text:
A transgenic non-human animal with a homologous disruption of the KSR-2 gene is disclosed. Methods for using transgenic mice so generated to screen for agents that effect cellular metabolism are also provided.
1. A method for screening an agent for the ability to modulate energy expenditure, comprising:
a) administering the agent to a transgenic mouse whose genome comprises a homozygous disruption of the endogenous KSR-2 gene, wherein no KSR-2 protein is expressed and said mouse exhibits a phenotype comprising increased obesity and reduced energy expenditure by 20-24 weeks of age;
b) measuring at least one energy expenditure parameter in the mouse of step a);
c) comparing the measurement obtained in step b) to that a transgenic littermate not administered the agent, thereby identifying agents which modulate energy metabolism in the treated mouse relative to the non-treated control mouse.
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Pursuant to 35 U.S.C. �202(c) it is acknowledged that the U.S. Government has certain rights in the invention described herein, which was made in part with funds from the National Institutes of Health, Grant Number, DK52809.
This invention relates the fields of recombinant DNA technology, transgenic animals and metabolic regulation. More specifically, a transgenic nonhuman animal is provided wherein the KSR2 gene has been altered. Methods of using such animals to assess KRS2's role in the modulation of energy expenditure, weight gain and diabetes susceptibility are also provided.
Several publications and patent documents are cited in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these citations is incorporated herein by reference.
The worldwide epidemic in obesity has brought with it dramatic increases in the prevalence of co-morbid, chronic conditions including insulin resistance, type 2 diabetes, the metabolic syndrome, and atherosclerosis. The rapid rise in these major public health problems underscores a growing need to understand the physiological and pathological bases of feeding and obesity, and the pathophysiological links between obesity and these associated morbidities.
Kinase Suppressor of Ras (KSR) is a conserved protein that positively regulates Ras signaling and functions as a scaffold for Raf, MEK, and ERK. However, the precise role of KSR is not well understood, and some observations have suggested that KSR might act in a parallel pathway. In C. elegans, ksr-1 is only required for a specific Ras-mediated process (sex myoblast migration) and is a nonessential positive regulator of other Ras-mediated developmental events. A second C. elegans ksr gene, ksr-2 has also been identified, which is required for Ras-mediated signaling during germline meiotic progression and functions redundantly with ksr-1 during development. Thus, while the ksr-1 and ksr-2 genes are individually required only for specific Ras-dependent processes, together these two genes appear necessary for most aspects of Ras-mediated signaling. The finding that ksr-2; ksr-1 double mutants have strong ras-like phenotypes and severely reduced or absent levels of diphosphorylated MPK-1 ERK strongly supports models where KSR acts to promote the activation or maintenance of the Raf/MEK/ERK kinase cascade.
It is an object of the invention to provide a whole animal model for studying these interactions, thereby identifying agents which modulate aberrant processes associated with abnormal KSR2 function.
In accordance with the present invention, a transgenic mouse comprising a homozygous disruption of the KSR-2 gene is provided. The mouse of the invention does not express KSR-2 protein and exhibits a phenotype comprising increased obesity and reduced energy expenditure. Such mice may be used to advantage to identify agents which modulate energy expenditure, weight gain and diabetes susceptibility. In another embodiment, the KSR-2 knockout mouse of the invention further comprises a homologous disruption of KSR-1. Also encompassed by the invention are cells isolated from such animals for use in screening methods to identify therapeutic agents which modulate KSR-2 and/or KSR-1 function.
In a preferred embodiment of the invention, a method for screening an agent for the ability to modulate energy expenditure in a whole animal model is disclosed. An exemplary method entails administering the agent to the transgenic mice described above, measuring at least one energy expenditure parameter in the treated mouse and comparing the measurement obtained to that of a transgenic littermate not administered the agent, thereby identifying agents which modulate energy expenditure in the treated mouse relative to the control, non-treated mouse. Preferably, the at least one energy expenditure parameter is selected from the group consisting of weight, body fat composition, adipose cell mass, adipose cell size, food intake, respiratory quotient, energy expenditure, glucose tolerance, locomoter activity and rectal temperature. A further aspect of the method invention entails isolating cells from said mouse and exposing said cells to said agent in vitro.
In yet another aspect, progeny animals obtained from the KSR-2 knockout mice are within the scope of the present invention.
Obesity is a major health problem in the western world with increasing prevalence in developing nations1. Obesity is typically a consequence of complex inherited traits and environmental impact2, though characterization of unique forms of monogenetic obesity has provided valuable insight into the molecular mechanisms that underlie the complex control of energy balance in humans3. Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR 2) potently regulate the MAP kinases ERK1/2 to affect multiple cell fates4-9.
Their effects on ERK can be ascribed to their ability to function as molecular scaffolds that facilitate signal transduction between upstream kinases and ERK5-7,10, though they may also dynamically regulate pathway output6,11. Disruption of KSR1 impairs growth factor-regulated ERK activation and causes resistance to Ras-mediated tumorigenesis in vivo and in vitro7,10,12 KSR1 disruption also impairs adipocyte proliferation in vivo and differentization in vitro5.
A transgenic animal carrying a "knock out" of KSR-2 is useful for the establishment of a nonhuman model for diseases involving KSR-2 regulation. In accordance with the present invention, mice comprising a disruption of KSR2 exhibit spontaneous obesity. Despite their increased adiposity ksr2−/− mice eat less that wild-type mice, are more active than wild-type mice, preferentially metabolize fat, but expend less energy than wild-type mice. Hyperinsulinemic euglycemic clamp studies reveal that ksr2−/− mice are profoundly insulin resistant. Similar to obesity-prone populations of southwestern native Americans13, these data demonstrate that ksr2−/− mice are energy efficient and reveal a novel role for KSR2 and MAP kinase signaling in the regulation of energy homeostasis and the control of glucose metabolism.
The phrase "energy parameter" as used herein refers to a parameter selected from the group consisting of weight, body fat composition, adipose cell mass, adipose cell size, food intake, respiratory quotient, energy expenditure, glucose tolerance, locomoter activity and body temperature.
The term "animal" is used herein to include all vertebrate animals, except humans. It also includes an individual animal in all stages of development, including embryonic and fetal stages. A "transgenic animal" is any animal containing one or more cells bearing genetic information altered or received, directly or indirectly, by deliberate genetic manipulation at the subcellular level, such as by targeted recombination or microinjection or infection with recombinant virus. The term "transgenic animal" is not meant to encompass classical cross-breeding or in vitro fertilization, but rather is meant to encompass animals in which one or more cells are altered by or receive a recombinant DNA molecule. This molecule may be specifically targeted to defined genetic locus, be randomly integrated within a chromosome, or it may be extrachromosomally replicating DNA.
The term "germ cell line transgenic animal" refers to a transgenic animal in which the genetic alteration or genetic information was introduced into a germ line cell, thereby conferring the ability to transfer the genetic information to offspring. If such offspring in fact, possess some or all of that alteration or genetic information, then they, too, are transgenic animals.
The alteration or genetic information may be foreign to the species of animal to which the recipient belongs, or foreign only to the particular individual recipient, or may be genetic information already possessed by the recipient. In the last case, the altered or introduced gene may be expressed differently than the native gene.
The altered KSR-2 gene generally should not fully encode the same KSR-2 protein native to the host animal and its expression product should be altered to a minor or great degree, or absent altogether. However, it is conceivable that a more modestly modified KSR-2 gene will fall within the present invention if it is a specific alteration.
The DNA used for altering a target gene may be obtained by a wide variety of techniques that include, but are not limited to, isolation from genomic sources, preparation of cDNAs from isolated mRNA templates, direct synthesis, or a combination thereof.
A type of target cell for transgene introduction is the embryonal stem cell (ES). ES cells may be obtained from pre-implantation embryos cultured in vitro. Transgenes can be efficiently introduced into the ES cells by standard techniques such as DNA transfection or by retrovirus-mediated transduction. The resultant transformed ES cells can thereafter be combined with blastocysts from a non-human animal. The introduced ES cells thereafter colonize the embryo and contribute to the germ line of the resulting chimeric animal.
One approach to the problem of determining the contributions of individual genes and their expression products is to use isolated KSR-2 genes to selectively inactivate the wild-type gene in totipotent ES cells (such as those described above) and then generate transgenic mice. The use of gene-targeted ES cells in the generation of gene-targeted transgenic mice has been previously described.
Techniques are available to inactivate or alter any genetic region to a mutation desired by using targeted homologous recombination to insert specific changes into chromosomal alleles. However, in comparison with homologous extrachromosomal recombination, which occurs at a frequency approaching 100%, homologous plasmid-chromosome recombination was originally reported to only be detected at frequencies between 10−6 and 10−3. Nonhomologous plasmid-chromosome interactions are more frequent occurring at levels 105-fold to 102-fold greater than comparable homologous insertion.
To overcome this low proportion of targeted recombination in murine ES cells, various strategies have been developed to detect or select rare homologous recombinants. One approach for detecting homologous alteration events uses the polymerase chain reaction (PCR) to screen pools of transformant cells for homologous insertion, followed by screening of individual clones. Alternatively, a positive genetic selection approach has been developed in which a marker gene is constructed which will only be active if homologous insertion occurs, allowing these recombinants to be selected directly. One of the most powerful approaches developed for selecting homologous recombinants is the positive-negative selection (PNS) method developed for genes for which no direct selection of the alteration exists. The PNS method is more efficient for targeting genes which are not expressed at high levels because the marker gene has its own promoter. Non-homologous recombinants are selected against by using the Herpes Simplex virus thymidine kinase (HSV-TK) gene and selecting against its nonhomologous insertion with effective herpes drugs such as gancyclovir (GANC) or (1-(2-deoxy-2-fluoro-B-D arabinofluranosyl)-5-iodouracil, (FIAU). By this counter selection, the fraction of homologous recombinants in the surviving transformants can be increased.
As used herein, a "targeted gene" or "knock-out" is a DNA sequence introduced into the germline or a non-human animal by way of human intervention, including but not limited to, the methods described herein. The targeted genes of the invention include DNA sequences which are designed to specifically alter cognate endogenous alleles.
Methods of use for the transgenic mice of the invention are also provided herein. Such mice may be used to advantage to identify agents which augment, inhibit or modify the activities of KSR-2. For example, disruption of KSR-2 causes spontaneous obesity. Accordingly, therapeutic agents for the treatment or prevention of obesity may be screened in studies using the KSR-2 knock out mice of the invention. For example, KSR-2 knockout mice may be treated with a test compound that modulates the regulation of energy homeostasis and the control of glucose metabolism. Such assays will not only facilitate the identification of agents which regulate metabolic rates, they should also be illustrative of the underlying biochemical mechanisms which underlie the development of obesity and/or type II diabetes.
In another embodiment of the invention, KSR-2 knockout mice can be used to produce an array of monoclonal antibodies specific for KSR-2.
The example set forth below is provided to illustrate certain embodiments of the invention. It is not intended to limit the invention in any way.
The following methods are provided to facilitate the practice of the present invention.
Standard gene-targeting techniques and homologous recombination were used to generate KSR−/− mutant mice. The Institutional Animal Care and Use Committee (University of Nebraska Medical Center, Omaha, Nebr.) approved all studies. Animals were maintained on a 12-hour light/dark-schedule (light on at 0600) and had free access to laboratory chow and water.
Post-nuclear membranes prepared from brain tissue were immunoblotted for KSR2. Tissue was prepared by homogenization using a Polytron at medium setting in 50 mM Tris (pH 7.5), 150 mM NaCl, 1 mM EDTA, 1% Triton X-100, 1 mM Na3VO4, 1 mM NaF and protease inhibitor cocktail (Sigma). Tissue and cell debris were removed by centrifugation. Protein concentration was determined with the BCA assay (Pierce). The resulting supernatant was used for immunoblotting.
Body Composition and Adipocyte Size
Body composition was determined by 1H magnetic resonance spectroscopy (Echo Medical Systems). Total adipose tissue from each depot was excised and the wet weight was determined. Abdominal subcutaneous adipose tissue was fixed in Bouins fixative, sectioned in a microtome and stained with hematoxylin and eosin. Adipocyte cross-sectional area was determined from photomicrographs of epididymal fat pads using IPLab software (Scanalytics Inc., Fairfax, Va.)5.
Metabolic Phenotype Analysis
Food intake was measured daily over five consecutive days in freely feeding mice. Locomotor activity was measured using automated video monitoring system HomeCageScan (Clever Systems). Total energy expenditure and relative rates of carbohydrate versus fat oxidation were determined by indirect calorimetry using a Customized Indirect Calorimetry system (TSE).
Metabolite Assays
Blood glucose was measured with an Ascensia Glucometer Elite (Fisher Scientific). Plasma insulin was measured with the Rat/Mouse Insulin Elisa Kit (ChrystalChem, Chicago, Ill.) using rat standards. Serum free fatty acids were measured using the NEFA-C kit (Wako Chemicals GMBH, Neuss, Germany) with oleic acid as the standard. Plasma triglycerides and glycerol were measured using the GPO-Trinder colorimetric assay kit (Sigma). Plasma leptin was measured using the Rat Leptin RIA kit (Linco Research, St Louis, Mo.).
Glucose and Insulin Tolerance Tests
Glucose tolerance tests were performed with an intraperitoneal injection of 2 mg/kg glucose in awake mice after a 10 h fast. Blood glucose was sampled from the tail vein at intervals from 0-120 min. Insulin tolerance tests were performed with an intraperitoneal injection of 0.75 U/kg insulin in awake mice after a 4 h fast. In both tests, blood glucose was sampled from the tail vein at intervals from 0-120 min.
Hyperinsulinemic-Euglycemic Clamps to Assess Insulin Action In Vivo
Following an overnight fast (˜15 hour), a 2-hour hyperinsulinemic-euglycemic clamp was conducted in awake ksr2−/− mice and wild-type littermates (n=8˜11) with a continuous infusion of human regular insulin (Humulin; Eli Lilly, Indianapolis, Ind.) at a rate of 15 pmol/kg/min to raise plasma insulin within a physiological range (˜300 pM). Blood samples (20 μl) were collected at 20 min intervals for the immediate measurement of plasma glucose concentration, and 20% glucose was infused at variable rates to maintain euglycemia. Basal and insulin-stimulated whole body glucose turnover was estimated with a continuous infusion of [3-3H]glucose (PerkinElmer Life and Analytical Sciences, Boston, Mass.) for 2 hours prior to the clamps (0.05 μCi/min) and throughout the clamps (0.1 μCi/min), respectively. To estimate insulin-stimulated glucose uptake in individual tissues, 2-deoxy-D-[1-14C]glucose (2-[14C]DG) was administered as a bolus (10 μCi) at 75 min after the start of clamps. Blood samples were taken before, during, and at the end of clamps for the measurement of plasma [3H]glucose, 3H2O, 2-[14C]DG concentrations, and/or insulin concentrations. At the end of clamps, mice were euthanized, and tissues were taken for biochemical analysis.
Plasma concentrations of [3-3H]glucose, 2-[14C]DG, and 3H2O were determined following deproteinization of plasma samples as previously described. Intracellular levels of 2-[14C]DG-6-phosphate (2-[14C]DG-6-P) in individual organs (i.e., skeletal muscle, white and brown adipose tissue) were determined using an ion-exchange column as previously described. Rates of basal HGP and insulin-stimulated whole body glucose turnover were determined as the ratio of the [3H]glucose infusion rate (disintegrations per minute; dpm/min) to the specific activity of plasma glucose (dpm/μmol) at the end of basal period and during the final 30 min of clamp, respectively. Insulin-stimulated rate of HGP during clamp was determined by subtracting the glucose infusion rate from whole body glucose turnover. Whole body glycolysis was calculated from the rate of increase in plasma 3H2O concentration, determined by linear regression of the measurements at 80, 90, 100, 110, and 120 min of clamps. Whole body glycogen plus lipid synthesis from glucose was estimated by subtracting whole body glycolysis from whole body glucose turnover. Since 2-deoxyglucose is a glucose analog that is phosphorylated but not further metabolized, insulin-stimulated glucose uptake in individual tissues can be estimated by determining the tissue (i.e., skeletal muscle, adipose tissue) content of 2-[14C]DG-6-P. Based on this, glucose uptake in individual tissues was calculated from plasma 2-[14C]DG profile and tissue 2-[14C]DG-6-P content.
Statistical Analysis
Data are expressed as mean�s.e.m. Differences between two groups were assessed using the unpaired two-tailed t-test and among more than two groups by analysis of variance (ANOVA).
To disrupt the ksr2 ORF, exon 4 was replaced with a neor cassette in DBA1/LacJ ES cells by homologous recombination (
ksr2−/− mice were identical in size and weight to ksr2+/+ and ksr2+/− mice during development in utero and at birth (
Disruption of ksr2−/− caused a doubling in fat mass and a 15% decrease in lean mass (
Hyperphagia contributes to obesity in other well-characterized models of obesity16. However, obese ksr2−/− mice consumed 10% less food than ksr2+/+ mice (
During their dark cycle, respiratory quotient (RQ) is suppressed in ksr2−/− mice relative to ksr2+/+ mice (
Obesity elevates serum lipids and predisposes rodents and humans to dysregulated glucose homeostasis20. ksr2−/− mice show modestly elevated triglycerides and free fatty acids (
ksr1 is a related gene whose protein product functions as a scaffold for the Raf/MEK/ERK signaling cassette, facilitating the activation of Raf and MEK7,10,21-25 Although ksr1−/− mice are lean and do not display metabolic characteristics observed in ksr2−/− mice (
The results presented herein demonstrate that disruption of ksr2 causes obesity through a more efficient expenditure of energy. A reduced rate of energy expenditure is a risk factor for weight gain in humans13. These observations reveal ksr2−/− mice to be a unique model of obesity with potential relevance to human disease. Moreover, both ksr1 and ksr2 appear to affect glucose homeostasis in mice. Analysis of ksr2 and is effectors may provide important insight into novel mechanisms regulating physiological control of energy storage and expenditure with implications for insulin resistance and diabetes. That molecular scaffolds regulating the activation of Raf, MEK and ERK can have a profound effect on fat accumulation suggests that this MAP kinase may have previously unappreciated roles in the regulation of energy balance.
While certain of the preferred embodiments of the present invention have been described and specifically exemplified above, it is not intended that the invention be limited to such embodiments. Various modifications may be made thereto without departing from the scope and spirit of the present invention, as set forth in the following claims.
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14 Toilet Paper Roll Craft Ideas
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Tissue Paper Rose Tree
By: Kathleen George for STYROFOAM* Brand Foam
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This psychedelic centerpiece is easy to make and fun to look at. Create from tissue paper and chenille.
- STYROFOAM™ Brand Foam:
- Cones: 24" x 6"; 21" x 5"
- Brightly colored tissue paper, several large sheets of each desired color
- White chenille stems, 12" long, 29
- Pencil
- Ruler
- Scissors
- Optional: Rotary cutter, cutting mat and metal ruler
- Low-temp glue gun and glue sticks
Note: Each tissue paper rose requires four squares of tissue paper, either one color or a mix of colors. For two cones, you will need a total of 56 six-inch tissue squares and 288 five-inch tissue squares. To save time, stack several layers of tissue paper and use rotary cutter to cut multiple strips of desired width, 5" or 6". Combine strips into stacks and cut multiple squares at a time. Keep squares separated by size.
1. Cut chenille stems into 4" lengths.
2. To make one rose, stack four 6" tissue squares. Fan-fold tissue stack into approximately 1"-wide folds. Use scissors to round off each end of folded stack to form petals.
3. Fold one 4" chenille stem in half and slip over center of folded tissue squares; tightly twist ends together at bottom to secure. Use scissors to trim excess wire.
4. Spread folded tissue out in a fan-shape on each side of chenille stem. Gently separate tissue layers with fingers, then pull up petals and arrange as desired. Bring two center petals together and slightly crush to ensure chenille stem is covered.
5. Repeat Steps 2 - 4 to create a total of 14 large roses (6" squares) and 72 medium roses (5" squares). Be sure to gently separate tissue layers of each flower before fluffing petals.Glue ribbon ends together to create hanging loop; glue ends to top center back of wreath.
6. Use glue gun to secure a row of large roses side by side around base of each foam cone; foam should be completely covered without crushing roses together. Glue medium roses to cone in rows to completely cover surface; glue a rose to each cone tip.
7. Place any remaining roses on table around base of cones.
®™ Trademark of The Dow Chemical Company ("Dow") or an affiliated company of Dow. For more project ideas, please see styrofoamstyle.com.
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subset: commoncrawl


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Posted by Josh Katzowitz
With the $125,000 in fines Steelers LB James Harrison has racked up this season, Pittsburgh owner Art Rooney II thinks there might be something to the idea that his squad is being scrutinized by the league with extra-sensitive eyes.
He's also worried the Steelers might stop playing as aggressively on defense because of the threat of fines for big-time hits.
So, is Pittsburgh being targeted?
"It certainly looks that way," Rooney told the Pittsburgh Tribune-Review. "Not that we're expecting much sympathy from other teams, but I think some of this will be part of the discussion after the season is over. Hopefully we'll all have our chances to express our opinions and at that point have a better understanding of where the owners in the league stand on some of this.
"I think we're sympathetic to the idea that we need to focus on player safety and particularly on helmet-to-helmet hits. The other side of it is it's still a football game, and I think we've got to be realistic about how the rules can be changed and what we expect of the defensive players in particular."
From the story:
Ray Anderson, the NFL's executive vice president of football operations, told the Tribune-Review yesterday that the league is not singling out Harrison.
Anderson did put the onus on Harrison to play within NFL rules. He added if the Steelers' sacks leader continues to run afoul of them that it could see him suspended.
"At the end of the day we have an important responsibility, and if that means at some point we have to remove a player from the field to get the message clearly in his mind and to protect players that he's violating, we will do so," said Anderson, whose office reviews every play from a given week and decides if any warrant fines. "But we hope that doesn't come to pass."
Harrison said earlier this week that he won't change his style of play and "will let the chips fall where they may."
Look, I have some sympathy for Harrison, because the NFL saw fit to change its rules in the middle of the season and because everybody is still confused about what is and what is not a legal hit.
But the fact of the matter is that these rulings are not going to change (this season, at least). So, if Harrison isn't going to adjust his style of play, he can expect the NFL to keep taking his money.
He can decry the fact he's been targeted – and you're crazy if you don't think officials are keeping an extra eye on him at all times (that's what happens when you develop a reputation like this) – but if other players can tweak their styles to avoid the potential for badly injuring players, it's not impossible for Harrison to do the same.
For more NFL news, rumors and analysis, follow @cbssportsnfl on Twitter and subscribe to our RSS Feed .
Blog Entry
Rooney thinks the NFL targeting the Steelers
Posted on: December 3, 2010 11:28 am
Category: NFL
Since: Dec 2, 2011
Posted on: January 29, 2012 8:46 pm
Rooney thinks the NFL targeting the Steelers
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Since: Dec 2, 2011
Posted on: December 30, 2011 4:56 am
Rooney thinks the NFL targeting the Steelers
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Since: Dec 2, 2011
Posted on: December 12, 2011 10:56 pm
Rooney thinks the NFL targeting the Steelers
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Since: Dec 2, 2011
Posted on: December 2, 2011 10:31 am
Rooney thinks the NFL targeting the Steelers
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Since: Oct 7, 2011
Posted on: October 18, 2011 7:31 am
Rooney thinks the NFL targeting the Steelers
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Since: May 12, 2010
Posted on: December 3, 2010 1:04 pm
Rooney thinks the NFL targeting the Steelers
This post is hilarious! I hardly know where to begin. 1). "Steelers are being targeted because they have the worst dirty, cheap shot artists" Aggressive, hard hitting play is not dirty or cheap, it's FOOTBALL! 2). "J Harrison on created this mess when he went live and stated he purposely tries to hurt people." There's not a linebacker or defensive back in the NFL who doesn't want it to hurt when he hits a receiver or running back coming through his territory. They want the offensive player to remember and think twice before doing it again. It's called intimidation, and it's the primary weapon every defender has. 3). "found him guilty of reckless behavior on the football field." In case you didn't know, just strapping on pads and stepping onto a football field is reckless behavoir. Large people will knock you down, and it will HURT. 4) "Dirty, cheating cheap shot player. Hope he gets suspended soon." So you're what... maybe 12 years old? Or maybe a girl? Coming from pansy liberal New England I would guess it could be either... or both! Either way, go watch soccer. Leave the real games to those who properly appreciate them.
Since: Jul 28, 2009
Posted on: December 3, 2010 12:26 pm
Rooney thinks the NFL targeting the Steelers
Even if Harrison were to "change his style", it would change nothing. The extra eye on him means border-line calls are going to continue to be flagged on Harrison and not on other players. Unjustified or not, it's the reality.
Since: Oct 10, 2006
Posted on: December 3, 2010 12:25 pm
Rooney thinks the NFL targeting the Steelers
Yes the Steelers are being targeted because they have the worst dirty, cheap shot artists J Harrison. J Harrison on created this mess when he went live and stated he purposely tries to hurt people. Opened his big mouth. Now he cry babies cause they started to look into it and found him guilty of reckless behavior on the football field. Hitting helmet to helmet. Dirty, cheating cheap shot player. Hope he gets suspended soon.


text:
This profile was last updated on 6/29/13 and contains information from public web pages and contributions from the ZoomInfo community.
Helga HoneyWrong Helga Honey?
Position In Administration
Local Address: Niagara Falls, Ontario, Canada
Binational Tourism Alliance Inc
143 Genessee Street
Buffalo , New York 14203
United States
Company Description: The BTA Board is made up of 30 Directors, 17 of which are voting members and 13 of which are non-voting. The 17 voting members of the Board are composed of 8... more
Pro2015_Iteration7.58[02] SEIDXWK-28


text:
More On Legal & Compliancefrom The Advisor's Professional Library
- Trading Practices and Errors When SEC-registered investment advisors conduct annual audits of firm policies and procedures, they should pay close attention to trading practices. Though usually not required to, state-registered advisors should look at their trading practices and revise policies that do not fully protect clients.
- Nothing but the Best Execution Along with the many other fiduciary obligations owed by RIAs, firms owe a duty to seek best execution of clients transactions. If they fail to do, RIAs violate Section 206 of the Investment Advisers Act.
Donald K. Runkle, who led the compliance operations of Raymond James' independent channel for more than 10 years, has left the firm. Runkle's last day at the firm was Friday, a spokesperson says.
"The firm's policy is not to comment on associates no longer with the firm," said Scott Curtis, president of Raymond James Financial Services, in a statement.
"Until a permanent RJFS chief compliance officer is identified, Alyssa Meyer and Jason Thackeray, both experienced directors of RJFS compliance, will act as co-CCOs. We're grateful for Don's contributions to the firm and wish him well in the future."
Runkle worked for A.G. Edwards from March 1992 to May 1993, before joining Raymond James in August 1993, according to FINRA records.
As of March 30, RJFS has 3,288 advisors in the United States, while its employee channel has 2,438. Its independent advisors are set to meet in Washington, D.C., from May 19-22 at the group's annual conference.
Last month, rival IBD LPL Financial (LPLA) said that Derek Bruton, formerly head of independent advisors services, resigned in connection with concerns over "interactions with other employees." The firm tapped Bill Morrissey as his replacement.


text:
ACC replaces SEC as top conference in AP poll
Updated: December 26, 2005, 2:37 PM ETAssociated Press
Tennessee is still the top team, but the ACC has replaced the SEC as the No. 1 league in The Associated Press women's basketball poll.
The Atlantic Coast Conference gained a fifth team on Monday when unbeaten Virginia Tech joined the poll at No. 25. Three of those ACC teams -- No. 2 Duke, No. 5 North Carolina and No. 6 Maryland -- are in the top six.
ACC newcomer Boston College joined last week and is now 24th.
After having five ranked teams last week, the Southeastern
Conference ...
Read full story
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Dave Field viewing Sugarlof Mountain from Bigelow last June on National Trails Day
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Prevalence of comorbid substance use disorder during long-term central stimulant treatment in adult ADHD
ABSTRACT Central stimulant (CS) therapy is a cornerstone in treatment of adult attention-deficit/hyperactivity disorder (ADHD). Substance use disorder (SUD) is a common comorbid disorder of ADHD and might complicate the treatment. Our main objectives were to investigate the prevalence of SUD during CS treatment, and identify variables associated with SUD during the treatment. The collection of data was based on a naturalistic, retrospective approach using the medical records of a cohort of all adult ADHD patients (N = 117) starting treatment with CS in a specific catchment area in the period 1997 to May 2005. A logistic regression model was applied to identify possible predictors of SUD during CS treatment. The study showed no onset of SUD during the CS treatment in the group of patients without comorbid SUD at baseline (mean CS treatment length 41.1 months). In the group of patients with comorbid SUD at baseline, 58.5 % had one or more relapses of SUD during treatment (mean CS treatment length 27.9 months). Younger age and comorbid antisocial personality disorder were associated with relapse. In a logistic regression analysis, cannabis abstinence for more than 12 months was a negative predictor for relapse of SUD. CS treatment does not precipitate onset of SUD in adults without previous SUD.
Article: Adults with ADHD: use and misuse of stimulant medication as reported by patients and their primary care physicians[Show abstract] [Hide abstract]
ABSTRACT: This study investigated the agreement on treatment for attention-deficit/hyperactivity disorder (ADHD) between adults with ADHD and the primary care physicians responsible for their treatment. Adults with ADHD and the primary care physicians responsible for their ADHD treatment completed a survey. The κ-statistic assessed physician-patient agreement on ADHD treatment variables. The eligible sample consisted of 274 patients with confirmed current or previous psychopharmacological treatment for ADHD and the physicians responsible for their treatment. We received 159 questionnaires (58.0 %) with sufficient information from both sources. There were no significant differences between participants and nonparticipants (N = 115) on ADHD sample characteristics. Participants' mean age was 37.6 years, and 75 (47.2 %) were females. There was high agreement for current pharmacological treatment for ADHD, current and last ADHD drug prescription, treatment for substance use, and misuse of stimulant medication. Agreement for nonpharmacological treatment for ADHD and treatment termination because of the side effects was low. A minority of participants from both sources reported misuse of stimulant medication. There was a moderate correlation between the physicians' clinical judgment and patients' self-report on current functioning. The study showed that primary care physicians and their patients agreed on the pharmacological but not the nonpharmacological, treatments given. They also agreed on patients' current functioning. Physicians and patients reported low levels of misuse of stimulant medication. The results show that pharmacological treatment for adults with ADHD can be safely undertaken by primary care physicians.ADHD Attention Deficit and Hyperactivity Disorders 08/2013; 5(4). DOI:10.1007/s12402-013-0116-8
Article: Factors associated with a positive occupational outcome during long-term central stimulant treatment in adult ADHD[Show abstract] [Hide abstract]
ABSTRACT: There is a lack of long-term studies of central stimulant (CS) treatment in adult attention-deficit/hyperactivity disorder (ADHD), and studies on functional outcomes like occupational status are rare. The current study investigated occupational status in adult ADHD patients before and after long-term CS treatment (median duration of treatment 33 months) and aimed to identify variables associated with improvement in occupational status. The collection of data was based on a naturalistic, retrospective approach using the medical records of a sample of all 117 adult ADHD patients consecutively starting treatment with CS in a specific catchment area in Norway in the period 1997 to May 2005. Most patients did not improve in occupational status during long-term CS treatment. The improved group had significantly higher baseline ADHD symptoms as measured by the general adult ADD symptom checklist (83.7 vs. 76.2, p = 0.024) and had a significantly shorter period from the first contact with adult psychiatry until they got the ADHD diagnosis (11.7 vs. 50.9 months, p = 0.001). The results indicate that long-term CS treatment itself may have limited effect on occupational status in functionally impaired and highly comorbid patients with adult ADHD. A high baseline ADHD symptom level may be related to a superior outcome in occupational status.ADHD Attention Deficit and Hyperactivity Disorders 04/2014; 6(4). DOI:10.1007/s12402-014-0135-0
- 01/2015; DOI:10.1007/s40501-015-0030-0


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SANTA FE, N.M. (AP) — Businesses could pay $20 million in higher taxes under a proposal by Gov. Bill Richardson's administration to shore up the program that provides unemployment benefits to jobless New Mexicans.
The unemployment insurance trust fund will run out of money by next year if the Legislature and governor don't agree on a rescue plan during the legislative session.
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VIEWS: 18 PAGES: 8 POSTED ON: 5/3/2011 Public Domain
Author manuscript, published in "International Deep Drawing Research Group (IDDRG) 2006 International Conference, Porto : Portugal (2006)" FORMABILITY INVESTIGATIONS FOR THE HOT STAMPING PROCESS Y. Dahan 1&2,*, Y. Chastel 1, P. Duroux 2, P. Hein 2, E. Massoni 1, J. Wilsius 2 1 CEMEF, Ecole Nationale Supérieure des Mines de Paris, 1 rue Claude Daunesse, BP 207, 06904 Sophia-Antipolis Cedex, France 2 ARCELOR Research Automotive Applications, 1 route de Saint-Leu, BP 30109, 60761 Montataire Cedex, France * corresponding author: email@example.com Abstract Arcelor Research is developing a numerical tool to support the feasibility analysis and to optimize the design of hot stamped parts made of USIBOR 1500P®. To provide formability data and to feed the development of a fracture criterion, experimental hot stamping tests are carried out at Cemef (Centre for Material Forming). These hot stamping experiments are based on a modified Nakazima-type test. Results reveal that the achievable strain levels depend on process parameters (stroke, velocity, temperature, friction and heat exchange) and blank parameters (initial temperature, thickness and shape). In parallel, a numerical model of these hot stamping tests has been developed with finite element softwares (Forge2®, Forge3® and Abaqus). The numerical simulations confirm the location and the magnitude of the blank thinning. Furthermore, the hal-00566427, version 1 - 16 Feb 2011 numerical results are similar to the experimental measurements in terms of punch load, cooling rate and strain distribution. A formability analysis is then performed to study the influence of the blank geometry and the blank temperature on formability. Keywords: Formability, Hot Stamping, Experiment, Numerical Simulation 1. Introduction The objective of automotive manufacturers is to combine safety improvements and weight reductions of their vehicles in order to comply with CO2 emission regulations. A non exhaustive list of the industrial solutions is given in [1]. As a response to these constraints, the hot stamping process of quenchable steels allows to obtain thinner parts with higher mechanical properties. It is a relatively novel process and it is increasingly used for automotive applications. This process consists in first heating up a blank in a furnace to reach a stable austenitic state. The hot blank is then moved into a stamping press where it is simultaneously stamped and quenched by the cold tools. The cooling rate of this process step allows obtaining the desired martensitic microstructure leading to superior mechanical properties on the formed part. It is the reason why the main target components are in the crash relevant parts of car structures: bumpers, side impact reinforcements, A- and B- pillars (see Figure 1). For this process, Arcelor developed USIBOR 1500P® 1, a quenchable C-Mn steel micro-alloyed with boron. The distinctive value of USIBOR® lies in the coating which avoids oxidation during the heating phase and saves a very expensive shot-peening step. With this material, a tensile strength of about 1500 MPa is reached on the quenched formed part. More details on the material, the process and some market trends are available in [2]. Figure 1. Crash relevant components hot stamped in USIBOR 1500 P® (darkened parts) [3] 1 USIBOR® is a registered trademark belonging to the Arcelor Group and protected throughout the world. Furthermore, Arcelor Group has filed numerous patents covering the principle of direct or indirect hot-stamping process of either aluminized-coated steel sheets and zinc or zinc-alloy coated steel sheets, and of the issued parts. Arcelor is developing a numerical tool to support the feasibility analysis and the design of hot stamped parts made of USIBOR 1500P®. This task is challenging due to the high number of process parameters, the thermo-mechanical and metallurgical interactions and their influence on formability (more details are presented in [3]). This requires both experimental tests and advanced numerical simulation tools. To provide formability data and to support the development of a fracture criterion, experimental hot stamping tests are carried out at Cemef (Centre for Material Forming). In this article we will mainly focus on the experimental results and the comparisons with the numerical simulations. Three types of non-conformities can be observed on hot stamped parts. They prevent from reaching the targeted mechanical properties defined in the specifications. First, the blank may only be partially quenched and thus not fully martensitic. The second type of non-conformity concerns the wrinkling and thickening zone. These defects are usually decreased by reducing the clearance between the die and the blank-holder or optimizing the initial blank shape. In this article, we will focus on the necking and/or fracture of the blank during hot stamping. 2. Process description To establish the formability criterion, hot stamping tests are performed with modified Nakazima-type tools and various product/process conditions. The axisymmetrical set-up is made of a hemispherical punch, a die, a blank-holder and a draw-bead which prevents any sliding motion (see Figure 2). Several parameters are recorded in-situ, such as the punch load and the local temperature history. A grid is etched on the blank and allows determining the strain distribution using pattern recognition systems. hal-00566427, version 1 - 16 Feb 2011 Vérins pneumatiques Pneumatic cylinder Tôle Blank Punch Poinçon Blank-holder Die Pyrometre Piromètre Prism Prisme Figure 2. Axi-symmetrical set-up for the modified Nakazima hot stamping tests Numerical simulation has been initially used for the physical understanding of the process. Numerical models of these hot stamping tests have been developed with different finite element softwares (Forge2®, Forge3® and Abaqus). Forge2® and Forge3® are being constantly improved at Cemef respectively for 2D and 3D analysis. Besides Arcelor developped a finite element environment dedicated to hot stamping in order to perform coupled thermo-mechanical simulations and make feasibility studies of hot stamped components [3]. In order to obtain correct results, a large number of model parameters have to be either defined with additional experimental tests (e.g. heat exchange coefficient, flow behavior) or adjusted by inverse iden- tification (e.g. friction, heat radiation). Some of them are defined in [4]. In this section, we will present the numerical results for a punch velocity of 30 mm/s, a 1,5 mm thick blank and an initial blank temperature of 780°C (when the forming starts). In the post-processing, we can see the temperature and strain rate distribution at different steps of the process (see Figure 3). A high cooling rate is measured at the centre of the blank, which is in contact with the punch. Nevertheless, the temperature of the free blank zone seems to be roughly constant during the process. The distribution of the Von Mises equivalent strain rate indicates an obvious strain localization in a zone called punch radius exit. Indeed, during the hot stamping process, the strains are usually localized in the hotter regions (free blank zone in our case), and especially at the exit of the punch radius. hal-00566427, version 1 - 16 Feb 2011 Figure 3. Results of numerical simulation for 10, 20 and 30 mm punch strokes: Evolution of the temperature [°C] (left) and Von Mises equivalent strain rate [/s] (right) Numerical simulation enables us to give results all along the process at a given location. Selecting a node near the exit of the punch radius, we plotted the nodal evolutions of the temperature and the equivalent strain rate in Figure 4. From 0 to 0,6 s, the punch is not in contact with the chosen node of the blank. So, obviously, it is at a constant temperature. The strain rate is increasing and reaches a maximum value at 0,6 s. At this moment, the node comes in contact with the punch and it is quickly cooled. As soon as the temperature drops down, the strain rate goes down as well. In fact, during the first time of the process, the blank centre is deformed and cooled down simultaneously. When this central zone is cool enough, the surrounding region, which is obviously hotter, is then deformed by the punch. In fact, due to the punch motion, a strain and a cooling wave is propagated away from the blank centre towards the exit of the punch radius. 2 800 1.8 700 Nodal equivalent strain rate (/s) 1.6 600 1.4 Punch contact Nodal temperature (°C) Nodal Equivalent Strain rate 500 1.2 Nodal temperature 1 400 0.8 300 0.6 200 0.4 100 0.2 0 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Time (s) Figure 4. Nodal evolution of the temperature and of the equivalent strain rate during the process Using an axisymmetric configuration enables us to check the model parameters defined previously. Figure 5 illustrates accurate comparisons between the numerical results and the experimental measurements for the punch load and the temperature at the centre of the blank. The punch force is directly dependent on the viscoplastic flow behavior of the material, the initial blank temperature and the blank thickness. The temperature distribution is mainly defined by the initial temperature gradient between the punch and the blank, and by the heat exchange coefficients. In [4], Garcia-Aranda et al. determined this coefficient as a function of the contact pressure and the clearance between the tool and the blank. This analysis confirms the accuracy of the parameters used to develop the numerical model. 45 800 40 750 700 35 Blank temperature (°C) 650 30 Punch force (kN) 600 25 550 20 500 15 450 Experimental temperature at the blank centre 10 Experimental punch load 400 5 350 Numerical temperature at the blank centre Numerical punch load 0 300 0 5 10 15 20 25 30 0 5 10 15 20 25 30 Punch stroke (mm) Punch stroke (mm) hal-00566427, version 1 - 16 Feb 2011 Figure 5. Experimental measurements and numerical calculations during the hot stamping process punch force (left) and temperature at the centre of the blank (right) The numerical model being checked and validated, we now focus on the strain distributions which are the key point for the formability analysis. 3. Predicted and experimental strain distributions Three types of stamped blanks can be obtained: conformed, with strain localization or fractured blank (see Figure 6). For a safe punch stroke, the blank shows no critical damage. For a higher punch stroke, a strain localization occurs in the exit of the punch radius which causes a local thinning called necking and can be determined by a technique developed by Hecker [5]. Once the maximum punch stroke is reached, the necking leads to a fracture which spreads over the exit zone of the punch radius. Figure 6. Conformed (left), necked (middle) and fractured (right) hot stamped blanks for various punch strokes. Fractography analysis has been carried out in order to analyze the fracture mode. In Figure 7, we observe a cross-section of the fractured zone. During hot stamping, strain localization occurs in the hotter region which leads to the thinning of the blank. The thinning appears in both a concentrated and continuous manner close to the fracture region. In addition, it seems to be symmetrical with respect to the blank neutral line. The front view of the fracture has been obtained by SEM. At the centre, the damage mode of the steel is observed in terms of intragranular microvoids characterizing a ductile fracture. Figure 7. Fractography analysis: binocular cross-section (left) and SEM front view (right) of the fracture zone Thanks to the quality of the coating and to an accurate method to preserve the grid, we managed to assess several strain distributions using pattern recognition systems. Uniform and random grids have been etched or painted on to the blank to be respectively analyzed by Asame and Aramis. This technique enables us to measure the strain distributions. The thinning values are then calculated considering volume conservation. hal-00566427, version 1 - 16 Feb 2011 Figure 8 compares the results given by Forge3® and Aramis for similar process configurations. The numerical simulations confirm the location and the magnitude of the thinning. Indeed, Aramis and Forge3® estimate that the maximum major strain is reached at the exit of the punch radius and that this extreme value was roughly 0,4. We can also notice that the blank centre is only slightly deformed due to the high cooling rate generated by the early contact with the punch. Figure 8. Major surface strain distributions obtained by Forge3® (left) and Aramis (right) Process conditions: punch stroke: 30 mm, punch velocity: 30 mm/s, blank thickness: 1,5 mm, blank initial temperature: 780°C The pattern recognition systems such as Asame and Aramis enable us to plot the strain distribution in the (ε1,ε2) space. This diagram is widely used for sheet metal forming when strain gradients in the thickness direction can be neglected. Figure 9 represents the numerical and the experimental strain states of the blank at the end of the hot stamping process. First of all, we can observe an excellent correlation between the numerical and the experimental results. In our simple configuration, strains are located between plane strain and biaxial expansion. Forge2® and Aramis results indicate that the maximum major strain is reached in a mixed mode, close to plane strain. The blank centre is obviously in an expansion state. We see that the major strain is 0,05 at the blank centre which is roughly the ratio of the blank thickness to the punch radius. According to [5], this value could be a simple bending effect due to the accumulated effects of high friction and heat exchange. The central zone of the blank quenched by the punch reaches a constant minor strain (≈ 0,04) all the way to the punch radius exit. In this region, the further from the blank centre, the higher the major strain. Beyond the punch radius exit zone, the strain quickly decreases. 0.2 Plane strain Punch radius exit Uniaxiale Expansion 0.18 tensile strain 0.16 0.14 Major strain 0.12 0.1 0.08 0.06 Blank centre 0.04 Aramis assesments 0.02 Numerical simulation External blank part 0 -0.12 -0.1 -0.08 -0.06 -0.04 -0.02 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 Minor strain Figure 9. Strain distribution given by Aramis assessments and Forge2® results Process conditions: punch stroke: 20 mm, punch velocity: 30 mm/s, blank thickness: 1,5 mm, blank initial temperature: 780°C hal-00566427, version 1 - 16 Feb 2011 4. Formability analysis The experimental determination of formability limits has to take into account several process characteristics in terms of temperature (anisothermal process), phase transformation (unstable austenitic structure), stress triaxiality (thickness effect), process speed (viscoplastic behaviour and heat transfer) and strain path (blank shape and friction). These parameters can be changed by varying the process time, the initial blank temperature (defined as the blank temperature at the start of the stamping), the thickness and the blank shape in order to analyze their respective influence on the formability. Only the influence of the blank shape and the of the initial temperature of the blank will be detailed in this article. Several hot stamping tests were performed for different blank widths. Each stamped blank is then analyzed and classified according to quality criteria. All failed blanks showed necking or fracture in the punch radius region (see Figure 10). The punch stroke is then plotted as a function of the blank width for safe parts, strain localization (necking) or fractured blanks. The formability is strongly dependent on the blank width: the larger the blank width, the lower the critical punch stroke. This observation is mainly due to the modification of the strain paths of the critical region from plane strain towards uniaxial tensile strain. 41 Safe 39 Necking 37 Fracture Punch stroke (mm) 35 33 31 29 27 25 0 0.1 0.2 0.3 0.4 0.5 0.6 Blank Width Reduction Ratio Figure 10. Hot stamped blanks with different width reduction ratios (left) and influence of the blank width on formability (right) The pattern recognition systems have been used to deduce the influence of the width on the strain distri- bution. The strain states for several widths of necked blanks are shown in Figure 11. Several remarks can be made from this graph. The lower the blank width reduction ratio, the closer to the uniaxial tensile mode is the strain state and the higher is the maximum major strain. As seen before, the critical and the expansion zones are still respectively the exit of the punch radius and the blank centre for the higher width. The strain value at the centre seems to be constant for all blank widths. Of course, the blank centre zone is not in an expansion state anymore for the narrowest blanks. 0.8 Uniaxial Plane tensile strain strain 0.6 Major Strain ε 11 Expansion 0.4 Blank Width Reduction Ratio = 1 Blank Width Reduction Ratio = 1/2 Blank Width Reduction Ratio = 1/3 0.2 hal-00566427, version 1 - 16 Feb 2011 Blank Width Reduction Ratio = 1/5 Blank Width Reduction Ratio = 1/10 0 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 Minor Strain ε22 Figure 11. Influence of the blank width on punch stroke and formability Asai et al. studied the influence of the heating temperature on the deep drawability of a hardenable C-Mn-B steel sheet [7]. In our case, varying the initial blank temperature from 600°C to 800°C allows us to analyze the influence of temperature on the formability. Figure 12 confirms the influence of temperature: the higher the initial temperature, the higher is the maximum punch stroke. According to these experimental results and with the given process conditions, a stroke of 27 mm is feasible only if the initial blank temperature is higher than 720°C. Below this temperature, necking and fracture in the critical zone of the blank are strongly likely. 32 31 30 29 Punch stroke (mm) 28 27 26 25 Safe 24 Necking 23 Fracture 22 550 600 650 700 750 800 850 Temperature (°C) Figure 12. Influence of the initial blank temperature on the punch stroke and the formability of the blank 5. Conclusion Hot stamping tests have been carried out with a modified Nakazima set-up. Safe parts, strain localization (necking) and fractured blanks were obtained. The fractography analysis of the fractured blanks shows intragranular microvoids characterising a ductile fracture. Thanks to the quality of the blank coating and to an accurate method to preserve the grid, we managed to assess several strain distributions using pattern recognition systems. Numerical simulations have been performed and show an accurate correlation with the experimental results in terms of punch load, temperature at the center of the blank and strain distribution. The numerical model confirms the location and the magnitude of the critical zone. Numerical simulations enable us to analyze the evolution of temperature and strain rate during stamping as a wave which propagates from the blank centre towards the die radius, following closely the exit of the punch radius. Formability analysis results show the influence of the width and the initial temperature of the blank. For the first analysis, the narrower the blank, the higher is the allowable punch stroke. Modifying the blank shape changes the strain path. Indeed, the strain distribution graph shows that the narrower the blank, the closer to the uniaxiale tensile mode is the strain state and the higher is the maximum major strain. A similar study has been performed for the influence of the initial blank temperature. It appears that the higher the initial temperature, the better is the formability. All these tests will be used to develop a necking criterion which takes into account several process para- meters such as the blank temperature, the blank thickness and the strain rate. hal-00566427, version 1 - 16 Feb 2011 6. References [1] Kolleck, R.; Steinhöfer, D.; Feindt, J.-A.; Bruneau, P.; Heller, T.; Lenze, F.: Manufacturing Methods For Safety and Structural Body parts for Lightweight solution. IDDRG 2004. Proc. of the conf. of the Int. Deep Drawing Research Group, p. 167-173, 2004. [2] Hein, P.; Kefferstein, R.; Dahan, Y.: Hot Stamping of USIBOR 1500P®: Part and Process Analysis Based on Numerical Simulation. Proc. of the conf. New Developments in Sheet Metal Forming, Institute for Metal Forming Technology, Stuttgart, Germany, May 2006 [3] Hein, P.: A Global Approach of the Finite Element Simulation of Hot stamping, Advanced Materials Research, Vol. 6-8 (May 2005), 763-770. Trans. Tech Publications Ltd., Switzerland. [4] Garcia-Aranda, L.: Etude thermo-mécanique et modélisation numérique de l'emboutissage à chaud de l'USIBOR 1500P®. Ecole des Mines de Paris. PhD-Thesis (in French), 191p, 2004. [5] Hecker, S.S.: Formability of Aluminium Alloy Sheets. ASME Journal of Engineering Materials and Technology, Vol. 97, 66-73, 1975 [6] Wang, G.; Ohtsubo, H.; Arita, K.: Large Deflection Of A Rigid-Plastic Circular Plate Pressed By A Sphere. Journal of Applied Mechanics, 533, Vol. 65, june 1998. [7] Asai, T.; Iwaya, J.: Hot Stamping Drawability of Steel. IDDRG 2004. Proc. of the conf. of the Int. Deep Drawing Research Group, p. 344-354, 2004. Acknowledgements The authors would like to thank S. Jacomet, G. Fiorucci and B. Triger from Centre for Material Forming (CEMEF) and C. Dessain, J.-P. Durbise and B. Tavernier from Arcelor Research Automotive Applications.
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Welcome to the Greater Boulder Youth Orchestras, the premiere youth orchestra experience in Boulder and the surrounding area!
This organization is under the musical leadership of Gary Lewis, the Director of Orchestral Studies and Professor of Music in the College of Music at the University of Colorado at Boulder.
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• Symphony, conducted by Gary Lewis, Artistic Director
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Music of Mozart, Gershwin, Offenbach, Dvorak, Bach and more!
Featuring Boulder Bach Festival Artistic Director and violin soloist Zachary Carretin!
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More music by Bizet, Tchaikovsky, Handel, Sibelius, Wagner.
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2014-2015 Season


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A 97-year-old man who wanted to watch a Milwaukee Brewers game called 911 to report someone had stolen his remote control.
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- //Kidz in the Hall
It's easy to see how Kidz in the Hall could rub people the wrong way. The Ivy League-educated duo of Chicago emcee Naledge and Jersey producer Double-O emanate an ostensible air of elitism upon first look. Their debut album School Was My Hustle came out of Rawkus' brief attempt to regain relevance in late 2006. At the height of the coke-rap phenomenon, the title was too easy to interpret as "while you were out selling drugs, I was getting an elite education which makes me better than you". Fortunately those inferences stopped at the title and School Was My Hustle turned out to be simply a good throwback to '90s hip-hop tall on homage to pioneers and short on "holier than thou" pretension.
With Rawkus' return apparently in limbo, it might have seemed that Kidz in the Hall would fade away; then they made an unexpected move by signing with Duck Down Records. As the home label for all factions of the Boot Camp Clik, Duck Down has come to represent the absolute grittiest, rawest street hip-hop more so than any entity outside of perhaps only the Wu-Tang Clan. Two educated, privileged kids signing onto this label still feels like an odd fit.
Kidz in the Hall
The In Crowd
(Duck Down Music)
US: 13 May 2008
UK: Available as import
The In Crowd is Kidz' sophomore LP and first for their new label. The title and album cover (which shows the duo clad in elite academic club apparel) appear to be meant in more of a satirical way but the whole school theme tends to get a little tired. Fortunately, like their last album, any bullshit one might associate with the album superficially is lost upon actually listening to the music. Where School Was My Hustle mostly paid homage to rap of the past with a slight modern touch, The In Crowd mixes revivalism with more contemporary sounds. A perfect example is lead single "Drivin Down the Block", which applies the current Houston Screwed-and-Chopped aesthetic to vocals from Masta Ace's classic track "Born to Roll". The juxtaposition provides an excellent commentary on the hypocrisy of hip-hop fans who consider themselves purists; while they complain about celebratory car tracks ruining hip-hop, a look back shows that one of their heroes was doing the same thing, on one of his best songs.
It's moments like these that show Kidz in the Hall at their best. Producer Double-O shows great ability in mixing old school with new school to create unique sounds. What was impressive revivalism on their last album has now taken on a level of uniqueness that should earn him a new level of respect among producers. As a rapper, Naledge has sufficient skill and generally writes creative lyrics but is yet to find a voice unique enough to propel him out of the underground.
One measure of a rapper would be how much or how little guest verses add to albums on which he is the principal emcee. Unfortunately, for Naledge at least, the guest spots on The In Crowd prove almost essential to the quality of the album. Guests like Phonte, Skyzoo, Guilty Simpson, Sean Price, Buckshot, Bun B, and Pusha T almost always steal the spotlight on the songs which feature them. Naledge is not a bad rapper by any means and holds his own with the aforementioned heavyweights; there is just a level of charisma he needs to find before he can really hold the attention of most listeners.
The In Crowd is a definite improvement upon the last Kidz in the Hall album. Their promise as a duo has increased in just about every category. If they can ditch the potentially polarizing school theme in their album titles and form their own unique voices a bit further, they could easily be respected for a long time.
Foxtails Brigade "Far Away and Long Ago" (video) (premiere) // Music
Three Thousand Rivers "Gut" (audio) (premiere) // Music
Twin River "Secret in a Séance" (video) (premiere) // Music
A Crooked and Unseen Highway: lowercase - "You're a King"
// Sound Affects
"Like too many great bands, Lowercase have never received their full due. Ragged, deeply, sometimes even awkwardly, personal music like theirs typically becomes the property of small but passionate fanbases.READ the article


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West Utica
1400 Noyes St
Utica, NY 13502 Phone number & directions
1400 Noyes St
Utica, NY 13502 Phone number & directions
License & Identifications
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Christine Ha:
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Specialties & Research
- She has special expertise in 7 areas:
- Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD)
- Bipolar Disorder / Manic Depressive Disorder
- Depression
- Depressive Disorder
- Insomnia
- Schizophrenia
- Sleep Disorders
Education & Awards
Dr. Ha graduated from Ewha Womans University, Seoul.
Home > Find a Psychiatrist > NY > Utica Psychiatrists > Dr. Christine Ha, MD
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- Additional Information
- Dr. Christine C Ha MD is a female Psychiatrist and practices in Psychiatry.
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Dr. Christine Ha practices Psychiatry near Utica, NY.
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Luxury Self-Catered Ski Chalet in Jochberg, Austria
100m from Ski Lifts - 100m from Ski Bus
Sleeps up to 2, from €276 per week.
Panorama Chalet 2B is in the Austrian ski resort of Jochberg and has Kirchberg in Tirol and Kitzbühel within reach for a days skiing.
What's Included?
Price Includes :- Accommodation Only
Map of Ski Chalets and Apartments in Jochberg
NOTE: Locations provided to us are not always precise; please check Accommodation Location when booking!
Panorama Chalet 2B is convenient for Skiing and Snowboarding in Austrian Ski Resorts including Jochberg, Kirchberg in Tirol and Kitzbühel.


text: Calibre - Archive by Metalheadz published on 2014/04/18 08:19:27 +0000 The wait is over - PB4 is here. Perhaps one of the most revered album series in drum & bass is back with a vengeance, and some are saying it maybe the best yet. It's hard to believe this is the debut track by Calibre on Metalheadz, and it's already a firm dancefloor favourite thanks to its skipping drums and variants in bass. The drums have the unmistakeable Calibre air to them, the air that grabs you by the hips and demands you move and paired with the aforementioned screwface bass, it really is a foregone conclusion that you're going to move. Metalheadz Facebook Metalheadz Website


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Find Your Degree Now
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Founded in 1906, Abilene Christian University has a long and proud heritage dedicated to educating students for Christian service and leadership throughout the world. The school and its instructors offer a curriculum that revolves around theological perspectives and core values. ACU currently offers a select number of graduate programs in an online format. Explore the opportunity to be a part of ACU's community.
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Find a Career Doing What You Love Learn the art and science of music at Pinnacle College If you love music and want to make it your career, you owe it to yourself to check out Pinnacle College. We understand your love of music and our faculty will help you learn to combine the art and science of creating it. In the Music Production –Recording Arts program, you'll receive a thorough understanding of formal production techniques. Our program will help you build a strong foundation and the practical abilities you'll need to become a producer - recording, composing,arranging, mixing, and marketing professional music and sound - on your own or in collaboration with others. Our alumni include Grammy and Oscar winners. Since 1972, we've been helping students on the path to careers in music production, engineering,mixing and mastering and composition. You'll work in professional-grade studios to hone the skills needed to perform at the highest level. But it's
Redstone College
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Join an elite community when you enroll in University of the Rockies. Develop specialized skills to become a thought leader. Certain degree programs may not be available in all states. Federal regulations require institutions to report certain information about students who enrolled in Title IV eligible educational programs that lead to gainful employment in a recognized occupation (GE programs). For program disclosure information, visit www.rockies.edu/programdisclosures.
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Cavaliers beat Clippers 108-101 to end 2-game skid
"There's not going to be a game where a team's not gunning for us, so we have to have the mindset that everybody's coming for us and we have to be coming for them even harder," Griffin said.
Waiters scored 12 of Cleveland's first 14 points to open the third, when they led by 13 early on only to see the Clippers cut it to six points going into the fourth. The Clippers shot 57 percent from the floor and regained a 16-10 edge in the paint to close within striking distance.
"When you have somebody going like that you just sit back and watch," Irving said about Waiters.
Cleveland's momentum carried into the second quarter when it outscored the Clippers 26-22 to lead 57-50 at the break, with Varejao's driving layup just beating the halftime buzzer. Irving had 16 points in the half to eight by Paul, whose team had 13 turnovers in the first two quarters.
The Cavs missed their first four shots of the game while falling behind by seven. They got going near the end of the first quarter, with consecutive 3-pointers by Daniel Gibson and Irving to take their first lead of the game.
Notes: Zeller left the court with 5:39 to play after taking an elbow to his left cheekbone under his eye. He was being examined after the game and Scott said the team would know more on Tuesday. ... Crawford had led the Clippers in scoring in each of their first three games. ... Paul had nine assists, ending his run of three straight points-assists double-doubles. ... The Clippers have sold out their first three home games, extending their streak of consecutive sellouts to 53. ... The Cavs won the teams' only meeting last season.


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Erase the guilt by paying for your newspaper: Gallinger
For years, I have been getting my paper for free. I don't like being a freeloader. What should I do?
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Q: I am a faithful, but cheating, reader of your column. I had subscribed to The Toronto Star for ages until I cancelled my subscription five years ago. It's not that I don't like the paper or can't afford delivery. But — being retired — I had developed the evil, slothful habit of doing the puzzles before anything else on my list, undisciplined soul that I am.
Imagine my surprise and pleasure when my carrier knocked on my door and asked, "Are you alright? Is everything okay?" I assured him I was fine and had simply made a decision to rearrange my priorities. He said, "I'll bring you an occasional paper when I have leftovers."
It started by frequently getting a free Saturday paper and the odd midweek paper as well. Very kind. How nice. And then it escalated to daily delivery, seven days a week, for years. It's reached a point where I expect daily delivery. And my paper comes early; it's here by 6:00 a.m., so I have the puzzle in time for breakfast.
Not only does this nice man deliver the paper to me for free, he delivers it carefully. Unlike carriers who fling the paper, he places it gently inside the door. This is important. I feed a colony of feral cats on my porch. They are there in the early hours, waiting for breakfast — and I don't want them harassed by a newspaper flung at them.
I see the carrier when I'm up early and putting out cat food. We exchange pleasantries. I receive his annual Christmas card and I give him a substantial tip, usually $50.
But I still feel guilty as hell. I don't like being a freeloader. And I certainly don't want to get my nice delivery man in trouble if he's doing something he shouldn't. But I did cancel the paper, so this isn't my fault.
This guilt has been nagging at me for five years now. I wish I could get free of it. What should I do?
A: Your carrier is a wicked, satanic man. He has ruined your noble intentions, led you to a life of guilt-ridden sloth, all the while violating the terms of his contract with this newspaper, cheating other customers who have to pay while you don't, accepting an outlandish annual bribe, and encouraging the uncontrolled copulation of wild cats that terrorize your neighbourhood. I suspect he only brings the paper so he can see you in your housecoat every morning. I will use my considerable influence here at The Star to get him fired.
Just kidding. What influence?
What should you do?
Dial 416-367-4500. Give The Star circulation desk your credit card number and subscribe. They'll charge you $3.69/week for the first 6 months.
I have lots of things in my life I feel that make me feel "guilty as hell." If I could solve even one of those problems for $3.69/week, I'd be the happiest man on earth.
It's nice that you tip your carrier, but what about other people? The editors, the photographers, the printing press people, the investigative reporters, the person who sweeps the lunchroom?
What about the incredibly talented columnists? Never mind them — what about me?
Pay for your freakin' paper.
Send your questions to firstname.lastname@example.com
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