text:
Quantum magic bullets by means of entanglement
JOSA B, Vol. 19, Issue 2, pp. 312-318 (2002)
Enhanced HTML Acrobat PDF (165 KB)
Two particles that are entangled with respect to continuous variables such as position and momentum exhibit a variety of nonclassical features. First, measurement of one particle projects the other particle into the state that is the complex conjugate of the state of the first particle; i.e., measurement of one particle projects the other particle into the time-reversed state. Second, continuous-variable entanglement can be used to implement a quantum magic bullet: When one particle manages to pass through a scattering potential, then, no matter how low the probability of this event, the second particle will also pass through a related scattering potential with probability 1. This phenomenon is investigated in terms of the original Einstein–Podolsky–Rosen state, and experimental realizations are suggested in terms of entangled photon states.
© 2002 Optical Society of America
OCIS Codes
(190.4970) Nonlinear optics : Parametric oscillators and amplifiers
(270.0270) Quantum optics : Quantum optics
(270.5290) Quantum optics : Photon statistics
(270.6570) Quantum optics : Squeezed states
Seth Lloyd, Jeffrey H. Shapiro, and Franco N. C. Wong, "Quantum magic bullets by means of entanglement," J. Opt. Soc. Am. B 19, 312-318 (2002)
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- C. H. Bennett and P. W. Shor, "Quantum information theory," IEEE Trans. Inf. Theory 44, 2724–2742 (1998). [CrossRef]
- A. Einstein, B. Podolsky, and N. Rosen, "Can quantum-mechanical description of physical reality be considered complete?" Phys. Rev. 47, 777–780 (1935). [CrossRef]
- A. Furusawa, J. L. Sørensen, S. L. Braunstein, C. A. Fuchs, H. J. Kimble, and E. S. Polzik, "Unconditional quantum teleportation," Science 282, 706–709 (1998). [CrossRef] [PubMed]
- L. Vaidman, "Teleportation of quantum states," Phys. Rev. A 49, 1473–1476 (1994). [CrossRef] [PubMed]
- S. L. Braunstein, "Error correction for continuous quantum variables," Phys. Rev. Lett. 80, 4084–4087 (1998). [CrossRef]
- S. L. Braunstein, "Quantum error correction for communication with linear optics," Nature 394, 47–49 (1998). [CrossRef]
- S. Lloyd and J.-J. E. Slotine, "Analog quantum error correction," Phys. Rev. Lett. 80, 4088–4091 (1998). [CrossRef]
- S. Lloyd and S. L. Braunstein, "Quantum computation over continuous variables," Phys. Rev. Lett. 82, 1784–1787 (1999). [CrossRef]
- J. H. Shapiro, and K.-X. Sun, "Semiclassical versus quantum behavior in fourth-order interference," J. Opt. Soc. Am. B 11, 1130–1141 (1994). [CrossRef]
- J. H. Shapiro and N. C. Wong, "An ultrabright narrowband source of polarization-entangled photon pairs," J. Opt. B 2, L1–L4 (2000). [CrossRef]
- H. P. Yuen and J. H. Shapiro, "Optical Communication with two-photon coherent states. III. Quantum measurements realizable with photoemissive detectors," IEEE Trans. Inf. Theory IT-26, 78–92 (1980). [CrossRef]
- M. D. Reid and P. D. Drummond, "Quantum correlations of phase in nondegenerate parametric oscillation," Phys. Rev. Lett. 60, 2731–2733 (1988). [CrossRef] [PubMed]
- P. D. Drummond and M. D. Reid, "Correlations in nondegenerate parametric oscillation. II. Below threshold results," Phys. Rev. A 41, 3930–3949 (1990). [CrossRef] [PubMed]
- Z. Y. Ou, S. F. Pereira, H. J. Kimble, and K. C. Peng, "Realization of the Einstein–Podolsky–Rosen paradox for continuous variables," Phys. Rev. Lett. 68, 3663–3666 (1992). [CrossRef] [PubMed]
- Z. Y. Ou, S. F. Pereira, and H. J. Kimble, "Realization of the Einstein–Podolsky–Rosen paradox for continuous variables in nondegenerate parametric amplification," Appl. Phys. B 55, 265–278 (1992). [CrossRef]
- S. Reynaud, C. Fabre, and E. Giacobino, "Quantum fluctuations in a two-mode parametric oscillator," J. Opt. Soc. Am. B 4, 1520–1524 (1987). [CrossRef]
- K. W. Leong, N. C. Wong, and J. H. Shapiro, "Nonclassical intensity correlation from a type-I phase-matched optical parametric oscillator," Opt. Lett. 15, 1058–1060 (1990). [CrossRef] [PubMed]
- J. Teja and N. C. Wong, "Twin-beam generation in a triply resonant dual-cavity optical parametric oscillator," Opt. Express 2, 65–71 (1998), http://www.opticsexpress.org. [CrossRef] [PubMed]
- J. H. Shapiro, "Long-distance high-fidelity teleportation using singlet states," in Quantum Communication, Computing, and Measurement 3, O. Hirota and P. Tombesi, eds. (Kluwer, New York, 2001), pp. 367–374.
- C. K. Hong, Z. Y. Ou, and L. Mandel, "Measurement of subpicosecond time intervals between two photons by interference," Phys. Rev. Lett. 59, 2044–2046 (1987). [CrossRef] [PubMed]
- M. Vasilyev, S. K. Choi, P. Kumar, and G. M. D'Ariano, "Tomographic measurement of joint photon statistics of the twin-beam quantum state," Phys. Rev. Lett. 84, 2354–2357 (2000). [CrossRef] [PubMed]
- S. Lloyd, M. S. Shahriar, J. H. Shapiro, and P. R. Hemmer, "Long-distance, unconditional teleportation of atomic states via complete Bell state measurements," Phys. Rev. Lett. 87, 167903 (2001). [CrossRef]
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« Evian Christ touring this summer (dates and streams) | Purity Ring reveal first 'Shrines' video: "Belispeak" (watch) »
Posted in metal | music | tour dates on May 31, 2012
Deviated Instinct at Maryland Deathfest (more by BBG)
Deviated Instinct have had a trying few days after their set at Maryland Deathfest this weekend. During a show at Now That's Class in Cleveland, the van they were sharing with the band Dresden disappeared and with much of their personal items with it:
Ok, so we managed to recover the van. It's beaten and the trailer was hacked into, but drivable. Dresden lost a fair amount of backline and many of us lost personal luggage but we're back on the road. Huge thanks to those who have donated to help Dresden cover some of their losses.While that comes as semi-happy news (we'll take what we can get), the UK crust/doom crew have some other much happier news to share: an updoming 12" due via Profane Existence.
Produced by From Ashes Rise's Brad Boatright,Liberty Crawls to the Sanctuary of Slaves is Deviated Instinct's first original work in 22 years and will be released July 10. Preorder yours at Profane Existence to get an exclusive colorway and stream it in full below! The band also has a split with Summon The Crows, available for order now via Nakkeskud.
Deviated Instinct is currently on tour, heading to Chaos in Tejas this week. All remaining tour dates, that stream, album art, and a live video from MDF are below.
Deviated Instinct - Liberty Crawls...
Deviated Instinct at MDF 2012
31.05.2012 Medusa, Minneapolis, MN, US
02.06.2012 Chaos in Tejas, Austin, TX, US
23.06.2012 K-Town Fest, Copenhagen, DK
13.10.2012 Subvert Fest, Bristol, UK
Comments (17)
What is with everyone's van getting stolen or broken into?
Posted by Anonymous | May 31, 2012 11:09 AM
How many times does it have to be said before these bands learn?
-Do not leave your hummus in a parked van overnight!!!
Posted by Anonymous | May 31, 2012 11:40 AM
Dresden Dolls? Dude sees van, thinks it's band's van, gonna jack some amps and guitars and shit, opens van and there's people tied up and stuff, dude becomes hero for freeing victims of trafficking :)
Posted by Anonymous | May 31, 2012 1:56 PM
Imagine the shit that would hit the fan here if Radiohead's stuff got broken into. Ahahahahaha!
Posted by Anonymous | May 31, 2012 3:27 PM
Played out YTIN.ASNIL comment - douchebag hipster late to the party asshole
Played out Sausage comment - douchebag in the closet hipster asshole
Played out Hummus comment - douchebag troll hipster asshole
You're all boring and no one's laughing, except all the rest of your clever hipster troll friends in flannel.
Posted by Anonymous | May 31, 2012 8:45 PM
I think that the sausage comments are hilarious, if only for the agita that it causes all you sausages (given your repressed homoerotic impure impulses simmering just ... under ... surface)
Posted by Anonymous | May 31, 2012 9:16 PM
Might be worth mentioning that Nakkeskudd and Terminal Filth is doing a european version of this 12" as well. It seems that Profane has forgotten to mention this info all the way.
Posted by Anonymous | June 1, 2012 2:20 AM
9:16: And I REALLY love the reactions you trendies get once you wind up testing HIV-positve. Too many Atlas Sound shows will do that to ya!
Posted by Anonymous | June 1, 2012 9:21 AM
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text: 10 Fun wedding trends for 2011 by Cara Davis Jul 27, 2011 Share Tweet Pin Share Save No need to excuse or explain nontraditional wedding plans – they've never been more in style. When planning for your big day, don't be afraid to have fun with out of the ordinary everything, from outfits to hor d'oeuvres. So throw that bouquet in the air and while you're at it, caution to the wind. Want to plan a modern, memorable wedding but aren't sure where to begin? Here's a look at ten playful wedding trends to get you started. Read Full Story


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Snow is a form of ice.[1] Snow forms when water in the atmosphere becomes frozen. Snow comes in all different shapes and sizes.
At the freezing point of water (0° Celsius, 32° Fahrenheit), snow melts and becomes liquid water. Sometimes, the snow will melt very fast and become water vapor. This is called sublimation. The opposite, where water vapor becomes snow, is called deposition.
Snow is used for some winter sport activities like skiing and sledding. People also commonly build things out of snow for fun.
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References[change | change source]
- ↑ "Science in Your Watershed - General Introduction and Hydrologic Definitions". water.usgs.gov. 2011 [last update]. http://water.usgs.gov/wsc/glossary.html#S. Retrieved 13 February 2011.
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A new study finds 45% of smartphone owners who plan to use mobile payment apps in the next 90 days will opt for the ...
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Lakewood comeback falls short on the gridiron
EVERETT — The Cougars threw just about everything they could at the Wildcats.
In a battle of the Cascade Conference's top football teams Oct. 1, Lakewood lost a wild one to Archbishop Murphy 35-28, though it wasn't for lack of effort — or creativity.
"We knew they scout really well and prepare for you, but if you throw some things at them that they hadn't seen before, you can catch them off guard," said Lakewood coach Dan Teeter. "And you've got to hand it to our kids — we threw some wrinkles in the play book — and they executed."
A flea-flicker, hook-and-ladder, an intentionally spiked lateral to a wide receiver who then threw it down field and three onside kicks — one recovered — helped the Cougars stay right with the top-ranked Class 2A team in the state, but in the end it wasn't enough.
The Cougars trailed 35-14 with eight minutes remaining in the fourth quarter, but scored twice in the next five minutes to bring them within striking distance. On a flee flicker, quarterback Justin Lane found Brandon Stott open for a 38-yard touchdown reception. The Cougars then recovered an onside kick and drove the ball down the field to score two and a half minutes later on a 4-yard pass from Lane to Justin Peterson.
The Cougars then forced an ATM fumble on a fourth-and-nine situation to get one more shot at tying the game with the ball back on their own 36 with under 35 seconds remaining. But an interception two plays later effectively ended the game.
"I was pleased with the way they battled," said Teeter. "It hurts to come up short, but that just shows that you worked hard in the summer because if you don't work hard, it doesn't hurt much when you lose and there are some tears out here on the field."
The Cougars started out fast, scoring on a 65-yard pass from Lane to tight end Dustin Stanton. Murphy countered with a pair of touchdowns and the score was 14-14 when Murray ran in a 1-yard score for Lakewood in the second quarter.
The Cougars worked mainly out of the shotgun to keep Murphy's tandem of Division 1 linemen prospects, Taniela Tupou and Julius Tevaga, from getting to Lane, who completed 16 of 32 passes for 317 yards and three touchdowns.
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The Sports Network
DATE & TIME: Wednesday, February 26, 8 p.m. (ET)
FACTS & STATS: Site: Tad Smith Coliseum (8,700) -- Oxford, Mississippi. Television: ESPN3.com. Home Record: Alabama 11-4, Ole Miss 10-5. Away Record: Alabama 0-9, Ole Miss 4-6. Neutral Record: Alabama 0-3, Ole Miss 2-0. Conference Record: Alabama 5-9, Ole Miss 7-7. Series Record: Alabama leads, 118-54.
GAME NOTES: Still trying for their first road win of the season, the Alabama Crimson Tide will head to Tad Smith Coliseum on Wednesday night to battle with the slumping Ole Miss Rebels in an SEC bout.
Alabama had lost six of its previous seven games prior to its Saturday victory over Missouri, 80-73, to improve to 11-16 overall this season and 5-9 in league action. The Tide have been dreadful away from Tuscaloosa, however, as they have lost all nine of their road games and are 0-12 away from home when counting neutral-court contests.
Ole Miss has faded fast from the SEC picture in recent weeks and has all but ruined its chances at an NCAA Tournament at-large bid with four straight losses to fall to 16-11 and 7-7 in the SEC. The Rebels lost to powerhouse Florida on Saturday, 75-71, and while they are 10-5 at home, they've dropped two in a row at Tad Smith Coliseum.
Alabama defeated Ole Miss in Tuscaloosa earlier this month, 67-64 on Feb. 11, to improve its standing in the all-time series to 118-54.
The Tide nearly saw a double-digit second-half advantage disappear in their contest versus Missouri, but after their lead dwindled to just one, they separated themselves from the Tigers thanks to a 14-4 run and they held on for the seven-point triumph. Levi Randolph had a career-night off the bench, shooting 11-of-15 from the field, including 5-of-7 from 3-point range for 33 points. Trevor Releford was also stellar, scoring 18 points to go with six assists and two steals.
Despite its losing record this season, Alabama is still able to slightly outpace its opponents, as it shoots 44.5 percent from the field for 68.3 ppg while allowing 67.9 ppg on 42.9 percent shooting, although it is hindered by poor showings from 3-point range (.333) and the free-throw line (.690). Releford is the unquestioned catalyst with 19.0 ppg and is one of the nation's most efficient shooters from the guard position at 50.8 percent from the field, 40.4 percent from beyond the arc and 88.6 percent at the free-throw line. Retin Obasohan (9.9 ppg), Randolph (8.9 ppg) and Nick Jacobs (8.4 ppg) bring modest contributions to the table.
The Rebels gave Florida all they could handle their last time out, as they battled through nine ties and 14 lead changes, but they ultimately couldn't hold on down the stretch as they suffered the four-point defeat. They shot a solid 45 percent from the field but were less than stellar from long range (8- of-25) and had minimal chances at the foul line (9-of-11). Marshall Henderson was only 7-of-20 from the field but still finished with a game-high 22 points. Jarvis Summers had 20 points on a much more efficient 8-of-12 shooting, while Anthony Perez added 10 points.
On the season, Ole Miss boasts an impressive scoring offense (75.8 ppg) thanks largely to its more than eight 3-pointers per game at 36.3 percent efficiency, but its scoring defense (72.2 ppg) and rebounding margin (-4.0) both rank near the bottom of the SEC. Henderson scores 19.5 ppg, and while his overall field goal percentage is just .368, his 108 3-pointers are third-most in the nation. Summers joins Henderson in the backcourt and has been much more efficient en route to his 17.1 ppg, shooting 49.7 percent from the floor and 47.1 percent from beyond the arc. Aaron Jones isn't much for scoring (6.3 rpg), but he's a mainstay in the frontcourt with 7.0 rpg and 2.2 bpg.
The Rebels have a perfect opportunity to end their slide in this one against an Alabama squad that has shown very little fight on the road this season.
Sports Network Predicted Outcome: Ole Miss 77, Alabama 66


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One of the primary reasons for the attrition of promising therapeutic agents from the drug development pipeline is the observation of treatment-related histologic injury to the kidney in animal toxicology studies. At the same time, the ability to recognize when a therapeutic intervention is damaging the kidneys in humans and to predict when removal of that agent would arrest further deterioration is severely limited. Progress in identifying, evaluating, and qualifying biomarkers of kidney injury would therefore yield great benefits in drug development.
This chapter describes the current state of biomarker use and development in four specific areas: (1) the qualification of new kidney safety biomarkers to bridge the gap between preclinical animal toxicology testing and early human clinical investigations; (2) the flawed gold standard (serum creatinine and blood urea nitrogen [BUN]) that plagues the assessment of new kidney safety biomarkers; (3) collaborations among drug developers, regulatory authorities, funding agencies, and investigators; and (4) the development of in vitro and other screening model systems that could identify lead candidates for drug development. In each of these areas, the major questions that need to be answered and the hurdles that need to be
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OCR for page 29
Assessing and Predicting Kidney Safety1
One of the primary reasons for the attrition of promising therapeutic
agents from the drug development pipeline is the observation of treatment-
related histologic injury to the kidney in animal toxicology studies. At
the same time, the ability to recognize when a therapeutic intervention is
damaging the kidneys in humans and to predict when removal of that agent
would arrest further deterioration is severely limited. Progress in identify-
ing, evaluating, and qualifying biomarkers of kidney injury would therefore
yield great benefits in drug development.
This chapter describes the current state of biomarker use and devel-
opment in four specific areas: (1) the qualification of new kidney safety
biomarkers to bridge the gap between preclinical animal toxicology testing
and early human clinical investigations; (2) the flawed gold standard (serum
creatinine and blood urea nitrogen [BUN]) that plagues the assessment of
new kidney safety biomarkers; (3) collaborations among drug developers,
regulatory authorities, funding agencies, and investigators; and (4) the
development of in vitro and other screening model systems that could
identify lead candidates for drug development. In each of these areas, the
major questions that need to be answered and the hurdles that need to be
1 This chapter is derived from a white paper prepared by Frank D. Sistare, Merck & Co.,
Inc., and Prasad Devarajan, Cincinnati Children's Hospital Medical Center, University of
Cincinnati, with additional input from workshop discussions. Panelists contributing to the
paper were Joseph Bonventre, Harvard Medical School, Brigham and Women's Hospital;
Frank Dieterle, Novartis Pharma; Robert Star, National Institute of Diabetes Digestive and
Kidney Diseases, NIH; and David Warnock, University of Alabama at Birmingham. Melanie
Blank, FDA, participated in the panel.
OCR for page 29
overcome are presented. The chapter then describes a vision for the future
development and use of kidney safety biomarkers in drug development. The
workshop's breakout session on kidney safety biomarkers, summarized at
the end of the chapter, focused on what needs to be done to achieve this
THE CuRRENT STATE
The current state of kidney drug development is characterized by sev-
eral notable deficiencies: a limited ability to screen compounds to predict
kidney toxicities; problems in identifying agents that would result in human
kidney toxicity; difficulties in confirming that in some instances, kidney
toxicities are specific for the tested animal species and are not necessarily
relevant to humans; and a limited ability to monitor kidney damage associ-
ated with drugs that have been approved for use in humans despite their
potential for nephrotoxicity because they provide health benefits or address
unmet medical needs. Current approaches to toxicity testing and decision
making can waste time and resources and may not identify or support
development of the best lead candidates for human use.
The kidney is a major site of drug metabolism and elimination, so
it is not surprising that toxicologic findings are more common in the
kidney than in most other organs. Merck has reported that renal injury
is the second-leading cause of drug attrition, after liver toxicity (Merck,
unpublished findings). Indeed, commercially marketed drugs with known
nephrotoxic potential are contributing factors in at least 25 percent of
acute kidney injury in critically ill humans, causing significant increases in
mortality, morbidity, and health care costs (Pannu and Nadim, 2008).
As noted, the current biomarker gold standard for kidney toxicity is
levels of serum creatinine and BUN. These measures of kidney function are
not sensitive indicators of structural injury, however, in part because of the
excess capacity—or "renal reserve"—of the kidneys (Ferguson et al., 2008;
Parikh and Devarajan, 2008). In the absence of more sensitive biomarkers
to detect acute changes in renal damage, early indications of kidney injury
cannot be monitored without histologic examination.
Histology provides accurate detection of kidney injury in preclinical
animal studies. However, the current standard of care for evaluation of
potentially nephrotoxic agents in human studies does not extend to surveil-
lance with renal biopsies. As a result of this inability to monitor for early
indications of kidney injury in human subjects, the development of com-
pounds found to cause kidney damage in preclinical animal studies may be
suspended, even when the relevance of the findings to humans has not been
established. Drug toxicities seen in animal studies account for more than
30 percent of the attrition of compounds from drug development (Kola and
OCR for page 29
Landis, 2004). It is important to note that adverse findings from one species
in animal toxicology studies are not always seen in other species, and only
40 to 60 percent of such findings are predictive of toxicities in human
trials (Olson et al., 2000; Knight, 2008). Thus, promising compounds are
dropped from the development pipeline even though adverse kidney effects
in humans might not ever occur or might be manageable through monitor-
ing with sensitive biomarker tests.
Qualification of kidney Safety biomarkers
As novel renal biomarkers for clinical use are developed to detect
early indications of nephrotoxicity, more reliance will be placed on these
biomarkers in making critical drug development decisions than is currently
placed on the results of animal studies (which as noted often are not accu-
rately predictive of human toxicity). It may be hoped that this will both
improve the safety of drugs and decrease the need to conduct exhaustive
preclinical studies (Sistare and DeGeorge, 2007).
Novel renal biomarkers may also ultimately play a role as surrogate
markers of drug efficacy. Many companies are working to develop new
drugs for treating diabetes, hypertension, obesity, heart failure, hyper-
lipidemia, and transplant rejection, conditions in which the possibility of
kidney injury is an ever-present risk. Since current biomarkers of kidney
injury and function lack sensitivity and specificity, it is difficult to properly
assess kidney status at baseline or after treatment. New drugs might actually
be ameliorating or slowing the progression of kidney diseases, but without
sensitive and specific measures of clinically meaningful renal injury and/or
function, improvements during treatment of these diseases is extremely dif-
ficult to assess. At this time, improvements in renal function can be assessed
only by conducting large and lengthy clinical trials (using doubling of serum
creatinine as the efficacy endpoint). Once it has been established that novel
renal biomarkers are predictive of future renal morbidity, they will likely be
accepted as surrogate markers of clinically meaningful renal disease and be
relied upon to assess renal benefits during drug development.
Biomarkers have already been developed as surrogates in other areas.
For example, large-scale trials have shown that statins reduce the risk of
adverse cardiovascular outcomes, and the reduction they cause in serum low-
density lipoprotein (LDL) levels is predictive of this effect. LDL cholesterol
is now accepted as a surrogate endpoint for regulatory marketing approval.
But examples of such biomarkers remain rare, and the burden of proof for
marketing approval is high.
Table 4-1 lists several promising translational biomarkers of acute
kidney injury that have been proposed in published studies (Dieterle et al.,
2008; Ferguson et al., 2008; Parikh and Devarajan, 2008). A number of
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TAbLE 4-1 Promising Translational Biomarkers of Acute Kidney Injuries
Urinary or Serum
Biomarker Proposed Structural/Functional Interpretations
Urine Albumin Biomarker for glomerular and tubular epithelium functional change
Urine α-GST Tubular epithelium cell membrane disruption and cytosol leakage
Urine KIM-1 Proximal tubule epithelium dedifferentiation and regenerative repair
Urine NGAL Distal tubule and collecting duct rescue signal to bind deleterious
substances, limit damage, and promote survival and proliferation
Urine TFF3 Decrease in concentration removes cellular maturation signaling,
allowing dedifferentiation
Serum Cystatin C Functional measure of glomerular filtration
Urine Cystatin C Biomarker for glomerular alterations or tubular damage that
interferes with efficient proximal tubular protein reabsorption
Urine Biomarker for glomerular alterations or tubular damage that
β2-Microglobulin interferes with efficient proximal tubular protein reabsorption
Urine Protein Biomarker for glomerular and tubular epithelium functional change
Urine L-FABP Biomarker of anoxia/ischemia signal in tubular epithelium and
potential oxidative damage signal
Urine Clusterin Biomarker for tubular epithelium regenerative repair response
Urine NAG Biomarker for proximal tubule lysosomal enzyme release and
proximal tubular damage
Urine IL-18 Tubular epithelium protein reflecting initiation of apoptotic
Urine GGT Tubular epithelium cell membrane disruption
NOTE: α-GST = glutathione-s-transferase alpha; KIM-1 = kidney injury molecule-1; NGAL =
neutrophil gelatinase associated lipocalin; TFF3 = trefoil factor-3; L-FABP = liver type fatty
acid binding protein; NAG = n-acetyl glucosaminadase; IL-18 = interleukin-18; GGT = gamma
glutamyl transferase.
groups are collaborating to advance understanding of these biomarkers
for specific uses (Box 4-1), some of which involve early drug development.
Many of these biomarkers could contribute unique and specific information
to an overall assessment of the state of kidney function, structural perturba-
tion of the kidneys, and the healing response. A prospectively defined and
systematically collected data set could allow some of these biomarkers to
gain broad acceptance and qualification for monitoring renal safety in early
clinical human registration trials.
Key questions that need to be addressed include the following:
• Qualification of a biomarker as fit-for-purpose for safety monitor-
ing is an antecedent to qualification of that biomarker as fit-for-
purpose for an efficacy outcome. Some biomarkers may be ideally
suited to safety monitoring and early detection of kidney injury but
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Initiatives to Advance Understanding of
Kidney Safety Biomarkers
AKIN: The Acute Kidney Injury Network was formed in 2004 as a multidisciplinary
collaborative network of members representing about 20 key societies in nephrol-
ogy and critical care, with additional experts in adult and pediatric acute kidney
injury. AKIN has promoted the definition of acute kidney injury and has developed
a research agenda to test the AKIN diagnostic and staging criteria for predicting
patient outcomes in clinical settings.
C-Path PSTC NWG: The Critical Path Institute's Predictive Safety Testing Con-
sortium Nephrotoxicity Working Group was formed in 2006. It includes repre-
sentatives of 16 companies working with academic advisors, the FDA, and the
European Medicines Evaluation Agency (EMEA) to establish and qualify trans-
lational bridging biomarkers for use in monitoring drug-induced kidney injury for
regulatory decision-making purposes in both animal toxicology studies and early
clinical trials.
ILSI/HESI Kidney Biomarker Committee: The Kidney Biomarker Committee
of the International Life Sciences Institute/Health and Environmental Sciences
Institute consists of 10 companies collaborating to evaluate promising accessible
biomarkers of drug-induced kidney toxicity in animals.
IMI: The Innovative Medicines Initiative is a European-based public–private
partnership between the pharmaceutical industry, represented by the European
Federation of Pharmaceutical Industries and Associations, and the European Com-
munities, represented by the European Commission. Its goal is to remove research
bottlenecks in the current drug development process. The first round of projects,
which start in 2009, includes one consortium that is investigating mechanisms of
drug-induced hepatotoxicity and nephrotoxicity and defining safety biomarkers in
different animal species, and a second consortium aimed at the clinical qualifica-
tion of safety biomarkers for monitoring drug-induced kidney, liver, and vascular
injury in humans.
Extramural NIH Studies: Examples include the Acute Kidney Injury Natural
History Cohort consortium, the Translational Research Investigating Biomarker
Endpoints in Acute Kidney Injury (TRIBE-AKI) consortium, the University of
labama-Birmingham/University of California-San Diego O'Brien Kidney Research
Core Center, the Chronic Kidney Disease Biomarkers Consortium, and the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Workshop on
Assessment of Kidney Function and Damage. Academic biomarker development
projects include those at Harvard University, the University of Cincinnati, and the
University of Colorado.
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may not be appropriate as surrogate endpoints of clinical efficacy.
Which data are critical for establishing that a specific biomarker is
fit-for-purpose (Wagner et al., 2007)?
• How can existing data sets from animal and human studies be used
most effectively to support qualification of safety biomarkers?
• How can diverse stakeholders best collaborate and set reasonable
expectations and evidentiary standards for fit-for-purpose qualifica-
tion of candidate safety biomarkers and generate any needed new
• How can the decision-making processes be made transparent to all
There are a number of opportunities for answering these questions:
• Biomarkers that appear to outperform changes in serum creatinine
measurements in animal toxicology studies need to be identified, and
a harmonized lexicon needs to be established for histopathology as
the gold standard for these preclinical studies.
• A critical review of published studies needs to be conducted to
identify the most promising new renal biomarkers. If possible,
data from these studies should be collected into a usable shared
• Standardized methodologies need to be used for preclinical and
clinical data collection, sample collection, histopathology interpre-
tation, biomarker measurements, and data interpretation. These
methodologies should reflect the collaborative efforts of experts
and vested stakeholders, including sponsors, investigators, and
regulatory scientists.
• Biomarker studies are needed to better understand such biological
processes as the anatomical region and cell types perturbed in kidney
injuries, the functions perturbed, and the recovery response.
• Tissue sample and biomarker banks need to be created. The use of
both fresh samples and archived, frozen, or formalin-fixed samples
should be optimized to minimize the drain on resources and maxi-
mize the knowledge gained from such studies.
• Prospective outcome-based human clinical trials need to be con-
ducted to assess the relative performance of biomarkers in real time;
the temporal profiles of changes in biomarkers relative to changes
in renal function should be assessed by more traditional methods.
• Collaboration needs to be improved across groups that have
common interests in the development of kidney safety biomarkers
to foster common goals and shared access to critical samples,
assays, data, and funding.
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• Funding needs to be optimized through partnering with NIH.
• Biomarker thresholds need to be established. Normal ranges based
on variance and intervention thresholds need to be determined
based on medical experiences with a variety of study populations.
• The output from diverse work streams needs to be directed to key
regulatory decision and policy makers at the same time that drug
developers are kept fully informed through written communications
and regular meetings that include all interested stakeholders.
• Issues surrounding the commercial development of biomarker assay
panels for use in human and animal studies need to be considered,
including technical and fiscal issues surrounding the identifica-
tion, validation, commercial development, and acceptance of multi-
marker panels.
The Flawed Gold Standard
When comparing the sensitivity and specificity of two or more tests,
it is important to have a standard against which to make the comparison.
Otherwise, one can see only how two measures correlate with one another,
and comparison of the sensitivity and specificity of new biomarkers to cre-
atinine or other more traditional biomarkers of kidney function and injury
in the clinical setting is difficult. For ethical reasons, kidney biopsy—which
would be an ideal standard for assessment of the performance of new
biomarkers when nephrotoxicity is suspected in the clinical setting—is not
possible. Unfortunately, as discussed above, the current gold standard of
serum creatinine and BUN is seriously flawed.
There are several major research opportunities for developing an
improved standard:
• Conduct studies to explore the utility of adjudication committees
or more complex algorithms of renal dysfunction as better gold
standards. Consider the value of incorporating other measure-
ments, such as casts or fractional excretion of sodium, into the gold
• Conduct preclinical studies to explore the best fit between other
laboratory variables (aside from novel renal biomarkers) and histo-
pathology changes.
• Explore through further discussion whether measuring the time
lag between early alterations in biomarkers and subsequent per-
sistent serum creatinine elevations and/or other traditionally used
biomarker changes (perhaps in a patient population with no renal
reserve) might be an adequate way to qualify renal biomarkers for
use in Phase 1 clinical trials.
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• Establish the relationship among novel biomarkers, kidney dam-
age, and serum creatinine by analyzing ongoing studies in which
human biopsy samples are available. Examples include protocol
transplant biopsies and biopsies of patients with hematuria or
proteinuria in whom serum creatinine may still be normal despite
kidney injury as reflected by histopathology.
While the initial focus must necessarily be on safety monitoring, the
ultimate application of these endpoint considerations to efficacy trials
should be kept in mind. To this end, it will be necessary to establish
the relationships between biomarker elevation and appropriate short-,
intermediate-, and long-term clinical outcome measures, such as dialysis,
death, and hospitalization days; repeated hospitalization, infections, or
resource utilization; or progression to chronic kidney disease, end-stage
renal disease, or cardiovascular disease.
Collaborations Among Drug Developers, Regulatory Authorities,
Funding Agencies, and Investigators
Many stakeholders share an interest in defining the appropriate use
of new kidney safety biomarkers. An efficient approach to assessing the
performance of emerging biomarkers, as well as gathering control patient
data on new biomarkers, would be to add such measurements to ongoing
animal and clinical trials. However, there currently are few incentives and
many disincentives to adding measurements from unqualified exploratory
safety biomarkers to such regulated studies (Sistare and DeGeorge, 2008).
Key questions that must be addressed include the following:
• How can regulatory authorities establish and communicate an
official regulatory policy to support the innovative development of
safety biomarkers within the context of product development?
• Can regulatory authorities provide encouragement or support to
advance the evaluation of a declared set of safety biomarkers using
samples from ongoing registration studies?
• Can other, nonregulatory federal agencies provide access to samples
from clinical trial sample sets that would allow a prioritized list of
new safety biomarkers to be developed?
Major opportunities exist for answering these questions:
• Transparent and realistic communications need to occur between
regulatory authorities and drug development scientists.
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• Disincentives under the current drug development framework need
to be removed.
• Issues of patient consent in clinical trials pertaining to testing of
novel biomarkers need to be resolved.
• Exploratory studies and studies of negative controls are needed.
• A role for NIH-sponsored clinical natural history studies and clini-
cal trials in this overall process needs to be identified.
• Roles for public–private partnerships and patient advocacy groups
need to be identified.
• FDA–industry–NIH partnerships for monitoring drug safety and
toxicity and providing broad access to study samples need to be
Development of in vitro and Other Screening Model Systems
In vitro and other screening model systems that could definitively rule
out human kidney toxicity caused by test compounds and identify specific
kidney toxicities in animal test species would be exceedingly helpful in drug
development. Key questions in this area include the following:
• Are such systems viable and close to being established?
• How can their evolution be fostered, and how can they be effi-
ciently validated?
There are several major opportunities for answering these questions:
• Studying the role and limitations of current primary cell cultures
and of embryonic stem cells for assessing new biomarkers.
• Studying the utility of other in vitro model systems of nephrotoxicity
(e.g., in zebrafish).
• Creating partnerships among academia, the pharmaceutical indus-
try, NIH, industry technology providers, and advocacy groups to
explore the advancement of in vitro and other model systems for
early drug toxicity screening.
A vISION OF THE FuTuRE
Table 4-2 summarizes a vision of the future for avoiding and addressing
kidney safety issues in early drug development. The main features of such
a vision are as follows:
• In vitro test systems would be available to predict the risk of kidney
toxicity, including glomerular and tubule cell injury and functional
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TAbLE 4-2 Current Deficiencies, Needs, and Proposals to Address
Kidney Safety Issues in Early Drug Development
Concept Current Needs Future Availability
Improved kidney injury • Qualified biomarkers and • In vitro and other screening
biomarkers and kidney screening test systems for model systems that can
toxicity screening identifying human-relevant predict kidney toxicity,
systems would help kidney toxicities injury, and functional
optimize the selection of • Qualified biomarkers to changes in preclinical and
leading candidates for monitor kidney toxicity in clinical studies
development and animals noninvasively • Expedited resource-sparing
provide for better drug study designs incorporating
development animal readily available
toxicology studies. commercial multiplexed
assays and tissue
biomarkers that report/
predict kidney toxicity in
Biomarkers that enable • Qualified biomarkers of • Translational qualified
early detection and acute kidney toxicity to biomarkers for monitoring
monitoring of toxicity translate from animals to kidney safety in animal
and structural and humans that outperform toxicology studies and
functional changes in currently employed early human clinical trials
humans would enable functional measures • Translational qualified
safety monitoring of • Once safety biomarkers predictive biomarkers for
both early and later have been established, kidney toxicity in humans
phases of clinical drug qualified biomarkers for that outperform currently
development. kidney toxicity in humans employed functional
that can predict clinical measures for safety
outcomes, could be used for monitoring in humans
individual patient dose • Qualified kidney safety
setting, and could be relied biomarkers to demonstrate
on for assessing the efficacy benefits of agents directed
of interventions against other diseases with
• Qualified biomarkers for kidney comorbidities
assessing improvements in
kidney involvement as a
known comorbidity of
underlying disease processes
changes, and to assess whether the toxicity is species-specific or is
relevant to all species, including humans.
• A limited number of rodent and nonrodent model systems would be
available for short-term toxicology testing using a validated, easily
accessible biomarker or multiple biomarkers that might include a
combination of tissue and accessible biomarkers (e.g., genomic,
metabolomic, protein, or imaging biomarkers). These biomarkers
OCR for page 29
would predict dose-dependent acute kidney injury in terms of dys-
function, anatomic alteration, or structural damage.
• Readily available qualified human biomarkers would be avail-
able to diagnose or rule out the involvement of specific anatomic
regions, to assess the severity of an injury, to signal the need
for early intervention, and to monitor the reversibility of injury-
associated processes.
• Sponsors and investigators would be encouraged by regulatory
authorities to demonstrate that a compound lacks the potential
to injure the kidney or that kidney toxicity can be monitored and
managed using qualified safety biomarkers that bridge the gap
between preclinical animal studies and early human clinical trials.
• Qualified predictive biomarkers for kidney toxicity in humans
would be available that would outperform functional measures
currently employed to predict important clinical outcomes and
the efficacy of intervention strategies. These biomarkers would be
defined according to their applicability to patients with chronic
kidney disease, as well as those with no known kidney disease.
• Where kidney involvement is a known comorbidity of disease,
qualified biomarkers would be available to assess the effects of a
drug on kidney processes in Phase II and III trials.
• Qualified biomarkers for kidney injuries would be used to diag-
nose and stage kidney diseases with pathologies related to kidney
HIGHLIGHTS OF THE bREAkOuT DISCuSSION
The breakout group that discussed biomarkers for kidney toxicity
focused on prioritizing what needs to be done to achieve the future vision
outlined above. Participants discussed the most critical obstacles and data
gaps that need to be addressed in the four areas reviewed in the above
section on the current state of renal biomarker development. In the ple-
nary session following the breakout, Prasad Devarajan of the Cincinnati
Children's Hospital Medical Center, University of Cincinnati, presented the
group's main conclusions:
Greater understanding of biomarkers—The group concluded that
new biomarkers should outperform those already available. The
current gold standard for preclinical biomarker discovery is animal
toxicity studies based on histopathology, and the use of that stan-
dard should continue. Also needed are biomarkers that indicate
the anatomic site of kidney injury in animal studies because differ-
ent agents can affect different nephron segments, and biomarkers
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should provide temporally ordered information regarding the stage
of kidney injury. Needed as well is greater understanding of what
biomarker combinations reveal about the stage of kidney injury or
Collection and analysis of data—Mechanisms for accumulating
standardized preclinical data and for sharing and interpreting the
data should be established through rules set by consortia. For
example, assessments of histopathology need to be harmonized
among the many groups working on kidney safety issues. Because
data on long-term clinical outcomes can take many years to
gather, it is important that short-term outcomes—including serum
creatinine, dialysis requirements, and mortality—be correlated with
Correlations with biopsies—Efforts should be made to correlate
human biopsy histopathology with biomarkers. While not all
patients with nephrotoxicity are biopsied, more can be learned from
the biopsies that are being done, such as the protocol kidney trans-
plant biopsies that are frequently performed in many institutions.
Biopsies of patients with blood in the urine and glomerular disease
should be simultaneously correlated with noninvasive biomarkers.
National biorepositories—Standardized national biorepositories need
to be established to enable comparison of biomarkers from ongo-
ing clinical trials. Researchers should have access to de-identified
samples, and it should be possible to share data generated from
these samples. NIH has a public–private partnership office that could
coordinate this cooperation. In addition, a system is needed for shar-
ing clinical data, including data gathered by industry.
Incentives, dialogue, and partnerships—Incentives could be struc-
tured to promote investigations of new safety biomarkers in regu-
lated studies that support new product development. Incentives also
need to be considered for exploratory studies and negative controls.
An open dialogue between industry and regulatory agencies could
identify and refine such incentives. In addition, an FDA–NIH part-
nership could consider funding research on biomarker development
for monitoring drug safety and toxicity, making the FDA a funding
as well as a regulatory agency.
Preclinical model systems—In vitro and other screening models
need to be developed for detecting nephrotoxicity. Clinical and
animal studies are expensive. Cell culture systems have not been
very reliable, but new systems, such as embryonic stem cells and
zebrafish models, are promising, and additional models may
emerge. A partnership between industry and NIH could accelerate
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the development of these in vitro and other systems for detecting a
compound's nephrotoxicity potential.
Dieterle, F., E. Marrer, E. Suzuki, O. Grenet, A. Cordier, and J. Vonderscher. 2008. Monitor-
ing kidney safety in drug development: Emerging technologies and their implications.
Current Opinion in Drug Discovery & Development 11(1):60–71. –71.
Ferguson, M. A., V. S. Vaidya, and J. V. Bonventre. 2008. Biomarkers of nephrotoxic acute
kidney injury. Toxicology 245(3):182–193.
Knight, A. 2008. Systematic reviews of animal experiments demonstrate poor contributions
toward human healthcare. Reviews on Recent Clinical Trials 3(2):89–96. –96.
Kola, I., and J. Landis. 2004. Can the pharmaceutical industry reduce attrition rates? Nature
Reviews. Drug Discovery 3(8):711–715.
Olson, H., G. Betton, D. Robinson, K. Thomas, A. Monro, G. Kolaja, P. Lilly, J. Sanders,
G. Sipes, W. Bracken, M. Dorato, K. Van Deun, P. Smith, B. Berger, and A. Heller. 2000.
Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory
Toxicology and Pharmacology: RTP 32(1):56–67. –67.
Pannu, N., and M. K. Nadim. 2008. An overview of drug-induced acute kidney injury. Critical
Care Medicine 36(Suppl. 4):S216–S223.
Parikh, C. R., and P. Devarajan. 2008. New biomarkers of acute kidney injury. Critical Care
Medicine 36(Suppl. 4):S159–S165.
Sistare, F. D., and J. J. DeGeorge. 2007. Preclinical predictors of clinical safety: Opportunities
for improvement. Clinical Pharmacology and Therapeutics 82(2):210–214. –214.
Sistare, F. D., and J. J. DeGeorge. 2008. Applications of toxicogenomics to nonclinical
drug development: Regulatory science considerations. Methods in Molecular Biology
Wagner, J. A., S. A. Williams, and C. J. Webster. 2007. Biomarkers and surrogate endpoints for
fit-for-purpose development and regulatory evaluation of new drugs. Clinical Pharmacol-
ogy and Therapeutics 81:104–107.


text: I never wanted to do this mod because I was non fond of cutting a factory wire! So I figured out a way to do it without cutting it. Actually two ways. First way remove grey wire from the modular plug then I found a modular plug in the same area not in use I think its for the factory security system. So I removed one of the wires from the unused modular plug and cut it back 6 in. Then inserted it were I removed the grey wire from the 4wd mod plug and put a ring terminal on other end. When I reinstalled the 4wd control box I just put the ring terminal under the bolt for ground perfect and neat! Second way is remove grey wire from modular plug put shrink tube over end to protect. Now open the black 4wd control box and slide out circuit board (very easy to do) Now on the back of the plug on the circuit board on the bottom row of metal strips from plug solder a jumper to connect the two middle ones. One is from the grey wire the other is a ground. this is a very neat and professional way to do it! My only word of caution is taking the wires out of the modular plugs is a BITCH.


text:
Anand Jon Alexander Sentenced to 59 Years in Prison
The judge said he showed "no remorse" for sexually assaulting a bevy of aspiring models.
READ MORE »The judge said he showed "no remorse" for sexually assaulting a bevy of aspiring models.
READ MORE »Also the final tulle gowns at Dior couture yesterday required two ushers to get the models through doorways.
READ MORE »The maximum sentence is life in prison.
READ MORE »Counting Crows lead singer Adam Durtiz laments the fact that he's 43, single, and sits home a lot. Alan Greenspan is worried about the economy, but he can't be that worried: He celebrated his 82nd birthday the other night with a pricey dinner at Le Perigord. Jimmy Kimmel says he bought his ex-wife an engagement ring from Costco. Bill Clinton says his favorite movie of the year was Michael Clayton, but that he hasn't seen There Will Be Blood. Defense attorney Mickey Sherman says he uses Otter's "It's the system's fault!" speech from Animal House to justify defending shady clients. Tina Fey thinks she's funnier than Jon Stewart.
READ MORE »Alexander McQueen shows in New York, Banana Republic goes green, and Paris Hilton's accessories send Lindsay Lohan into a tizzy.
READ MORE »Earlier this year, New York designer Anand Jon was slapped with 32 criminal charges, including sexual battery and committing a lewd act on a child. Yesterday a Los Angeles court revealed that Jon was indicted with a whopping 54 felony counts (and five misdemeanors). He's now accused of sexually assaulting twenty teenage girls, and the charges include "forcible rape, sexual battery by restraint, lewd acts upon a child, sexual penetration by a foreign object, using a minor for sex acts, forcible and attempted forcible oral copulation, assault with intent to commit a felony, possession or control of child pornography and contributing to the delinquency of a minor." Which is, you know, an epic amount of evilness. His lawyer says the case is "made up out of whole cloth" (ooh, a fashion metaphor — appropriate and tasteful), but Jon is also under investigation in New York. If you're not familiar with his design work, check out his Website AnandJon.com. As Defamer points out, you'll quickly see that the only thing left out of his charges are extensive crimes against taste. Grand Jury Indicts Celeb Designer On Sexual Assault Charges [KNBC] READ MORE »
Designer Anand Jon, who's charged with multiple counts of sexual assault, is a publicity whore and total creep. Among the dogs in Lindsay Lohan's life right now are a Yorkie, a Jack Russell, and Jude Law. Uma Thurman and André Balazs officially broke up yesterday. Nicole Richie collapsed on the set of The Simple Life in Malibu. A woman once died in Jay McInerney's bed. The Jewish Theater of New York wants the Times to fire drama editor Rick Lyman for allegedly passing on reviewing Last Jew in Europe because of pressure from the Polish government. NY1 political anchor Dominic Carter wrote a book about his hard-knock childhood. Country-music star Merle Haggard backs Hillary Clinton for president but is not ready to fully commit to her. Florida advertising mogul Jordan Zimmerman is backing Mitt Romney for president. Two more top editors from Life & Style quit.
READ MORE »After eight days, 26 shows, and a handful of parties, we are reduced to a sputtering heap (not unlike that Zac Posen dress) on the floor of Newark Airport. Time to recall our favorite moments.


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*Sonlight Core 6, World History Part 1, Instructors Guide by John & Sarita Holzmann, 2005, Excellent condition, with Sonlight binder & Sonlight tab dividers. New $64.00 for curriculum; $19.99 for binder & dividers; Asking $50.00 for IG; binder & tab dividers Asking $10.00 Readers Core 6 In very good condition with no writing. Non-smoking home. Payment by Paypal only; postage is extra. Please respond directly by email and include zip code for calculating postage. Thank you.


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ORLANDO, Fla. -- Half of CEOs and business executives want better delivery from IT, yet only 10% of CIOs think they have an execution problem.
That's what Gartner Inc. analysts told the thousands of CIOs and managers at its Symposium/ITxpo here this week, highlighting the disconnect between what end users want and what IT delivers.
"[Business leaders] don't think they can get what they need from existing IT leaders, so new IT leadership roles are being created," said Peter Sondergaard, senior vice president of research at Gartner, during his presentation here this week.
Chief digital officer positions are popping up as companies try to understand the data-driven market, and chief marketing technologist jobs have been created in 70% of companies, according to Gartner.
These new chief digital officer positions won't be permanent, however.
"They are mainly change agents, and by 2020, they will be obsolete because their mission of digitalization will be complete," Sondergaard said.
By then, IT people in general will be responsible for digital technology architecture, cyber security and risk, information architecture, industrialized IT infrastructure and most importantly, digital leadership, he said.
The IT jobs website
Continue Reading This Article
Enjoy this article as well as all of our content, including E-Guides, news, tips and more.
The top five IT skills that are in demand today, with more than 1,000 postings on Dice.com, are jobs around big data (up 94% year over year), cyber security (up 59%), JIRA (up 53%), Hadoop (up 47%) and customer relationship management (up 45%).
IT careers evolve on cloud, mobility
IT job roles have shifted, due largely to cloud computing, in positive and negative ways. One IT manager here at the ITxpo who works for a global company said that since moving some of their operations to cloud service providers, a significant number of IT positions have been eliminated.
But those who transition to a cloud career cash in, particularly for those with OpenStack skills or Amazon Web Services experience.
DevOps is another area that Dice expects to gain significance in the future as more companies adopt cloud technologies, a Dice spokesperson said.
Meanwhile, other IT job roles are changing as companies focus on mobilizing existing infrastructure and determine how to handle bring-your-own-device management issues.
One ITxpo attendee, a director of IT for a management company based in Los Angeles, said his team's main challenge is to mobilize its website and create a way of providing services to customers using tablets. Then, they must develop mobile applications.
Both mobile and cloud initiatives demand software developers, albeit for new types of platforms.
Indeed, software developers will continue to be the key to success, said Google Executive Chairman Eric Schmidt during his public interview with Gartner analysts here.
"Almost every business can be made more efficient by adding software programmers," Schmidt said. "Any [company] that doesn't have software people will be lagging [behind] others."


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Interesting point. But did not realise the UK leaving the EU was a particulary likely outcome in the same way as scottish independance not likely. Have not looked at stats on the polls or gamling odds on UK leaving the EU so maybe missing something.
Outside some in conersvative party and ukip not sure if a pressing urge to leave the EU is real issue that most people have. Although of course depends what way the properganda machine swings as one of those things that indeference could make a lot of swing voters. So may be is a real possibly.
Waste in EU corruption etc as in all government be it westminster scottish or local council. Some popular stores about EU law, not sure about the insurance changes. Things such as human rights homersexual in armed forces, BA air hostess right to wear cross to work ( dont know what BA were playing at irrespective of the law)or even voting in prisons at least in prinple makes sense in my view.
For a party in westminster can see why they may wish to have no superiour in a sense, but this could be the same scottish government or indeed could problery find it in a council if looked for it.
How would united states view be on this, (may say why does matter) but if dont want to be part of EU,would reliee on more united states organizations from bail out, to poltical power, defense. Not sure there is a vaceney for the 52 state as may be better for uk being in EU for american eu matters.
Think the eu thing in a sense one of the silly things in converstive party that is pushed beyond any imdiate concern. Get a silly things in all parties. May be some good aguments to leave as stay but would have though more imdiate matters than a frizlous in short term concern over EU.
IN HIS Daily Telegraph column today, Fraser Nelson makes an interesting point:
If an in-or-out referendum is made conditional on a 2015 Tory majority, the nervous Eurocrats will be able to breath easily. Mr Cameron may as well make his referendum dependent on Scotland voting "yes" in an independence referendum, Nick Clegg being ejected as Liberal Democrat leader by Christmas or the new royal baby being a blonde.
Perhaps I don't know enough about Scottish politics, but would it really be so outrageous if David Cameron made his offer of a referendum dependent on Scotland voting 'yes' in its independence referendum?
After all, Europe is popular there. Scotland's Parliament is dominated by two strongly pro-European parties: Labour and the Scottish National Party. In Westminster, there is only one Scottish Conservative MP, David Mundell. The SNP is currently being torn up by a debate about whether or not an independent Scotland would automatically be granted membership of the EU.
If Scotland votes 'no' to independence in 2014 (as seems extremely likely), then it votes to stay in the United Kingdom—and with it, the European Union. So what happens if, a few years later, English votes carry a 'yes' vote for Britain to leave the European Union, but a majority of Scots vote to stay in? Won't they feel rather hard done by? What does it mean for devolution, given that Scotland is expected to be given more powers regardless of how it votes in 2014?
No doubt lots of people will argue that by voting to stay in the UK, the Scots would commit themselves to whatever the (mostly English) majority wants to do. But everyone assumes that Scotland will get more devolved powers after 2014—and so more say over domestic policy. In that context, the possibility of Scotland being forced to give up the perks of EU membership by English voters seems very odd indeed.


text:
Results tagged ' White Sox '
The 2013 Angels, or how I Learned to Stop Worrying and Accept that Buttercup Might Be the Name of the Season
To paraphrase Lou Brown, easily one of the best fictional baseball coaches ever to grace the cinematic Majors: OK, we won a game Saturday. And we won Sunday. That's called "two in a row". And if we win again tomorrow, that's called a "winning streak." It has happened before!
Now, clearly, quoting the infinitely quotable Major League in reference to the 2013 Angels is hardly an original thought and I'm not even the first to sling this particular gem around this week. However, I would dearly love to be one of the last because, much like Lou Brown in his follow up comments to this bit of awesomeness, I would like to believe that the Angels are heating up. Really, I would. But this season?? Always there is the Big B…what a Buttercup!
Let me 'splain (and, you know, see if I can throw in any more random movie references from the depths of my crazed brain while I'm at it!). Towards the end of the sad, sad debacle that was Wednesday night's pitching implosion, abandon all hope…no, no, wait, here comes the Angels offense!…Nope, just kidding, more LOBsters than a large seafood chain could handle…Waaaaaiiiit, just kidding again, check out that offense!!…*facepalm* Nevermind, more LOBsters…emotional whiplash of a game, I tweeted, 'This is such a buttercup game. And the Angels have just buttercupped all over the buttercupping thing. Blah.' And, you know what? Even though the Angels have a proto-winning streak going on here – potentially their third of the season, talk about *facepalm*! – that sentiment actually sums up the whole season so far for me. Because, yes, I was in part being cute and trying to interject some much needed levity into the situation by using the name of the Angels' much hated – at least by, let's call it, all fans in their right mind; the rest of you are highly suspect – 7th inning stretch ditty as a stand in for the long, drawn out f-bomb that most of us were feeling at that point. However, my word choice meant so much more as well. Let us review the lyrics of the song, shall we?:
Why do you build me up (build me up) Buttercup, baby Just to let me down (let me down) and mess me around And then worst of all (worst of all) you never call, baby When you say you will (say you will) but I love you still I need you (I need you) more than anyone, darlin' You know that I have from the start So build me up (build me up) Buttercup, don't break my heartForget all of the perfectly rational, 'who in the hell thought that this song would be an appropriate rooting-for-the-home-team-at-a-sporting-event song and would they please turn their marketing card in…right now!' thoughts you're having at this moment because, sadly, this season they're beside the point. Thus far the 2013 Angels are the Buttercup Angels — always building us up, just to let us down again for another inning, another game, another streak, of the 'you don't want one' kind. Offense starts coming back. Starting pitching blows a herd of goats. Starting pitching gets it done. Offense goes to sleep and/or the Angels bullpen decides to go all "flashback" on us and turns Arson Squad. Sweep the Tigers. Lose the next 5 – yes, count them, 5! – series. And so on, and so forth. So this proto-streak? I want it to be the real thing. Dear God I want it to be the real thing and the start of something great, but I just…I just don't know.
But if you're about to throw the B word at me, you just zip your lip right there. There is no bandwagon. There never was. Seth and I are bleeding red fans who have nothing to jump off of. We love this team, even if this season, like oh so many in the not so distant past, it's a heavily frustrated, profanity laced, shouting kind of love. We're still watching every game we can on TV. We're still buying tickets to the Big A though, being less excited, we'll probably attend closer to 15 games than our customary 20 – 25. It's just the focus that has shifted. In another tweet this week, I confessed to fellow Angels fans that, even though it makes me feel like a bad fan, at this point I'm just hoping for the team to straighten up enough that they're at least fun to watch play again…you know *cue hope and optimism yet again* like the last two games were! Anything more than that seems so farfetched that I just can't bring my brain to contemplate it without the Angels themselves providing significantly more incentive. But the minute they do? (And, so help me, I can feel it starting already.) Well, I'll let them build me up once more, praying the whole way that, this time? This time it's real, and they don't let me down…again.
A Little Morning Before the Game Levity: Trout Heads and Angels Wins
Oh, please excuse me. Just indulging in a bit of morning-before-the-game-after-an-off-day-and-Angels-moved-another-half-game-closer-to-a-wild-card-berth levity over here, with apologies to Barnes & Barnes and, of course, Dr. Demento.
Ah the Trout heads, as fans and various Angels vendors affectionately refer to these goofy, bright red, fish shaped, nerf weapon of a piece of head gear if I ever saw one, hats. So disturbingly silly they're absolutely awesome, am I right? Of course I am. Look, even Angels players know how great these things are:
Basically, the way I see it, these hats are but one more strong testament to the unbelievable power of Mike Trout. Don't buy it? Look, Southern Californians simply do not wear stupid hats. Not for team spirit. Not for unity. Not for nothing, unless they're Mickey Mouse ears or, apparently, Trout heads. See that? No stats or proof of increased game attendance needed. Simply put, Angels fans are awesome and Mike Trout is bigger than Mickey Mouse. :)
…and all of this – the photos, the parody, the silliness – because the Angels successfully completed their sweep of the White Sox, the A's lost to Texas last night while the O's moved no further ahead in the standings, and I am getting so excited for this next series I can barely contain myself! Thank you for indulging me in my silliness, dear reader. We now return you to your regularly scheduled MLBlogs programming.
This post was brought to you by letters S, G and K, the number 27 and the zany stir craziness an off day this late in the season has been shown to produce in lab animals and the occasional friendly neighborhood Angels blogger.
The Crack of the Bat! The Slap of the Glove! The Long Uncomfortable Silence of the Error?
Okay, so it's only Spring Training. The sights and sounds of the game are never going to be the same in Spring Training as they are when the real deal begins. Still, after so many long days without, they sound pretty darned musical to me. So, after two entire Angels games, one of which only aired on the radio and one we watched this evening via that faithful friend of the working stiff, the DVR, I have a few thoughts.
It's only Spring Training. And believe you me, if it were going badly I would absolutely be emphasizing how much Spring Training games don't really mean anything, a fact I don't forget just because things are going well. However, it makes me really happy to see:
- Albert Pujols and that gorgeous swing looking good from the first at bat.
- C.J. Wilson looking like he's in season shape already or pretty darn close to it.
- The regular infielders doing their regular season thing in the field and at the plate.
- One possible incarnation of the outfield doing their regular season thing in the field and at the plate.
- Alberto Callaspo belting the ball and playing his position with an "Ahem. I'm still here!" swagger and chip on his shoulder.
- Angels infielders turning two in March with a decidedly May kind of ease and precision. Have you ever noticed that the sound of the ball slapping the glove during a solid 6-4-3 or 4-6-3 is just a little different than it sounds during any other play? Three fast, solid thunks in precisely measured succession. It's a lovely sound!
- Power from the catcher's position!! Yeah, yeah, yeah. Spring Training ball parks. Blah, blah, blah. I don't care. I have now seen current Angels catchers look like they actually know what they are doing in the batter's box in two back to back games. And after last season? Yeah, that's a big deal.
- Angels ball players looking relaxed, rejuvenated, and very at ease with one another…until they start talking about the coming season and then there is a fire in their eyes. Love that!
Meh. It's only Spring Training:
- Oh my word, the errors. With every team, in every game. Balls zinging out of gloves. Sailing lazily past gloves. Dropping softly at the outfielders' feet… Throws going into the outfield. The backstop. The dugout. The stands… And some of the pitching and hitting? Ugh. Yes, this is why we have Spring Training but it is also why Spring Training will never be as good as the regular season.
- I'm not particularly impressed with most of the Angels kids so far. Not last season's rookies or Mike Trout who spent a fair bit of time in the Bigs last year. I think my appreciation of their efforts and the breath of fresh air they bring has been thoroughly documented on these virtual pages. No, I mean the younger prospects. I really like Alexi Amarista whose gutsy, athletic, maximum effort style of play in a diminutive package reminds a bit of Dustin Pedroia. And I like Andrew Romine who has demonstrated great instincts and a gift for pulling plays out of thin air in the past. Other than that, I don't see anything that impressive yet…of course, I wasn't that impressed with Tyler Chatwood last Spring Training, so I can't claim to have the best eye for the subtle nuances of a rookie-to-be's performance.
- The usual: No one stays in the game for very long, even when they're doing well. Small stadiums make for quiet games. Even the announcers…heck, even the sound and picture quality seem to be in training right along with the players.
We got to watch baseball. Real, current – if not precisely live – baseball over dinner for four days running now. And this evening my husband looked from the game to me with a very contented smile, all of the strain of the day gone from his face, and sighed. This is a nice evening, he said. It's great to have the back game on. I couldn't agree more…and that part needs no Spring Training specific header. That part is universal.
Keep Him In Coach. We Need Him to Play.
Hel-lo gor-geous bats! Where have you been all my season? Well, looking at the stats for the last few games, they've been in AA Arkansas with Mike Trout. Check this out:
The Angels have played ten games since Mike Trout was recalled from the minors and in that time they are 5 and 0 in games where Trout has started and 2 and 3 in games where Trout did not play or entered the game as a pinch hitter in the 8th inning. And one of those losses? That would be Friday night against Texas. Upon entering the game in the 8th inning, Trout continued a rally begun by Howie Kendrick. His hit moved Howie into position to score on Mark Trumbo's line drive single and set the stage for Russell Branyan's three run homer. Imagine what could have been if Trout had started the game?
No, I'm not saying Mike Trout is the chosen one, a one man offense here to single handedly save the Angels. But I do think he is proving himself to be the missing spark this team needs. It's not that the Angels don't have any bats, it's that we don't have enough bats and that there are far too many dead spots, all but guaranteed outs, dotted through the lineup in between them. How many times have we watched a mini rally start only to die without a single man scoring? Or bases loaded with one out turning into one measly run followed by someone grounding into a double play? This happens to every team, but it happens to the Angels so often that we've grown to expect it every inning this season. How excited do we Angels fans get when the team scores just four runs? 'Nuff said.
But what if we had just one more clutch bat in between our existing bats, someone to keep the offensive outburst going once Macier or Bourjos or Howie starts it? Someone to knock Torii Hunter in when he gets on base? Heck, just one more guy not grounding into an inning ending double play? Well, we'd have our sweep of the Orioles, or last night, or our win against Texas on Saturday, or what Friday night against Texas very easily could have been if we'd had just one more clutch bat in the game a few innings earlier.
Yes, Mike Trout is young, not even a month past 20. But he doesn't seem overwhelmed in the slightest. In addition to his bat makes good decisions in the outfield, has a fantastic glove, runs great routes for the ball and, with his speed, is a perfect complement to Peter Bourjos in the outfield and a terror on the base paths. And the frightening part is, he's still growing into his skill set and showing a lot of improvement, even just since his last trip up to the majors. His arm looks a little stronger and then there's that bat! Trout returned to the majors with a .163 batting average – hey, he only played in a handful of games on either side of the All-Star Break and, like a lot of rookies, it took him a few at bats first to connect and then to stop hitting it right at people. After five additional full games in the majors and two single at-bat pinch hit appearances, Trout has dramatically increased his batting average to .246. Between that and two homeruns and five RBIs last night, making Trout the youngest Angel to have a two-homerun game, I think it's safe to say he is no longer overly impressed by Major League pitching. What do you think?
So, this post was originally going to be a plea to Mike Scioscia to put Mike Trout back in the lineup tonight. Because, of course, he reads this blog and takes my opinions into careful consideration before making lineup decisions, why do you ask? ;) But, much to my delight, they just posted the lineup and Trout is already there!!! And suddenly I am even more excited for this game. Go Angels!!
So, I was wondering instead…Sosh, pretty please, with zesty homemade marinara sauce and good imported parmesan on top, can we keep him in the lineup now??? He'll be the offense's new best fri-end. Thanks, ever so!
– An Angels Fan on the Edge of Her Seat
Angels: Not the Series I Had in Mind…Again
You all know the feeling. You have a really long day at work (or school), or even an outright bad day. You come home and all you want to do is relax in front of a good game, preferably cuddled up with your honey, and cheer. But, alas, this time it's not a good game. And somehow the day is just that much more deflating for it. This has been the story of my last week and change.
I am in the final stages of a huge project and I've been working 12 hour days during the week and eight to ten hour days on the weekend to get it done. It's a great project and I am thrilled to be involved but these have been long days, days in which I hoped to help the the last few hours of work (or, you know, the first few hours of the weekends work) feel less like work by completing them in front of a good game. Instead, I got last week's not-the-series-we-wanted-it-to-be against the White Sox, followed by the weekend's not-the-series-we-wanted-it-to-be against the Rangers and then this latest mini really-not-the-series-we-wanted-it-to-be against the A's. Sure there were a few high points, but they were buried in a mound of blah. And it just didn't pay to be an Angels starter this weekend. Come on Angels, haven't you considered my needs in all of this? ;)
This evening, as you might have inferred from the score, was especially terrible. Shut out 14 – 0. Ouch. The Angels had no pitching. No bats. And I swear someone rubbed butter in a few of the gloves just to see what would happen. MST3K-ing our way through Transformers II this Saturday? An excellent strategy for turning a bad, bad movie into a really fun evening and a nostalgic nod to the bad movie Fridays of our college years. MST3K-ing our way through an Angels game, on the other hand? That's a last resort coping mechanism I would prefer not to employ again. But, desperate times, my friends. Desperate times.
…First, a brief digression for the sake of the uninitiated:
MST3K (n) – Mystery Science Theatre 3000. a cult American comedy series featuring a human and his robot sidekicks living on a space station, forced by an evil scientist to watch a series of bad Sci-Fi C and D movies for research. The audience watches the so-bad-it's-laughable movie with the series characters, who are depicted as silhouettes at the bottom of the screen and provide a hilarious running narrative to that episode's feature.
MST3K (v) – the act of improving any less than desirable spectacle by providing your own snarky, ideally hilarious, running commentary to the events in question. MST3K-ing is best when indulged in by a moderate sized group of quick wits, though it only outright requires two.
And now we return you to your originally scheduled MLBlogs programming…
So, my question for the team (Of course, they read this blog and take my comments very seriously. Why do you ask? ;) ) is this. Are you done now? With the botched plays, the WTF base running, the broken clutch at the plate, the wasted great starts, the self-destructing bullpen and all of the unnecessary "excitement" between outs two and three? Every team has off games and every team experiences minor slumps over the course of the season. So, are you done with that now? Are you ready to put it all behind you and play great baseball again? This season you have already shown that you can hit, you have great gloves and boy can you pitch and, this last week notwithstanding, all in the same game even. I love you guys like crazy and will keep watching no matter what you do, but I think we'd all have a lot more fun if you wrapped up this slumping thing and moved on from it like I know you can…oh, and someone give Jordan Walden a hug please, because boy did he look like he needed one after Monday night's game.
* * * * *
So, about Kendrys Morales. He got a second opinion on the broken ankle. He will have additional surgery soon and be out for the rest of the season. And my reaction? I'm thrilled. Yes, you read that right. Between the plateau, the setbacks and the pain he it sounds like he was continuing to experience, I had serious concerns about scar tissue and his ability to return to playing in any kind of good condition. I want Kendrys back and playing now as much as anyone, but I want him to have a career playing like he used to even more. I would rather do without him for the rest of the season, than bring him back too early and risk killing his career.


text:
polka dots white and black jeans
, motelrocks.com/shop/product…, in Motel Polka Dot Denim Pants
Men used to rule the world.
Women weren't allowed to wear pants in public. Women couldn't vote.
So many things changed in so little time.
Although my society remains non-100%-equal, women are more and more powerful each day!
This outfit reminds me of that power!
How we can do the same things as men, and sometimes even better!
We're smart, beautiful and sensitive! Nobody can hold us down!
Kiss kiss


text:
Using group-based interaction to change stereotypes about people with mental disorders
Gee, A., Khalaf, A. and McGarty, C. (2007) Using group-based interaction to change stereotypes about people with mental disorders. Australian Psychologist, 42 (2). pp. 98-105.
*Subscription may be required
A large body of research has examined intervention methods designed to improve attitudes towards people with mental disorders, in particular education, contact and protest. After a short review of these interventions, this paper provides a brief introduction to a new intervention that involves group-based discussion to strengthen commitment to the aims of the mental health advocacy movement. Research to date demonstrates it produces significant and lasting positive change in attitudes and willingness to participate in future action to promote the aims. Ongoing research examines the required conditions for the intervention and explores its potential to develop a cooperative community in which more members of the community, professionals and people with mental disorders work together to achieve common goals in reducing stigma.
Publication Type: | Journal Article |
Murdoch Affiliation: | School of Psychology |
Publisher: | Taylor and Francis |
Copyright: | Australian Psychological Society |
URI: | http://researchrepository.murdoch.edu.au/id/eprint/3149 |
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text:
Credits & Info
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- 4.80 / 5.00
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- 07/28/2012
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- Illustration
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- 902 x 1221 px
- 579.5 kb
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- propaganda
- ww2
- rockwell
- area21
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Author Comments
a WIP for a upcoming poster in Area 21 (possibly) - Not done with it, still needs text, some tidying, and equipment needs to be finished. just wanted to share for some advice.
(EDIT: redid some things advised by some friends on the forum! thanks guys!)
(EDIT: Added the Text that will go in place, the words may change, but the placement is the same. Itss still a WIP, almost completed though!)


text:
quick shipping, great communication, thanks :)
great price, love the jeans! thanks again.
fast payment, great communication + very positive attitude!
see you around :)
thanks :)
quick payment, easy transaction! thanks.
thanks! prompt payment!
thanks again :)
very understanding! infinite amount of patience. thank you so much!
would definately work with again :) excellent HF member!
local pickup, really nice girl! excellent communication :) thanks!!
looking forward to future transactions with you :)


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Alternating cerebral hemispheric activity and the lateralization of autonomic nervous function. | |
MedLine Citation:
PMID: 6874437 Owner: NLM Status: MEDLINE |
Alternating dominance of cerebral hemispheric activity was demonstrated in humans by use of the electroencephalogram (EEG). Relative changes of electrocortical activity have a direct correlation with changes in the relative nostril dominance, the so-called nasal cycle. The nasal cycle is a phenomenon where efficiency of breathing alternates predominantly through right or left nostril with a periodicity ranging from 25 to greater than 200 minutes. Relatively greater integrated EEG value in one hemisphere correlates with predominant airflow in the contralateral nostril, defining a new interrelationship between cerebral dominance and peripheral autonomic nervous function. |
D A Werntz; R G Bickford; F E Bloom; D S Shannahoff-Khalsa |
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Publication Detail:
Type: Journal Article |
Journal Detail:
Title: Human neurobiology Volume: 2 ISSN: 0721-9075 ISO Abbreviation: Hum Neurobiol Publication Date: 1983 |
Date Detail:
Created Date: 1983-09-23 Completed Date: 1983-09-23 Revised Date: 2004-11-17 |
Medline Journal Info:
Nlm Unique ID: 8211530 Medline TA: Hum Neurobiol Country: GERMANY, WEST |
Other Details:
Languages: eng Pagination: 39-43 Citation Subset: IM |
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MeSH Terms | |
Adult Autonomic Nervous System / physiology* Cerebral Cortex / physiology* Dominance, Cerebral / physiology* Electroencephalography Female Humans Male Nasal Cavity / innervation Pulmonary Ventilation Respiration |
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Hominid [Box-Killa]
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- 05/27/2009
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- 2.61 / 5.00
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Pico - The After Years 2 by AsthmaticHamster
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EDIT: This is one of my older songs. The mastering is very poor and there is much clipping and ear breaking loudness. I would edit it but I accidentally deleted the Fruity loops file. I would delete it but it is too awesome :D
This would be a nice song to remix, especially so you could make it sound very nice :D
Best listened on speakers!
Hey Yall! This is my mega song inspired by the game made by behemoth. It has a pretty cool vibe, hope you like it. Oh and by the way, this will be my final song for this month since I've got exams :D Oh joy. Anyway, have fun!
Edit: Ok i got rid of the clipping with the effects, ( I think), added some punch and stomach to the bass to make it sound whole. Post grained the guitar, equed the dums, and reverb to the drums, tried to kill some clipping.
Lol i probably just made more problems, meh.
Rated 5 / 5 stars
i like it
damn that guitar is waaay to loud. Im an idiot lol
Rated 4.5 / 5 stars
It's been a while since I've liked a tech song.
A real drum beat on techno :O
Interesting, and amazing, great job.
I like how much it changes as to never bore me,
real epic win at 1:05 With the guitar>
hehe yeah I thought i'd make something anti-repeditive for a change lol. Thx for the review lol :D
oh yeah and most of my songs are alternate techno lol


text:
Dhulkhed, M H (1981) Occurrence of small sized seer fishes S. Guttatus and S. Commerson at Karwar (Karnataka). Marine Fisheries Information Service, Technical and Extension Series, 33 . pp. 18-19.
| PDF 544Kb |
Small sized s. Guttatus and s. Commerson were obsereved at karwar.they could be identified based on some external features. The second dorsal fin in s. Commerson is tinged as brightly yellow as its caudal fin, whereas in the other species it is lacking. In s. Guttatus the teeth on the lower half of the jaw are of villiform type and are more in numbers whereas in the other there are 6-7 prominent teeth pointing backward
Item Type: | Article |
Uncontrolled Keywords: | S. Guttatus; s. Commerson; Karwar; fin; caudal fin; villiform; |
Subjects: | Marine Fisheries > Marine Fishing Demersal Fishes > Seerfishes |
Divisions: | CMFRI-Cochin > Marine Capture |
ID Code: | 3011 |
Deposited By: | INVALID USER |
Deposited On: | 23 Sep 2010 10:49 |
Last Modified: | 23 Sep 2010 10:49 |
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