I don't think there's much point in bemoaning the state of the world unless there's some way you can think of to improve it. Otherwise, don't bother writing a book; go and find a tropical island and lie in the sun.
Experiments involving non-human animals (hereinafter referred to as animals) were the predominant technology in the life sciences from the 1920s to the 1970s. Increasingly, animal-based procedures have been complemented and superseded by other approaches; yet, they still have an enormous reputation as an apparent definitive answer to many scientific and, especially, regulatory questions. They have been questioned first for ethical reasons: Can we justify making animals suffer for scientific inquiry? Simply said, people have different views on this question, but the general public views animal experimentation more and more critically. The animal research community has sought a compromise between those who would like to see the end to the use of animals sooner rather than later, and those who think animal research is indispensable. The societal response has included regulation and oversight of animal experiments (e.g., requiring formal justifications and permission), as well as support for the development of alternative methods.
Building on the legislation of some of the more progressive Member States, the European Union (EU) has twice advanced the legislative oversight of animal experimentation and the push for alternative methods. Already in 1986, European lawmakers reasoned that harmonized animal testing legislation was needed within the common market, both to level the playing field and to limit animal testing. Since then, and revised and strengthened as Directive 2010/63/EU, the EU requires that practically available alternatives to animal experiments have to be used (European Parliament, 2010). The EU also tasked the European Commission and the Member States with furthering the development and validation of alternatives. The 2010 Directive continued to expand the scope of the legislation and added enforcements. It also included an important reversal of the burden of proof: the legislation does not restrict the free use of animals in science, but it grants an exemption from the prohibition of animal tests upon sufficient justification (Hartung, 2010a). Noteworthy, the scope of Directive 2010/63/EU was extended to include the entire animal life cycle, from breeding to the conclusion of the experiments; and it was extended to late stages (last trimester) of embryonic development as well as to cephalopods, such as octopus and squid. The legislation also requires the application of the 3Rs and encourages their further development, as well as requiring the systematic evaluation of projects, including prospective and, for certain experiments, retrospective assessments of pain, suffering, and distress caused to animals.
While these general provisions apply for basic research as well as the applied use of animals for product development and safety testing, it is quite remarkable that the safety testing part (i.e. toxicology) has become the primary battleground over animal experimentation and its alternatives. This area accounts for only about 10% of overall animal use in science (Daneshian et al., 2015), according to statistics from the EU and elsewhere; yet, it is probably fair to say that 90% of the work to develop alternative methods, in the sense of one-for-one replacement, has taken place in this field (see Stephens and Mak, 2013) for a comprehensive look at the history of pursuing alternative methods in toxicology). Consequently, toxicology has a lighthouse function for other areas. If we can substitute for animals in the area of human safety, we can undoubtedly do the same in other areas.
A key recent development is that animal experiments are being challenged on more than just ethical grounds (Hartung, 2017a, b). Animal experimentation is resource intensive, in terms of both expense and duration (Bottini and Hartung, 2009), and we are increasingly realizing the limited predictivity of animal models for humans based on both the limited reproducibility of their results, and the differing results across animal species (Hartung, 2013; Pound et al., 2004; Pound and Bracken, 2014). Humans are obviously not 70kg rats (Hartung, 2009a). Within toxicology research, the costs have become particularly evident as companies start to tackle the backlog of testing of industrial chemicals under the European Registration, Evaluation, Authorisation and Restriction of CHemicals (reach) program (Hartung and Rovida, 2009). The comprehensive assessment of a single substance amounts to several million US dollars of testing costs. We simply cannot afford to test tens of thousands of substances using the usual methods, and we also do not even have the laboratory capacities to do so. Often overlooked, we also need about 20kg of a substance to run a comprehensive toxicity profile; for novel and costly substances such an amount is often impractical to synthesize.
The most important issue—the limited predictivity of animal experimentation—was underscored by recent findings that the high failure rate of new substances in the pharmaceutical industry is based, at least in part, on the misleading findings of the animal models used during the course of development (Hartung, 2013). Two major assessments by pharmaceutical companies, one by Amgen and one by Bayer, showed that animal-based research studies were reproducible in only 11% of 53 projects (Begley and Ellis, 2012) and in about 20%–25% of 67 studies (Prinz, Schlange and Asadullah, 2011). This and similar findings have fueled a more general discussion about the reproducibility crisis in science (Baker, 2016). It is important to note that this issue is simply one of replicating the findings of earlier animal studies in later animal studies of similar design; this is quite apart from the issue of extrapolating such results to humans. The reproducibility crisis increasingly calls into question whether animal studies should serve as the ultimate gold standard of scientific work in the life sciences. Indeed, more than 95% of substances that show promise in animal experiments (Arrowsmith, 2011a, b, 2012) fail in later stages of drug development when assessed in human trials (Hartung, 2013). To be sure, the drug development process continues to deliver new entities but at costs in the billion US dollar range (DiMasi, Grabowski and Hansen, 2016), making it more and more difficult to sustain this business model.
A scientific discussion challenging animal experimentation would be fruitless if there were no alternatives. When acknowledging the shortcomings of animal experimentation, many animal researchers will essentially argue that it is better to have something imperfect than nothing at all. But are they just imperfect, or are they downright misleading? Nobody knows how many promising drugs have never made it to human trials because the animal tests wrongly sorted them out as inefficient or harmful. It is somewhat frightening to realize that aspirin would probably not make it to the market today because it fails a number of animal-based safety tests (Hartung, 2009b).
As stated above, formal replacement of animal-based procedures by alternatives has been pioneered mainly in the field of regulatory testing, i.e. the toxicological assessment of drugs, medical devices, chemicals, pesticides, cosmetics, and other consumer products prior to marketing, as well as the batch-release testing for vaccines. Why the focus here on alternatives to animal-based tests? Governments tend to fund the development of alternatives to the animal procedures they prescribe (safety sciences); and legislation, such as the European cosmetics test ban (Hartung, 2008) and reach (Hartung, 2010b), have spurred these developments. Hence, regulatory toxicology has the potential to be an important driver for animal replacement research more generally. Noteworthy, the cosmetic ban was the consequence of public pressure voiced by animal protection groups to policy makers, not a consequence of scientific progress or perceived regulatory needs. Much of the new science came after the legislative ban took effect; and after the ban was embraced by industry and regulators, first in the EU and then elsewhere.
Regulatory testing has formed a bit of an island because, until recently, it has been outside of the normal competition of ideas, failing to keep pace with technological advances. In contrast, there is pressure to employ the latest technologies in drug development. After patenting a lead compound, there is a race to bring the drug to the market, as a single day of delay costs the company, on average, US$1 million to recuperate the almost US$3 billion of average development costs (DiMasi et al., 2016). This means that drug development companies readily explore and apply technologies that hasten decision making and may bring a competitive advantage. It has been suggested that our knowledge in these areas doubles every seven years. In comparison, many approaches in regulatory science are decades old: acute and repeated-dose testing originate from the 1920s, skin and eye irritation from the 1940s, and reproductive toxicity testing from the 1960s. This unusually static situation has inadvertently allowed the long-term, systematic targeting of these assays in recent decades. In other areas of biomedical research, development and validation projects of 10–20 years (not uncommon in the testing arena) would be quite pointless, because the technology changes so much over time that the validated test becomes obsolete. So, to some extent the development of alternatives for regulatory animal tests has become the sparring partner for other areas of research, as it elucidates general needs for addressing the definition and reporting of experiments, their combined use, and their relevance, quality assurance, and validation. This also helps to transform, more generally, the mindset of researchers, creating awareness of the availability and the need of alternatives.
Education plays a key role here. By training the next generation of scientists with an openness to the new technologies and with a critical eye towards the use of animals—certainly not hailing them as the ultimate tool of generating knowledge—the basis for a balanced use of different tools is set (Daneshian et al., 2011; Hartung, Blaauboer and Leist, 2009). Internet-based teaching and training is facilitating this sea change. The emerging professorships for alternative methods in Konstanz, and other places in Germany; Baltimore; Utrecht; and elsewhere, and their collaboration with each other, represent an enormous opportunity. An important element is the parallel replacement of animals in the teaching of all areas of the life sciences. Nowadays, alternative teaching models, computer simulations, and movies can effectively substitute for repeatedly carrying out the same demonstration of an animal test. The non-animal approaches help to underscore a mindset of avoiding animal use. But it is not only about the next generation. Especially important is the continuous education of regulators, which at the moment often form a bottleneck for the broader use of new approaches. Such continuing education plays an important role in accelerating change across all areas of animal-based research.
The obvious principal alternatives to animal use are in vitro and in silico approaches, i.e. methods based on cell culture or on computer modeling. Although not without their own scientific limitations, these approaches can at least be focused on human biology, and they are typically cheaper and faster than animal tests. We also have increasingly technical solutions (Marx et al., 2016) and quality assurance tools (Coecke et al., 2005) to overcome the limitations of the early cell-culture technologies. Stem-cell technologies now make high-quality human cells more broadly available, and bioengineering allows the reproduction of organ architecture and function in cell culture. Such advanced organotypic cell models are now often called microphysiological systems. They promise to provide all life sciences, including safety sciences (Andersen et al., 2014; Marx et al., 2016; Smirnova et al., 2018), with more meaningful functional organ models, overcoming many of the shortcomings of traditional cell culture (Pamies and Hartung, 2017) and, thereby, making them more competitive to animal experimentation. Our own development of human mini-brains from stem cells (Pamies et al., 2017) may serve as an example for the many models mushrooming as a consequence of stem-cell technologies and advances in bioengineering.
The ultimate quality control and the basis for replacing an animal method is formal validation of alternative methods (Leist et al., 2012). This started with the creation of the first validation body, the European Centre for the Validation of Alternative Methods (ecvam) in 1991 (which the author headed between 2002 and 2008). Since then, validation has been internationally harmonized and also required for new animal test methods by the Organisation for Economic Co-operation and Development (oecd) (2005). The validation process was developed for regulatory tests (mainly originating from drug safety testing, but with a focus on their application to cosmetics and industrial chemicals), where safety is at stake, and is not generally considered necessary for other areas of the life sciences. However, the elements and principles of validation are very much advisable to any type of experimental work (i.e., the clear definition of the method—its purpose, execution, and applications—and the assessment of its reproducibility and relevance) and are vital to moving away from animal experiments. Successful examples of validation include testing for skin and eye corrosion and irritation, phototoxicity, skin sensitization, pyrogenicity, and batch testing for several vaccines in international test guidelines from the oecd and different pharmacopoeias. The reader is referred to the websites of validation bodies, such as ecvam and its US counterpart, the Interagency Coordinating Committee on the Validation of Alternative Methods (iccvam); and the independent website, AltTox.org, which keep track of the status of the validation and acceptance of testing methods.
Validation has taught us, first of all, that clear definitions of a test and its purpose are needed. It is astonishing to see how often these are not clearly stated in scientific literature and the whole field of animal research. Second, validation formally addresses reproducibility. While requiring ring trials of a new method is certainly going too far, a more formal reporting on reproducibility (starting with a clear distinction between what was done repeatedly, and what was done in parallel technical replicates only) is an important element of addressing the prevailing reproducibility crisis. The most overlooked element of validation within the life sciences is to formally establish the relevance of a test. This might sound odd to a lay audience, but in science we often produce results in a model system and then uncritically translate them to the system being modeled (usually humans).
Often lacking in our scientific papers are formal assessments of the scientific basis of the new methods (are the relevant mechanisms reflected?) and their interspecies predictivity, as well as a demonstration that the model gives meaningful results with well-known reference compounds. The "cherry-picking" of the literature backing our results creates enormous bias. A change in scientific paradigm is needed towards evidence-based approaches. Here too, within the preclinical sciences, it is toxicology and the search for alternatives that are spearheading relevant developments, i.e., the creation of evidence-based toxicology (Hoffmann and Hartung, 2006), with systematic reviews of the literature (Stephens et al., 2016).
Much of what has been written above is centered on in vitro methods. In silico methods have undergone similar developments making them a central tool in the life sciences and regulatory assessments (Ekins, 2014). Ever-increasing computer-power allows more and more applications of these methods. However, their limitations so far prohibit regulatory use on a large scale (Hartung and Hoffmann, 2009); this seems to result from the fact that most approaches have looked for an exact formula to describe parts of the chemical universe from the structures of the chemicals. This has proven to be difficult owing to the quality problems of the animal input data and the quite small datasets generally available. More recently, however, in silico methods have gained ground, especially the very pragmatic area of data-gap filling by read-across. Read-across is based on the principle that similar chemicals have similar toxicological effects; i.e., it suggests taking over the results from similar chemicals with the respective reasoning about similar chemistry, chemicophysical properties, uptake, metabolism, and biological effect. The use of read-across flourished in the context of reach (Patlewicz et al., 2014), but the extent of its applicability and how to conduct and report it are under debate. This has prompted the development of Good Read-Across Practices (Ball et al., 2016) and ideas for a more automated read-across (Hartung, 2016). The latter development also makes use of the emerging large toxicological databases (Luechtefeld et al., 2016). These machine-learning approaches are agnostic to the biological effect studied and are similarly useful in drug discovery. Other in silico approaches, which are mushrooming, include modeling from receptor binding to cells, organs, and organisms. In short, the informatics revolution fuels the replacement of animal tests with increasing pace (Ekins, 2014).
Increasingly, in vitro and in silico methods are combined, forming integrated testing strategies, acknowledging that one method alone does not satisfy all information needs (Hartung et al., 2013; Rovida et al., 2015a). While the idea is rather simple, the systematic composition, optimization, and validation of such strategies are still in their infancy. Again, the safety sciences are spearheading the concept, also combining it with a more mechanistic approach (Tollefsen et al., 2014); but the needs and opportunities are not very different for other areas of the life sciences. Mechanistic toxicology has been boosted by the recent cataloging of mechanisms as adverse outcome pathways (aop) (Leist et al., 2017), which have been systematically developed under the umbrella of the OECD and which help the discussion and design of integrated testing strategies, among others. Similarly, modern drug development integrates different testing tools, though this could often benefit from a more formal integration of tests. It is interesting what can be learned from the mass testing of environmental chemicals. Simply said, for tests, 1+1 is more than 2 when well integrated.
In the life sciences, the increases in molecular and mechanistic understanding—as exemplified by the mapping of the human genome—have given rise to mechanistic models throughout experimental medicine (Langley et al., 2015). The new approaches do not simply replace or complement animal tests; they are enabling technologies that outperform the animal-based procedures as soon as sufficient mechanistic understanding shows their physiological relevance. The increasing use of non-animal methods corresponds with this stronger mechanistic emphasis of research: biochemistry and molecular biology have dramatically changed how we understand physiology and disease. It is very difficult to identify a mechanism leading to disease in the whole animal organism, and it is very difficult to test selectively for a certain mechanism employed by a test substance using a complex animal model. An understanding of pathways increasingly allows the modeling of (patho-) physiology as a systems biology (systems toxicology) approach (Hartung et al., 2012, 2017, Smirnova et al., 2018). The scientific progress that is demanding more tailored experimental systems has been automatically making animal testing superfluous to needs (Rovida et al., 2015b). Figure 28.1 illustrates these developments.
The technological developments in alternative methods in toxicology (Busquet and Hartung, 2017; reproduced with permission). Technologies listed as today refer to the more broadly available new technologies, while those only emerging are listed as future.
The major obstacle for the development of new non-animal models is the prevailing over-reliance on the value of animal-based procedures as an information source in the life sciences. As long as researchers believe that they cannot produce the high-level publications needed to enhance their career without a new gene knock-out mouse, many researchers will choose animal experiments. A transparent and objective assessment of animal research's shortcomings is, therefore, key for opening the scientific community to change. The reproducibility crisis noted in the life sciences is, therefore, a godsend for those who want such a discussion about the shortcomings and misdirection of animal tests and models.
For decades, our desire to study the complexity of the human organism and its diseases seemed feasible only through using animals. Increasingly, however, very different complex systems are now used. These new approaches challenge the value of costly and time-consuming animal models and erode the justification for causing animal suffering. In vitro and in silico tools are cheaper and faster and, thus, can usually be carried out more readily and with greater ease of quality control. With such quality control, sometimes supported by validation, they represent robust methods for data generation. They are simplistic and partial, i.e. only reflecting a small fraction of (patho-) physiology. However, this is overcome by two principal approaches: reproducing complexity in the models (e.g., [multi-] organs on a chip); and combining pieces of information in integrated testing strategies or modeling (e.g., systems biology). Ultimately, all alternative approaches come with limitations too; but compared to animal models, these limitations can be surmounted by combining these new advanced animal-free models. With the ongoing improvements of these technologies and their (combined) use, we will be able to rely less and less on the evidently unsound animal component in this mix.
Many developments summarized here hint at an upcoming scientific revolution, changing the paradigm and predominance of animal experimentation in the life sciences. In his influential book, The Structure of Scientific Revolutions (1962), Thomas Samuel Kuhn (1922–1996) laid out some principles that nurture this expectation (Hartung, 2008). Our current belief system is being shattered by, among other things, the reproducibility crisis. Kuhn (1962) remarked that "normal science […] often suppresses fundamental novelties because they are necessarily subversive of its basic commitments" (p. 5); a good description of how alternatives have been perceived by many in the scientific establishment. The revolution takes place when "the tradition-shattering complements to the tradition-bound activity of normal science" (p. 6) hit. This is exactly what we observe with accelerated technological opportunities to transition into mechanistic, cellular, and even molecular understanding. The old (animal) model simply does not fully meet the needs of scientific and economic progress; it fails in cost, speed, level of detail of understanding, and human relevance. On top of this, animal experimentation lacks acceptance by an ethically evolving society. So let us embrace the revolution.
The input and editing by Martin Stephens are gratefully appreciated. The author is aware that many references are only to his own earlier publications; this is not meant to say that others have not published similar ideas, but these publications fully reference them and thus give the interested reader access.
The author is the Founder of Organome LLC, Baltimore, MD, which aims to make brain organoid technologies from Johns Hopkins University commercially available. He also consults Underwriters Laboratories on computational toxicology, with shares of their respective sales, and consults AstraZeneca on organoid technologies and testing.
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Stephens M.L. K. Betts N.B. Beck V. Cogliano K. Dickersin S. Fitzpatrick J. Freeman G. Gray T. Hartung J. McPartland A.A. Rooney R.W. Scherer D. Verloo and S. Hoffmann (2016). The Emergence of Systematic Review in Toxicology. Toxicological Sciences152 pp. 10–16.
Tollefsen K.E. S. Scholz M.T. Cronin S.W. Edwards J. de Knecht K. Crofton N. Garcia-Reyero T. Hartung A. Worth and G. Patlewicz (2014). Applying Adverse Outcome Pathways (AOPs) to Support Integrated Approaches to Testing and Assessment (IATA). Regulatory Toxicology and Pharmacology70 pp. 629–640.


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Big Head Blues Club at the Cedar, Minneapolis (03 Nov 2016)
Big Head Blues Club Setlist
I Want to be Loved*
Good Advice (Willie Dixon cover)^
Bring It On Home (Willie Dixon cover)^
The Seventh Son (Willie Dixon cover)
My Love Will Never Die#
Spoonful (Willie Dixon cover, w/ Howlin' Wolf and David Honeyboy Edwards versions)
I'm Your Hoochie Coochie Man (Willie Dixon cover) / Intro to Willie Dixon stories
Midnight Lover*
Pretty Thing (Bo Diddley cover)
That Same Thing (Muddy Waters cover)◊
Let Me Love You Baby (Buddy Guy cover)#
Hidden Charms (Howlin' Wolf cover)
Sittin' and Cryin' the Same Blues (Willie Dixon cover)
It Don't Make Sense (If You Can't Make Peace) (Willie Dixon cover)^
Crazy Mixed Up World (Little Walter cover)
You Need Love (Muddy Waters cover)*
-- Encore --
Little Red Rooster (Willie Dixon cover)
Trouble No More (Muddy Waters cover)*
Wang Dang Doodle (Willie Dixon cover)◊
* Mud Morganfield on vocals
^ Billy Branch on vocals
# Ronnie Baker Brooks on vocals
◊ Erica Brown co-lead vocals
11/12/16 York, PA Strand-Capitol Perf.
11/13/16 New York, NY HighLine Ballroom
11/15/16 Morristown, NJ Mayo Performing Arts
11/16/16 Troy, NY Troy Savings Bank Music Hall
11/17/16 Tarrytown, NY Tarrytown Music Hall
11/18/16 Elmira, NY Clemens Center
11/20/16 Poughkeepsie, NY Bardavon
Big Head Todd
This Colorado-based trio has built a career on years of solid touring throughout every college town and a strong DIY ethic. CRIMES OF PASSION is Big Head Todd and the Monsters' eighth album. …
With the Chicago Cubs winning their first World Series in 108 years, it was perfectly understandable that the party continue on another night—
And with the Big Head Blues Club in town at the Cedar Cultural Center celebrating Chicago blues legend Willie Dixon and others, the blues never sounded so celebratory and stirring.
The collective has actually become a re-occurring foray for Colorado group Big Head Todd and the Monsters as they pay homage and are joined on stage by some of the blues legends that inspired their own music.
The new album is Way Down Inside: Songs of Willie Dixon (on their own Big Records) and even if you're not familiar with the pioneering artist they are authoring, any listening to early Led Zeppelin, Jimi Hendrix, Cream, Rolling Stones, etc., clearly shows how much of an impact the blues in general, and Dixon in particular, have influenced all of their sounds.
This installment (the first album covered Robert Johnson) sees Todd and band joining up with three second-generation blues stars- Mud Morganfield, Billy Branch, and Ronnie Baker Brooks as well as guest vocalist Erica Brown, for a rousing two-hour show that showed why the art form is so vital and influential.
Morganfield, the eldest son of Muddy Waters, got things started by taking the reins for 'I Want to be Loved', dressed in a dapper suit, smiling and sitting while singing. Three-time Grammy nominee Billy Branch was next, spotlighted on 'Good Advice', and who knew Dixon better than others as he did a stint as harmonica player in his Blues All-Stars band.
Ronnie Baker Brooks was solid all night on guitar, he the son of Chicago blues master Lonnie Brooks and letting his guitar cry on the soulful 'My Love Will Never Die'.
Todd Park Mohr took us through what is maybe the first blues mash-up as he combined three versions of the classic 'Spoonful' then each told short stories around a killer 'I'm a Hoochie Coochie Man', a song that almost singlehandedly defines the blues.
After a stomping 'Pretty Thing' (featuring whistling and that classic Bo Diddley guitar rumble) Erica Brown pounced on stage to help sing 'That Same Thing', jumping and crying out like someone half her age, then disappeared again as quickly. Though Dixon was the focus of the night, his Chess Records label mate, Buddy Guy couldn't be ignored (also being from Chicago) and was also honored with a cover of 'Let Me Love You Baby'.
With all the recent social and political unrest, Billy Branch's take on 1971's 'It Don't Make Sense' seemed as much or more relevant today, than when it was originally written. Morganfield reprised his father's role, taking the lead for a rousing 'You Need Love' (which Led Zeppelin shamelessly stole for 'Whole Lotta Love') which closed the main set and on 'Trouble No more' for the encore.
The stage filled with everyone joining in for the evening finale of 'Wang Dang Doodle', with Brown's voice raising to the rafters on the chorus and sung mostly to Chicago "leading lady of the blues" Barbara LeShoure, who was in attendance, watching from a wheelchair just off stage.
"The blues are the roots, the rest are the fruits", it was said from the stage and no truer words were spoken, especially after witnessing this show.
For blues fans, this show is a no-brainer to attend; for everyone else, rest assured that this installment of the Big Head Blues Club is not only an elite combination of musicians to witness, but a history lesson as well into a unique American art form, and is one of the most musically satisfying shows of the year.
Erica Brown
Ronnie Baker Brooks / Billy Branch
Todd Park Mohr
Big Head Blues
Big Head Blues Club at Cedar Cultural Center, Minneapolis (03 Nov 2016)
john (johnc@weheartmusic.com) ♥ weheartmusic.com ♥ twitter.com/weheartmusic
Posted at 02:49 PM in Big Head Blues Club, Big Head Todd, Billy Branch, Cedar Cultural Center, Erica Brown, John, Minneapolis, Mud Morganfield, Ronnie Baker Brooks | Permalink | Comments (0)

redpajama_set_name: RedPajamaCommonCrawl


We're pleased to welcome Claire Messud to the bookstore to celebrate the paperback release of her most recent novel, The Burning Girl! Claire's talk and reading will be followed by a Q&A session.
The Burning Girl is a bracing, hypnotic coming-of-age story about the bond of best friends, from the New York Times best-selling author of The Emperor's Children.
Claire Messud is a recipient of Guggenheim and Radcliffe Fellowships and the Strauss Living Award from the American Academy of Arts and Letters. Author of six previous works of fiction including The Burning Girl, she lives in Cambridge, Massachusetts, with her family.


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Titan -- Oct. 14, 2010 (raw)
NASA's Cassini spacecraft took this raw image of Saturn's moon Titan on Oct. 14, 2010, kicking off an action-packed long weekend that took the spacecraft by eight other moons. The camera was pointing toward Titan at approximately 207,643 kilometers (129,023 miles) away. This image has not been validated or calibrated.
This image has not been validated or calibrated. A validated/calibrated image will be archived with the NASA Planetary Data System in 2011.
For more information on raw images check out our Frequently Asked Questions section.
Credit: NASA/JPL/Space Science Institute
Saturn Moons
This detailed view of Saturn's mid-B ring shows intriguing structure, the cause of which has yet to be explained by ring scientists. The image shows a radial location located between approximately ...
Mysterious B Ring
This graphic shows in a series of three images how Saturn's rings, after they became tilted relative to Saturn's equatorial plane, would have transformed into a corrugated ring. Images taken after...
Tilting Saturn's Rings
The F ring shows off a rich variety of phenomena in this image from the Cassini spacecraft.
F Ring Zoo
This image of the Earth is one of 60 frames taken by the Voyager 1 spacecraft on Feb. 14, 1990 from a distance of approximately 4 billion miles and about 32 degrees above the ecliptic plane.
Solar System Portrait - Earth
Engineers too eager to wait for image processing hand-colored this first-ever TV image of Mars in 1964.
First TV Image of Mars (Hand Colored)
MESSENGER's Earth flyby on Aug. 2, 2005, not only adjusted the spacecraft's path to Mercury - the gravity assist maneuver allowed the spacecraft team to test several MESSENGER science instruments b...
Twins Image
The ring moon Prometheus continues its work shaping the delicate F ring as Dione looks on. It is easy to see how Prometheus has an irregular, oblong shape, while Dione is quite round. The rings ar...
Prometheus With Distant Dione
Artist's concept of Cassini orbiter crossing Saturn's ring plane.
Crossing the Ring Plane
These raw, unprocessed images of Saturn's moon Dione were taken on Dec. 12, 2011, by NASA's Cassini spacecraft. Although Cassini obtained more detailed images on previous flybys of Dione, this was ...
Dione Rev 158 Raw Preview -- Image 2
This animation shows "beacons" of hot air seen in the infrared that appeared during a great springtime storm on Saturn from January 2011 to March 2012. These infrared hotspots in Saturn's northern ...
Infrared Hotspots in a Monster Saturn Storm
NASA's Dawn spacecraft obtained this image with its framing camera on August 6, 2011. Old and heavily cratered terrain is shown on Vesta. The framing camera has a resolution about 280 yards (260 me...
Old and Heavily Cratered Terrain on Vesta
Our robotic emissary, flying high above Saturn, captured this view of an alien copper-colored ring world. The overexposed planet has deliberately been removed to show the unlit rings alone, seen fr...
Ring World
These images from NASA's Dawn spacecraft show the ~20km diameter Numisia crater on asteroid Aster, after which Numisia quadrangle is named.
Topography and Albedo Image of Numisia Crater
These images from NASA's Dawn spacecraft, located in asteroid Vesta's Marcia quadrangle, in Vesta's northern hemisphere, demonstrate a special analytical technique, which results in shadowed areas ...
Revealing Shadows 3
The rich dynamics of Saturn's F ring are on display in this image taken by the Cassini spacecraft. Most of the features seen here are believed to be due to the ring's interactions with its shepherd...
Ring Shines
Looking upward from beneath the ringplane, the Cassini spacecraft spies Saturn's "wave maker" and "flying saucer" moons. Daphnis (8 kilometers, or 5 miles across at its widest point) and its gravi...
Atlas and Daphnis
This mosaic of Titan's south polar region was acquired during Cassini's first and distant encounter with the smog-enshrouded moon on July 2, 2004. The spacecraft approached Titan at a distance of a...
Tracing Surface Features on Titan -- Mosaic
+ View Related Story At the end of the formation of Saturn's satellites, a Titan-sized satellite spirals inward towards the planet due to interaction with the primordial circumplanetary gas disk...
Tidal Stripping of Ice from a Titan-Sized Satellite
In this image obtained by NASA's Cassini spacecraft on its closest flyby of Saturn's moon Rhea, the heavily cratered surface of the moon appears in great detail. Just to the bottom right of the ce...
Battered Rhea
These are the highest-resolution color images of any part of Saturn's rings, to date, showing a portion of the inner-central part of the planet's B Ring.
Colorful Structure at Fine Scales
Io, the most volcanic body in the solar system is seen in the highest resolution obtained to date by NASA's Galileo spacecraft.
High Resolution Global View of Io
This image from NASA's Dawn spacecraft of asteroid Vesta Fabia shows Justina crater, located in Vesta's Urbinia quadrangle, in Vesta's southern hemisphere.
Justina Crater
This wide and sweeping view of the sunlit rings of Saturn takes in the impressive variety in their structure -- from the clumpy and perennially intriguing F ring to the many waves, ringlets and gap...
So Much to See
Musical Rings September 27, 2004 Full-Res: PIA06485 Looking something like the fibrous bow of a viol...
Musical Rings
This set of images shows the areas mapped so far on Saturn's moon Titan by the Cassini radar mapper using its synthetic aperture radar imaging mode. Labels represent the approximate central longitu...
Titan Viewed by Cassini's Radar


Could you tell us hotels in Thrissur that provides 24 hours check-in check-out facility?
There are many hotels in Thrissur that offer 24 hour checkin facility. Some luxury hotels in city that offer 24 hour check in are Hotel Mangala Towers, Kallada Holiday Inn, and Dream city centre.You could also try these budget hotels Hotel Mangala Towers and Dream city centre that offer this facility.
Suggest us few good hotels in Thrissur that provide wifi.
These days Wi-Fi is part of basic facility that most hotels in Thrissur offer. These budget hotels in city offer free Wi-Fi service Dream city centre.
Could you suggest us few hotels in Thrissur that has free parking facility?
There are few hotels in Thrissur that provides free parking facility Dream city centre.
Can you suggest us hotels in Thrissur that offers rooms under Rs. 1700/-?
There are many hotels in Thrissur that offers hotels under Rs. 1700/-. For best options you can check Hotel Pearl Regency, Hotel Cee Pee Towers, and Dream city centre under 1700/-.
Can you suggest me hotels that have pay@hotel options in Thrissur?
Most hotels in Thrissur prefer that you pay some advance to book a room. However, there are some hotels that give you an option to pay@hotel like The Garuda Hotel, Hotel Pooram International, and The River Retreat Heritage Ayurvedic Resort.
Please suggest me 5 star hotels in Thrissur.
There are a lot of options for comfortable stay in Thrissur. Check this hotels for comfortable stay The Garuda Hotel.
Can you suggest few hotels with good front desk facility in Thrissur?
Yes, there are a lot of hotels in Thrissur that has good front desk service available. Check this hotels The Garuda Hotel, Joys Palace, and Hotel Pooram International.


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The predominant online source for Hawaiian and Polynesian art, artifacts, and antiques!
Kimo, Hawaii: Artist's Proof - by John Melville Kelly
Kimo. Hawaii, ca. 1934, Artist's Proof with original exhibition label. Archivally framed in superb premium Koa wood frame, ready to hang. Drypoint etching printed with tint plate. 10 x 8 in. (25.4 x 20.32 cm.) **If you are interested in this item, PLEASE CONTACT US at 808-227-2931 or mkg@maunakeagalleries.com for more information and accurate shipping rates to your location. --- Born in Oakland, CA on Nov. 2, 1879, John Kelly began his art studies at the Mark Hopkins Institute and Partington Art School. He worked for 14 years as an illustrator for the San Francisco Examiner before he and his wife, sculptor Kate Kelly, moved to Hawaii in 1923. The original plan was to stay for a year, but they fell in love with the islands and the people and stayed. Kelly produced numerous etchings and aquatints with Hawaii as a subject, primarily of human figures. He authored and illustrated "Etchings and Drawings of Hawaiians" in 1943, and "The Hula as Seen in Hawaii" in 1955. John Melville Kelly died in Honolulu in 1962.
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Available size options come on 1/8" canvas boards or 3/4" stretched canvasses because they are the easiest to ship and frame for you. Larger pieces I tend to use 1-1/2" thick stretched canvas which can be hung without a frame but I tend to think that frames really finish off an artwork. Shipping deeper and larger canvasses can also be a little more expensive.
Acrylic paints are professional grade and varnished to last a very long time. Once you've purchased you're selection, you will get an email from me to begin the process of discussing your special image request.
An acrylic commission can take up to two weeks to produce, depending on the commissions I have before yours, and the complexity of your request. Then allow for 5 business days for shipping.


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Solving Malfatti's high dimensional problem by global optimization
NACO Home
Derivatives of eigenvalues and Jordan frames
2016, 6(2): 127-151. doi: 10.3934/naco.2016004
Output feedback overlapping control design of interconnected systems with input saturation
Magdi S. Mahmoud 1,
Distributed Control Research Lab, Systems Engineering Department, KFUPM, P. O. Box 5067, Dhahran 31261, Saudi Arabia
Received March 2015 Revised April 2016 Published June 2016
In this paper, we establish new results to the problem of output feedback control design for a class of nonlinear interconnected continuous-time systems subject to input saturation. New schemes based on overlapping design methodology are developed for both static and dynamic output feedback control structures. The theoretical developments are illustrated by numerical simulations of a linearized nuclear power plant model.
Keywords: LMIs., dynamic output feedback, input saturation, Interconnected continuous-time systems, observer-based output feedback.
Mathematics Subject Classification: Primary: 58F15, 58F17; Secondary: 53C3.
Citation: Magdi S. Mahmoud. Output feedback overlapping control design of interconnected systems with input saturation. Numerical Algebra, Control & Optimization, 2016, 6 (2) : 127-151. doi: 10.3934/naco.2016004
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Ran Dong, Xuerong Mao. Asymptotic stabilization of continuous-time periodic stochastic systems by feedback control based on periodic discrete-time observations. Mathematical Control & Related Fields, 2019, 0 (0) : 0-0. doi: 10.3934/mcrf.2020017
Alexei Pokrovskii, Dmitrii Rachinskii. Effect of positive feedback on Devil's staircase input-output relationship. Discrete & Continuous Dynamical Systems - S, 2013, 6 (4) : 1095-1112. doi: 10.3934/dcdss.2013.6.1095
Gonzalo Robledo. Feedback stabilization for a chemostat with delayed output. Mathematical Biosciences & Engineering, 2009, 6 (3) : 629-647. doi: 10.3934/mbe.2009.6.629
Ta T.H. Trang, Vu N. Phat, Adly Samir. Finite-time stabilization and $H_\infty$ control of nonlinear delay systems via output feedback. Journal of Industrial & Management Optimization, 2016, 12 (1) : 303-315. doi: 10.3934/jimo.2016.12.303
Jian Chen, Tao Zhang, Ziye Zhang, Chong Lin, Bing Chen. Stability and output feedback control for singular Markovian jump delayed systems. Mathematical Control & Related Fields, 2018, 8 (2) : 475-490. doi: 10.3934/mcrf.2018019
Ahmadreza Argha, Steven W. Su, Lin Ye, Branko G. Celler. Optimal sparse output feedback for networked systems with parametric uncertainties. Numerical Algebra, Control & Optimization, 2019, 9 (3) : 283-295. doi: 10.3934/naco.2019019
Ruth F. Curtain, George Weiss. Strong stabilization of (almost) impedance passive systems by static output feedback. Mathematical Control & Related Fields, 2019, 9 (4) : 643-671. doi: 10.3934/mcrf.2019045
N. U. Ahmed. Existence of optimal output feedback control law for a class of uncertain infinite dimensional stochastic systems: A direct approach. Evolution Equations & Control Theory, 2012, 1 (2) : 235-250. doi: 10.3934/eect.2012.1.235
Huijuan Li, Junxia Wang. Input-to-state stability of continuous-time systems via finite-time Lyapunov functions. Discrete & Continuous Dynamical Systems - B, 2020, 25 (3) : 841-857. doi: 10.3934/dcdsb.2019192
James P. Nelson, Mark J. Balas. Direct model reference adaptive control of linear systems with input/output delays. Numerical Algebra, Control & Optimization, 2013, 3 (3) : 445-462. doi: 10.3934/naco.2013.3.445
Xiu-Fang Liu, Gen-Qi Xu. Exponential stabilization of Timoshenko beam with input and output delays. Mathematical Control & Related Fields, 2016, 6 (2) : 271-292. doi: 10.3934/mcrf.2016004
Andrey Olypher, Jean Vaillant. On the properties of input-to-output transformations in neuronal networks. Mathematical Biosciences & Engineering, 2016, 13 (3) : 579-596. doi: 10.3934/mbe.2016009
Quoc T. Luu, Paul DuChateau. The relative biologic effectiveness versus linear energy transfer curve as an output-input relation for linear cellular systems. Mathematical Biosciences & Engineering, 2009, 6 (3) : 591-602. doi: 10.3934/mbe.2009.6.591
Fritz Colonius, Guilherme Mazanti. Decay rates for stabilization of linear continuous-time systems with random switching. Mathematical Control & Related Fields, 2019, 9 (1) : 39-58. doi: 10.3934/mcrf.2019002
Farida Benmakrouha, Christiane Hespel, Edouard Monnier. Drawing the output of dynamical systems by juxtaposing local outputs. Conference Publications, 2011, 2011 (Special) : 145-154. doi: 10.3934/proc.2011.2011.145
Joon Kwon, Panayotis Mertikopoulos. A continuous-time approach to online optimization. Journal of Dynamics & Games, 2017, 4 (2) : 125-148. doi: 10.3934/jdg.2017008
Hanqing Jin, Xun Yu Zhou. Continuous-time portfolio selection under ambiguity. Mathematical Control & Related Fields, 2015, 5 (3) : 475-488. doi: 10.3934/mcrf.2015.5.475
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Harry L. Johnson, David Russell. Transfer function approach to output specification in certain linear distributed parameter systems. Conference Publications, 2003, 2003 (Special) : 449-458. doi: 10.3934/proc.2003.2003.449
Impact Factor:
Magdi S. Mahmoud


A girl stood in the deep shadow of the corner house. Her head was covered by a shawl, and I could not see her face, but her figure showed youth and a certain grace.
" 'Ello!" she said, without moving.
"When you goin' to get merried?" asked young Alf.
"When it comes," replied the girl softly. The voice that falls like velvet on your ear and lingers in your memory is rare. Wendell Holmes says somewhere that he had heard but two perfect speaking voices, and one of them belonged to a German chambermaid. The softest and most thrilling voice I ever heard I encountered at the corner of one of the lowest slums in London.
Interesting. I looked up Clarence Rook and found he is known for the "Hooligan Nights" series.
This article debates the likelihood that it was Victorian slum reportage, rather than Victorian fiction, but the author insisted it was rooted in fact. I think it seems like a mix of the two.
I'm guessing something this old may be available at Project Gutenberg or something like it.
Last edited by Pcdunn; 02-13-2018, 10:18 PM. Reason: Correcting typo.
"The Hooligan Nights" is a classic, and you really ought to read it, if you're at all interested in the Late Victorian demi-monde.
Bizarrely, the verb "to nark (on someone)" makes its appearance here, in 1899, no less, meaning exactly what it does today. I'd always held the unexamined assumption, as I'm sure that most of my generation did, that it derived from the practice of calling a narcotics officer a "narc". It's much older than that.
I downloaded it free in pdf format. Well worth reading. It's a great period to study, so much is out of copyright!
As you discovered, the original meaning of the slag word "nark" as in "narking" on someone, had nothing whatever to do with drugs, although as you say the present-day presumption is that it does have a link to drugs.
A learning moment for me, yeah.


Walk through the Stations of the Cross with your tour guide (or on your own), reading Bible passages, singing songs, and seeing the places where Jesus agonized on his walk to the cross. Take your time thinking about and meditating on the significance of Jesus' world-changing action. Tours begin every hour on the hour and last for nearly the full hour. The last tour starts at 4:00 p.m.
Click HERE for a link to last year's video of Stations of the Cross.


Mar 08,2019 , 10:10 AM IST Hyderabad: Man sets himself ablaze on road A man set himself ablaze on road at Snehapuri colony of Sanathnagar on Friday morning. Venkatesh Gupta is said to have come out of his home and doused himself with petrol before setting himself on fire. He was dead on the spot with severe burn injuries. It is learned that Gupta was depressed over the losses incurred in his businesses and committed suicide. Further details are awaited.


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Meteor fireball soars over Belgium, France, Germany, the Netherlands and Switzerland
Sun, 13 Oct 2019 14:55 UTC
© Roger Spinner - www.ogvt.org
The American Meteor Society (AMS) received 238 reports of a fireball over Belgium, France, Germany, the Netherlands and Switzerland on October 13, 2019. Several AMS members captured photos and videos of the event.
Video footage from AMS members 'Marco H' and 'Christophe F':
Comment: Just a few days before, a fireball was widely reported over France.
Meteor fireball seen flying over Washington state, southern British Columbia
© Greg K.
On October 6, 2019, the American Meteor Society (AMS) received 35 reports of a meteor over Washington state and southern British Columbia, Canada. AMS member 'Erik K.' from Seattle captured footage of the fireball on his doorbell camera:
NASA footage shows huge explosion of meteor fireball in skies above Arizona
The Express (UK)
Meteor shock: NASA footage shows huge explosion in skies above Arizona
The video showed a fireball travelling at more than 200,000 kilometres per hour light up the night sky over Arizona yesterday. The space rock was part of the relatively newly-discovered meteor shower, the October Ursae Majorids, which was only deemed separate from the usual October Orionid and Taurid meteors in 2007. NASA said the small object was travelling at a staggering 57.2 kilometres per second - or 205,920 km per hour - when it crashed into and exploded in Earth's upper atmosphere.
The NASA video showed the object streaking across the night's sky before producing a flash which outshone the Moon.
NASA has traced the meteor back to the Big Dipper constellation, which allowed the space agency to confidently state it is part of the October Ursae Majorids shower.
The meteor shower peaks during mid-October, and on clear nights one fireball can be seen per hour on average.
No debris from the meteor has yet been discovered on the ground.
Slow-moving bright meteor fireball over Trinidad and Tobago
Kim Boodram
Trinidad & Tobago Express Newspapers
SOME lucky citizens were on Tuesday night treated to what appeared to be a meteor blazing its way into Earth's atmosphere, looking much like a comet as it streaked across the sky.
The fireball appeared to have been visible mostly to those living in Central and Northern Trinidad and a number of people yesterday posted video clips of the celestial activity, accompanied by exclamations of wonder.
According to the Trinidad and Tobago Weather Centre, most people said the event took place between 9 p.m. and 10 p.m.
One video, recorded from a vehicle, also showed two smaller, round lights that at first appeared to be following the meteor, but many surmised that these were generated by the lens of the camera.
While "shooting stars" are commonly spotted, they are usually much smaller and burn up quickly.
The much larger object making its way across the local sky elicited a variety of comments.
Some were extremely pleased at the opportunity, while others joked that the object may have been the reviled "soucouyant" of local lore, an alleged vampire fabled to be an older woman who sheds her skin at night to stalk her victims.
Watch: Meteor fireball over the Mediterranean
Cathy Elelman
Euro Weekly
Tue, 15 Oct 2019 16:43 UTC
© Meterorides.net
The fireball originated from a rock from a comet entering the earth's atmosphere
A Spectacular fireball passed over the Mediterranean just off the coast of Almeria in the early hours of Sunday morning.
SMART project detectors at the Calar Alto observatory in the Filabres mountains and at observatories in the Sierra Nevada and Seville captured stunning images of the fireball as it made its way across the night sky at 3.44 am on October 13 at an altitude of some 95 kilometres.
Meteoroides.net explained on social media that the "beautiful and slow" fireball originated from a rock from a comet entering the earth's atmosphere at a speed of around 58,000 kilometres per hour.
Brilliant midnight meteor fireball lights up sky over northeast China
Tariq Malik
© CCTV
A meteor lights up the midnight sky over the northeastern China provinces of Jilin and Heilongjiang in this dashcam and surveillance camera video views taken on Oct. 11, 2019.
It turned night into day.
What appears to be a dazzling meteor lit up the sky over northeast China on Friday (Oct. 11), appearing as a brilliant fireball in surveillance videos of the event.
The meteor occurred at about 12:16 a.m. Beijing Time, turning night into day and casting dark shadows as it streaked through the sky, according to the state-run CCTV. Videos of the fireball were captured by surveillance cameras in the city of Songyuan in the province of Jilin, as well as by many residents across northeast China, CCTV reported.
Over 100 report seeing large meteor fireball over Indiana, Kentucky, Ohio, Pennsylvania and West Virginia
Jeff Booth
WBNS
Mon, 07 Oct 2019 18:09 UTC
© TravelLife/Shutterstock
If you saw a fireball streak across the sky on Saturday evening you're not alone.10TV received several reports from people in central Ohio who saw a bright meteor with a long trail across the sky.
The American Meteor Society says it received more than 130 reports about the fireball, seen over Indiana, Kentucky, Ohio, Pennsylvania and West Virginia.
It was likely a product of the South Taurid meteor shower.
The shower is caused by leftover debris from Comet Encke. It's not very active, you're lucky to see five to seven meteors an hour at its peak, but it is known to produce fireballs.
Comment: On October 5th, the American Meteor Society received 119 reports of a meteor over the southeastern US.
We received 119 reports about a fireball seen over AL, FL, GA, NC, SC and TN on Saturday, October 5th 2019 around 10:26 UT.
AMS member Salvatore T. caught the fireball on his doorbell camera:
Meteor shower or space junk? Geologists probe mystery of fireballs over Chile
Fri, 11 Oct 2019 19:10 UTC
© National Park Service
When a barrage of fireballs recently rained down on Chile, many assumed it was a meteor shower and moved on. However, analysis has since dismissed that theory and experts are struggling to explain the unidentified falling objects.
The mysterious, fiery phenomena crash-landed in seven locations in Dalcahue City on the Chilean island of Chiloé late last month. They sparked a flurry of blazes which firefighters had to scramble to extinguish.
Initial news reports claimed that the fireballs were likely a meteor shower, however an analysis by geologists from Chile's National Geology and Mining Service has since found that none of the seven crash sites contained any traces of meteorite.
Meteor fireball widely reported over France
© American Meteor Society (screen capture)
Observers map of AMS event 4940-2019
The American Meteor Society (AMS) has received 246 reports about a meteor fireball seen over France (Auvergne-Rhône-Alpes, Île-de-France, Bourgogne-Franche-Comté, Bretagne, Centre-Val de Loire, Grand Est, Hauts-de-France, Normandie, Nouvelle-Aquitaine, Occitanie, Pays de la Loire and Provence-Alpes-Côte d'Azur) on Wednesday, October 9th 2019 around 17:47 UT.
A video of the event (4940-2019) was uploaded to the AMS website.
Meteor fireball lights up sky across California
© Twitter/Courtesy of @AardwolfEssex
California residents took to social media Monday night to report a glowing fireball across the night sky over multiple cities including Sacramento, Lynwood and San Diego.
One social media user caught a video of the fireball shooting across the sky while he was driving. (See below)
Although unclear, the object appears to fit the description of a fireball, which is a meteor that burns as brightly as the planet Venus in the morning or evening sky, according to the American Meteor Society.
According to several reports, the annual Draconid meteor shower is expected to generate around eight shooting stars every hour starting Tuesday.


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Q: Javascript scroll fullpage.js. How to make so that at a strong scroll several sections were scrolled, instead of one? I want to scroll several pages after strong one-time mouse scroll. By now after any scroll there is only a change of one section. How to do it with fullpage.js or JavaScript in general (also jQuery would be ok)?

A: There's currently no way of differentiating between an actual scroll or an inertial one and there are only a few attempts to solve this issue using Javascript. (which are not perfect either)
Javascript doesn't provide a good solution for this problem known as "kinetic scrolling".
fullPage.js deals internally with it but it is far from perfect.

A: I found a simple solution, but, unfortunately, it is imperfect.
document.getElementsByTagName('body')[0].addEventListener('wheel', function (e) {
    if (e.deltaY > 100)
        $.fn.fullpage.moveSectionDown();
    else if (e.deltaY < -100) {
        $.fn.fullpage.moveSectionUp();
    }
}

redpajama_set_name: RedPajamaStackExchange


"Breaking Bad" ran for five seasons from 2008 to 2013 and told the story of Walter White, a chemistry teacher who turns to making meth after a cancer diagnosis and enlists the help of former student Jesse.
The Hollywood Reporter first reported the news and also says that Netflix will screen the film first and then it will air on U.S. network AMC, a reverse of how Breaking Bad was first shown.
Per THR, the film "will follow the escape of a kidnapped man (Paul's Jesse) and his quest for freedom".
For Netflix and AMC to share the Breaking Bad follow-up is fitting as the two outlets share the credit for the success of the original series.
Deadline is reporting that Vince Gilligan's Breaking Bad movie is headed to AMC and Netflix. The Breaking Bad series aired originally on AMC, with seasons subsequently made available for streaming on Netflix. Even Gilligan himself acknowledged that when accepting the show's first Emmy for Best Drama. In the past, he has directed a number of episodes of Breaking Bad, Better Call Saul, and The X-Files, so we expect big things from this. Deadline's report says it's still unknown if the project will air as one feature film, or be cut into episodes. I don't think our show would have even lasted beyond season two [if not for Netflix].
Though it hasn't been confirmed officially, Revenge of The Fans claim to have seen the official cast list, and states Bryan Cranston will reprise his role as antihero Walter White, alongside Todd, Badger and Skinny Pete.
Per the New Mexico Film Office, a film titled "Greenbrier" was scheduled to film in Albuquerque from November to mid-February.


CHAPEL HILL – RENCI and the School of Information and Library Sciences (SILS) at UNC Chapel Hill have joined a nationwide effort to build an integrated data management infrastructure that will help scientists better understand the complex processes of the planet Earth, from meteorology to solid earth sciences to hydrology and oceanography.
RENCI team tackles the challenge of securing sensitive medical research data For medical researchers, clinical data means opportunities and risks: Opportunities for experiments and analyses that will lead to new knowledge about human diseases; and risks because the burden of keeping personal medical data secure usually falls on the shoulders of the researchers.
CHAPEL HILL, NC, July 16, 2009—Almost a year after the Data Intensive Cyber Environments (DICE) research group moved from the University of California at San Diego to the University of North Carolina at Chapel Hill, the internationally recognized research group has established deep ties to the Renaissance Computing Institute (RENCI).


A delightful concert showcasing the talented winners of the 2018 Ryde Eisteddfod. Artists include Kanon Ito - pianist; Jae Won Kim, Timothy Nunn and Chloe Robbins - vocalists; James Birch - strings; Matilda Rose Williams - Brass; and Nicholas D'Silva - woodwind. Light refreshments included at interval. There is no reserved seating.
Full-time Students and Children - Free.
Cash sales only at the door as there are no credit card facilities available.


What makes Oliver Johnson's The Lord of Shadow Keep so memorable? It's a question I've been asking myself for nearly thirty years. After all that time, the only answer I have, while not particularly satisfying, is that it's talent. It's artistry. It's a dash of what we call genius.That's what makes the difference between a simple solo dungeon and an imaginative journey you can believe in.
You see - being honest now - Oliver is not great on rules. Unlike me, he won't do a detailed map and intricate flowcharts. Having a background in English literature, he doesn't share my scientist's delight at probabilities, patterns and problem-solving. And he doesn't write as fast, while I can churn this stuff out by the yard.
By day you sail on lavender waves under a vault of azure and gold. By night the sails gleam dazzlingly white in the rays of the moon, and each star finds its twin in the dark ocean depths.
So there's some poetry in my soul too. It's not all equations and graphs. But literary talent has never been about pretty writing - it's about that and much more. It's the ability to convey a palpable atmosphere, a resonance of theme, to vividly evoke character, and to give the sense of the author's personal presence through the voice of their writing.
So if I had written Shadow Keep - or co-written it, as originally intended - you would have got an adventure with some clever puzzles, a map that made sense, encounters that were balanced according to the statistics of 2d6 rolls. Even nice writing. But you wouldn't have got that strange, Gothic-drenched, opiated dream quality that Oliver does as naturally as breathing, because it's something he absorbed into his pores while studying Byron and Shelley and those other poetical fellows. The only recent example of such exquisite pre-Victorian Gothic Romanticism to match it is in Fumito Ueda's Ico and Shadow of the Colossus games. Watch for that same flavour in Oliver's forthcoming fantasy series The Knight of the Fields.
The Shadow Keep cover painting by Bruno Elletori (or Elettori, or Ellitori, depending on how long the cover designer spent at lunch that day) is not really ideal. The illustrations should have been by a Victorian artist thoroughly steeped in Gothic. For the interiors on this new edition, we've used Irish artist Harry Clarke, best known for his Edgar Allan Poe illustrations. I know purists will grumble. We'll get some withering reviews on Amazon for changing things around. But you can still get the original version for a penny, so no harm done.
If you want to see the Gothic design for the new edition, it's out now from Fabled Lands Publishing. At a cost of more than a penny, I'm afraid, but we'll be sure to spend the profits on laudanum, quills and parchment for the next great Johnson opus.
I have this book (of course) but haven't read it in well...i don't know, over 25 years probably (which yes, means i was a child when i last read it...i've been working my way through my 200+ gamebooks but it takes a while though all the other Golden Dragon i've reread in the past two years). Now I want to go and reread it.
It's too bad that in the original version these pretty covers were all a little ruined by that awful logo (which i know you complained about many times before) and sometimes too the font of the titles. I also have the french ones and the covers are easier to appreciate on those.
Anyway, they might not cost a penny but 6$ or so is a damn good price for a new book! Wouldn't that have been about what they cost way back in the day? It's like i'm back in 1986 except we have the internet! I think the low price + new illustrations means you have me convinced. I think i'm gonna be getting all of them now. You know what this means right? Having to conceal those purchases from my gf lest i want to face the uncomfortable "but...don't you already have those?" question to which i can only lamely answer something like "Yeah but see these are a different edition and and..." followed by mumbling while gf raises an uncomprehending and somewhat disapproving eyebrow. Sometimes people they just DON'T understand.
Bruno had a kind of Frazetta-lite style that makes me realize now I was very lucky to get him. The US covers of the Golden Dragon books, though... what were they thinking?


By creating a comfortable concierge environment, Progressive Eyecare has gone beyond the standard of service among eye care health providers to ensure that each patient's experience is personal and unique, rather than just another visit to the clinic. We are the leading provider of optometry services and vision care products in North Las Vegas.
Our goal is to provide you with a professional level of personalized care and to ensure that you receive the service you expect. We pay careful attention to details during each consultation, taking time to listen to you so we can provide the appropriate solution in no time.
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Finding a reliable North Las Vegas optometrist doesn't have to be hard if you first look to Progressive Eyecare. Give us a call today at (702) 368-2021 or fill out an appointment form to schedule an exam.


SUNDAY, Traditional Worship takes place in the Sanctuary at 9:00 am. Enjoy a traditional flow of worship, sing hymns accompanied by our organist, and take in the music of the Fargo Faith Choir. And each week, Pastor Ray delivers a message, of course!
Sunday School takes place at 10:00 am. Sunday School classes for K-5, 6-12, and adults are offered at Fargo Faith.
Our Coffee Fellowship also takes place at 10:00 am in the Fellowship Hall. Visit with our church family and get to know some new people over a cup of coffee and a delicious treat!
Our Contemporary Worship Service takes place at 11:00 am in the Sanctuary. Enjoy the feel and flow of a true worship service with a more modern feel featuring music and worship under the leadership of the Big House Band and take in a message by Pastor Ray!
We aspire to be a Christian community of action.
We seek to support our local community and the global community. We challenge all to go into the world in service, putting personal faith into action.
We aspire to be a caring and nurturing community.
We seek to proclaim the good news and live the example of Jesus, creating a community of love, compassion, and forgiveness where people encounter God and are transformed and renewed by Christ's love.
We aspire to be a community of faith that welcomes all people.
We seek to invite and welcome all people to experience the love of Christ. All people are welcome at Faith United Methodist Church.


text:
Katy Hanna
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Actor. West End. Excited for next adventure!!!
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Training: GSA Conservatoire, 1st Class BA Hons in Musical Theatre. Katy was also a member of the National Youth Theatre, National Youth Choir of Great Britain and Laudibus – National Youth Chamber Choir.
Theatre includes: The Phantom of the Opera (Her Majesty's), first cover Madame Morrible/ensemble in Wicked (Apollo Victoria), swing in Les Miserables (Queen's), ensemble in The Phantom of the Opera 25th Anniversary concert (Royal Albert Hall), swing in The Phantom of the Opera (Her Majesty's), choir in Les Misérables 25th Anniversary concert (O2 Arena), swing/Factory Girl in Les Misérables (Queen's) and understudy Johanna/ensemble in Sweeney Todd (Royal Festival Hall).
Television and recordings include: Laudibus – Song of Songs(Delphian Records), The Susan Boyle Story (ITV), Les Misérables 25th Anniversary concert (Universal Pictures) and The Phantom of the Opera25th Anniversary concert (Universal Pictures).
Currently appearing in
Open Date: 9 Oct 86
Part: Cast (from 3 Sep 2018)
THE PHANTOM OF THE OPERA Far beneath the majesty and splendour of the Paris Opera House, hides the Phantom in a shadowy existence. Shamed by his physical appearance and feared by all, the love he holds for his beautiful protégée Christine Daaé is so strong that even her heart cannot resist. The musical opened at Her Majesty's Theatre on 9 October...
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Here are a few other Performers appearing in this Show that you may like to check out. Click the + icon above to view more!
Adam Robert Lewis
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Part: Swing
Alistair So
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Part: Ensemble / First cover Raoul
Andrei Teodor Iliescu
Part: Slavemaster
@bentyler21
Part: Ensemble
Bridget Costello
@bridgetcostell0
Part: Alternate Christine Daaé
Britt Lenting
@BrittLenting
Part: Carlotta Giudicelli
Open Date: 25 Sep 85
In October 2010 Cameron Mackintosh's legendary production of Boublil and Schonberg's Les Misérables celebrated its 25th anniversary in London and is now the world's longest-running musical. This international award-winning musical sweeps its audience through an epic tale of passion and destruction, against the backdrop of a nation in the grip of r...
Open Date: 7 Sep 06
Part: Ensemble / First cover Madame Morrible (24 Jul 2017 to 21 Jul 2018)
WICKED When Dorothy famously triumphed over the Wicked Witch, we only ever heard one side of the story. Gregory Maguire's acclaimed 1995 novel, Wicked: The Life and Times of the Wicked Witch of the West, re-imagined the Land of Oz, creating a parallel universe to the familiar story written by L Frank Baum and first published as The Wonderful Wizar...
Related News and Features
Cast changes are announced for the West End cast of The Phantom of the Opera with Josh Piterman playing the title role
As The Phantom of the Opera heads into its incredible 34th year in the West End, Andrew Lloyd Webber and Cameron Mackintosh have announced that Australian singer and performer Josh Piterman will make his West End debut as The Phantom from 9 September 2019, with Britt Lenting as Carlotta Giudicelli and Richard Woodford as Monsieur André. Do you feel the music of the night calling you back to Her Majesty's Theatre?
Unmasked: Tim Howar is the West End's new Phantom as Lloyd Webber's musical celebrates 33 years
Joining Tim Howar, who plays the title role in the London production of The Phantom of the Opera for an initial run from 3 September to 8 December 2018, are Kimberly Blake as Carlotta Giudicelli and Ross Dawes as Monsieur Firmin.
Thrillifying cast: Alice Fearn & Sophie Evans are Wicked's new Elphaba & Glinda
We love it when an understudy steps fully into the spotlight so splendiforous congrats to Alice Fearn, who is a standby Elphaba no more. She's joined by Sophie Evans as Glinda and several other WICKED newbies from 24 July 2017 at the Apollo Victoria...


Use this converter to convert weight or mass values from stone to kilogram ( 1 stone equals 6.35029318 kilogram). Enter weight to find how many kilograms in stones.
Value in kilogram = 6.35029318 x Value in stone.
How to convert Stone to Kilogram.
There are 6.35029318 kilogram in a stone ie. 1 stone is equal to 6.35029318 kilograms. So if we are asked to convert stone to kilogram we just have to multiply stone value with 6.35029318.
54 stone equals 54 x 6.35029318 kilogram i.e 342.91583172 kilogram.


For the gaints, i think it will look beter when you make the "N" complete instead of mixing in the "Y"
The giants monogram seems too much like a corporate logo to me, It also reads as an M at first glance. I love what your doing thus far, but I think you should scrap the giants one and restart from scratch. The Giants logo will be hard to redesign, but I can't wait to see what you have in store!
What if with the Giants logo, you made the top hooks (?) match the bottom hooks, so that they're all facing outward?
I'll come back to the Giants. I'm very open to any ideas you may have for them.
I concur with Suededesigns. A more pointed tip/top as if you were looking at the building from the bottom up.
This is one of my favorites so far, simple but amazing.
The giants looking good to me now.
And the LA Rams are my favorite so far, realy good job!!
Absolutely love the Jets Logo... perfect!
Giants, I really like the first one... maybe make the perspective a little deeper, like the updated one. And add a cap. think Chrysler Bldg top.
Rams, I like a lot. A LOT!
Still not feeling this one, maybe you could do something more aligned with their current logo but add some character to it. Definitely some red in the logo too. I love the rams logo though!
I think your first Giants logo had more potential. Possibly lengthening the center arm of the Y so that it mimics a spire would make it seem a bit more tall building-y.
Green Bay Packers: What to do with the greatest logo of all time (pardon my bias)? Well I started by making the green a bit more blue, then moved back to the football shape that was originally intended. That didn't feel like enough of a divergence from the original, so I started playing with laces. This one's going to need some C&C.
Nice move on the packers, it is very dificult to rebrand this logo. But I like it with the laces, nice concept.
Maybe you have to try somthing with the "G" mixed in the "B" or with their logo from the 60's?


This item (P13190) is not currently available for purchase.
This beautiful prelit wreath is decorated with blue and silver balls. A large blue bow with two blue and silver bells is the focal point of this ornate piece. It even plays music when a motion senor is activated. Lit by 18 cool white LED lights. This piece will brighten your holidays.