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Viable mouse gene ablations that robustly alter brain Aβ levels are rare
Accumulation of amyloid-β (Aβ) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of Aβ, but not all are equally tractable for drug discovery.
To search for novel targets that affect brain Aβ without causing toxicity, we screened mouse brain samples from 1930 novel gene knock-out (KO) strains, representing 1926 genes, using Aβ ELISA assays. Although robust Aβ lowering was readily apparent in brains from a BACE1 KO strain, none of the novel strains exhibited robust decreases in brain Aβ, including a GPR3 KO strain, which had previously been proposed as an Aβ target. However, significantly increased Aβ was observed in brain samples from two KO strains, corresponding to genes encoding the glycosylphosphatidylinositol mannosyl transferase PIGZ and quinolinate phosphoribosyltransferase (QPRT).
Thus, gene ablations that are permissive for mouse survival and that also have a robust effect on Aβ levels in the brain are rare.
The amyloid hypothesis states that Alzheimer' disease (AD) is caused by accumulation of toxic forms of the amyloid-β (Aβ) peptide in the brain. Aβ is a secreted peptide formed through consecutive proteolytic cleavages of the amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1), which releases the N-terminal end of Aβ, and γ-secretase, which releases a range of Aβ C-terminal ends resulting in Aβ peptides of typically 37-42 amino acids in length. The predominant form of Aβ has 40 amino acid residues, and is denoted Aβ40, whereas the disease-associated Aβ42 has two additional C-terminal residues
APP itself is a direct target of small molecule modulators of Aβ production
In addition to the regulation of Aβ biosynthesis, Aβ clearance is also regulated. Clearance of Aβ combines several mechanisms, including the LXR/ABCA1/APOE pathway
Thus, it seems reasonable to anticipate numerous molecular targets capable of altering Aβ levels, and that at least some of the targets should be relevant to Aβ formation in the brain. The ideal target should have the potential for robust brain Aβ-lowering without toxicity, and characteristics that facilitate development of inhibitors. We therefore took the approach of direct screening of brain Aβ levels in novel mouse gene knock out (KO) strains, an approach that has the dual advantages of providing evidence both for target effectiveness in Aβ-lowering and for target safety. Given that even optimized drug molecules may not be capable of 100% ablation of target function, we were most interested in finding KO strains with 50% or more reduction in brain Aβ levels. A total of 1930 viable homozygous gene ablations, representing 1926 genes, were tested. Surprisingly, none of these gene ablations exhibited robust decreases in Aβ. In addition, we also evaluated GPR3 KO mice, recently proposed as an Aβ target
A screen of mouse KO strains for altered brain Aβ levels
Mouse knock-out (KO) strains were generated over a period of four years, and brain samples were collected and assayed during this time on an ongoing basis. Figure
Figure 1
Outline of screening tiers
Outline of screening tiers. Aβ40 in four brain samples (sagittal left halves) from 1930 different mouse KO strains were determined. Of these, 77 KO strains were selected for further Aβ40 determinations, and in some cases Aβ42 determinations, of the corresponding right brain halves. The gene information for four of the KO strains is reported in the current study. Prioritization for possible drug discovery efforts was then based upon multiple considerations, including the robustness of Aβ inhibition, tractability of the target for small molecule inhibition, and relevance of the target to AD.
Table 1
Summary of genes by class
Gene class
Ion channel
DNA enzyme
G-Protein coupled receptor
Membrane and secreted
Nuclear hormone receptor
Putative secreted
Receptor associated protein
Transcription factor
The results of the primary Aβ40 screen for 1930 different KO strains are illustrated in Figure
Figure 2
Primary screen of Aβ40 levels
Primary screen of Aβ40 levels. Panel A - The median values of Aβ40 relative to baseline for each of 1930 KO strains is shown in red. Assay plate values for BACE1, BACE2 double KO brains are shown in blue, and values for Aβ1-14 synthetic peptide-blocked wild type brains are shown in green. The results for the PIGZ KO and the QPRT KO are indicated by arrows. Panel B - Same as panel A, except mean values of Aβ40 are plotted.
For 77 selected KO strains, particularly those exhibiting a median Aβ value more than 2 sd below control values, repeat Aβ40 assays, and in some cases Aβ42 assays, were carried out using the right brain half (Figure
Figure 3
Aβ levels in left and right brain halves of selected KO strains
Aβ levels in left and right brain halves of selected KO strains. Panel A - Median values of Aβ40 in right brain halves were plotted against median values in left brain halves. An ellipse highlights the results for UBE2R2 and ADRM1. The results for the PIGZ KO and the QPRT KO are indicated by arrows. Panel B - Same as panel A, except that mean Aβ values were plotted. Panel C - Relative values of Aβ40 and Aβ42 from left and right brain halves in individual animals is shown for four named KO strains. Note that left and right are not directly comparable because different extraction and assays procedures were used (see Methods). Bars represent the mean value.
Table 2
Left vs. right comparisons
Mean difference
2.40 (3)
0.24 (3)
-2.48 (3)
0.72 (3)
Ablation of GPR3 did not affect total brain Aβ levels
Deletion of the orphan G protein coupled receptor GPR3 has recently been reported to decrease hippocampal Aβ40 and Aβ42 in APP transgenic mice by a mechanism that involves the regulation of γ-secretase
Figure 4
Effect of GPR3 KO on brain Aβ levels in young mice
Effect of GPR3 KO on brain Aβ levels in young mice. Panel A - Aβ42 was assayed in brain extracts from ten GPR3 wild type (GPR3+/+), ten heterozygous (GPR3+/-), and ten homozygous GPR3 KO (GPR3-/-) mice. Brain Aβ42 was also determined in BACE1, BACE2 homozygous double KO (B1/2 dKO) and wild type (BACE+/+) control mice. Bars represent the mean values. Panel B - the same brain extracts were assayed for Aβ40. Panel C - the same brain extracts were assayed for Aβ1-x.
Figure 5
Effect of GPR3 KO on brain Aβ levels in aged mice
Effect of GPR3 KO on brain Aβ levels in aged mice. Aβ40 and Aβ42 were determined in one year aged mice for 13 GPR3 wild type (G3+/+) and 13 homozygous GPR3 KO (G3-/-) mice. For comparison, Aβ40 and Aβ42 for five young wild type (B1/2+/+) and four young BACE1, BACE2 homozygous double KO (B1/2 dKO) are shown. Values are expressed as percentage of mean value in the GPR3 wild type mice. One individual GPR3 wild type mouse with a value of 624% was excluded from the analysis.
Table 3
Comparisons between GPR3 KO and wild type animals using independent samples
Mean Difference
Aβ40 young -/- vs +/+
-1.76 (18)
Aβ40 young +/- vs +/+
-1.71 (18)
Aβ42 young -/- vs +/+
-1.37 (18)
Aβ42 young +/- vs +/+
-0.34 (18)
Aβ1-x young -/- vs +/+
-0.82 (18)
Aβ1-x young +/- vs +/+
1.90 (18)
Aβ40 old -/- vs +/+
-1.17 (24)
Aβ42 old -/- vs +/+
-0.86 (24)
To identify novel molecular targets relevant to regulation of Aβ levels in the brain, we screened viable mouse KO strains for decreased brain Aβ40. A total of 1930 different gene ablations giving rise to viable homozygous mice were evaluated. Two of the strains, PIGZ KO and QPRT KO, showed an unequivocal increase of Aβ40 and Aβ42 in the screening samples, whereas changes in Aβ were less obvious for the other KO strains. The two KO strains showing the lowest values of Aβ40 and Aβ42 in the screen, UBE2R2 and ADRM1, were of uncertain significance given the small number of samples tested.
Given the wide variety of mechanisms and proteins that have been reported to affect Aβ, and the relatively large number of gene KO strains tested, it was surprising that we did not identify a single new gene KO strain that caused a robust (≥50%) decrease in Aβ. A combination of several reasons may account for this. First, the choice of gene KO strains entering the screen was based on the 'druggable genome', which mostly limited the KO strains to proteins in gene families known to interact with small molecules. Second, the gene KO strains entering the screen were limited to those strains that resulted in viable homozygous adult mice. Approximately one third of the gene KO constructs made were homozygous embryonic lethal, and were consequently not included in the brain Aβ screen. Therefore, effective Aβ-lowering targets such as presenilin 1, for which genetic ablation is deleterious, would not have been tested in this screen. Third, functional redundancy, e.g. the genes encoding the Aph1B and Aph1C subunits of γ-secretase
Brain Aβ40, Aβ42 and Aβ1-x levels in GPR3 KO mice were evaluated more thoroughly by using a larger number of mice. No changes in brain Aβ42, Aβ40 or Aβ1-x were detected in sagittal brain halves from these mice. This contrasts with the results reported by Thathiah
Two gene ablations, corresponding to the PIGZ and QPRT enzymes, exhibited significantly increased Aβ40 and Aβ42 in the screening samples. While further substantiation of the results for PIGZ and QPRT using larger groups of homozygous KO mice is clearly desirable, plausible molecular mechanisms for increased Aβ can be proposed. PIGZ, also known as SMP3, is a mannosyl transferase that catalyses addition of a fourth side chain mannose to the glycosylphosphatidylinositol (GPI) protein anchor precursor
The two KO strains for which the lowest values of Aβ40 and Aβ42 (ca. 30% lowering) were observed in our screen corresponded to the UPS proteins Adrm1 and Ube2R2. Adrm1, also known as hRpn13, associates with the proteasome 19S regulatory particle, and is required for recruitment of the Uch37 deubiquitinating enzyme to the proteasome
Gene ablations that have a robust effect on brain Aβ appear to be rare, at a rate of approximately one in a thousand of the genes reported here. However, several pathways including GPI anchor metabolism, the kynurenine pathway of tryptophan degradation, and the UPS may be worth further evaluation for their roles in brain Aβ regulation.
Mouse KO strains and brain samples
Experimental procedures with mice were authorized by, and in compliance with, the Lexicon Pharmaceuticals Animal Care and Use Committee, and the Bristol-Myers Squibb Animal Care and Use Committee. The BACE1, BACE2 and GPR3 KO strains were provided by Lexicon Pharmaceuticals under the terms of the LexVision® Database and Collaboration Agreement. The BACE1/BACE2 double KO obtained by intercrossing the BACE1 and BACE2 KO strains has been described previously
Preparation and storage of brain samples
For the primary screen of brain Aβ levels, four mice from each KO strain were euthanized at three months of age by CO2 asphyxiation and sagittal brain halves lacking cerebellum were frozen and stored at -80°C. Samples were shipped on dry ice from Lexicon Pharmaceuticals to Bristol-Myers Squibb as they became available over a period of four years. Because the availability of individual mice occurred with varied timing, and because multiple different KO strains were in production simultaneously, the order of acquisition of brain samples was variable. This resulted in the four samples from any given KO strain arriving at different times, and thus the Aβ ELISA being carried out usually on different assay plates and different assay dates for each sample of a given KO strain. The Aβ primary screen values obtained even for a given gene KO therefore represented essentially all of the sources of variability to which the data were subject.
Aβ sample preparation and ELISA assays
The assay used for the primary screen of all brain samples has been partly described previously
Evaluation of Aβ results
To maintain consistency in the Aβ40 determinations between assay plates, the baseline value of Aβ40 was set equal to the mean value of all wells containing brain samples, excluding the BACE1/2 double KO or Aβ1-14 inhibited wells. Thus, the plate baseline generally depended on the mean value of 72 wells per plate. Alternative baseline values determined from known concentrations of synthetic Aβ40 peptides, or determined from pools of brain extracts from wild type mice, were found to be less consistent over time, and were therefore not used for evaluation of Aβ40 baseline levels. Median values of Aβ40 were calculated to avoid the potentially disproportionate effect of unusually high or low individual samples that could occur if using mean values, however, in the final analysis, use of mean or median values yielded the same outcome. Initially, calculations were carried out using data from a limited number of KO strains, and therefore some initial follow up assays were carried out for KO strains for which the median Aβ40 value was less than 2 sd from baseline.
Authors' contributions
JHT directed the project for part of its duration, designed and optimized Aβ assay methods for mouse brain, carried out data analysis, and wrote the manuscript. X-AL, MWT and VG carried out Aβ assays and data analysis. JEM carried out data analysis and directed the project for part of its duration. SS designed and optimized Aβ assay methods for mouse brain. NB carried out brain dissection for the GPR3 KO studies. JC evaluated genes that were of potential interest. AM carried out statistical analysis. DLS directed initial stages of the project, data analysis and mouse husbandry. MH carried out mouse husbandry and brain dissection. CFA, TL and RSW provided strategic guidance and project coordination. All authors read and approved the manuscript.
We thank Camellia Symonowicz, BMS, and Doreen Hewston, BMS, for management of the GPR3 KO colony, Jinwen Huang, BMS, for PCR genotyping of mice in the GPR3 KO colony, Timur Güngör, BMS, and J.D. Wallace, Lexicon Pharmaceuticals, for help during preparation of the manuscript.
Evidence that Aβ42 is the real culprit in Alzheimer's disease
The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics
Targeting APP metabolism for the treatment of Alzheimer's disease
Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics
Strategies for disease modification in Alzheimer's disease
Cell biology, regulation and inhibition of β-secretase (BACE-1)
β-secretase protein and activity are increased in the neocortex in Alzheimer disease
Increased expression of the amyloid precursor β-secretase in Alzheimer's disease
Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients
β-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: Implications for Alzheimer's disease pathogenesis
Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer's mice
Interferon-γ and tumor necrosis factor-α regulate amyloid-β plaque deposition and β-secretase expression in swedish mutant APP transgenic mice
Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression
Hypoxia-inducible factor 1α (HIF-1α)-mediated hypoxia increases BACE1 expression and β-amyloid generation
Oxidative stress activates a positive feedback between the γ- and β-secretase cleavages of the β-amyloid precursor protein
Phosphorylation of the translation initiation factor eIF2α increases BACE1 levels and promotes amyloidogenesis
An aging pathway controls the TrkA to p75NTR receptor switch and amyloid β-peptide generation
A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1
PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1
Glycosylphosphatidylinositol-anchored proteins play an important role in the biogenesis of the Alzheimer's amyloid β-protein
Lipid rafts play an important role in Aβ biogenesis by regulating the β-secretase pathway
Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precurso protein
GSK3α regulates production of Alzheimer's disease amyloid-β peptide
RAC1 inhibition targets amyloid precursor protein processing by γ-secretase and decreases Aβ production
Regulation of Alzheimer's disease amyloid-β formation by casein kinase I
The orphan G protein-coupled receptor 3 modulates amyloid-β peptide generation in neurons
The C-terminal fragment of the Alzheimer's disease amyloid protein precursor is degraded by a proteasome-dependent mechanism distinct from γ-secretase
Compounds that bind APP and inhibit Aβ processing in vitro suggest a novel approach to Alzheimer disease therapeutics
Substrate-targeting γ-secretase modulators
The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production
Inhibition of glycosphingolipid biosynthesis reduces secretion of the β-amyloid precursor protein and amyloid β-peptide
Reticulon family members modulate BACE1 activity and amyloid-β peptide generation
Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid β-protein
LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease
Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein
Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing
Alpha-secretase as a therapeutic target
ADAMs family members as amyloid precursor protein α-secretases
Evidence for defective retinoid transport and function in late onset Alzheimer's disease
Disruption of the retinoid signalling pathway causes a deposition of amyloid-β in the adult rat brain
The selective muscarinic M1 agonist AF102B decreases levels of total Aβ in cerebraospinal fluid of patients with Alzheimer's disease
M1 receptors play a central role in modulating AD-like pathology in transgenic mice
The neuropeptide PACAP promotes α-secretase pathway for processing Alzheimer amyloid precursor protein
Protein kinase C ε suppresses Aβ production and promotes activation of α-secretase
Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice
Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM10
The LXR agonist LO901317 selectively lowers hippocampal Aβ42 and improves memory in the Tg2576 mouse model of Alzheimer's disease
Amyloid-degrading enzymes as therapeutics targets in Alzheimer's disease
Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease
Lymphatic drainage of the brain and the pathophysiology of neurological disease
Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer's disease mice
Microglia mediate the clearance of soluble Aβ through fluid phase macropinosytosis
Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation
ApoE promotes the proteolytic degradation of Aβ
Resveratrol promotes clearance of Alzheimer's disease amyloid-β peptides
γ-Secretase heterogeneity in the Aph1 subunit: Relevance for Alzheimer's disease
A comparative analysis of brain and plasma Aβ levels in eight common non-transgenic mouse strains: Validation of a specific immunoassay for total rodent Aβ
The essential Smp3 protein is required for addition of the side-branching fourth mannose during the assembly of yeast glycosylphosphatidylinositols
Human Smp3p adds a fourth mannose to yeast and human glycophosphatidylinositol precursors
Alzheimer disease Aβ production in the absence of N-palmitoylation-dependent targeting of BACE1 to lipid rafts
Kynurenines in the CNS: from endogenous obscurity to therapeutic importance
Indolemine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer's disease hippocampus
Mass spectrometric detection of quinolinic acid in microdissected Alzheimer's disease plaques
Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and diprenyl
The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease
BACE1 suppression by RNA interference in primary cortical neurons
Oxidative stress increases expression and activity of BACE in NT2 neurons
β-Site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinase pathways
Oxidative stress potentiates BACE1 gene expression and Aβ generation
Rapid appearance of β-amyloid precursor protein immunoreactivity in glial cells following excitotoxic brain injury
A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes
Proteasome recruitment and activation of the Uch37 deubiquinating enzyme by Adrm1
A genome-wide analysis of ubiquitin ligases in APP processing identifies a novel regulator of BACE1 mRNA levels
Role of the ubiquitin proteasome system in Alzheimer's disease
P-glycoprotein efflux and other factors limit brain amyloid β reduction by β-site amyloid precursor protein-cleaving enzyme 1 inhibitors in mice
Knockouts model the 100 best-selling drugs - will they model the next 100?
Demonstration of a common artifact in immunosorbent assays of brain extracts: Development of a solid-phase extraction protocol to enable measurement of amyloid-β from wild-type rodent brain
A simple statistical parameter for use in evaluation and validation of high throughput screening assays

subset: commoncrawl


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Kim Rogers® Women's Gold Mesh Link Watch
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Shipping your purchase is easy on belk.com. Depending on the destination of your package, you can expect it to arrive within 4-7 business days. Shipping Information
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Oklahoma is one of the fastest states in the U.S. for finalizing an uncontested divorce.
You have met the minimum in-state residency requirement if at least one spouse has lived in Oklahoma for six months.
If you and your spouse are no longer compatible, you can file a no-fault divorce.
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You have qualified to use DivorceWriter to complete your Oklahoma divorce papers online. Select "Continue" to start the interview.


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Magnuson Hotel Lansing
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It's Been A While...
... bbq. We had such a great evening with him and his wife Kim and their kids and grandkids. Again, such a great perk of this new career being able to see family that lives far from home. Jacksonville is a very nice town, although our hotel was very blah. Needed many, many updates. After Jacksonville it was on to Miami! Wow! What a beautiful place! I think a retirement home in Miami is definitely in my future! Haha! However, I'd need ...
And we're off!!!
... of our adventures. She'll turn 93 when we return and we can't wait to tell her all about our adventures!
Thank you to my parents for a delicious Tuscan dinner to get us ready for Italy. We are all looking forward to tasting the food in Italy....okay maybe not Emery so much. Max Hornak, Emery may follow in your footsteps and be ordering a lot of pizza!
As a friend said in his recent blog posts from Italy....
Ciao for now!
In Owosso
6/24 Spent this day in Owosso MI. Theresa had to work so it gave us a day to reorganize a lot of the camper. As you recall the slide out would not retract in part due to the weight of canned goods under the dinette seat. Peg had packaged up a lot of the cans into bundles in clear plastic bags recycled from sheets or other packaged goods. This does a good job of keeping them from scattering all over. So with the retraction problem we had taken ...
Lansing Michigan, Delphi, and Traveling North
... metal artists studio was located here, It was closed, but he had many of his sculptures in the yard. They were quite unique, large, awesome...and expensive. Leaving Leland I turned south to travel around Grand Traverse Bay. This was a beautiful drive, and Traverse City is quite large. There were many sailboats on the bay and one large "ship". Home tonight was the Michigan State Park just across the highway from Traverse Bay. ...
Lansing - The final destination
... the beginning. But honestly, its a very nice, clean home - just half the size we are accustomed to.
Tomorrow (Sunday) we are renting a Uhaul truck, filling it full of the boxes we shipped previously, and then making a stop off to the furniture stores to pickup our couches, beds, etc.
And so ends another road adventure, but a new adventure in Michigan awaits ...


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ED Magedson – Founder
Ripoff Report
Meetme.comInternet USA
Meetme.com Infringement Internet
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
Meetme.com's 23 year old admin has harrassed me many times but that alone isn't enough to take action
however today I was informed of him taking pictures of both myself and my girlfriends pictures and saving them to a device I have a screenshot of the message.
also I was robbed of the company in a way of speaking, I'd payed for spotlight and all spotlights were taking down within five minutes of when this kid logged on. I have a copy of what the terms of service were at that moment in time and none of them were broken.
Therefore my money was taken and I was not given what I had been told I would recieve. I am jimmy and am more then willing to provide screenshots if it means removing this site.
This report was posted on Ripoff Report on 08/27/2013 10:01 AM and is a permanent record located here: http://www.ripoffreport.com/reports/meetmecom/internet/meetmecom-infringement-internet-1079433. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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ED Magedson – Founder
Ripoff Report
ACN1000 Progress Place Concord, North Carolina United States of America
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
ACN advertises unlimited opportunity but doesn't deliver. They get you to sign up all your friends and family for cellphone, telephone, television plans that you would be better off getting directly from the provider.
They re-sell the same plans, slightly more expensive, than direct providers like sprint, ATT, Direct TV, Verizon. It is a total ripoff in which you sign up and actually pay slightly more in the hopes that you'll get compensated from ACN. Nine months later and no checks from ACN, even after signing up other people and meeting all my goals as set forth by ACN.
The only one getting paid is ACN!
To make matters worse, the cell phone I got through them needed repair and the insurance plan doesn't replace the phone (like most NORMAL/HONEST companies). I have to ship the phone to an independent company to get it fixed, going without phone for almost a week.
Save yourself a HUGE headache and steer clear of this company, they are a bunch of scammers that make money off of empty promises and poor results. Try calling their "support" lines to get answers about their products. You'll see.
Don't submit your friends and family to ACN. They'll never look at you the same way again!
This report was posted on Ripoff Report on 08/14/2009 09:17 AM and is a permanent record located here: http://www.ripoffreport.com/reports/acn/concord-north-carolina-28025-2449/acn-acn-telecommunications-acn-video-phone-worst-cell-phone-insurance-planpyramid-concord-479825. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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#1 Consumer Comment
SUBMITTED: Friday, December 04, 2009POSTED: Friday, December 04, 2009
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
#2 Author of original report
SUBMITTED: Thursday, December 03, 2009POSTED: Thursday, December 03, 2009
Let's get a few things clear.
First, the video phone. The phone itself costs over $200 once you add in extra fees and will add additional cost to your phone bill. Also, what they don't tell you is that the video phone cannot be hooked up in all areas.
This is a very expensive alternative to webcam and internet options that do the exact same thing. Go to a yard sale and buy an 8-track if you want to spend money on obsolete technology, but don't drop 200 bucks on a phone for your house.
As for everything else, ACN is just a wholesaler.
CELL PHONES You'll get same AT&T plan from AT&T. The main difference is you'll save money with AT&T because they won't CHARGE you to ship phones like ACN. Also the insurance plan is MUCH better. Their insurance plan on cellphones requires you to mail phone to them where they fix it. The entire process takes about 3 weeks. WOW!!!
DIRECT TV Call Direct TV DIRECTLY, ACN doesn't have a special plan.
ACN actually discourages you from "investigating" the difference in their pricing and direct pricing because there is NO SAVINGS.
Why don't you tell the good folks what your meetings are like? I've never seen such blatant groupthink and peer pressure exerted on a meeting to get people to attend national company meetings or buy promotional material.
If you are going to respond, come with FACTS. Explain the pricing. Explain the cell phone insurance. Don't bring the same old-tired "I'm makin' mad money"bull that everyone in ACN says. The only check I ever saw was for a few hundred dollars, from ANYONE.
It's always a friend of a friend that is really successful isn't it?
ACN is a great company if you enjoy taking advantage of others and pressuring your family into "helping you out".
Do you guys still use Michael Jordan as a reference for everything good?
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
#3 Consumer Suggestion
SUBMITTED: Thursday, December 03, 2009POSTED: Thursday, December 03, 2009
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StyleTap Platform for iPhone v0.9.010 Released
StyleTap Platform for iPhone® v0.9.010 is now available for download through Cydia and provides the following:
- An updated WebTools utility that should eliminate the initial "hang" problem.
- Due to popular demand, the iPhone keyboard will no longer automatically pop up when a field is given focus. However, when the user presses the keyboard button, StyleTap will still attempt to scroll the screen down to show the field if necessary.
- The "Quit" and "Menu" buttons have been moved down to increase the distance between these buttons and the application window.
- EvtResetAutoOffTimer has been implemented.
- Fix to display problem in some applications (BackupMan).
- Fix to problem in some HandDBase applications.
- Certain iPhone models do not provide country information and this was causing a crash on startup. This has been fixed.
NOTE: If you already downloaded the initial version of StyleTap, by simply running Cydia again, it will show this version as an available update on the "Change" button. Installing the new version of StyleTap should preserve your registration code and any applications and databases that you have installed.
Many Thanks!
We thank the many of you who sent emails asking questions and offering suggestions and congratulations for finally getting the product out the door. We're glad that we are able to enable so many of you to keep running those key applications that you can't live without.
Lastly, we especially offer our sincere thanks to the customers who patiently worked with us to isolate and fix these early issues – it is very appreciated!


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Americas Best Value Inn - Pittsburgh Airport
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- Continental Breakfast
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Another Goodbye >>>
But many many happy memories.
It was sad to leave our friends @ Germantown, near Washington. Once again, we are reminded how generous people are with their time and hospitality.
Our journey will now take us in a north-westerley direction with our eventual goal being the Yellowstone National Park in Wyoming before the winter sets in.
On the way we will meet up with some other friends who we last saw in 2003 in Chad's home ...
Today was again a pretty good start with a bit of a sleep in. Today we had planned to go to beaver falls, another place where my dad grew up, and see more houses there and spend the day in that town. When we got to beaver falls it seemed like a town with many units and it was like out of a TV show were every knows everyone. But it was a ...
Today we got a fair sleep in because we didn't have to do much traveling today as all we did was walk around the city of where my dad grew up as a kid, and spent a bit of coin on some souvenirs. It started off with a buffet breakfast, the buffet was pretty small to be honest. There was only a few cereals, a few types of toast and then ...
2014 Pittsburgh- Priest Lake State Park, Coolin,ID
... Bruce. Bruce is in his second enlistment in the Air Force and is excited about his future. He is thinking and acting a lot more maturely now. It's fun watching these kids grow up. That didn't happen for me till I was in my 40's. Or maybe 50's? While we were in Rapid City we decided to "rest" a couple of days and do some exploring. The Black Hills is truly an awesome area. We drove through Custer State Park and saw a bunch ...
Warm and Fuzzies!!!
... better about ourselves. You simply make people feel like they matter. And that is not a gift that everyone has. The other reason that it really is hard to lift up your positive qualities is that you are so humble and immediate in your serving of others that sometimes it can almost go unnoticed. Whenever someone asks you to do something, or you would be assigned a task or chore, or someone would even just voice a need that someone had, you simply just go ahead and do it. You never say ...


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Never Mind the Economy, Killer Apps!
The stock market looks to head higher, but the reasoning is a bit off-kilter. Jobless claims rose again, throwing into question whether that figure, a good indication of the status of the labor market, is indeed showing improvement. Apple, the biggest seller of the kind of stuff people spend money on without care, reported strong earnings, boosting shares by 4.6% headed into the opening bell.
But United Parcel Service, an economic bellwether because, well, they're responsible for shipping all sorts of consumer goods around the country, said first-quarter net revenue dropped 56%. The stock was off by 3.5%, but Dow futures gained more than 50 points and the S&P 500 futures rose nearly six points as investors looked set to add to positions after Wednesday's pullback.


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Tired in Tennessee
Dear Tired in Tennesse,
Your husband is still chasing you around the house after 41 years and you are moaning? You should be grateful he still has the energy at his time of life. He is even prepared to take medication to be able to do this.
Obviously, you are not aging as well as your husband and need your rest so all i can suggest is you discuss with Gus about him getting a younger model to play with so he can be 'young at heart' while you can just relax and take things easy.
Hope this helps.
Next letter
Dear Marius,
My boss at work has got a serious odour problem. We have to work closely together at times and I am seriously choking at the stench.
I have tried to be sensitive about this by buying him aftershave for Christmas and constantly spraying the room.
How can I tell him without offending him and losing my job? I feel it would be easier to have my sense of smell permanently removed.
Suffering in Silence


text:
NEW YORK (AP) The staffs of The Times-Picayune of New Orleans and The Sun Herald of south Mississippi captured Pulitzer Prizes for public service on Monday for chronicling the catastrophic aftermath of Hurricane Katrina despite life-changing damage to their own homes and workplaces.
Tears flowed rather than champagne in the Times-Picayune newsroom, which the staff had to evacuate just eight months earlier for about six weeks. At The Sun Herald, staff members cheered and fought back tears.
The Sun Herald won for its "valorous and comprehensive coverage ... providing a lifeline for devastated readers" and The Times-Picayune for its "heroic, multi-faceted coverage" to "serve an inundated city even after evacuation of the newspaper plant," the Pulitzer citation said.
The Washington Post won four Pulitzers, The New York Times three and The Times-Picayune and the Rocky Mountain News each won two.
In the arts categories, the fiction prize went to March, Geraldine Brooks' novel imagining the life of the father in Louisa May Alcott's Little Women, and the general non-fiction prize went to Caroline Elkins for Imperial Reckoning: The Untold Story of Britain's Gulag in Kenya. The Pulitzer board declined to award a prize for drama.
The Times-Picayune staff was awarded a second Pulitzer, for breaking news, for Katrina, and The Dallas Morning News was honored "for its vivid photographs depicting the chaos and pain" of the disaster.
Like their communities, The Sun Herald and The Times-Picayune took a beating from Katrina. Their buildings were damaged, advertisers and subscribers were displaced, and circulation dropped.
The Times-Picayune evacuated about 240 employees in the back of newspaper delivery trucks as water from a levee breach rose around its plant. Many staffers saw the disaster unfold in their own neighborhoods.
The newsroom erupted in applause at the news of the Pulitzers, but there was no champagne.
"It was a national tragedy," said Peter Kovacs, the Times-Picayune's managing editor for news. "It would not be appropriate to have champagne because of the nature of the event."
As reporters quietly sobbed, Editor in Chief Jim Amoss stood on a table and said: "As our city was being ravaged and our citizens were dying ... as all these things happened, we came together as a team and fulfilled a mission that is sacred to us."
The Sun Herald toasted its prize with sweet tea and cookies because the paper does not allow alcohol on its property.
"We never missed a day of publication and that's a testament to everybody in this room," said Ricky Mathews, president and publisher of The Sun Herald, whose coverage area includes hard-hit Gulfport and Biloxi, Miss. "We will arise from this terrible situation," he added. "I think our best journalism is still ahead of us."
Executive Editor Stan Tiner dedicated the Pulitzer to the residents "whose magnificent hearts and spirit moved us every day that we have been privileged to tell the story of their struggle and triumphs."
"They will not be defeated — not by Katrina nor anything," he added.
At The Washington Post, Susan Schmidt, James V. Grimaldi and R. Jeffrey Smith won the investigative reporting Pulitzer for stories on the Jack Abramoff scandal; David Finkel won for explanatory reporting on the U.S. government's attempt to bring democracy to Yemen; Dana Priest won the beat reporting category for stories on secret prisons and the government's counterterrorism campaign; and Robin Givhan won for "her witty, closely observed essays that transform fashion criticism into cultural criticism."
James Risen and Eric Lichtblau of the Times and the staffs of the San Diego Union-Tribune and Copley News Service won for national reporting — the Times for stories on the Bush administration's domestic eavesdropping, the Union-Tribune and Copley for disclosing the bribe-taking that sent former Rep. Randy "Duke" Cunningham to prison.
Joseph Kahn and Jim Yardley of the Times won the award for international reporting for coverage of China's legal system.
The Pulitzer for commentary went to Nicholas D. Kristof of the Times for focusing attention on genocide in Darfur.
"The Pulitzer judges have put a premium on watchdog journalism — on journalism that demonstrated the press standing up to power, often with substantial consequences," Times Executive Editor Bill Keller said in a newsroom speech.
"Prizes don't always say anything terribly important about the state of our business, but this year's Pulitzers do, and what they say is: The country has never needed us more than it does today."
Jim Sheeler of the Rocky Mountain News was honored for feature writing for his story on a Marine major who helps families of comrades killed in Iraq cope with their loss. The newspaper's Todd Heisler received the prize for feature photography for his accompanying pictures in a package called "Final Salute."
Rick Attig and Doug Bates of The Oregonian of Portland won for editorial writing focused on abuse inside a mental hospital. Bates wrote the 1991 book The Pulitzer Prize: The Inside Story of America's Most Prestigious Award.
The prize for editorial cartooning went to Mike Luckovich of The Atlanta Journal-Constitution.
The Sun Herald, whose offices are less than a mile from the Mississippi Sound, never missed an edition during the crisis. Before the storm hit Aug. 29, managers arranged to have the newspaper printed at a sister paper in Columbus, Ga., and then shipped back to Mississippi.
To ensure delivery back home, the entire staff pitched in and handed it out free at tents, damaged homes, shelters and elsewhere.
In the first days after Katrina, The Times-Picayune was published only online. The first printed editions came Sept. 2 and were published through an arrangement with The Courier newspaper in Houma, La. The Times-Picayune has regained about two-thirds of its circulation, which was 260,000 on weekdays and 285,000 on Sunday.
For the first time, applicants in all categories were allowed to include material published online as part of their entries.
The Pulitzer for public service carries a prize of a gold medal. The other prizes come with cash awards of $10,000.
The awards are given by Columbia University on the recommendation of the 18-member Pulitzer board. The Times-Picayune was not named as a finalist for public service, but the Pulitzer board voted to award it the prize, along with The Sun Herald, said Sig Gissler, administrator of the Pulitzers.
The Pulitzers were created under the terms of the will of newspaper publisher Joseph Pulitzer, who died in 1911. He endowed the journalism school at Columbia, and dictated that money be set aside for the prizes. The first awards were handed out in 1917.
Copyright 2006 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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Area Business News
The Hampton Roads economy grew by 0.5 percent in 2011 and 1.2 percent in 2010.
The project is part of Dominion's Solar Partnership Program.
The new business is a sister store to Tech Zone, located in Shops at Gloucester.
Crossfit Gloucester is expanding its high performance exercise facility at White Marsh Shopping Center.
Benick said she will oversee performance coaches at centers in Gloucester and Newport News.
The award is designed to recognize businesses in Gloucester which have taken an active role in promoting a clean environment by maintaining an attractive business site, supporting a no-litter community, and demonstrating pride in the community.
The business had previously operated for four years a couple of miles north.
The business recently doubled its space and now carries more firearms and a larger selection of gun accessories.
Gary and Noelle Galluzzi bought the business Nov. 1 from longtime owners Ralph and Mary Valdrighi of the Glebe.
Supervisors held a public hearing Nov. 6 in the colonial courthouse, where two people spoke in favor of the zoning amendment.


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preponderancenoun [ S ]uk /prɪˈpɒn.dər.əns/ us /prɪˈpɑːn.dɚ.əns/ formal
Thesaurus: synonyms and related words
(Definition of "preponderance" from the Cambridge Advanced Learner's Dictionary & Thesaurus © Cambridge University Press)
(Definition of "preponderance" from the Cambridge Academic Content Dictionary © Cambridge University Press)
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Word of the Day
something made in an earlier period that is collected and considered to have value because it is beautiful, rare, old, or of high quality


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Sunlight, Vitamin D and Skin Cancer
Volume 624 of the series Advances in Experimental Medicine and Biology pp 16-30
Solar Ultraviolet Irradiance and Cancer Incidence and Mortality
- William B. GrantAffiliated withSunlight, Nutrition and Health Research Center (SUNARC)
* Final gross prices may vary according to local VAT.Get Access
Rates for many cancers are generally higher with increased distance from the equator. The first paper positing a link between sunlight and reduced risk of cancer was published in 1937.1 Persons in the US Navy with greater "skin irritation" (actinic keratosis and skin cancer) had lower risk of internal cancers. A second paper appeared then reported that residents of sunnier states had lower cancer risk.1 Although many studies have tried to explain these geographic variations, including differences in dietary factors and socioeconomic status, the most promising is that solar ultraviolet-B (UVB) (290–315 nm), through production of vitamin D, reduces the risk of cancer incidence and increases survival chances. Data at the World Health Organization3 indicated large latitudinal gradients in cancer mortality rates recorded as early as 1955 for breast, colon, intestinal, lung, prostate, rectal and renal cancer. However, rates were also low for countries where much fish was consumed, such as Iceland and Japan and in countries where animal products were a small fraction of the total energy supply, such as Egypt. Thus, it would have taken a clever researcher to suggest that solar UVB and fish were important sources of vitamin D and could explain much of the variance.
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- Title
- Solar Ultraviolet Irradiance and Cancer Incidence and Mortality
- Book Title
- Sunlight, Vitamin D and Skin Cancer
- Pages
- pp 16-30
- Copyright
- 2008
- 10.1007/978-0-387-77574-6_2
- Print ISBN
- 978-0-387-77573-9
- Online ISBN
- 978-0-387-77574-6
- Series Title
- Advances in Experimental Medicine and Biology
- Series Volume
- 624
- Series ISSN
- 0065-2598
- Publisher
- Springer New York
- Copyright Holder
- Landes Bioscience and Springer Science+Business Media
- Additional Links
- Topics
- Industry Sectors
- eBook Packages
- Editors
- Jörg Reichrath (6)
- Editor Affiliations
- 6. Clinic for Dermatology, Venerology and Allergology, The Saarland University Hospital
- Authors
- William B. Grant (7)
- Author Affiliations
- 7. Sunlight, Nutrition and Health Research Center (SUNARC), San Francisco, CA, USA
Continue reading...
To view the rest of this content please follow the download PDF link above.


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South Indian Bank Clerk Recruitment 2015 Hyderabad Region
South Indian Bank Probationary Clerk Recruitment 2015 Hyderabad Region Apply Online, South Indian Bank 35 Clerks recruitment 2015 Online Application.
The South Indian Bank Ltd. a premier Commercial Bank in India, invites applications from Indian Nationals for filling up vacancies of Probationary Clerks for Branches in Andhra Pradesh & Telengana states under Bank's Hyderabad Region.
Total Vacancies : 35
Eligible Candidates are requested to apply ON-LINE through Bank's website www.southindianbank.com. No other means/modes of applications will be accepted. Before the registration, candidates are requested to ensure that there is a valid email id in his/her name. All future communications in this regard will be notified in our website including the hall ticket for the written test. Please submit the printout of online application in an envelope super scribed as "Application for the post of Pro Clerk – Application ref ID – ….. (please fill in)…..†for ….. State and send to "DY.GENERAL MANAGER, THE SOUTH INDIAN BANK LTD, REGIONAL OFFICE- HYDERABAD, CHAI COMPLEX, 157/6, STAFF ROAD, DIAMOND POINT, MANOVIKAS NAGAR P.O SECUNDERABAD-500 009" along with self attested copies of mark lists and certificates to prove qualification and age, documentary proof for the residential status and Demand Draft favouring The South Indian Bank payable at Hyderabad.
South Indian Bank Probationary Clerk Recruitment 2015 Online Application Important Dates:
Online registration opening from : 06.02.2015
Online registration closure on : 14.02.2015
Last date for receipt of application(system generated),with Demand Draft and other documents : 21.02.2015
Minimum Educational Qualification:
Graduation from a recognized University having completed a regular 10+2+ (3/4) course securing at least 60% marks from 10th standard onwards. Candidates should be proficient in computer operations.
Age Limit: Age Not more than 26 years as on 31.12.2014.Upper age limit will be relaxed by five years in the case of SC/ST candidates
Selection Procedure: Candidates are selected based on written test and interview.
More details and Online Application visit : www.southindianbank.com


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Arizona Heart Institute, Phoenix, AZ
Surgical mortality for repair of thoracic aortic pathologies is high, hence percutaneous endoluminal grafting (ELG) is being investigated as an alternative therapy. The purpose of the study is to describe the outcomes of ELG in patients eligible or high risk for open surgical repair.
Between March 1998 and December 2003, ELG of the thoracic aorta was performed in 201 patients (mean age 70; 124 male, 77 female). Gore-Excluder graft was used in 115 cases, Endomed in 63 and Talent in 23. Demographics, aortic morphology, sac changes, CT scans and complications were recorded.
Aortic pathology included aneurysms 55%, dissections 22.4%, aortobronchial fistulas 2.5%, pseudoaneurysms 9%, traumatic transactions 2.5%, and penetrating ulcers 6%. A single graft was used in 122 (60.7%), 2 grafts in 57 (28.4%), and 3 or more in 22 patients (11%). An emergent treatment was rendered in 44/201 (22%) for ruptured aneurysms. All cases were classified from Level I thru IV based on morphology of <60° angle curvature. There were 87 (43.3%) level I, 61 (30.7%) level II, 24 (11.9%) level III, and 7 (3.9%) level IV. Overall morbidity was 23% with respiratory failure (4.4%), bowel ischemia (2.4%), acute renal failure (3%), ruptured vessel (2%), graft migration (1.5%), collapsed graft (2%) and open surgical conversion in 1 patient. Paraplegia and paraparesis occurred in 4 and 6 patients, respectively. Regression analysis revealed type of graft (Talent) (p= .0001), retroperitoneal approach (p=.048), and number of grafts (3 or more) (p=.007) to be predictors of paraplegia. Aortic morphology level IV was an independent predictor of early interventions (p=.015), and type of graft (Talent) of endoleak (p=.049). A 30 day mortality was 5.4% (11 patients). Mean aneurysmal sac changed from 6.2cm preoperatively to 5.23cm postoperatively (p=.0001).
Patients with thoracic aneurysms can benefit from endoluminal grafting, however, morphology, type of graft, and approach, graft sizing and number are of paramount importance in case selection.
Endoluminal grafting is evolving as a primary treatment in thoracic aortic pathologies.
J. Rodriguez, None.
Tuesday, October 26, 2004
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It only takes a minute to get started. Fill out our uncomplicated sign up form and login to the website.
This step is optional but will seriously raise your chances of getting noticed by other people on the website. Type a little about yourself, your hobbies and upload your best photo.
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Mobile App
SIPEW Kolkata
State Institute Of Physical Education For Women
West Bengal
Total Students
Fees Range
How to reach
State Institute Of Physical Education For Women is situated at HASTINGS HOUSE, 20/B, JUDGES COURT ROAD, ALIPORE, KOLKATA-27. in Kolkata.
Courses Offered
- 1 Years
- B.Ed.
- Languages / Arts / Literature
- 2 Years
- M.Ed.
- Languages / Arts / Literature
State Institute Of Physical Education For Women - SIPEW Kolkata - SIPEW
The State Institute of Physical Education for Women (SIPEW) is located in a sprawling campus which was once the residence of Warren Hasting, Governor of India and later the first Governor General of India After independence, the property was taken over by the Govt. of India and was subsequently handed over to the Govt. of West Bengal for establishment of an educational complex devoted to Womens' education. The idea started taking shape with the establishment of a teacher education college for women in the residential building of Hasting and the whole complex came to be known as Hastings House'. Several other institutions, viz. the Multipurpose Girls' high school, primary Teacher Training Institute and a Balwadi Nursery School came up in the campus in the year 1975,on the occasion of the International Womens' Year, the Govt. of West Bengal ventured into a new dimension in the field of Womens' education by establishing a womens' collage for Physical Education. The collage was named 'State Institute of Physical Education for Women' and enjoys affiliation of the University of Calcutta. It started with the B.P.Ed. programme of study with an intake capacity of 30.Mrs. Liia Dey took charge of the college, first as Office-in-charge and later as the Principal. The enrolment later increased to 75.
Nearby Hangout
|Food & Entertainment
|Health & Grooming
|Shopping / Daily Needs Shop
|Bank / ATM
|* Information provided by students
Why join Sipew
The college has well state-of-the-art infrastructure facilities.
2 Type Courses Available
- 1 UG Courses
- 1 PG Courses
State Institute Of Physical Education For Women Placements
State Institute Of Physical Education For Women (SIPEW) provides placement assistance to all its students. The dedicated placement cell regularly conducts grooming sessions of the students in areas like soft skills, interview facing skills, behavioral skills hereby making them industry-fit. In the recent years the college has witnessed some well known recruitment companies walking-in and being invited for campus placements.
Visiting Companies
Student Placement
At State Institute Of Physical Education For Women (SIPEW) the students are endowed with all convenient amenities that make their life 'go easy' in college hours, alongside make learning more interesting. Some of the facilities include well ventilated classrooms, recreational areas, hostel facility for boys and girls, indoor and outdoor games, stocked library, seamless internet/wifi connectivity, medical facilities etc.
Nearby popular spots within 5 KM from the campus
|Mainland China (Restaurant)
|Fire And Ice (Bar)
|Kewpie's (Restaurant)
|Red Hot Chilli Pepper (Restaurant)
|Oh! Calcutta (Restaurant)
|Priya Cinema (Movie Theater)
|Tamarind Restaurant (Restaurant)
|Balwant Singh's Eating House (Restaurant)
|Hatari Restaurant (Restaurant)
|The Flying Monk (Restaurant)
|Bon Appetit - The Cafe (Cafe)
|Fillers (Restaurant)
|One Step Up (Restaurant)
|Jong's Restaurant (Restaurant)
|B. P. Poddar Hospital & Medical Research Limited. (Hospital)
|Sawasdee Namaste Spa (Spa)
|Levi`s Store (Clothing Store)
|The French Loaf (Bakery)
|Allahabad Bank (Bank)
|Bank Of India - Bhowanipur Branch (Bank)
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The Perfect Playlist
To Make Your Wedding One To Be Remembered
Want to Make your Event Special? Click To See More
Audio Extremes Entertainment is your Akron Wedding DJ & Ohio event experts. Audio Extremes offers everything you need to make your special event the party of a lifetime. We provide services for Weddings, School Dances, Bar/Bat Mitzvahs, Corporate Parties and Sweet 16's. We travel most of the state with no travel, no setup or take down fees and will rock your party with the very best in DJ Entertainment. Many extra Services like Photo Booth, Greenscreen, Uplighting, Dance in Cloud 9, and Digital Graffiti Wall are available. Whatever your style or event type, Elegant to Extreme we will keep your night flowing with ease, keep your dance floor full and provide professional and fun entertainment services for a successful event and compliments to you for picking the right entertainment company.
Pack the Dance Floor
Northeast Ohio & Akron Wedding DJ that offers A no-cheese disc jockey approach and A full-line production service for all events. We offer elite dj entertainers and professional assistants to guide you through the night, play the music you want to hear and build a timeline that works for you. We also have a variety of packages to give your event a once in a lifetime-customized approach. We can offer standard sound system for smaller groups or A large premium sound system. Not for the faint of heart is our mammoth 12 speaker concert level sound that offers prestine sound quality with over 30,000 watts. We can also provide colorful light shows, uplighting or optional video screens for your logo, graphics & music videos. Audio Extremes also offers ceremony music and microphone systems that can also be added along with videography and photo booth options to complete your package. Learn about custom Disc Jockey Services Here
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Elegant Lighting Design
Up Lighting, Monogram Lighting and Pinspots can transform any room into a visual treat. With pretty pink, outrageous orange, or super sea foam green. The color selection can match nearly any color combination. We are a David's Bridal Preferred Vendor with easy access to swatch and color codes to match your exact colors. You can even match the colors of your party theme. Weddings, Schools, Parties, and Corporate events, all can benefit from the power of lighting and uplighting. Create a lounge style feel or beautiful accent lighting shining up the walls or pillars at your selected venue. We have a staff lighting designer to help create the perfect atmosphere for you and your guests. Wired and Wireless uplights, Animated and non-animated monograms and pinspots are also available. All lighting design includes delivery, setup, and end of event pickup see your lighting design options here.
Ready to create your perfect atmosphere?
Capturing The Memories
Your moments captured in Full HD Cinematic Style. Once we you are ready to begin planning you will work with our team of video professionals to prepare a timeline, site locations, and storyboard ideas. Audio Extremes will provide you with the memory keepsake of a lifetime on USB, DVD, or BluRay. The perfect time capsule of your special day you can share and watch over and over again. See Samples Here
Ready to capture the memories of a lifetime?
Fun With Photos
Photo Booths, Greenscreen, Flip Books, Digital Graffiti and custom Photo favors. All designed to complete your event. Take yourself to far away destinations with our Greenscreen system or be as crazy as you can with props galore in our Photo Booth; show off your artistic side with our Digital Graffiti and Art Wall or just flip out with Flip Books.
Ready to get silly and capture the fun?
Client Love
Great DJ!!!! My guest were dancing the entire time. Knew what music to play to keep my guest entertained and played music we requested. Also through in a wedding game, that my husband and I played, that my guest absolutely loved. After our first meeting with owner Dwayne, I knew I could take a deep breath, and relax, my reception entertainment was in good hands. I highly recommend Audio Extremes!!!!
If I could give Dwayne and the rest of the crew at Audio Extremes a 6/5, I would. I cannot fathom working with another DJ company, they were amazing throughout the whole process. Dwayne is like a long lost friend that you never knew you had, and goes above and beyond what you need for your big day.
Continue reading here: WeddingWire.com
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ModelLynsey Model
DawnyasPhotographer No gender Kirkland, Washington, US
My MM URL: http://www.modelmayhem.com/Dawnyas
Mayhem # 1870314
About MeWe have worked with a few in the industry and have enjoyed every minute of it. We are now just able to get some free time to get my MM portfolio going. I have helped many models get started and MM seems the way to keep in touch with the people I work with and the models in general.
We hope to meet new and exciting prospects as well as network with many others the photography world has to offer. Over the last few months I have met many new people that have helped me get to the next level in my career.
I am looking to get published work, print, and fashion shoots and I am hoping that MM pushes me to this goal.
I am avaliable for shoots anytime just send me a line of what you have in mind and we can go from there. I work out of a few different studios that cater to different styles and wall background textures. So if you have ideas in mind I am sure I can achieve your goal.
Thanks D
Have you worked with Dawnyas? Add Credits for Dawnyas! >>
Credit NotesUrban Light Studios, This place is awsome (Kevin)
Pam Grieco, Thanks for our last shoot we had a great time MM 1261319
Krissy, at Hawthorne Fashions has the most amazing clothing MM 1501472 , MM 375252
Stoncia MM 1716539 You were great to work with, hope we can work together again.
Tonya No MM but will thanks for a great shoot at Urban
ModelLynsey Model
Greyson Taylor Model
SallyAnnette Model
Amy Cavanaugh Model
Nikieta Minkena Model
Genevieve_97 Model
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We are your wedding specialists with over 25 years experience and 2,500+ successful weddings. We DJ and MC weddings, class reunions, holiday parties and school events In SW Washington and NW Oregon. PLease call and find out why nobody DJ's an event like Mobile Mic Entertainment, and what makes us the #1 DJ service in SW Washington! We have karaoke too!
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Copyright © 2001-2017 OneWed Inc.
All Rights Reserved.
Copyright © 2001-2017 OneWed Inc. All Rights Reserved.


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Find Hotels in Le Tronchet
Le Tronchet Hotels & Accommodation
Browse through the list of Le Tronchet hotels to find the right hotel at a great price. Each hotel in Le Tronchet has many photos, reviews and a map of its location in Le Tronchet to make sure you get the most out of your stay. Booking your hotel in Le Tronchet couldn't be simpler. Just find a hotel, check the rates and proceed to the checkout. We'll have you enjoying your Le Tronchet hotel in no time. Quick, easy and secure.


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Berlin, Germany
Posted on Oct 01 2015 (over 1 year ago)
Since 2002, we produce graphics software that performs most of the painstaking work of creating data-driven slides for professional Excel and PowerPoint users. From a business perspective, the key to our success is a unique solution to a pressing business problem. Our customers and users are influential professionals that are extremely satisfied with our software and help spread it by word of mouth.
We take great pride in our software, and have an excellent reputation for our technical support. Independently, you handle problems from the receipt of a support ticket to its analysis, tracing problems all the way to their resolution in development.
When you receive a ticket, our customer should get timely and reliable feedback, usually within a few hours, either with the solution or a suggestion for further troubleshooting. If a phone call or a remote support session is needed, you will quickly realize that our customers are busy people, and that you must use your time well. Ask the right questions, be perceptive of the little things, and use the right tools to find the unusual configuration, the virus, the third party tool, the particular file or action that is causing trouble.
Once you have found the problem and talked it through with one of the developers, we will make sure that this same problem does not bother you again. If it is in our code, we will fix it, no questions asked. If the bug is in third party code, you will contact the vendor and convince them to fix it. Quite often they do, even the big names. If they don't, you write a knowledge base article, which is searchable on our web site. 90% of your time you will spend on problems that you have never seen before, which will keep up the challenge.
Besides working on tickets, you will evaluate new tools that may help you in your work, or even write them yourself or work with one of our developers. We have our own automatic error reporting framework and ship a diagnostic tool, both of which are constantly being improved - soon, perhaps, by you.
The qualities we are looking for are similar to those of a software developer, with the same strong problem-solving abilities, but a bit less emphasis on algorithmic skills and in return more emphasis on organizational and communication skills. Experience with the Windows architecture and Intel assembly code are a plus. If you have analyzed a minidump before, even better. Since you will be managing our many international customers in addition to our German customers, this position requires that you are fluent in both German and English.
More similar jobs: www.edelweissconsulting.de/jobs
Do you have any question or comment for EDELWEISS Management Consulting GmbH about their position Support Engineer?


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The Luxury Visionaries 2016
What do Ivan the Terrible, Catherine the Great, Napoleon Bonaparte, George Washington, Leo Tolstoy, John Wayne, and Bob Dylan have in common? Answer: they all were or are enthusiastic chess players. I can't number myself among this illustrious company – Bridge is my game – but I am captivated by chessmen, and not just the players, but also the 32 pieces used to play the game, many of which are very collectable.
Chess originated in India around the 6th century AD, and spread east and west, reaching Britain in the 11th century. Its military-like nature was evident from the outset in its Sanskrit name: Chaturanga, meaning the four divisions of an Indian army – chariots, cavalry, elephants, and foot soldiers. Together with a Shah and a vizier, these provided the original models for chess pieces. In Western countries these figures gradually evolved into an essentially feudal hierarchy: each side comprising a king, a queen, two bishops (in lieu of elephants), two knights, two castles (or rooks, in lieu of chariots) and eight pawns (the foot soldiers).
There are, however, many variations: kings have been replaced by emperors, as in the numerous sets of Chinese origin, or by generals, statesmen, or politicians, while jesters have been substituted for queens, and horses for camels. Similarly, old enmities are represented in the form of Greeks v Persians, Saxons v Vikings, and French v English, to name but a few. And while some sets are naturalistic, others are abstract – some of the latter figures being stylised to the point of pure symbolism.
There's one set, however, that has attained near-universal recognition, and since 1924 has been used by the World Chess Federation for all international tournaments. The Staunton – after Howard Staunton, who endorsed it while dominating the chess world in the mid-19th century – was designed by Nathaniel Cook and Jaques of London in 1849 to meet the need for a set that could be easily replicated at reasonable cost. It's enduring success, however, is down to its clarity of design: there is no ambiguity as to which piece is which – which can be the case with some sets.
In addition to stylistic variations, there are diverse materials of manufacture to choose from, including highly tactile ivory, bone, and wood. There's also ceramics, stone, bamboo, crystal, amber, Bakelite, and various metals – some precious. Most surviving sets, outside of museums, date from the late 17th century onward, and most don't come with a board. However, some retain their original box (which can be a combined box/board). Most are unmarked, but some bear labels, usually on their boxes – notable British makers including Jaques of London, and John Calvert of Fleet Street. As to prices, the accompanying examples are representative of desirable examples in good condition.
But what if, like me, you don't play? Personally, I wouldn't let that preclude you from collecting. The sculptural qualities of chessmen are such that even players buy some sets solely to display as works of art in their own right. So, with prices steadily rising year-on-year, and if you'll forgive the informality, perhaps you should check it out now mate.


text: The Takeaway Published by The Takeaway Fear Factor: How the economy affects our psychological health (and vice versa) Download this audio Want to embed this player? Use the code below. More info. <iframe frameborder="0" scrolling="no" height="130" width="100%" src="https://www.wnyc.org/widgets/ondemand_player/takeaway/#file=/audio/json/6738/&share=1"></iframe> Share on Facebook Share on Twitter Email a Friend The market meltdown is not just a pocketbook issue — it's become a psychological one. The economy's downward spiral is taking our sense of well being with it. And as our anxiety and panic levels rise, we are creating a kind of feedback loop: The less confidence we have in our future, the less likely we are to go out and spend. That behavior, of course, only diminishes our chances of economic recovery. Guest: Dr. Karina Davidson, clinical psychologist at Columbia University and president of health psychology of the American Psychological Association.


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MicroDyne Technologies LLC
The World Leader In Sourcing Solutions For Mass Hiring
When staffing a single position, traditional recruiting methods often suffice. But when a company has bulk hiring needs, it requires a mass sourcing solution that...
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Filling the top of your recruiting funnel is our specialty with the world's most state-of-the-art sourcing technology.


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PANTHER JUNIOR NICK Blelloch was part of a Middlebury College foursome who swept the high hurdles race at last Friday's Middlebury College Invitational.
Independent photo/Trent Campbell
MIDDLEBURY UNION HIGH School sophomore Andrew Gleason avoids a Woodstock check during Saturday's game played at Middlebury College. The Tigers won the game, 14-2.
RIPTON ELEMENTARY SCHOOL second-grader Beth McIntosh and Jeh Kulu Dance and Drum Theater member Sidiki Sylla keep their eyes on each other while rehearsing a dance at the school last Thursday morning. Jeh Kulu, a traditional West African performance group, was at the school last week working with all grades to stage a celebration on Friday night.
JEH KULU DANCE and Drum Theater, a Burlington-based group that performs and teaches traditional West African music and dance, spent last week with students at Ripton Elementary School. Here Jeh Kulu dancer Sidiki Sylla leads first- and second-graders in a Thursday workshop.
STUDENT MATTHEW MCINTOSH sways to the beat during a class with instructors from the Jeh Kulu Dance and Drum Theater at Ripton Elementary School this past Thursday.
RIPTON ELEMENTARY SCHOOL student Mckenna Raymond moves gracefully around the school gym on Thursday during a dance class with the Burlington troupe Jeh Kulu.
PATRICIA A. HANNAFORD Career Center Automotive Technology students were busy in a full north campus garage last Thursday as Josh Hotte, left, Justin Seguin and Kelsey Kimball removed snow tires.
MAXX RHEAUME, LEFT, and Patrick Covell perform some general repairs a the Patricia A. Hannaford Career Center North Campus last week.
MOUNT ABRAHAM UNION High School students Britney Ramsey, left, and Richard Tracy lift a car in the Patricia A. Hannaford Career Center North Campus Automotive Technology garage last Thursday morning. The students were swapping out snow tires.
HANNAFORD CAREER CENTER Automotive Technology student Kelsey Kimball does a little welding at the center's garage this past Thursday.
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1966 Wantagh Ave Wantagh, NY 11793 (800) 649-3739
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In-Depth, All-Inclusive, Residential Retreat in
The Netherlands
July 10-16, 2017*
All sessions will be presented in English.
The first three days of this event will be silent, until the second session of each day (14:30), allowing our realizations and connection to Self to deepen. After the second session, any respectful form of socializing, co-creation and fun are encouraged!
We intend to have a DJ dance party with Frans Iradi 1 or 2 nights during the week. Stay tuned for updates. The following schedule is subject to change and will be updated periodically.*
Monday, July 10:
16:00-22:00–Check-in and registration (please arrive on time to help support a smooth registration process)
Tuesday-Saturday, July 11-15:
8:30-9:30–Therapeutic yoga/pranayama (energy-breathing)/concentration/meditation class
11:00-12:30–Opening session with Bentinho
12:30-14:30– Silent Presence during lunch & break (+ exercise/focus/homework)
14:30-16:30–Session with Bentinho
16:30-18:00–Integration/co-creation session
20:30-22:00–Closing session with Bentinho
Sunday, July 16:
8:30-9:30–Therapeutic yoga/pranayama (energy-breathing)/concentration/meditation class
11:00-12:30–Opening session with Bentinho
14:30-16:00–Final session with Bentinho!
This retreat is ALL-INCLUSIVE, residential and affordable. Hundreds of committed spiritual adepts will become present with each other within this gorgeous, castle-style venue, with an aligned intention and powerful attitude for transformation.
Together, we will make this retreat truly unforgettable and profound. By the end of this event, we will send a powerful pulse/wave of light out to the planet–helping humanity to shift into a higher parallel timeline.
If more than 170 people sign up, we can have the entire castle to ourselves. If over 500 people sign up, we can have the entire castle grounds property to ourselves. We can take up to 1300 participants. Just imagine the intensity of presence we could summon with such a large and powerful group!
Take a Virtual Tour of the Venue!
Explore the tranquil retreat grounds in between sessions, go on a hike, venture off by yourself and sit in meditation, or practice an exercise assigned by Bentinho that day. The castle grounds provide many wonderful spaces in which to connect with other retreat participants, meet in smaller groups to discuss and explore the teachings in-depth, and of course, sit together with a thousand other beautiful souls in silence and presence during the official sessions, as Bentinho guides us collectively into some of the most powerful guided meditations we've ever experienced.
Bentinho's teachings provoke us to look deeply into ourselves to discover what is holding us back in all areas of our life. As we clean out our closet of beliefs, we can move more powerfully forward into our life and into our own ascendance, as well as penetrate more experientially into the deeper levels of Consciousness/Absolute/Existence.
As always, during Bentinho's retreats, there will be spontaneous realizations, hearts bursting open, profound silence, vibrational amplification, transformative healing, dynamic Q&A, empowering laughter, along with inspired, constructive plans for action in the world. We do this all in service to an awakened humanity. By honoring our deepest calling for being alive at this particular timing, we can empower ourselves to bring our gifts into every moment of our lives, for the benefit of all.
The Bentinho Massaro Event Team is beyond excited for this event's intention and environment! Every time we speak about this event with Bentinho, we find ourselves chuckling at his signature grin, which spreads across his face. Bentinho feels extremely aligned with the intention that is so effortlessly generating this event, and we expect his presence at this retreat to be the most powerful we have seen from him yet.
This will be Bentinho's first in-depth event after he returns from a personal retreat where he will spend two consecutive weeks in total darkness (absence of physical light) by himself. Bentinho has been looking forward to this personal retreat since he was 16 years old. Who knows what he will be teaching us in this next phase of his life as he emerges from his own retreat! He's been so busy being available to others over the past 10 years; we are very excited he will have the opportunity to immerse himself in his own realizations in total absence of visual stimuli, to see "what's new" and how deeply he can dissolve into union with the Infinite One.
Let's see what he brings back from the depths...One thing is for certain–he will make every effort to leave a skillfully crafted, digestible trail behind to whatever experiences he feels are valuable for the masses. It is Bentinho's wish to help others accelerate their own journey into the inner realms of eternal bliss–to perfect the balance of love and wisdom–and into the outer realms of living–to become the fullest expression of one's calling. We do this not only for ourselves, but for the awakened world we are here to bring forth.
Breakfast, lunch and dinner are included for all 6 days. We've received many requests from Europeans for a longer, more affordable retreat, and we are happy to congratulate you on your collective co-creation! Hop on a bus, drive your car, or fly to this magnificent venue. Let's come together to enjoy meals, enjoy the breathtaking surroundings and a transformative and memorable retreat. Whether you live inside or outside of Europe, we encourage you to attend!
We look forward to being with you for this once in a lifetime opportunity. Do whatever it takes (with integrity) to create your presence at this retreat. We are holding the intention that everyone who wants to participate will be able to do so. We want this retreat be an experience you will remember for the rest of your life!
If you really want to attend this retreat but do not believe you can manifest the funds, contact firstname.lastname@example.com to inquire about receiving a partial sponsorship
Things you need to know before booking:
- If you desire a single/private room, you must stay off-site. Everyone who books a double room or a dorm room will share a room with one or more people. If you do not give a preference for whom you want to share a room with, we will decide for you.
- If you are camping, you MUST bring your own tent and camping supplies. The venue will not provide any equipment.
- Roommate requests will be on a first come first served basis.
- If you desire to share a double room with someone you know, please indicate the person's first and last name on the checkout form. Please note that, due to the size and the layout of this event, roommate requests are not guaranteed. However, we will do our very best to accommodate your request.
- If you are registering for the dorm option, please indicate on the checkout form if you would like to be placed in the male, female or mixed-gender dorm room. You may also indicate if you do not have a preference. Again, we will do our very best to accommodate your request, but it is not guaranteed if you book late.
- Meals will be served buffet style. There will be a variety of options–meat, fish and vegetarian. If you have special dietary requests, please note this in the checkout form.
- There are several hotels nearby the venue, if on-site accommodations sell out or if you prefer to stay off-site. Please scroll to the bottom of this page for links to the off-site accommodations.
- Each person attending this event must register individually and agree to the terms and conditions.
Policy on kids attending this retreat:
Children 14 years or older are welcome to attend, as long as they are sincerely interested in the nature of this event and have experience with concentration, meditation and visualization. They must have the attention span and sense of respect that one would expect from a conscious adult. If you, as their parent, know this is not the case, please do not bring them to this event, as it will pose a vibrational distraction to the group consciousness. Pricing for children 14+ is the same as for adults.
Children 13 years old or younger are not permitted to this retreat. We want to keep this retreat focused on the advanced nature of Bentinho's teachings with minimal distractions. All participants, both adults and kids 14 years and up, should be highly interested in the nature of this event in order to attend. Thank you for your cooperation.
Refund & Cancellation Policy
Refunds will not be issued for last-minute cancellations. Cancellations made on or after June 10, 2017 will not be eligible for a refund. If you cancel prior to June 10, 2017, we will issue a refund. A $50 processing fee will be charged for all cancelations. Tickets are not transferrable to another person.
Airport and Transportation
The 3 closest airports:
1. Düsseldorf in Germany is the closest (DUS).
2. Eindhoven in the Netherlands (EIN).
3. Brussel in Belgium (BRU).
From the airport, you can hire a car to drive you to the castle or you can take the train to either the Venlo or Roermond train stations. Both stations will take you to Bus 77. This bus has a stop just in front of the Castle. It's a three-minute walk from the bus stop to the castle.
Off-Site Accommodations and Lodging
Questions? Concerns? Email email@example.com


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