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Label-free: The way to be?
February 2011
As advances continue to be made in screening technologies, the use of labels in traditional drug discovery screening assays has been criticized as producing undesirable and unanticipated interactions that can compromise screening data and lead to false conclusions. Critics also argue that labeled technologies typically require the use of genetically modified cell lines that can alter cellular behavior.
Label-free detection, on the other hand, is proving to be a highly sensitive method of measurement for endogenous targets in live cell assays, and eliminates the need for tags, dyes or specialized reagents or engineered cellsreducing the resources required for assay development, simplifying assay design, minimizing liabilities created by the use of labels and enabling the use of native cells for greater biological relevance.
In the last year, ddn has reported on many business developments in the label-free technology market. In December 2009, we reported that Caliper Life Sciences entered into an agreement with SRU Biosystems to use its label-free BIND technology to offer new functional assays as part of its discovery alliances and services. The same month, we also reported that Corning Inc. and PerkinElmer Inc. partnered to combine the companies' expertise in optical label-free and multimodality detection in an effort to advance the development of next-generation label-free technologies. In April 2010, we reported that ForteBio chose Tecan as its preferred automation partner for real-time, label-free assays to support bioprocess and drug discovery workflows. In November 2010, we brought you the news that ACEA Biosciences Inc. and Vivo Biosciences Inc. agreed to work together to develop label-free and real-time cell-based assays for the xCELLigence System, which is co-developed by Roche and ACEA and marketed by Roche Applied Science. And most recently, last month, we reported that Activiomics and Belgian biopharma UCB will apply Activiomics' Targeted In-depth Quantification of cell Signaling (TIQUAS) phospho-proteomics platforma system that is quantitative, label-free and applicable to cell and tissue samplesin a collaborative effort to elucidate signaling mechanisms of therapeutic antibodies in relevant cell-based systems.
Label-free technologies enable drug discovery researchers to monitor a wide array of target types that play a role in the study of diseases such as diabetes, obesity, cancer, inflammation, neuromuscular disorders, pathological pain and psychiatric disorders. The technology has been shown to be applicable to all major classes of drug targets, including GPCRs, kinases, enzymes, ion channels, and protein-protein and protein-ligand interactions, enabling broader research applicability.
However, as these technologies are new and still in their infancy, they are not without challenges and limitations. ddn recently reached out to several companies that are blazing the label-free trail to discover how these technologies are being used, where they are most beneficial and where this market may be headed.
Sharing their views on label-free technologies are: Christopher M. Silva, vice president of marketing at ForteBio Inc.; Dr. Achim von Leoprechting, vice president of imaging and detection technologies at PerkinElmer Inc.; and Philippe Mourere, head of sales, marketing and business development for Caliper Discovery Alliances & Services (CDAS).
ddn: What applications do label-free technologies make possible that are either impossible with current technologies, or so impractical as to have made them unapproachable without label-free technology?
Silva: Measurement of real-time rate constants for the binding of two biomolecules, such as proteins, peptides, oligonucleotides and small molecules, and their dissociation is obtained via label-free, real-time biosensor techniques; these measurements are not routinely feasible with labeled techniques. All applications in biotherapeutic discovery and development such as epitope mapping and binning and antibody screening are impossible, or at least highly cumbersome, with labeled techniques. In small-molecule lead characterization, label-free assays are playing a pivotal role in validating the direct binding of small molecule and fragments to target protein. Also, labeled assays show end-point results only and do not allow real-time kinetic measurements such on- rates, off-rates and affinity measurements, which lead to critical information being missed, or weak binding compounds being missed in a screen.
von Leoprechting: I don't believe there are new applications, per se. Novel pharmacologies have been seen using label-free technology and then confirmed using other orthogonal approaches. These responses, which haven't been seen using other screening methods, can provide crucial additional information to researchers working with cellular phenomenon such as biased agonism, functional selectivity and dimerization. This allows them to use labeled technologies in a more targeted and efficient way.
Mourere: Cell signaling, functional assays in native target expression cell hosts conditions can be very challenging using typical approaches. Conventional receptor overexpression in recombinant cell lines, combined with second messengers (cAMP, calcium, etc.), are sometimes misleading, especially when assessing partial-agonist drug pharmacology. Those same assay technologies also show limitations of sensitivity and assay robustness when used to measure GPCR activation and inhibition in native expression conditions in primary cells and stem cells. The label-free approach is well suited for protein-protein interactions studies. Inherent challenges of ligand/molecule radiolabeling, fluorescence labeling or antibody coupling are totally overcome. Those protein modifications necessary to measure a specific protein-protein interaction signal can potentially affect the conditions in which both protein partners interact in physiological conditions.
ddn: What are the benefits of label-free assays in comparison to traditional methods using radioactive or fluorescent tags?
Silva: Label-free assays eliminate issues such as photobleaching that are common in most fluorescent tags. They also eliminate the need for optical filters and reduce the restriction on distance dependence of the binding interaction that plague some fluorescent resonance energy transfer (FRET) assays. Label-free assays do not have the physical exposure hazard that is inherent in radiolabeling. Labeling can in some cases either block the active site of target proteins, or lead to significant changes in conformation of the protein that affects its function. Label-free assays overcome these deficiencies, reduce assay time and expedite workflow. The ability to characterize binding pairs without having to develop reagents or labels is a huge benefit. In some cases, you are unable to tag these samples as they exist in a crude milieu, or because the compounds are simply not characterized to do any labeling. In other cases, you can't label a whole antibody library of 2,000 or so compounds if you are trying to find the optimal therapeutic candidate.
von Leoprechting: Global pathway independent cellular response; the sensitivity required to enable research with endogenous and non-recombinant cells as well as recombinant cells; an added level of sensitivity to monitor weak biological interactions, allowing you to see effects that can be difficult to detect; a non-invasive technique that is more physiologically relevant and also opens up the possibility of reusing precious cells for more data; no disposal issues, such as radioactive materials and other labeled waste.
Mourere: In the cellular context, drug cell response measured is holistic and gives a more complete representation of the biological effect of a drug. It is not limited to the quantification of a single event (second messenger level, for example) and takes the complexity of the whole cell into account. The response measured is a better representation of the signaling pathways involved in the drug response. This provides a clear opportunity to identify new signaling pathways involved in a drug response with the potential of uncovering off-target effects and identifying unsuspected targets. A major advantage is that label-free is a more natural system. Labels as well as dyes can affect ligand-binding affinities. Also, dye loading times and conditions have to be controlled. Some dyes are proprietary, and there would be no way to predict or explain dye-ligand effects. GPCR response coupled to Gi is easier to do on label-free rather than working with inhibition of a cAMP increase or GTPgammaS binding with [35S] radioactivity. So really, the utility is that label-free avoids some problems that occur in traditional GPCR measurement systems. CDAS has also been able to use label-free in fragment-screening assays of small molecules versus a protein target. We have been able to look at interactions of small proteins and screen for inhibitors. Developing and validating labels for these last two processes would add significant cost.
Another major advantage of label-free is the ability to see the time course of the response for multiple wells at once. The pattern of the response can also be interpreted to understand a blended type of response, for example a mixed Gi/Gq response for a GPCR.
ddn: Which label-free technologies are most popular right now? Which are being underutilized? Are any being overly relied upon compared to other types of label-free technology?
Silva: The most common technologies in use are Surface Plasmon Resonance (SPR) and BioLayer Interferometry (BLI). While SPR has been actively utilized for label-free assays for about two decades now, BLI has gained strong acceptance in just a few years. Being the fastest growing label-free technology, BLI is certainly the one most underutilized right now. On the other hand, SPR is the more traditional technique that may be on the wane.
von Leoprechting: Most popular: Surface Plasmon Resonance (SPR) for binding kinetics studies; optical sensor label-free in high-throughput screening. Underutilized: Optical sensor label-free as a front-end screening tool based on binding strength prior to SPR; optical sensor and impedance in academic research, particularly GPCR's, ion channels and Receptor Tyrosine Kinases (RTKs); stem and primary cell work, as well as to exploit the time and cost benefits of reusing cells for a secondary orthogonal assay.
Mourere: There are really two major families of label-free. One uses traditional analytical chemistry techniques such as mass spectroscopy and NMR. The other covers cellular impedance (Cell-Key) and optical techniques. The field is still young enough that the technologies are still evolving, so it is difficult to assess popularity.
ddn: In what applications have label-free assays been most successful to date, and why?
Silva: Label-free assays have been successful in many biochemical screening applications, which involve protein-protein, protein-DNA, protein-peptide and protein-small-molecule interactions analysis. They are most commonly employed in hit-to-lead validation in drug discovery to parse hits obtained in primary screening methods that employ labeled assays. Label-free assays have recently been applied with great success to biotherapeutic discovery and development for epitope binning, crude antibody screening and affinity ranking and bioprocessing to rapidly monitor protein expression in crude cell culture supernatants. Methods have been developed, and companies such as ForteBio continue to release off- the-shelf biosensor chemistries to support these applications.
GPCR's and other cell-based assays, due to pathway independent response. Binding studies have also been successful due to high sensitivity, including fragment screening.
von Leoprechting: Structure Activity Relationship (SAR) studies due to their sensitivity to small changes in potency from subtle changes in molecular structure; compound profiling, due to label-free's ability to show interesting pharmacologies in compounds previously dismissed by calcium activation assays, for example.
Mourere: CDAS mostly uses the SRU BIND label-free technology for cell-based GPCR, ion channels and assays in both recombinant and native receptor cell expression conditions. The same approach is used for protein-protein and protein-ligand interactions assays. Main applications of interest at CDAS are custom assay development for primary and secondary screening, lead optimization, drug SAR and pharmacology response characterization in more relevant physiological assay conditions.
Our most popular approach is to develop GPCR assays using cloned receptors in CHO cells. The large signal-to-noise responses and good Z prime values give us high confidence in the assays. We have access to a large number of cell lines, either actively growing or division arrested, with which to work. We are pursuing development of ion channels and receptors mediated by tyrosine kinase. We have had success with a fragment-based screening project and with protein-protein interaction. These cell-free assays are more difficult to develop due to the small signal that results and require clear hands-on experience.
ddn: What technologies, if any, are label-free technologies going to make obsolete?
Silva: I would say label-free technologies are replacing certain ELISA assay segments such as those in ligand binding and cell line development. An ELISA assay that takes four hours or longer can be completed in less than 30 minutes utilizing BLI, with real- time measurements providing more information about the binding pair. Since the analytical tool set used in drug discovery is diverse, I am not sure if label-free assays are quite yet replacing any technologies completely. However, there is a promise to replace certain assay segments within major technologies.
von Leoprechting: None, in our opinion. We see label-free techniques as complementary to other labeled technologies.
Mourere: Label-free technologies are complementary to conventional technologies, and although they have very promising future applications, we foresee the coexistence of label-free and conventional technologies with increased market segmentation. End users now have a larger arsenal of approaches at their disposal to meet their specific needs. For example, if we obtain a weak response on the label-free system, we will develop an assay using a calcium dye or simply use a calcium flux assay from our off-the-shelf list, if available, for the target of interest. Also, the specialized techniques are useful to distinguish the type of response, particularly when the response is atypical.
ddn: How do techniques such as resonant acoustic profiling, (RAP), optical biosensors and surface plasmon resonance (SPR) compare? Describe those you are most familiar with along with their strengths and weaknesses.
Silva: Label-free biosensors can be based upon SPR, interferometry, resonant waveguide grating, micro-electromechanical (MEM) or acoustic technology, among others. Among these, SPR is the earliest technology to have achieved commercial success. However, SPR has continued to be plagued by lack of throughput, complicated microfluidics, expensive chips and cumbersome use. Also, it is facing increasing competition from non-SPR techniques. Bio-layer interferometry is the most successful such technique and is likely to continue to grow in stature and acceptance based on its strengths of reliability, robustness in performance, affordability and ease of use. Systems based on resonant waveguide grating technology have applications in biochemical and cell-based assays. However, they suffer from their inability to measure kinetic rate constants and the availability of other competing techniques that reliably measure cell-based binding events. Other label-free technologies have not gained much traction, mainly because they do not offer a compelling advantage over established techniques.
von Leoprechting: SPR has the advantage of giving binding on/off rates in protein-protein interaction studies, as well as binding strength, but some of the dominant SPR systems are limited by low throughput. They are very limited in their ability to perform cellular assays and in protein-small-molecule binding assays. Optical sensor label-free has an immense advantage because of its application to both cellular and biochemical assays, but cannot give binding on/off rates. Impedance-based systems are limited by their inability to perform biochemical assays, when the market is demanding technologies that can do both cellular and biochemical assays.
We are most familiar with the SRU BIND system. While we are not physicists, our understanding is that this is similar to SPR. For the SRU system, the instrument measures a change in the wavelength of the reflected light as run through a gold-colored grating on the bottom of the plate. As the mass increases at the plate surface, there is an increased response (peak wavelength value). It is interesting in that CHO cells align themselves like compass needles along the plate grating as they attach to the well bottoms.
ddn: What are some up-and-coming areas of study using label-free technology more routinely?
Silva: Fragment screening, ligand binding assays, protein expression monitoring, epitope binning and screening assays seem to be popular if one were to attend meetings such as Drug Discovery Chemistry, AAPS, Antibody Engineering and PEGS.
GPCR screening and research, especially in areas such as biased agonism, dimerism and allosterism.
von Leoprechting: RTK and toll-like receptors; stem and primary cells; and hit-to-lead studies, particularly for SAR studies within lead optimization.
Mourere: Chemotaxis assay, antibody-based assays to replace EIA, ion channels and tyrosine kinase receptors.
ddn: Antibody discovery seems to have been one of the earliest areas to make use of the advantages of label-free technology. How much does it dominate (or not) the field right now?
Silva: I'd say antibody discovery is one of the strongest applications and continues to grow as it supports the expansion of the biotherapeuetic drugs, which is growing in the teens.
von Leoprechting: It will continue to be an important area, however, other application areas are emerging due to developments of other label-free technologies, such as optical label-free detection.
Mourere: It represents a small proportion of routine applications.
ddn: Has label-free technology enhanced/improved the growing arena of systems biology? If so, how? Also, in what ways might it pose complications or challenges in systems biology work?
Silva: Systems biology relies on the ability to collect large quantities of high-quality data to reliably develop an integrated model of interactions in biological systems. Monitoring protein-protein interactions is a big part of the analysis of the dynamics and interactions within a cell. With the availability in recent years of high-throughput label-free methods such as the Octet, which is capable of simultaneously detecting different molecular species such as genes and proteins, systems biology is starting to see a positive impact. Biomarker research has benefited greatly as simultaneous detection of multiple markers in small volumes of samples using simple assay steps without the need for complex labels reduces the complexity in identifying and revising disease-specific molecular fingerprints. The challenge, however, remains in efficiently processing the large amounts of data generated with such high-throughput to create truly predictive molecular models that advance our understanding of cellular function.
von Leoprechting: Label-free is able to identify more complex cellular interactions, such as cross regulation of signaling pathways and dimerization. The challenge is then to use orthogonal assays to further elucidate the exact nature of the interactions.
Mourere: In a cellular context, a drug response signal can be complicated to analyze and follow up with relevant follow up confirmation experiments. Using the label free technology in a CRO context with many off-the-shelf, fully optimized functional and binding assays greatly facilitates follow-up confirmation studies and maximizes the outcome of the label free study. More specifically, label-free can help with systems biology in that we can use one technique to answer many questions. For example, we can obtain a GPCR ligand library and screen it on a cell line, and determine which GPCRs are functional. Thus, it is complementary to DNA microarrays and phosphorylated protein arrays in determining the state of the cell. As we understand cells, we see that, the presence of mRNA does not indicate that a functional protein is produced, and the presence of a protein does not indicate if it is transported to the proper location, with the proper number and with the appropriate cofactors and in the absence of inhibitors. Caliper has a long history of profiling cells to look at receptor expression. So we see label-free as the kind of broad technique necessary to ask and answer many questions quickly. It should complement the multiplex technologies such as bead-based measurement of interleukins, in cell-kinase activity and similar cell products.
ddn: What are the major challenges to the use, application or adoption of label-free technology?
Silva: Scientists' understanding of how label-free technologies are enabling, and high capital and running costs as well as weekly maintenance costs of SPR systems, have relegated label-free platforms to the well-funded labs and academic core labs. SPR platforms are also complex to run, making them not suitable for the multi-user laboratory.
von Leoprechting: Capital cost; perception of high-assay costour goal is to show that the overall cost of a label-free assay is comparable to the cost of standard research methods; and understanding of the benefits. With the advent of more affordable platforms, researchers who would not have looked beyond the capital cost of label-free hardware will now be open to understanding the benefits because a benchtop system now makes label-free more accessible to them, with no compromise in the label-free performance of more expensive systems.
Mourere: The implementation of the label -free technology requires in-depth training and scientific dedication to maximize the potential and the outcome. The cost of dedicated consumables greatly varies between vendors, but can represent a barrier to adoption or to use in drug screening.
ddn: Some researchers have been critical of label-free technologies, saying they have not lived up to expectations. Where is this true, and why?
Silva: I believe this is true with cell-based label-free assays, where the cell is pretty much a black box. For this reason, we have not seen growth in any of the cell based label-free technologies such as resonant wave guide- and impedance-based methods. With SPR, due to the above-mentioned challenges of throughput, costs and complexity, this technology's growth has also tapered off. However, BLI offers promising growth.
von Leoprechting: It's important to understand what those expectations were and difficult to respond without that information. The most common argument against label-free in my experience has been that label-free is a "black-box" technology. Some of the biggest fans of label-free have made the point that they agree that in some ways it's a black box, but nevertheless, black-box technologies have been invaluable to scientific research for centuries and are invaluable to them for the reasons given above.
Mourere: Vendors of label-free technologies play an important role in the wider adoption. Their ability to continue developing innovative, enabling applications overcoming challenges of existing technologies is key. This will probably require the development of more high-content, label-free instrumentation/applications. As the technique evolves, technical innovations by the researcher and the instrument vendor and decreased instrument and consumable costs will make label-free a real workhorse for the biological community.
Code: E021128
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Lifetime Membership in the New Jersey Ghost Hunters Society!!$25.00
Membership allows you to participate in private investigations and cemetery hunts. NOTE: You must complete at least 2 NJGHS Cemetery Hunts or Base Training Workshop before you will be considered for a private investigative team. Your membership card will be sent to you via EMAIL AS A PDF ATTACHMENT. You are responsible for printing it out and bringing it with you on every cemetery hunt and private investigation. Also, you must have a Photo ID with your name as it appears on your membership card for verification at said hunts & investigations. Other event registrations paid for online can be easily verified by the Membership List the Founder has on file.
Also, as a member of the NJGHS, you get the discounted rate for any workshops or conferences we sponsor. 10% discount on the paranormal books & calendars we sell.
Membership purchases by PayPal ONLY. No more in person purchases at Monthly Meetings. PDF of membership card will be sent to the email provided on the PayPal account with the name specified in the purchase within 24 hours of purchase. If you do not provide a name for the card, the one attached to the PayPal account will be used. ALL SALES ARE FINAL. NO REFUNDS FOR INCORRECT NAMES AS SUBMITTED BY PURCHASER.
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Hammer Strength Plate-Loaded
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Hammer Strength machines offer several convenience features depending on the piece. Standard weight horns allow weights to be stored on machines for space efficiency, and rubber feet protect the base of the frame and prevent slipping


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After registration you will receive a letter with a password and a link for activation of your account. If you do not specify a password, it will be generated automaticaly.
Registration was successful
Check your email and click on the link in the email to complete registration.
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Editors' note: As of December 2011, the WD TV Live reviewed here has been updated to add a variety of new channels, including Vudu, Flixster, XOS College Sports, and SEC Digital Network. Western Digital has also released compatible iOS and Android remote apps.
Following the success of the WD TV Live Hub, Western Digital has now introduced the diskless version in the new WD TV Live (2011). The new Live adds a couple more killer features, namely built-in Wi-Fi and support for the Spotify music-streaming service, to the already long list of services and file formats handled by its predecessors. And all for only $99--the same price as the Roku XS, the Apple TV, and the Logitech Revue (Google TV). It has one of the prettiest interfaces of all the streamers, even if it can be hard to use at times, but its main appeal over those other devices is its broad file support, an extra that should appeal mainly to people who make heavy use of downloaded video files. The only thing we wish for, aside from Amazon and Vudu support, is an App controller. The WD TV Live isn't yet the ultimate streaming device, but it comes pretty close.
The box shares the same footprint of 3.9 by 4.9 inches as the original WD TV Live HD (fall 2009) and WD TV Live Plus (summer 2010) but sheds their rounded "bookishness" for something blockier yet sleeker. It's also much lighter at 6.72 ounces, which is actually a negative in our experience; the collected mass of cables and USB keys can make it rear up like a seesaw ridden by one person.
Then there's the remote. That wonderful, hateful remote. It's decently ergonomic with indents underneath that enable it to sit naturally in your hand. All of the buttons are well-marked and, interface aside, easy to use.
Our problem was with the buttons. They're tall, rubbery blighters that take some effort to press quickly in succession, making inputting anything, especially long lists, tedious. We'd swap this out for a quality universal remote as soon as possible.
The addition of Wi-Fi to the WD TV Live is crucial, since its lack was the weakest point of the Live Hub. Western Digital has also made sure wireless setup is straightforward. When you turn the device on for the first time, you are greeted by a language screen, and are then asked to choose your wireless access point and input your password.
With the newfound wireless freedom, Western Digital has been sure to boost the number of services offered compared with the Live Hub, more than doubling them from 9 to 19. Joining Netflix and Spotify are the streaming services Hulu Plus, YouTube, Blockbuster, CinemaNow, DailyMotion, Pandora, TuneIn Internet radio, and Shoutcast, among others. The major missing items are Amazon Instant and Vudu, both of which are available on Roku. The WD's apps include Facebook (but not Twitter), Picasa, and Accuweather.
The Live inherits the Mochi interface from the Live Hub, and it's friendly even if the small "colored button" icons used for some navigation are a little indecipherable.
The reason you'd buy this over the Roku, though, is if you have a large library of digital files. The laundry list of supported types misses very little and includes notables such as FLAC, AAC, MKV, DivX, and even ISOs. The small Dolby TrueHD logo on the top suggests that the device will also play Blu-ray "rips" with full-quality sound (although we didn't test this).
Where the Live Hub had the real estate for a wealth of connectivity, the Live is more modest. It eschews its forebear's extras, such as a component output, for just HDMI, a composite AV breakout, two USBs (one front, one back), optical digital, and Gigabit Ethernet.
The device features an onscreen keyboard but text input can be laborious because of the clunky remote and the keyboard being alphabetical and not QWERTY. Thankfully the WD accepts USB keyboards, which makes setup much quicker.


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| 6.6°C Belfast
Media regular Ofcom has warned broadcasters to be vigilant about briefing guests on live TV shows in the wake of a four-letter outburst from a Tory MP during a lunchtime political programme.
Former prisons minister Nick Herbert used the term "f***wit" while appearing as one of the guests on BBC2's Daily Politics programme in May this year which led to an apology from the corporation
Ofcom received five complaints from viewers and investigated the incident as a possible breach of standards but is not taking any further action over the broadcast.
Mr Herbert defended his actions at the time, pointing out he used the term "disapprovingly" while quoting from a disparaging comment he claimed had been made by a fellow guest, former police officer Peter Kirkham, in reference to Home Secretary Theresa May.
Presenter of the programme Jo Coburn upbraided Mr Herbert and cautioned him to speak "without repeating any of those expletives". She later offered an apology to viewers and said the language was unacceptable.
Ofcom said today that because of the presenter's swift intervention and apology, together with the fact it was unlikely children would be watching, it concluded that the matter has been "resolved".
But in a report published today it said: "Ofcom reminds all broadcasters that they should consider carefully their processes for briefing guests appearing on live programmes."


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NM health officials offer flu shot clinics
Free Flu Shots Offered Thursday
New Mexico health officials are hosting a series of flu shot clinics around the state.
The state Department of Health says free walk-in immunization clinics are now being offered in Portales, Hobbs, Lovington and Roswell. Clinics also have been held in other cities.
Health officials say everyone six months of age and older should get vaccinated each flu season, especially people who are in high risk categories or those who care for such patients.
Flu shots are especially recommended for pregnant women, people 50 and older and those who have certain chronic medical conditions such asthma, diabetes, lung or heart disease.
Flu season can last as late as May. The highly transmittable disease can cause fever, muscle pain, headaches, fatigue, nausea, sore throats, runny noses and more.


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Resources and topics from numerous sources that address substance abuse, child welfare and courts.
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Includes links to future conferences and presentation files for past conferences related to substance abuse, child welfare, and family court.


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There will be Black Friday specials everywhere, but for many of you, GameStop's will likely be the most important. So here, courtesy of discount specialists CheapAssGamer, are what's reported to be the specialist retailer's deals.
The standout deal is obviously the pair of home console bundles offered on Friday, in particular a 250GB Xbox 360 with Skyrim, Forza 4 and Call of Duty Blacks Ops II all for $250 (though the 250GB PS3 with all Infamous releases, Uncharted and Uncharted 2 for $200 isn't bad either).
Considering Black Ops II has only just been released at full price, and will likely remain the holiday season's biggest-selling game, that's one hell of a saving for anyone looking for a 360 under the Christmas tree this year.
There's also some extra gains to be had on certain trade-ins and a whole range of titles discounted to between $10-$30. The full list is below.
Black Friday / Brown Thursday Video Game Deals 2012 - GameStop added! [CAG, via Wario64 @ NeoGAF]


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When you're the head of a large financial services organization, gravitas is your byword. So when a high-powered, high-profile fellow like Bernie Clark shows palpable excitement, and about a younger generation no less, you take notice.
I experienced this first last year at a New York breakfast meeting with Clark, who at the time had just met with a group of college students studying financial planning. He waxed enthusiastic about those younger people's passion, about how social they were, but also about the similarities they have with the older generation of advisors. The conclusion: The advisor industry, and clients, will be in good hands with the next generation of advisors.
In an April interview for the IA 25, Clark warmed quickly to the subject. "The generation that's coming behind: They look familiar, they talk about having balance in their lives, they want relationships, almost 70% want to be in relationship management. They're very social and do so electronically. We'll have to bridge some of those gaps, but it's still social—they'll look to social to help them make many of their decisions." Because of their social media bent, the next generation of advisors may be able to accommodate more clients per advisor, he suggested, but their approach to life will also "favor a fee environment." The next generation of advisors and clients is interested in "making long life choices and will be socially responsible," Clark said, "but so was ours."
That investment in the next generation of advisors is evidenced by Schwab's intern program. In the first year of the program, under which students intern at Schwab offices, "five of 10 people got hired quickly; this year we've got 20 people in Orlando and Phoenix." Schwab, he said, "may hire one or two of them, but our objective is to be in their local community" and for those students "to be talking about Schwab on their campuses."
At the same time, Clark "worries mostly about diversity" in both the advisor and especially the client ranks. "After decades of talking," he said, "how do we put into action" steps to improve diversity? "Women are underrepresented as clients," and in general, "young people who walk into an advisor's office will want someone to walk along with them, not somebody with 30 years' experience," he said. "Ethnicity and diversity will be more important in practices."
However, Clark said that as the industry "creates these solutions" for younger clients, "we can't forget that some boomers will love these new solutions and will communicate through these new channels." Moreover, these social solutions will change the makeup of advisory practices. "Firms will become de facto national firms; they're already starting to feel more like national firms because of their client base."
He then turned to the importance of Schwab Advisor Services to Charles Schwab the company and Charles Schwab the person. "This business is half the company's assets and a quarter of its revenue," he said, and internally at Schwab, "we needed to not compete with each other, but rather act as one firm creating solutions along a continuum." Schwab's retail advice operations are "in the same business as advisors, who are in the high end." He admitted that there may be "some open competition" between Schwab retail and Schwab's RIAs, "but if a client happens to straddle the line, we may make a referral to an advisor or continue for a while at retail." He mentioned that "I just met with Chuck the other day," and that Chuck Schwab "looks at this business and sees the merit of it." He "will be doing some print and digital advertising," talking about the importance of Schwab's RIA custody business, Clark said.
Robo-Advisors and Advisor Worries
As for the issue of robo-advisors and whether these providers of online advice pose a competitive threat to advisors, Clark believes "electronic offerings will complement what exists today. We've done a lot of work that shows most individuals still want a relationship" with a human advisor. "That doesn't mean they don't want to dabble or model; this generation wants to be hands-on," but he suggested the solution may be for advisors to use some of the robo-advisors' modeling tools "in their practices" and use them "for clients below their minimums, or children of clients."
He concluded by pointing out that online advice hasn't had to perform in difficult markets. "If we have five years of the markets heading straight up," robo-advisors "will do well; if we have three years up and two years down," investors "will want to talk to somebody."
What are advisors worried about? Where do they need help? Clark said that while advisors "don't see regulation as evil" and "embrace it internally, enforcement-based regulation doesn't provide more protection for clients." He recalled that in 2008 and 2009, "when we started getting nervous about FINRA as an SRO," there was appropriate concern among advisors that "a rules-based regulator would be a big burden, especially for some small advisors," and reiterated that "having 400 more rules will not be as friendly to the client."
Then there's the question of how advisors will market themselves. "Advisors are focused on branding—how to differentiate themselves," he said, pointing out that "as they grow, they become more like each other, so how do they tell their story differently?" As for the fiduciary issue, he said there's an "altruistic" benefit to clients, but worries that embracing a fiduciary duty is "going away as a differentiator," especially if any SEC fiduciary standard doesn't include disclosures that brokers are "still making a lot of money from proprietary products or IPOs."
What about Schwab's competition? "We're starting to see that our share of wallet is growing much faster—partly because it's operationally efficient, especially among larger advisory firms." When Schwab Advisor Services does "see assets going away, it's because [competing custodians] are offering something like a referral program or iRebal." What will be "critical for our success in the next five to 10 years," he said, is Schwab's business consultancy efforts, such as its Insights to Action program, helping advisor clients "think about their practices, their people, their transitions and their clients' transitions."
At Schwab, Clark said, "we're pretty paranoid about staying ahead of the curve."
(Check out Investment Advisor's full IA 25 for 2014 list on ThinkAdvisor.)


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Discover the world-renowned wetlands on the north shore of Phillip Island.
The mangroves and mudflats of Rhyll Inlet are a significant site for the wading birds that fly thousands of kilometres to feed here during the summer months. The wetlands are recognised under the Ramsar international wetlands agreement.
Boardwalks of varying lengths loop through the mangroves, saltmarsh and mudflats, and walkers are rewarded by the presence of spoonbills, oyster catchers, herons, egrets and cormorants.
Climb the Conservation Hill Observation Tower for panoramic views of the wetlands and surrounding woodland reserves.
Rhyll Inlet mangrove boardwalk
'Walk on water' with the elevated boardwalks through the saltmarsh, mangroves and tidal flats. Start at Conservation Hill information shelter. Follow the green arrows. 1.2 kms, 45 mins return: easy. Follow the signs to continue to the historic seaside village of Rhyll (a further 4 kms return).
Swan Lake bird hide
This freshwater lake, situated just before the Penguin Parade, is a significant site for Aboriginal people and provides great bird watching. Walk along an easy track to bird viewing hides. Start at Swan Lake information shelter. 1.3 kms, 40 mins return: easy.


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Where We Drink: Anfora Wine Bar, West Village
Editor's note: We tell you every day about where we're eating in New York, but we want to share where we're drinking, too. Serious Eats editor and wine and beer writer Maggie Hoffman kicks off the first edition of Where We Drink.
Anfora is not a wine bar I'd recommend to everyone. If you like wine as the background music to a nice meal, and you're happiest with your regular Shiraz, you may be turned off by a wine list with nearly nothing you recognize. But if you're a little tired of everyday sipping and you want wine to surprise you—if you're willing to get a little dirty and a little funky, if you like your cheeses smelly, your chocolate salty, and your palate stretched a bit—then Anfora is the wine bar for you.
Joe Campanale's six-month old bar isn't meant for kids, though he practically is one at 26. The black leather banquettes are not quite cushy (though the exposed-brick wall and warm lighting helps the room feel less austere.) The music alternates between lively and sultry, but the din's just a little loud for any sort of romance to be taking place.
Except, of course, your romance with the wine. Campanale seeks out artisanal wines made by producers who avoid using chemicals in the process. His list includes his personal favorites, like the fascinating, terroir-driven wines from the slopes of Mt. Etna and the Canary Islands. He features a few that are aged in the anfora for which the bar is named (these are terra-cotta clay pots that were used by the ancient Greeks and Romans to store and age wine). Campanale also likes to offer a few wines from the same producer, giving his customers the chance to understand a single producer's style better. He claims that it's not just a bar for industry folk and wine geeks (though plenty of those do stop by), it's also just New Yorkers seeking a low-key spot to enjoy a glass of wine or a cocktail.
We started with a remarkably rich Domaine de la Pepiere Muscadet de Sevre et Maine Sur Lie Les Gras Moutons (2009, $13). It was mineral-driven, herbal, and so lusciously smooth you might not recognize it as Muscadet. The Lopez Heredia Gran Reserva Rosado Rioja "Viña Tondonia" (2000, $15) is beloved among wine geeks. This slightly oxidative wine is nutty yet fresh, evocative of roses, peaches, and strawberries dipped in caramel, with a toastiness (and hint of marzipan) supported by delicate acidity. It's the perfect wine to linger over as the weather gets cold.
The showstopper, though, was the Coda di Volpe "Sophia" Cantina Giardino from Campania, Italy (2007, $16). This wine spent a year on the skins in the anfora, and was being served from a magnum around room temperature. This giving, slightly smoky wine is nearly brown in the glass, unfiltered and rich with notes of apple skins and nut butter. It's a wine that demands and rewards your attention. When asked about it, Campanale lights up: this is what he's here for, to share weird and wonderful wines that he's excited about, and to pour you something you may not find anywhere else in the city.
That's not to say there's nothing approachable on the list. Jean-Paul Brun's Beaujolais is delicious and easy-drinking, with bright acidity and juicy plum, raspberry, and licorice notes.
It can be a little confusing to figure out who's going to take your order, but once you do, be sure to ask for a plate of the spicy chorizo and avocado crostini. Charcuterie platters are served with excellent marinated olives and sweet pickle slices. Cheeses come with honey, grainy mustard, and a sweet-spicy mostarda with raisins. Skip the rather uninspiring Taleggio, and go for the fantastic creamy goat cheese from Haystack Mountain in Colorado. There are sandwiches, too, and they're good (though some complain that the scent of them cooking can be a bit overwhelming in the small space). I never really mind.
"What's good?" a friend asks as he bellies up to the bar next to me, pointing at the wine list. It depends, I say, on what you want. "Are you up for something weird?" I ask. "The weirder the better," he answers. I assure him he's found the right place.
34 Eighth Avenue, New York NY 10014 (map)


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Two years ago on Rays Index, we were perplexed about why many were making such a big deal about Curt Schilling's statement that he would be willing to play for the Rays. Saying outlandish things is what Schilling does.
Curt Schilling Just Wants You To Talk About Him [Rays Index]


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The National Association of State CIOs (NASCIO) has again polled state CIOs to determine what's hot and what's not as we head into&...
The National Association of State CIOs (NASCIO) has again polled state CIOs to determine what's hot and what's not as we head into 2010. Here's my take on their survey results.
Government Technology Magazine summarized the results into two categories. The top three in each category are:
A. Priority Strategies, Management Processes and Solutions
1. Budget and cost control: managing budget reduction , strategies for savings, reducing or avoiding costs, activity-based costing
2. Consolidation: centralizing, consolidating services, operations, resources, infrastructure, data centers
3. Shared services: business models, sharing resources, services, infrastructure, independent of organizational structure
B. Priority Technologies, Applications and Tools
1. Virtualization (storage, computing, data center, servers, applications)
2. Networking, voice and data communications, unified communications
3. Document/content/records/e-mail management (repository, archiving, digital preservation)
I am not surprised by budget issues leading the list. That almost goes without saying during these difficult economic times. Consolidation and shared services are also pretty obvious choices, with the cost control and efficiency being the major themes for CIOs right now. We need to work together to do more more with less, and partnering with others can certainly help.
What surprises me most from the "A" list is that security dropped to #6. Expect that to change next year. I fully expect security to rise back to the top three as Web 2.0 and cloud computing strategies try to battle with the inevitable threats that will surface from cost cutting.
The other surprise from list A is that infrastructure was #8. If you look at the top items on list B, they are infrastructure items like virtualization and networking. I can't quite figure that one out. List B also shows a drop for identity management from 2009, which will eventually need to be addressed in building more end-to-end trust and for moving forward with ambitious cloud computing plans.
The overall trend is "follow the money." Federal stimulus dollars are raising items like broadband to a new level of importance. Governments across the nation are looking at grant opportunities as well as making the most out of investments that they have already made.
In summary, I have a hard time arguing with any of the items on either list, based upon our economic realities. Michigan's list is similar, with a few exceptions like consolidation - which we've already tackled.
What are your thoughts? Do these priorities match your plans for 2010?
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Set a Concrete Goal "Eating better" or "working out more" doesn't really give you much to strive for. Find a goal and set a deadline: Seek out a long-distance bike tour you'd like to ride, a running race you'd like to run (charity-sponsored ones are great because others are counting on you, too), or aim for a particular social event (say, a wedding you're attending) or milestone (even your own birthday!) for which you want to feel good about yourself. Or, if you're so inclined, put your money where your vow is with Stickk.com.
Give Up Your Gym Membership That's right — cancel it. If you're not going, it's probably because you don't like it. And if you don't find your exercise options inspiring — or at the very least, not dreaded — you may never get into the swing of it. Instead, find something physical that you like to do: a dance class, a basketball league, a neighborhood yoga studio. Curious about something but not sure it's your thing? Most places will let you check out a session or two before committing. Or do what I do and dabble. Buy into daily-deal offers for a certain number of classes or a finite membership length (like a month) — and then go get your money's worth.
Get a Buddy Pair up with a fellow aspiring runner, find a friend who'd also like to learn how to belly dance, or check with your gym to see if it has some sort of matchmaking system. It's harder to bail on a workout when someone else is expecting you. Need more? Make it a challenge. Track down your competitive friend (we all have one), and push each other to run faster, swim harder, etc. (See me with my biking buddies, top right.)
Actually Watch What You Eat Diet really is a four-letter word (hey, it's a bumper-sticker slogan for a reason). Rather than restricting foods willy-nilly, start by keeping a food diary so you can see where you might be overdoing it. I've been using the free My Fitness Pal for the last month, an app and a website that make it pretty easy to log your eating habits — the app even has a barcode scanner to make fast work of entering packaged food. I like seeing how my meals add up, and also my intake of key nutrients such as iron and calcium. But my favorite part is logging in workouts to "earn" more calories — or just to revel in what I've burned.
How have you made your resolution stick? Tell us about it in the comments below.


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Cornell College's Event Publishing System
Plan. Publish. Share.
Submit Your Events to the Master Calendar
Students, faculty, and staff can now enter events on the online master calendar. All submissions are subject to approval and editing. Event submissions will be reviewed and/or revised to fit the calendar style and format. Events that are approved will automatically appear as calendar items on Today@Cornell on the day of the event.
Please log in using your Cornell Username and Password.


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Word Count
Writers Talk About Writing
Why We "Stave Off" Colds: It Started With Wine
April 22, 2015By Merrill Perlman
"I'm trying to stave off a cold," a friend said. Another responded, "Wine will work for that." Neither probably realized that, indeed, to "stave off" has its origins in wine, or something like wine. Continue reading...


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Mike Rowe, we love your stuff on the Discovery Channel. Dirty Jobs! But one job that isn't dirty is being a grillmaster, when your grill is an imaginary grill that's actually a metal shelving unit in a Ford advertisement. Yum!
According to Gizmodo tipster Anna, Mike is using a shelf from Metro, which also makes fine carts, cabinets and other flat surfaces. Notice the complete lack of flame, or anything underneath the "grill" except air and eventually grass. Perhaps he will grill on a cabinet next time. [Thanks, Anna!]


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The Louisiana Cancer Research Center (LCRC) was founded in 2002 under the direction of the Louisiana State Legislature. Our mission is to promote education and conduct research in the diagnosis, detection and treatment of cancer, while pursuing a National Cancer Institute (NCI) designation.
Through our coordinated approach, we recruit world-class faculty, educate future scientists, focus on discovery and development of therapies leading to clinical treatment programs, and implement statewide outreach initiatives. Our programs are designed to support research efforts and develop improved tools or new opportunities for early detection, treatment and prevention of cancer, while reaching out to Louisiana communities.
The clinical research program offers emerging therapies and strategies to our patients as investigational alternatives to routine care. We examine innovative treatments and medical approaches designed by our LCRC faculty in collaboration with colleagues throughout the world. The LCRC consortium is affiliated with six federally funded cooperative research groups in addition to industry sponsored drug developers.
LCRC works with colleagues in the community, throughout the state and beyond to share information about news and events related to cancer prevention, early detection, research and other topics of interest to those who are fighting for a cure.
The Tobacco Free Living program implements and evaluates comprehensive tobacco control initiatives designed to prevent and reduce tobacco use and also exposure to secondhand smoke.
It may start with research but it's really about a child with leukemia, a mother with breast cancer, a father with lung cancer, a sister with ovarian cancer, a grandmother, a brother…
Research isn't about what we think we want. It's about what they need us to be. LCRC brings together LSU, Tulane, Xavier and Ochsner to find ways to fight cancer. Our focus is on research and outreach to serve a population who experience some of the highest cancer mortality rates in the nation.


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Koehler, Fernandez excited for Wrestling Night at park
MIAMI -- Hours before Saturday night's game between the Marlins and Rockies, ballpark personnel began setting up a ring on the west plaza of Marlins Park for Legends of Wrestling Night.
Starter Jose Fernandez, who enjoys watching the postgame fireworks and concerts, said he would be doing the same when the wrestling legends put on a show for the Saturday Spectacular following the game.
Right-hander Tom Koehler visited the ring, practicing moves from his childhood, such as The Rock's "People's Elbow" and Stone Cold Steve Austin's "Stone Cold Stunner."
"I ran in the ring about an hour ago and jumped around in there and it hurt a little bit and I wasn't getting hit by anything," said Koehler, who grew up a fan of Hulk Hogan and Austin. "Obviously it takes a lot of skill and practice to do what they do."
From the wrestling world, the Nasty Boys (Brian Knobbs and Jerry Sags), Goldberg and The Hart Foundation (Bret the Hitman Hart, Jim the Anvil Neidhart, Jimmy Mouth of the South Hart) were among those in attendance.


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Card dimensions 150 x 150mm.
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Visit us at 14 Topsfield Parade, Tottenham Lane, Crouch End, London, N8 8PR.
Email us at: firstname.lastname@example.com
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Global Fund Extension of HIV Prevention Programmes
Global Fund Extension of HIV Prevention Programmes for People at High Risk for HIV in Russia Will Save Thousands of Young Lives
International AIDS Society and International
Harm Reduction Association
Call on Russian Government to Simultaneously Expand Access to HIV Prevention Programmes for People Who Inject Drugs 13 November 2009 (Geneva, Switzerland) - The International AIDS Society (IAS) and the International Harm Reduction Association (IHRA) today welcomed the announcement by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) to extend by two years its funding of HIV prevention programmes (known as the GLOBUS grant) in the Russian Federation at a cost of US$24 million.
"This two-year extension will save thousands of lives," said Robin Gorna, IAS Executive Director. "While this decision is very welcome, it is nevertheless a band-aid measure, not a long-term solution. External funding cannot prop up Russia's HIV response forever. The onus is still on the Russian Government to listen to the science and 20 years of proven practice and put in place long-term harm reduction prevention programmes that will save tens of thousands of young Russian lives."
The GLOBUS Project (Global Efforts Against AIDS in Russia, 2004-2009) is Russia's first approved GFATM project, with funds amounting to almost US$89 million. The project is active in 10 administrative territories: City of St. Petersburg; Regions of Nigegorod, Orenburg, Pskov, Tomsk, Tver and Vologod; Republics of Buryatiya and Tatarstan; and Krasnoyarsk Kray.
GLOBUS addresses the needs of specific groups including prevention programmes specifically targeted at people who inject drugs, sex workers and men who have sex with men. Funding for GLOBUS ended on 31 August 2009, potentially leaving projects in ten regions subject to staff layoffs and closures, despite the fact that they have averted an estimated 37,000 HIV infections.1
An estimated one million people are living with HIV in Russia, 80 percent of whom are under the age of 30. An estimated 1.85 million Russians, two percent of the adult population, inject drugs, one of the highest rates in the world. In 2007, 64.5 percent of new HIV infections in Russia were the result of injecting drug use.
Despite considerable external funding, needle and syringe programmes remain very limited in the Russian Federation and there is no state funding for these programmes. Effective drug treatment is inaccessible and there are no confidential and free drug treatment services. Rehabilitation programs are rare and opioid substitution therapy (OST) programmes such as methadone are prohibited under the Federal Law on Drugs.
Against this backdrop of the fastest growing HIV epidemic in the world, there are deep concerns that the Russian Government's new strategic health plan promoting "healthy lifestyles" will not include HIV prevention programmes. Russia's Chief Public Health Officer Gennady Onishchenko told the Eastern Europe and Central Asia AIDS Conference in Moscow two weeks ago that the Russian Government was "emphatically against" the use of drug replacement therapy and at the same criticized clean needle exchange programs.
"Pressure on the Global Fund to maintain programmes that address the issue of HIV and injecting drug use has succeeded where lamentably, pressure on the Russian Government to implement similar interventions continues to fall on deaf ears," said Gerry Stimson, Executive Director of IHRA. "Ten years ago we were looking at 100,000 Russians having HIV, not even a decade later that figure is one million and rising. The Russian Government has to leave ideology aside and introduce some long-term harm reduction measures or else it is looking down the barrel of a severe long-term health crisis."
The IAS and IHRA are calling on the Russian Government for increased financial resources, widespread availability of confidential and free drug treatment services, and the removal of legal and regulatory barriers that inhibit evidence-based HIV prevention and drug treatment programmes. The groups specifically urged the repeal of laws that limit or prohibit opioid substitution therapy (OST) and access to clean needles and syringes.
The effectiveness of OST and access to clean needles and syringes is well-documented. According to the World Health Organization (WHO), OST reduces HIV prevalence and risk of HIV transmission and infection, while also reducing the proportion of users who inject drugs and the frequency of infection. For those infected with HIV, OST increases access and adherence to antiretroviral therapy. WHO also concluded that there is compelling evidence that increasing the availability and utilization of sterile injecting equipment by people who inject drugs reduces substantially the spread of HIV. The programmes are cost-effective, have no convincing evidence of unintended negative consequences, and show evidence of increasing recruitment into drug treatment.


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Complete Story
Legislative panel backs surcharge for 911 upgrade
By: Patrick Marley And Steven Walters , Milwaukee Journal Sentinel
Madison - People would see a surcharge of up to 75 cents on their monthly phone bills to pay for upgrading 911 services under a state budget provision adopted Tuesday by the Legislature's Joint Finance Committee.
The 9-6 vote made it likely that the full Legislature will go along when it passes the budget this summer, and the fee could begin in October.
The committee also voted to extend state pensions to teachers aides and school clerical employees who work as few as 440 hours a year, even though officials have not received an actuarial study of what the changes would cost.
Democrats who control the Legislature pushed through both votes.
The surcharge would apply to cell phones, land lines and any other device that can connect to 911 - in all, 6.9 million wireless lines and land lines.
"I think it's much further than any of us wanted to go," Sen. Alberta Darling (R-River Hills) said.
The fee would raise $61 million a year, $59 million of which would go toward one 911 center in each county. It would pay for 911 training, equipment and computer-assisted responses to emergency calls.
"I think this is very important to public safety," said Sen. Lena Taylor (D-Milwaukee).
County supervisors would decide which center would get the help in counties with more than one center.
A past surcharge on wireless phones, which ranged from 43 cents to 92 cents per line to help upgrade and maintain 911 centers, expired in July. The committee voted to use a $20.3 million surplus in that account as part of aid payments to local governments. Otherwise, cell phone owners would receive a one-time credit on their bill of $5 on average.
Although representatives of the City of Milwaukee, other large cities and police and firefighter unions had said they wanted a per-line fee of $1 or $1.50 to help pay for local emergency services, no Finance Committee member offered that proposal Tuesday.
The committee adopted the fee, with Sen. John Lehman (D-Racine) and Rep. Cory Mason (D-Racine) joining all four Republicans in voting against the proposal.
Source: http://www.jsonline.com/news/statepolitics/43387192.html


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This is what I find on ifunny xD Tons of people on...
- by XxBetterOffDeadxXx
- Rating:
- Published: 6 Sep 2016
- Updated: 13 Jan 2018
- Status: In Progress
These are songs that I've found, love, can relate to. They're how I express myself half the time. There's pop, pop rock, rock, heavy metal, lil bit of country, alternative, alternative rock, punk. Anything really. Hope you enjoy^~^
Join MovellasFind out what all the buzz is about. Join now to start sharing your creativity and passion
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Apple and Google will dominate the emerging digital economy while Facebook "is toast," claimed George Colony, CEO of Forrester, in the opening key note of the analyst group's European forum in Paris.
Colony's provocative predictions came at the conclusion of a session where he challenged IT leaders to "disrupt or be disrupted" and pushed Forrester's theme that Chief Information Officers and the departments they manage need to transform themselves to focus on business technology
The Forrester CEO focused on the accelerating pace of innovation and predicted that mobile engagement will bring as profound a change to business technology as the client-server revolution of the 1980s.
Mobile engagement, built on architectural change brought about by the app internet will replace the broader Web as the focus of innovation and change, he said.
For CIOs it means, "You are going to put your company in the pocket of customers so that when they need you, they are in contact and you are there for them anytime, anywhere."
Mobile engagement brings insight from a range of technologies:
Devices and sensors -- essentially location, identity and behavior. Historical perspectives from records, such as purchase history, order status, supply chain inventory and customer records.Social media.Public as-a-service capabilities, such as mapping smart products, which offer personal insights, such as health data.
These technologies feed into predictive analytics to yield what Colony dubbed "prognostics" -- or guides to action and available choices.
Colony insisted that the old PC model is dead and more controversially that the Cloud Computing model was also dead because it "doesn't leverage power in your pocket." Future architecture will marry powerful data capabilities, held in the Cloud, with powerful apps on personal devices, he said.
Looking at the vendors that will dominate the future, Apple and Google will thrive in this mobile engagement dominated world, said Colony, while Amazon will also be a competitor. Microsoft, which yesterday announced its tablet computer, has a chance.
"I don't know if it will be successful," said Colony. "We haven't lived with Windows 8 yet."
He then described Facebook as "half way there," before adding: "I think Facebook is toast. The company is in major trouble around mobile engagement and the app Internet."
Why else would CEO Mark Zuckerberg buy Instagram or be talking about launching a mobile phone, he asked.
This story, "Facebook Is Toast, Forrester CEO Says" was originally published by Computerworld UK.


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"The Closed Door" (衝撃 閉ざされた扉, Shōgeki Tozasareta Doa) is episode 170 of the original Naruto anime.
Naruto awakens in the girl's hut, where she identifies herself as Isaribi. Upon thanking her, Naruto realises that she is being ostracised by the local residents, and he angrily chases away the children that have arrived to torment her. Meanwhile, Orochimaru is meeting with Amachi, a scientist conducting experiments under his direction. Sasuke Uchiha is also present, and ends their conversation when it's directed towards him. The remaining members of Team Anko have arrived at the island, where they are briefed on the payment schedule that they have to defend, and they locate the Demon of the Ocean (Kaima) in the meantime. However, Naruto arrives, and identifies the Kaima as Isaribi. The arrival of Yoroi enables Isaribi to escape, and the two escape. Anko attempts to pursue but is paralysed by pain from her cursed seal. Anko falls unconscious from the pain caused by the cursed seal.


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a friends HDD is having some major issues and i am trying to recover data.
Windows will blue screen due to the hdd failure, even using another PC with windows installed the diskmanagement tool hangs when the drive is connected until such time it determines the drive to be blank and require formatting. The HDD is having many read/io errors and making some clicking noises during these errors.
I have tried instead to access it in ubuntu as i have in the past in such situation as ubuntu does many things windows cant.
I have allowed ubuntu to auto mount the drive but im having issues accessing a windows 7 created partition's user directory. I can navagate the directory structure without issue until i try /users/USERNAME (equivilent in windows "c:\users\USERNAME").
When i do the window manager freezes for 10-30 secconds then returns a blank directory.
Under the assumption this is a permissions issue as its a users home directory i reverted to using dd with noerror to duplicate the data to another hard drive so i can mount that in windows to try again. The issue is this drive is 750gb and the ammount of io errors slowing the process means it is running at 2.2MB/s and dropping. (its been running since 10am (now 4pm) and has completed 23 GB...).
Does anyone have some information that may be useful in this situation as it is time sensitive and the data required from the drive is assignment work for a corse due imminently.
I have checked for issues relating to NTFS permissions and mounting methods but i can RW to other directories so i assume the mounting method is not the issue.
I am unsure if this issue related to folder ownership in windows?


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The frontend process (mythfrontend) is responsible for anything that requires interaction such Watching Recorded Programs or Watching Tv. It provides the GUI you use on your TV/Monitor as well as the LiRc, keyboard, or other input handling for Frontend Navigation. In addition, any MythTv Modules, or plugins, that are installed execute on the same machine that the user is interacting with. As such, the hardware requirements for a frontend are those necessary to support these features. Underpowered machines may not have enough processing power to decode recordings in software while the same machine could perform these functions if hardware decoding is available.
The MythTV architecture supports a theoretically unlimited number of frontend processes connecting to backends. A frontend process can run on the same machine as a backend in the instance of a combined machine, but is often found running on smaller, quieter, more stylish hardware since it the piece of equipment that usually sits within view of the user. When used on a separate machine from a backend, the frontend process connects over a network, either wired or wireless. It communicates with the backend to retreive the Electronic Program Guide and recorded content which is either streamed to the machine or directly accessed if the frontend has access to the same HardWare/File Storage the backend does.
The frontend process also has the widest platform support. Frontends have been ported to the Xbox and MacOSX (see the Myth On Mac Osx guide) as well as the standard Linux Distros with additional work being done to port it to Windows under Cygwin.
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Daily Show leads with Allen's 'Macaca'
When Senator George Allen pointed to a campaign volunteer for his Democratic opponent James Webb and uttered the words, "Let's give a welcome to our friend Macaca here" at a rally over the weekend, it was a gaffe so bizarre that it cried out to be lampooned on a certain 11pm fake newscast. As it turns out, the incident not only got the Daily Show's attention, but Jon Stewart and company led with it on the August 15 episode.
After playing portions of the clip in which Allen singled out UVA fourth-year S.R. Sidarth– who is Indian-American and has been video taping Allen for the Webb campaign– Stewart said it wasn't nice for the Webb camp to try to capture Allen on film "because George Allen says some really stupid sh*t." He then brought in "correspondent" Rob Corddry who delved into the more scatalogical interpretations of Allen's remarks before finally concluding, "It sure as sh*t sounds racist, and here in Virginia, I'm still not sure if that helps or hurts."
Allen has since apologized for the remarks, telling the Washington Post "I would never want to demean him as an individual. I do apologize if he was offended by that. That was no way the point."
Nobody's quite sure what, if anything, Allen meant by calling Sidarth "Macaca," but it has the Internet abuzz with "Macaca" and "George Allen" being the second and fourth most blogged-about topics on the web right now, according to Internet aggregator Technorati.
20 comments
Watch the video! Sen. Allen's comments were unbelievable. Reminded me of being a "Jungle Bunny" in third grade.
In any case, I made up some funny t-shirts and other stuff to celebrate the end of Allen's campaign. Thought you might want to check it out.
I'm donating 30% of the profit to Allen's competitor, Democratic candidate Jim Webb.
As funny as this clip is, does anybody really believe Allen meant "macaca" as a racial slur in and of itself? After having watched it a few times, it seems like he was just fishing for some nonsense word because he didn't know the guy's name. It was a poorly chosen nonsense word, to be sure, but I don't think he meant "macaca" to be taken as anything more than nonsense.
We ALL KNOW...some of us just have our heads in the sand.
Racists call people with different skin colors offensive names and treasure Confederate flags and stuff like that. They use "code words" to let other racists know they're with them in the fight to purify America. George doesn't...wait a minute...
DailyKos deconstructs Allens "apology" quite nicely. http://www.dailykos.com/storyonly/2006/8/15/193311/003
George will win this race, and he has a shot at the GOP nomination in 2008. He's a dirty, sarcastic, mean person willing to ridicule anybody who disagrees with or criticizes him. In George's world, just like the "other" George's world, you're either with him or against him. If you're against him, you're of no value - he goes out of his way to make that clear. And he has lots of money to get his word out.
I was watching that last night and got a good laugh. That conclusion of "It sure as sh*t sounds racist, and here in Virginia, I'm not sure if that helps or hurts," had me rolling off the couch and I knocked my cereal over.
So Very Virginia.
There's a great article -- or title of the article anyway -- on slate.com -- check it out ---
"Is George Allen Too Stupid to Be President?" hehe -- answer: Certainly not if W set the bar.
We can never know what George's thought process was, all we know - and we do know - is that he directed racial slurs at and said things that clearly were demeaning toward a person who isn't White like him.
I expect a hell of a lot more out of my Senator. Don't you?
Virginia is for... haters
Using excuses like "he didn't know the guy's name" would work pretty well except for the fact that the young man in question introduced himself to Allen a few days before the Macaca incident. Is it a nonsense word? I don't think so. http://www.thefreedictionary.com/macaca
I doubt he meant to call the dude a racial slur, but what he most definitely did was make a minority the target of
ridicule as 100 or so rednecks whooped it up with approval. S-K-E-T-C-H-Y.
So long proportion, you have been blown out. Nobody can know what his intentions were with the word, the honorable thing to do would be believe he was not throwing out a "closet" racial term and move on. But since I haven't and won't move on from Howard Dean screaming like a pro wrestler, I guess I'm not the one to throw stones.
DVD, I meet a lot of people whose names I can't remember two minutes later. And I meet way fewer people than does George Allen. So that means nothing.
This will be forgotten quicker than the fact that Hezbollah started the conflict.
We can't know what his intentions were? Yeah, right. The "welcome to America" comment explains everything. Allen is a racist, plain and simple, and he is unfit to serve.
I don't think Allen will win the nomination, Romney will, but I believed it before this. Everybody that has posted on here has said something they want to take back. Something that can be construed as racist, since pretty much anything can if you want it to badly enough. Arguing over a word whose connotations have to be really stretched to be construed as racist is like someone getting fired over the use of the word "niggardly." Oh, wait.
There's no way GOP primary voters will elect Romney due to his Mormon faith.
Jesus! How'd I miss that?!
Aww, come on. He didn't mean to call the kid by a racist slur; he only meant to call him a shithead! And no, I'm NOT making that up: http://hotlineblog.nationaljournal.com/archives/2006/08/a_new_explanant_...
Allen needs to get himself some spin doctors who actually graduated from grade school.
Here are some definitions of the word Allen used:
1. 'Macaca' - French : racist slang; similar to English 'nigger,' used to describe Arabs.
2. 'Macaca' - English : racist slang; similar to 'nigger' used to describe Arabs.
3. 'Macaca' - English : racist slang; used by American white supremacists in 'insider' talk about African-Americans.
The French term is particularly used by French colonists in Northern Africa, which Allen's mother was. She is French and from Tunisia. Still think it was a nonsense word?
The fact that Allen said what he said isn't surprising. The fact that he said what he said when the kid had a video camera pointed at him and Allen knew it was a video camera owned and operated by the opposition says a lot. It says that Allen considers himself above criticism, and believes what he says is RIGHT. What he said was at best insulting and derogatory, and at worst outright racist. When you combine that with the fact that he said he wished he had been born in Iowa (said while campaigning for president in Iowa), and combine that with the notion that he's (at least now) planning to run for president in '08, maybe we should elect somebody who doesn't hate anybody who opposes him, and who will is committed to serving the full six year term.
He's a moron.
Dave should be careful. The term "rednecks" is racist to me...I am Appalachian-American and don't ever
forget that.


text: читатель жу-жу (chitatel_zhuzhu) wrote, 2020-01-12 17:00:00 читатель жу-жу chitatel_zhuzhu 2020-01-12 17:00:00 Previous Share Flag Next Camilla Forchhammer Christensen (ROX Jewellery 2019) Tags: ля фам Subscribe Posts from This Journal "ля фам" Tag (by Hans Krum) … (by Galina Zhizhikina) … (by Gerd Hannemann) … (by Milan R) … Polina Malinovskaya (Social Media, 2020) … (by Ed Coffman) … promo chitatel_zhuzhu Buy for 10 tokens Journal information Current price10 LJ Tokens Social capital1 126 Friends of537 Duration24 hours Minimal stake10 LJT View all available promo Buy promo for minimal price. Post a new comment Error We will log you in after post We will log you in after post We will log you in after post We will log you in after post We will log you in after post Anonymously switch LiveJournal Facebook Twitter OpenId Google MailRu VKontakte Anonymously default userpic Your IP address will be recorded When you submit the form an invisible reCAPTCHA check will be performed. You must follow the Privacy Policy and Google Terms of use. Post a new comment Preview comment Help 0 comments Post a new comment 0 comments


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You might be familiar with deviantART as that place you go to find awesome wallpapers or Team Fortress 2 fan art. It is, primarily, a community for artists and creative types—people who like to draw and paint and sketch. But in early 2010, the site's developers wanted to try something new.
It dawned on company CEO Angelo Sotira that there should be a way for the community to create and publish new art directly on the site, with nothing more than a modern browser. The question, however, was to build or buy?
In other words, Devious Technology—the team responsible for all of deviantART's design and development work—could either develop the technology for a web-based drawing application themselves, or license or buy a piece of pre-existing software from someone else.
Sotira's situation was not uncommon. Even here at Ars, we often bemoan the lack of a good story scheduling tool, and wonder if it's worth building our own. In the end, deviantART launched its web-based drawing tool, called deviantART muro, in late 2010—and it was designed and developed entirely in-house. But it wasn't an easy decision to make.
"Whenever you're doing a buy versus build analysis, you typically want to buy," Sotira told Ars. After all, in many cases, you're not just getting the product, but the team responsible for its development too. "What you get is an expert," he continued, "and somebody that has some pattern recognition in the product, so that they know what's good and what's bad."
Initially, this was the route Sotira considered taking. The team investigated numerous other web-based drawing tools, but none of them quite seemed to fit with what deviantART had in mind. For example, they found most of the tools available at the time were built in Flash, which was slow and ill-suited for pen-based input. Rather, "HTML5 had become this label for cutting edge stuff," said Simon Murray, Devious Technology's director of product management, and the development team wanted to use that instead.
"It wouldn't be fair for me to say we didn't go out and further analyze the market—we did," continued Sotira. "We went and looked at all the drawing software that existed when we actually thought about building muro, when muro started to evolve."
It's important to note that other companies with other needs don't always come to the same conclusion. In late April, for example, Ars wrote about Google's decision to sell its SketchUp 3D modelling software to a company called Trimble, which sells mapping, geolocation, navigation, and surveying equipment and software. In this case, Trimble already had a suite of 3D tools it had developed in-house for enterprise use, but bought SketchUp to "enhance [their] ability to extend our existing market applications."
What's interesting is that, while deviantART muro wasn't directly acquired, some of the primary talent behind the project was. In 2005, deviantART acquired a website called DrawHere.com, which Sotira describes as "graffiti for the web." Users could essentially draw over other websites and share the resulting digital graffiti with friends. Sasha Lerner, now VP of engineering, and MichaelDewey, now deviantART muro's lead developer, were both brought on-board in the deal, but worked on other deviantART projects and tasks before the idea of a drawing app was even tabled. However, having that past experience already present within the company—not to mention the rest of deviantART's vast engineering team—meant that Sotira wasn't forced to hire additional staff to make deviantART muro a reality. They already had the skills within.
That's not to say there weren't still certain challenges during muro's development. Sotira says that, for a site as large as his, where all of the infrastructure is handled in-house, it was hard to lose the engineering efforts of people such as Dewey to something that wasn't related to the day-to-day infrastructure and management of the site. From the time development officially started in February 2010, it would take ten more months of work until launch. "You don't just get to swap somebody else in," Sotira said. "We felt that strain and that stretch of growth. But that's awesome."
In the end, deviantART believes the move paid off. The team was able to create a tool that fit with their vision, with input from across the company, and could be iterated upon over time. Just this week, for example, the team launched Redraw, a new version of deviantART muro with a tweaked interface, and more importantly, the ability to playback every brushstroke in a piece of work and see the artistic process from start to finish.
"Any piece of software that's not designed with the vision it intends to fulfill in mind is going to be a piece of software that has to get rebuilt anyway, in order to fulfill that vision," says Sotira. And while buying or licensing a pre-existing piece of software might have satisfied the company's short term needs, he believes the extra time and effort needed to develop an in-house product were worth it.


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Municipal clerks say new vote-counting machines that many Maine communities received as part of a federal initiative drastically cut down the time previously spent hand-counting ballots a week ago, on Election Day.
Even so, the new technology didn't come without hiccups. Some voters in Belgrade and Waterville witnessed problems in the way the machines took the ballots, resulting in slight delays.
Most election clerks raved about the new machines, however.
"We had the totals by 9:30, and that's including the few hand counts," Sidney Town Clerk Shawna Foye said. "We probably would have been there till 4 or 5 in the morning with a couple tables if we had to hand-count."
The election staff in Waterville was concerned initially when one of the machines that accepts ballots appeared to stop working, but City Clerk Patti Dubois said she discovered it was simply being "finicky." Waterville already had electronic ballot-counting machines, but it received new ones for this year.
"It will still accept the ballots if you orient the paper in a certain way," she said later on Election Day. "It won't affect anything."
In Belgrade, some voters had similar issues inserting ballots into the machine; it would reject a ballot several times before accepting it. Executive Secretary Mary Vogel said she wasn't aware of any machine-related issues, and Town Clerk Cheryl Cook wasn't available for comment.
Megan Sanborn, spokeswoman for the Department of the Secretary of State, said the office received some similar complaints on Election Day, but "if there were problems, they were few and far between."
Staff members from the secretary of state's office held regional training sessions before the election for all municipalities that received new machines, she said.
Most of the 64 municipalities that received the machines had been hand-counting ballots before that, according to Sanborn.
Maine is leasing the machines for five years for $1.4 million from Election Systems & Software with no additional cost to the municipalities, she said, besides any transportation cost incurred by election workers attending the training.
Foye said the training she and three other town election workers received helped make Election Day go smoothly.
The next phase of updating municipal election equipment will come in January, when the state begins to replace machines in the 120 cities and towns that already have them. The goal is to make sure all cities and towns are using the same machines, which will mean voters across the state will fill in ovals on their ballots, rather than connect arrows, Sanborn said.
Leasing the machines for the towns and cities this year, upgrading the rest using different machines and any training required will cost around $3 million to $4 million over the next five years, according to Sanborn.
One minor issue most clerks cited was the difficulty in inserting absentee ballots, which are folded, unlike Election Day ballots.
Chelsea Town Clerk Lisa Gilliam said they had to open the side compartment in the machine only twice to ensure the absentee ballots were received. She said they worked perfectly, other than those minor glitches.
Farmingdale Town Clerk Phyllis Weeks said the new machines were well-received by the residents, with the exception of one older man complaining that he liked the previous way better.
The only thing she'll change next year is taking advantage of the ability to count absentee ballots before the election, instead of afterward.
"It didn't take them quite as rapidly as they could have," she said. "Other than that, it was an absolutely positive experience."
Funding for the machines, software and training comes from the $17 million Maine received from 2002's Help America Vote Act, which aimed at improving elections after ballot-counting problems arose in Florida during the 2000 presidential election, in which the principal candidates were George W. Bush and Al Gore.
Besides providing funding to replace voting equipment and improve election administration, the act established provisional voting, voter registration databases, voter identification procedures and administrative complaint procedures.
Staff writers Sue Cover and Matt Hongoltz-Hetling contributed to this report.
Paul Koenig — 621-5663
[email protected]
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