Sacrifice in Canaanite and Israelite Religion: A Study in Mulk and Molech (1975) similarly argued in support of the theory that child sacrifice (molk) to Yahweh was practiced until the Deuteronomic reform of the 7th century BC.
Moshe Weinfield (1972) once again revived the "februarist" position, suggesting that the practice of "passing through fire" prohibited for the Israelites in Leviticus did not refer to actual child sacrifice but to a symbolic rite in which infants were passed across a flame. Smith (1975) responded to this proposal by arguing that the Hebrew phrase implies a translation of "to burn" rather than "to pass between flame".
John Day (1989) argued for the existence of a god named Molek based on Ugaritic evidence.
In the 21st century the myth of Moloch has been referred to by Asturian political parties with the name of Molloch and also by Iberian patriotic writers specialized in the myth of Saturn, once painted by Francisco Goya, to describe some regional editions based in Barcelona.
And black GEHENNA call'd, the Type of Hell."
He is listed among the chief of Satan's angels in Book I, and is given a speech at the parliament of Hell in Book 2:43 – 105, where he argues for immediate warfare against God. He later becomes revered as a pagan god on Earth.
Then further back, higher than the candelabrum, and much higher than the altar, rose the Moloch, all of iron, and with gaping apertures in his human breast. His outspread wings were stretched upon the wall, his tapering hands reached down to the ground; three black stones bordered by yellow circles represented three eyeballs on his brow, and his bull's head was raised with a terrible effort as if in order to bellow.
Chapter 13 describes how, in desperate attempt to call down rain, the image of Moloch was brought to the center of Carthage, how the arms of the image were moved by the pulling of chains by the priests (apparently Flaubert's own invention), and then describes the sacrifices made to Moloch. First grain and animals of various kinds were placed in compartments within the statue (as in the Rabbinic account). Then the children were offered, at first a few, and then more and more.
The brazen arms were working more quickly. They paused no longer. Every time that a child was placed in them the priests of Moloch spread out their hands upon him to burden him with the crimes of the people, vociferating: "They are not men but oxen!" and the multitude round about repeated: "Oxen! oxen!" The devout exclaimed: "Lord! eat!" and the priests of Proserpine, complying through terror with the needs of Carthage, muttered the formula: "Pour out rain! bring forth!"
The victims, when scarcely at the edge of the opening, disappeared like a drop of water on a red-hot plate, and white smoke rose amid the great scarlet colour.
Nevertheless, the appetite of the god was not appeased. He ever wished for more. In order to furnish him with a larger supply, the victims were piled up on his hands with a big chain above them which kept them in their place. Some devout persons had at the beginning wished to count them, to see whether their number corresponded with the days of the solar year; but others were brought, and it was impossible to distinguish them in the giddy motion of the horrible arms. This lasted for a long, indefinite time until the evening. Then the partitions inside assumed a darker glow, and burning flesh could be seen. Some even believed that they could descry hair, limbs, and whole bodies.
Night fell; clouds accumulated above the Baal. The funeral-pile, which was flameless now, formed a pyramid of coals up to his knees; completely red like a giant covered with blood, he looked, with his head thrown back, as though he were staggering beneath the weight of his intoxication.
Italian director Giovanni Pastrone's silent film Cabiria (1914) was largely based on Salammbô and included an enormous image of Moloch modeled on Flaubert's description. American antisemite and anti-communist agitator Elizabeth Dilling, and her husband Jeremiah Stokes, wrote an antisemitic work, The Plot Against Christianity (1964). Re-released under the title The Jewish Religion: Its Influence Today — with Talmudic writings annotated by Dilling — it quoted Flaubert's description as if it were historically accurate. Information from the novel and film still finds its way into serious writing about Moloch, Melqart, Carthage, and Baal Hammon..
A rhetorical connection between abortion and the child sacrifice to Moloch has been drawn by the anti-abortion movement since the late 19th century.
The savage, like ourselves, feels the oppression of his impotence before the powers of Nature; but having in himself nothing that he respects more than Power, he is willing to prostrate himself before his gods, without inquiring whether they are worthy of his worship. Pathetic and very terrible is the long history of cruelty and torture, of degradation and human sacrifice, endured in the hope of placating the jealous gods: surely, the trembling believer thinks, when what is most precious has been freely given, their lust for blood must be appeased, and more will not be required. The religion of Moloch — as such creeds may be generically called — is in essence the cringing submission of the slave, who dare not, even in his heart, allow the thought that his master deserves no adulation. Since the independence of ideals is not yet acknowledged, Power may be freely worshipped, and receive an unlimited respect, despite its wanton infliction of pain.
During the growth of vehicle ownership in the United States, the concern for automobile deaths prompted at least one editorial cartoonist to label the automobile "the Modern Moloch," viewing the car as a machine of death.
In letters of the Munich Cosmic Circle the name Moloch was used to symbolize a Jewish God, hostile to life.
He had called from the depths of defeat the dark and savage furies latent in the most numerous, most serviceable, ruthless, contradictory and ill-starred race in Europe. He had conjured up the fearful idol of an all-devouring Moloch of which he was the priest and incarnation."
In Allen Ginsberg's poem "Howl" (1955), Moloch is used as a metaphor for industrial civilization and for America more specifically. The word is repeated many times throughout Part II of the poem, and begins (as an exclamation of "Moloch!") in all but the first and last five stanzas of the section.
In H.G. Wells' novel The Time Machine (1895) and subsequent movies, the antagonists were futuristic creatures called 'Morlocks' who routinely ate childlike 'Eloi' (which suggests he was making a biblical analogy).
In Fritz Lang's Metropolis (1927), the industrial machinery of the factory is envisioned as a sacrificial temple to Moloch. It lacks the ability to connect hands to heart.
At a later period and almost universally the Newts themselves came to accept a different faith, whose origin among them is unknown; this involved adoration of Moloch, whom they visualized as a giant Newt with a human head; they were reported to have enormous submarine idols made of cast iron, manufactured to their orders by Armstrong or Krupp, but no further details ever leaked out of their cultic rituals since they were conducted under water; they were, however, believed to be exceptionally cruel and secret. It would seem that this faith gained ground rapidly because the name Moloch reminded them of the zoological "molche" or the German "Molch," the terms for Newt.
In the science fiction show Stargate SG1, Moloch (Moloc) was a Goa'uld who demanded that all female Jaffa (warrior caste among Goa'uld society) in his domain be sacrificed shortly after they were born. He was eventually assassinated by Stargate Command.
In Supernatural, Season 12 Episode 18, Sam and Dean Winchester investigate missing youths in Tomahawk, Wisconsin, only to find out they are being sacrificed to Moloch.
In the TV series Dirk Gently's Holistic Detective Agency, season 2, Project Moloch is a code name for one of the gifted people kept by the government facility called Blackwing.
On the 2012 album Noctourniquet by The Mars Volta, Moloch is mentioned in both the title and the lyrics of the song "Molochwalker".
In the TV Series Sleepy Hollow (2013 - 2017) Moloch was the creature that raised the four horsemen in an attempt to start the Apocalypse.
The 2018 film Solo: A Star Wars Story has a minor villain named Moloch in the first act.
^ D.D. Hughes, Human Sacrifice in Ancient Greece, London: 1991, S. 115 ff.
^ following a widely-adopted suggestion going back to Abraham Geiger (1857), e.g. "Molech". Britannica Online Encyclopedia. Encyclopædia Britannica Online. 2008. Retrieved 2008-03-22.
^ Amos 5:26 ("ye have borne the tabernacle of your Moloch") is cited in Acts 7:43, as "Yea, ye took up the tabernacle of Moloch" (καὶ ἀνελάβετε τὴν σκηνὴν τοῦ Μολὸχ[...] ὑμῶν), the only occurrence of the name Moloch in the New Testament.
^ a b George C. Heider, Cult of Molek: A Reassessment (1985), p. 10.
^ a b c George C. Heider, Cult of Molek: A Reassessment (1985), 36f.
^ "Then did Solomon build a high place for Chemosh, the abomination of Moab, in the hill that is before Jerusalem, and for Molech, the abomination of the Sons of Ammon." (KJV) Here, למלך lmlk ("for Molech") is vocalized לְמֹלֶךְ lĕ-molek, while the Septuagint translates τῷ βασιλεῖ αὐτῶν "for their king".
^ In addition, 1 Chronicles 8:9 mentions an unrelated Malkam, son of Shaharaim, of the tribe of Benjamin.
^ Of Roman-Carthaginian diplomacy leading up to the final confrontation, A. E. Astin, F. W. Walbank, M. W. Frederiksen, (Rome and the Mediterranean to 133 B.C., Cambridge Ancient History VIII, "Rome and Carthage" 1989:149) note that the sources, "principally Appian and the Epitome of Livy are contaminated by more or less obvious falsehoods, especially the Epitome. The reason for this was of course the desire of contemporary and, even more, of later Romans to justify Rome's conduct".
^ Edward Augustus Freeman (1894). The History of Sicily from the Earliest Times:Volume IV. Oxford University Press. Retrieved 5 December 2011.
^ Attributed, for example, by Moses Margoliouth, A Pilgrimage to the Land of my Fathers 1850:125.
^ George C. Heider, Cult of Molek: A Reassessment (1985), p. 2.
^ Selden, De Dîs Syris (1617), 93f.
^ G. F. Daumer, Der Feuer- und Molech-dienst der alten Hebräer als urväterlicher, legaler, orthodoxer Kultus der Nation, Brunswick (1842). F. W. Ghillany, Die Menschenopfer der alten Hebräer, Nuremberg (1842).
^ Baudissin (d. 1926) continued to publish influential treatises on the subject of Molek for a period of fifty years, notably the relevant articles in Schaff–Herzog Encyclopedia of Religious Knowledge, second and third editions, and substantial chapters in his Adonis and Esmun (1911) and Kyrios (published posthumously in 1929).
^ Friedrich Schwally (1919), see George C. Heider, Cult of Molek: A Reassessment (1985), 24f.
^ Otto Eissfeldt, Molk als Opferbegriff im Punischen und Hebräischen und das Ende des Gottes Moloch (1935).
^ so in B. G. Jefferis, J. L. Nichols, Searchlights on Health: Light on Dark Corners A Complete Sexual Science and a Guide to Purity and Physical Manhood, Advice To Maiden, Wife, And Mother, Love, Courtship, And Marriage (1894), p. 139 ("The abiding interest we feel in the preservation of the morals in our country, constrains us to raise our voice against the daily increasing practice of infanticide, especially before birth. The notoriety this monstrous crime has obtained of late, and the hecatombs of infants that are annually sacrificed to Moloch, to gratify an unlawful passion, are a sufficient justification for our alluding to a painful and delicate subject, which should 'not even be named,' only to correct and admonish the wrong-doers.").
^ 99% Invisible: "The Modern Moloch" PRX. April 3, 2013.
^ Karl und Hanna Wolfskehl – Briefwechsel mit Friedrich Gundolf. Edited by Karlhans Kluncker. Castrum Peregrini Presse, 1977 ISBN 90-6034-032-9 "Aus Anspielungen der Propheten muss man schliessen, dass Moloch von seinen Verehrern mit dem Nationalgott Jahwe kombiniert wurde."
González Wagner, C. & Ruiz Cabrero, L.A. (2007). El Sacrificio Molk. Madrid: Ediciones del Orto. ISBN 84-7923-394-X.
Grena, G.M. (2004). LMLK—A Mystery Belonging to the King vol. 1. Redondo Beach, California: 4000 Years of Writing History. ISBN 0-9748786-0-X.
"Molech". Britannica Online Encyclopedia. Encyclopædia Britannica Online. 2008. Retrieved 2008-03-22.
Ruiz Cabrero, L.A. (2008). El Sacrificio Molk entree los fenicio-púnicos. Madrid: Universidad Complutense de Madrid. Servicio de Publicaciones. ISBN 978-84-669-3039-0.
Isidore Singer, George A. Barton, "Moloch (Molech)" in Jewish Encyclopedia (1971/2).
Moloch, Cult of, Encyclopedia Judaica (1906).
F. Gigot, Moloch, in Catholic Encyclopedia (1911).
Chisholm, Hugh, ed. (1911). "Moloch" . Encyclopædia Britannica (11th ed.). Cambridge University Press.
Look up Moloch in Wiktionary, the free dictionary.
A Preliminary Report on the Incirli Stele (Discussion of a stele with Phoenician text which may equate molk/mulk to first-born son).
HelgaSeeden, "A tophet in Tyre?" 1991. from Bertyus 39 (American University of Beirut).
This page was last edited on 11 April 2019, at 22:19 (UTC).


As we approached the bridge straight out of a Tarzan movie, all ropes and wooden slats, with a 300' drop, our Captain said pointing at the sign, ALL PERSONAL MUST DISEMBARK BEFORE CROSSING, RIGHTO, everybody out, 12 personal jumped off the 6x6 International tractor ( Australian Army calls artillery trucks - tractors) (why?) who knows?. The Captain turns to me, right gunner, off you go.
There I went, crawling over this rope bridge, speedo not even registering, as I got to the centre of bridge, it starts to sway, oh great, mumbling to myself, as the bridge swings about a metre off centre, all the while still pushing ahead, hate to imagine if there was a wind, as I crawled off the bridge, I lit a ciggie to calm my nerves, looking down the ravine as the rest started walking across.
if the bridge collapses, we only lose a gunner and a tractor, simple logic don't you think. RIGHTO, smokes out, everybody climb on board and off we went on our adventure.
From what I've heard, the Engineers have demolished the bridge, good thing I took a photo.


text:
Detective Conan Movie 22: Zero the Enforcer (Dub)
Action, Detective, Drama, Mystery
In the film's story, there is a sudden explosion at Tokyo Summit's giant Edge of Ocean facility. The shadow of Tooru Amuro, who works for the National Police Agency Security Bureau as Zero, appears at the site. In addition, the "triple-face" character is known as Rei Furuya as a detective and Kogorou Mouri's apprentice, and he is also known as Bourbon as a Black Organization member. Kogorou is arrested as a suspect in the case of the explosion. Conan conducts an investigation to prove Kogorou's innocence, but Amuro gets in his way....
In the film's story, there is a sudden explosion at Tokyo Summit's giant Edge of Ocean facility. The shadow of Tooru Amuro, who works for the National Police Agency Security Bureau as Zero, appears at the site. In addition, the "triple-face" character is known as Rei Furuya as a detective and Kogorou Mouri's apprentice, and he is also known as Bourbon as a Black Organization member. Kogorou is arrested as a suspect in the case of the explosion. Conan conducts an investigation to prove Kogorou's innocence, but Amuro gets in his way.


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