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Video utility now supports Wi-Fi sync and can create ringtones.
A year and a half later, Softorino YouTube Converter looks positively quaint compared to the powerhouse sequel, which dramatically improves upon the original in every way. It’s not perfect—and no longer free like the original was—but the convenience more than makes up for the cost.
Like to watch 4K videos on your iPhone 7? Softorino YouTube Converter 2 now supports those huge downloads, as well as VR 360 and high frame rate videos.
The first Softorino YouTube Converter 2 ($20) improvement is wireless connectivity. Like Softorino’s equally handy Waltr 2, YouTube Converter 2 now recognizes iOS devices set up in iTunes for Wi-Fi sync, which appear as a transfer destination without being tethered to your Mac or PC.
Wi-Fi worked for me straight away, but you’ll want to double-check the preference setting for enabling wireless connectivity; there’s also a short tutorial video that walks users through this process. You can still connect using Lighting or 30-pin cables; YouTube Converter 2 is compatible with all Apple devices dating back to the original iPod in 2001, and in my tests, transfers were equally fast wireless or wired.
Speaking of speed, the entire application boasts a 4x improvement over the original, which was already quite peppy to begin with. This is mostly noticeable when downloading larger 4K Ultra HD videos, and YouTube Converter 2 now supports VR 360 and high frame rate videos up to 60fps as well.
Softorino YouTube Converter 2 adds the ability to search for YouTube videos without leaving the app, but you’ll have to copy a URL for the other 52 supported websites.
Despite the name, YouTube Converter 2 is not limited to downloading YouTube videos. At present the utility works with 53 different websites just by copying a URL, which is automatically picked up by the software and ready to download in one click. The list includes Funny or Die, Discovery (including sister sites like Animal Planet), Bandcamp, SoundCloud, and more.
YouTube Converter 2 includes one major improvement for downloading funny cat videos and the like from Google’s service, however. In-app search makes it easy to find whatever you’re looking for without a web browser. Just type in the search field, and a panel appears at left with your results.
Select a video, and you can quickly queue it for download to your Mac, iOS device, or directly to iTunes without invoking the Command-C copy shortcut. It would be nice if this worked with other supported websites as well, but frequent YouTube downloaders will definitely appreciate the bump in convenience.
Speaking of handy, YouTube Converter 2 now converts downloads to ringtones as well as video or audio files. You have the option of saving the entire song or only the first 30 seconds, but sadly there’s no way to trim a specific section. It’s worth noting that transferred ringtones are lost when syncing via iTunes, so you’ll want to save audio and add them to your Mac or PC library as Tones in that case.
One-click ringtones are convenient, but you can’t trim the selection and files are lost when syncing Tones with iTunes.
YouTube Converter 2 addresses a few shortcomings of the original. You can now double-click the title to customize the file name prior to conversion, grab an entire playlist at once, and automatically include subtitles. But other limitations remain, such as sparse or non-existent metadata, often poorly-cropped music artwork, and the fact YouTube Converter 2 can only add videos to the Home Movies section of the TV app.
Technical limitations aside, Softorino YouTube Converter 2 is the most convenient way to download website videos to iOS devices.


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In general, shopping in Canada is similar to shopping in the United States. There is a combination of large malls, with other large chain stores built nearby, and individually owned shops, boutiques and chains located throughout the cities and towns. Mostly what is sold in the malls is clothing, whereas one would go to large chain stores nearby for office, computer, or household products. Some Canadian malls in downtown areas start underground and go up for six or seven floors. The neighborhoods all have stores that are designed to aid the shopper who has run out of something at the last minute – whether it be a kind of food, stationary supply or article of clothing.
In Quebec, there is usually one large flea market per city, which is open on a daily basis. At a “marché aux pusses,” one can expect to find anything and everything small and unexpected – from used jewelry to radio batteries to clothing to household items, all at prices which have been negotiated.
In general, stores are open Monday through Wednesday from 9:00 a.m. to 6:00 p.m., on Thursday and Friday from 9:00 a.m. to 9:00 p.m., Saturday from 10:00 a.m. to 5:00 p.m., and on Sunday, from 12:00 noon to 5:00 p.m.
"Flowers for a Mother's Birthday"

industry_corpus2: Real Estate & Construction


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Star Wars fans may be looking to the future, but one Rebels hero was just written into the epic Battle of Hoth. The movie series may be best known for its space battles (or 'star wars' if you will) as opposed to planetside conflicts, but The Empire Strikes Back defied expectations with its first Rebel/Empire face-off. Not to mention set the standard for Rebel bases existing on some of the harshest, most dangerous, and least habitable worlds in the Star Wars galaxy. And in a new comic series from IDW, it's the franchise's fighting women who are getting the spotlight.
With Star Wars: The Last Jedi resembling Hoth in more than one way, it seems the perfect time to revisit the snowy planet in the new, Disney-approved canon. That's one of the stories set to be told in the series, beginning with Star Wars: Forces of Destiny - Leia #1. And now that the first pages of the book have been revealed ahead of its January release, the Star Wars canon needs a change. Because Rebels heroine Hera Syndulla is also on Hoth before The Empire Strikes Back begins.
It's not the first time that Hera in particular has been woven into new parts of Star Wars (especially those that take place close to, or alongside Rebels). She's included in a Rogue One cameo as "General Syndulla," confirming her promotion from where Rebels finds her. And in the animated series that preceded the Forces of Destiny comic, it was also confirmed that Hera was at the Battle of Endor. Now, she was also riding Tauntauns across Hoth with Han and Leia before the Empire even discovered the Rebels' new hideout.
The preview only gives away this small cameo appearance, with Hera Syndulla's full role in the issue hard to predict. Of course, for Star Wars fans looking to see where and how the new canon is being expanded and interconnected, every new link is to be celebrated (and mentally logged for future reference). Now that Hera Syndulla has shown up as a key member of the Rebellion at both Hoth and Endor (the major battles of Episode V and Episode VI), fans will certainly ask... did Hera play a role in the Battle of Yavin, too? The Death Star is coming to Star Wars: Rebels at some point, so anything is possible.
Those drawn to the idea of seeing more Star Wars heroines get time in the spotlight are in for even more of a treat than a Leia-Hera team-up. Issue #2 of Forces of Destiny will be shifting focus to a story from Rey's own life. Issue #3 will be a story following Hera as the protagonist, and Issue #4 will reunite Padmé Amidala and Ahsoka Tano. And as a special treat to fans of the recent blockbuster Star Wars: The Last Jedi, the final instalment of the five-issue series will star Paige and Rose Tico, sisters whose bond plays a central role in the movie's new Resistance heroes.
Star Wars: Forces of Destiny - Leia #1 will be released on January 3, 2018.

industry_corpus2: Film & Entertainment


text: Rich returns despite what happened last time! The first ever tie for book of the week! Orko's killing it, and by 'it' I mean Superman. Pete's guilty pleasure returns with a vengeance.

industry_corpus2: Literature & Emotions


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Though views like this show how much human activity goes on at Cát Bà Town on Cát Bà Island, most of this incredibly biodiverse haven is still undeveloped. A third of the island, and a portion of the bay, are preserved as Cát Bà National Park. With little more than 110 square miles of land, Cát Bà contains a variety of environments, from mangrove swamps to rocky karst cliffs. These cliffs are home to the island’s rarely seen, and very endangered, primate, the golden-headed langur.
Cat Ba is the largest of the 367 islands spanning 260 km² that comprise the Cat Ba Archipelago, which makes up the southeastern edge of Ha Long Bay in Northern Vietnam. Cat Ba island has a surface area of 285 km² and maintains the dramatic and rugged features of Ha Long Bay. It is commonly used as an overnight hotel stop on tours to Ha Long Bay run by travel agents from Hanoi. This island belongs to Haiphong city – the most famous city of industry in Vietnam.

industry_corpus2: Travel & Geography


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It seems these days that there is not a single movie series from the past left untouched when it comes to remakes, prequels of sequels. While some might argue that it’s out of pure lack of inspiration and the almost certain success the film will receive, others don’t really mind, and just sit back to enjoy a new release of their favorite franchise. This time, it’s the Ocean’s films that get a sequel with Ocean’s Eight. No George Clooney or Brad Pitt this time though, but badass women such as Sandra Bullock and Cate Blanchett.
Debbie Ocean (Sandra Bullock) is a convicted felon and sister of Danny Ocean (you remember, George Clooney’s character in the Ocean’s trilogy), but after serving a good deal of her sentence, she is released from prison early. While she promised to be good this time, it doesn’t take long before she goes down a shady path once again. As soon as she’s released from prison, she goes to visit an old friend, Lou (Cate Blanchett), who used to be her partner in crime but is now the owner of a nightclub. Debbie comes to Lou with a clear plan: rob a 150 million necklace that will be worn by the famous actress Daphne Kluger (Anne Hathaway) at the Met Gala, THE event of the year for fashionable New York.
Lou is in on the plan, but they won’t be able to do this on their own. That’s why they call in the help of some other cunning women: Nine Ball (Rihanna), a hacker, Constance (Awkwafina), a common thief, Rose Weil (Helena Bonham Carter), a fallen fashion designer, Tammy (Sarah Paulson), a thief become housewife, and last but not least Amita (Mindy Kaling), a jeweler’s daughter. Together they plan one of the biggest heists in American history. Question is: will they succeed?
For fans of the Ocean’s trilogy, this movie must come as a bit of a déjà vu. Just like Danny in the Ocean’s Eleven movie, Debbie concocts a plan for the biggest heist ever seen while she’s in prison, then she’s let out early, and immediately forms a team around her to execute her plan. Danny’s men went for the casino, Debbie’s women for the diamonds at the Met. Even though the stories are very similar, Ocean’s Eight is still quite a fun film to watch. The story is quite slow, but does really take the time to zoom in on each character. While it slows the story down, it could also definitely be seen as a good aspect, as with so many characters, things could easily get too complicated without a proper introduction.
Just like the Ocean’s trilogy, Oceans Eight too has an absolute top cast. It’s rarely seen that so many celebrities star in a film like this, where there’s actually one storyline where they all fit in. Sandra Bullock and Cate Blanchett show once more what diverse characters they can handle. Helena Bonham Carter’s character Rose Weill is quite unstable, which is a characteristic that often comes back in her roles. Also celebrities from other branches such as Rihanna and Awkwafina joined the ranks. Definitely Rihanna was actually quite convincing.
The Blu-ray edition of Ocean’s Eight offers some interesting content that actually contributes to the movie as a whole, rather than simply lengthen it by throwing useless snippets at us. You’ll see how the Met Gala was recreated and how the director worked together with Vogue and those of the institution to make a fictional Met Gala that could rival the real one. Other than that, there’s more inside information about the characters and why some actresses were chosen to perform in this movie. There are also some deleted scenes to vie if you’re into that.
Let’s make one thing clear: Ocean’s Eight is definitely not a bad movie. A lot of references are made to the original Ocean’s Eleven film, almost to the point where you could say it is a remake, but with women in the lead this time. Nonetheless, there was still an original touch to the whole. Acting was on point, and the extras of this Blu-ray release are actually worth something. It may not be better than the original, but you will definitely have a good time watching this one if you enjoyed Ocean’s Eleven, Twelve and Thirteen.


text: Published 1925. Reprinted 1953. Print code: 1000/53.

industry_corpus2: Others


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I was brimming with excitement all of Thursday. I couldn’t stop thinking about my date with Seabiscuit. I was very excited about his joining me at the theater plus the night adventures that would follow.
I hurried home after work, took a quick shower, and headed out. It had been a warm day, and I was doubtful that I needed my jacket; however, then I remembered being cold at a previous performance in the evening. Even though I had checked the weather and saw Orinda was only predicted to be in the low 60s in the evening, I knew that up in the hills, where the theater is actually located, it can get much colder. I felt foolish carrying such a large jacket on BART and felt too warm to need it, but better safe than sorry.
It was good I did. By the time I arrived at the theater, it was significantly cooler. I was happy without a jacket but realized that once the sun finished setting, I would need to put it on. I waited for Seabiscuit to arrive, and was excited to see him clean-shaven–as I had ordered as his Mistress. How good that he should obey so well! And he finally looked like one of his own photographs.
I told him previously that he appeared to be a servant of the Many-Faced God because his face never seemed to match from one photograph to another. The angles were off or something seemed so strange about it. He didn’t look like his photographs. I knew it was him, but how strange and different they all seemed.
There was a crowd, and I could tell he felt a bit shy. We hugged and kissed each other’s cheeks, then held hands as we walked up the hill from Will Call to the theater.
He bought dinner for us at the café, and we continued holding hands. The line was long, and we really only had 10 minutes to eat before needing to be seated. He was impressed by my tickets and how close we were to the stage. The temperature had dropped significantly, so I put on my jacket when we were seated but he was astounded that I didn’t close it until after intermission. I held his hand in his lap during the first half.
During intermission, he rented a blanket while I used the restroom and got my free bag of Peet’s coffee for renewing my subscription for the theater. We shared the blanket, and for the second half, he held my hand on my lap.
The performance was amazing, as all the shows I have seen there have been. CalShakes has done very well at selecting and directing plays that resonate with race issues going on currently, and this play was exceptionally well done in that regard. Seabiscuit enjoyed it greatly, and I told him he should return with me for all of next season. He said he would love to. It was his first time going to the theater in a very long time, and he said the final scenes with the bed on stage would linger in his memory for a long time.


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Opening Question: If you could learn one thing and become a master of it by the snap of your finger, what would that one thing be?
– Going to talk about being smart today!
– The Bible has some interesting perspectives on what it means to be smart.
Question: What do you think it means to be smart?
– The Bible is talking about being wise.
– Therefore, there must be a difference between human standards of wisdom and spiritual standards of wisdom.
Question: What do you think it means to be smart spiritually?
Question: Who are some people today that are known for being smart?
Question: What would determine whether or not God thinks they are smart?
– The Bible spells out what spiritual wisdom looks like as opposed to worldly wisdom.
– One comes from Heaven and the other comes from the devil.
Question: What are some of the characteristics that come from God? From Satan?
Question: Do you think being smart in a worldly way is good?
Question: Ultimately, How do we know if someone is a smart person according to this scripture?
Challenge: Being smart from a worldly point of view doesn’t help people in a way that really matters. The only thing that matters is that we’re smart enough to go after a relationship with God! I want to challenge you to make the smartest decision of your life: start studying the Bible with the person who brought you to our Bible discussion!

industry_corpus2: Subject Education


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This paper is the result of years of teaching both music history and world history. Formally a musicologist by training, my experience with the world history curriculum has afforded me a broad perspective of Europe’s position in the context of the larger sphere of world history. As a result I have come to view the Western tradition of music history not as a single line of progress that began with the singing of chant in early Christian rites and can be traced to today; but rather, as but one part of the world’s musico-cultural tradition, not being as isolated from other traditions as we have been formerly and formally taught.
This paper examines the points of contact between Western “classical music” and non-Western cultures at the borders of Europe. One of the most extensive of these was between the Muslim world and European civilizations. Most of the eras generally covered in Western music history courses, from the medieval to the modern, coincide with the presence of Islam at the borders of Europe; however, this fact is usually ignored or at best marginalized. Much of this period of world history included the rapid spread of Islam westward and eastward from Arabia from the mid-seventh century onward, the clash of cultures and religions in the wars collectively known as the Crusades, the conquest of the Byzantine Empire by the Ottoman Turks in 1453 and the subsequent 400-year presence and at times dominance of the Ottoman Empire in southeastern Europe. Because of the dominant presence of the Muslim world at the very borders of Europe throughout much of its history, this paper targets Islamic influence on Western traditions. My method is to examine three particular topics frequently covered in Western music history courses, each from a different era: the Mozarabic rite in eighth-century Spain; the Florentine Camerata in sixteenth-century Italy, and Beethoven’s Ninth Symphony in early nineteenth-century Austria.
The questions I explore are, first, what effect did the earliest occupation of Arabs have, in their spread of the Muslim faith, on the practice of Christianity in Spain? Second, how did the Florentine Camerata become intrigued with and find source material for ancient Greek musico-dramatic practices? Finally, during the Ottoman reign from 1453 to 1918, how were Islamic musical practices and culture incorporated into the Western tradition? In a particular example, what was Beethoven’s reason for inserting a Turkish march into the finale of his Ninth Symphony? My thesis is that the European music tradition can not be studied as a historical line in itself. It must include an adequate understanding of its general history in relationship to the developments of other peoples within its sphere of contact. Neither in the medieval era nor in any other age was Europe as isolated as we have been led to believe. My method in preparing this study was to compare the discussion of these topics in three college-level textbooks in Western music history survey courses, followed by a comparison of the pertinent general history in three college-level world history textbooks.
I draw first from the Schirmer History of Music, a 1982 publication and the oldest of the textbooks here under consideration. This was published under the general editorship of Léonie Rosenstiel, with detailed sections written by sub-specialists.1 As far as I know, this textbook has not been revised. Second, I refer to the 2006 edition of A History of Western Music by J. Peter Burkholder, Donald Grout, and Claude Palisca, a revision of a publication that goes back to 1960. This is the standard textbook for music history courses and is now in its seventh edition. The third textbook is the most recent of these three, now in only its second edition, published in 2006. By Mark Evan Bonds, this is the History of Music in Western Culture. The world history textbooks I reference are Howard Spodek’s The World’s History, published in 1998; Jeremy Bentley’s Traditions and Encounters, 2003 edition; and John McKay’s A History of World Societies, 2007 edition.
According to Schirmer History of Music, Medieval European music had its origins in three major sources: classical Greek culture, Jewish religious practices, and Byzantine religious rituals. All of these traditions, however, had already greatly declined in influence long before the rise of medieval music. Greek culture had been absorbed by the spreading Roman Republic by 146 BCE; the Jewish diaspora in the Mediterranean had begun as early as 70 CE with the destruction of the Jewish temple at Jerusalem by the Roman army under the leadership of Titus, and the Byzantines had long before reached the height of their influence in western Europe under the reign of Justinian, who temporarily regained Italy and North Africa between 527 and 565 CE. Furthermore, bitter differences between the churches in Rome and in Constantinople, culminating in the schism of 1054 CE, heightened the increasingly separate spheres of the two largest expressions of Christianity at the time. There is not much awareness that in the seventh and eighth centuries the rapid spread of Islam in the Middle East, across North Africa, and into Spain created a much larger, single, and contiguous sphere of influence along much of the borders of Europe than any of the three influences cited in the Schirmer History. This is by no means to argue or doubt the importance of Greek, Jewish, and Byzantine elements in the early Christian rites, but to acknowledge a contemporary, continuous, vibrant, and wide-spread powerful new culture spreading rapidly along Europe’s borders.
Burkholder speaks also of the Greek, Jewish, and Byzantine influences on medieval Christian music. In his discussion of European society from 800-1300, he does, however, also acknowledge the influence of a contemporary world outside the realm of Christian Europe. He notes that by the ninth century, in addition to the empires of the Byzantines and of Charlemagne, the former waxing strong and the latter on the wane, “the strongest and most vibrant was the Arab world.” He furthermore states that “European culture owes much to all three empires.” He notes that, among other achievements, the Muslims became prominent patrons of literature, architecture, and “other arts.”2 We can only assume that these other arts, for Burkholder, would include music. In his prelude to the medieval era, Bonds presents a different view. He describes a Europe isolated from the rest of the world primarily due to declining commerce “as Arabic armies conquered North Africa and most of Spain . . . reducing contact between western Europe and the rest of the Mediterranean world.”3 Unlike Burkholder, he stresses the limiting factor of the boundary.
Contact with Muslims took place in other ways as well. The Crusades in the twelfth and thirteenth centuries opened up much contact, and provided much subject matter for music, literature, and art. In the late twelfth century, European scholars came into contact with a particularly influential and learned Muslim scholar, a judge of Seville, by the name of Ibn Rushid, known to the West as Averroës. His influence in spreading the teachings of Aristotle to the Latin speaking academic world became an important factor in the rise of scholasticism in European universities during the high Middle Ages.
Moving forward to 1453, Europe experienced another major conquest by Muslims as it had earlier in Spain. This time the location was southeastern Europe. When the Ottoman Turks toppled the failing Byzantine Empire by conquering Constantinople in 1453, a 400-year presence of Muslim rule began from the eastern edge of Europe; one that would spread at its zenith to the borders of Vienna in central Europe. What does this have to do with the history of music in the western tradition? For one thing, when Constantinople finally toppled, many Greek scholars, especially those desiring to preserve the primary source writings of Classical Greece, fled the advancing Turks. Many fled to Italy and brought with them a knowledge of classical Greek thought, drama, art, and music that shaped the direction of European thought from the Renaissance onward. Along with scholars like Averroës, they brought to Europe a first hand knowledge of classical Greece. A revival of interest in primary sources took place. This influenced humanism, which slowly replaced scholasticism. Note, however, that Greek thought was foundational to both.11 Approximately 100 years after the initial Turkish conquest of Constantinople, an influential group of poets, noblemen, and musicians met from 1573 to 1587 in Florence, Italy to discover the secret of Ancient Greek music’s power to move the emotions as reported in those early writings. This group, meeting at the home of Count Giovanni de’ Bardi, became the famous Florentine Camerata, to whom musicologists point as the group responsible for the birth of opera.
Although two of the music history texts discuss the origins and contributions of the Florentine Camerata, none discuss the reasons that caused Renaissance Italy to turn its artistic eye towards ancient Greece. Burkholder does, however, acknowledge that some Renaissance writers, such as Girolamo Mei and Vincenzo Galilei, had considered the nature of Greek music, although without pinpointing the revival of interest in ancient Greece. Bonds also points to Galilei and another, Nicola Vicentino, who explored the adaptation of ancient music to modern practice, but also does not mention other factors contributing to this growing interest. Because of gaps in the discourse such as those mentioned above, it is very important to understand what was happening at the so-called border of Europe. The developments in music were very much affected, either directly or indirectly, by the interactions between European and non-European peoples. The knowledge of Europe’s relationship to the rest of the world at this time is of extreme importance in understanding the western musical tradition. Burkholder does mention the fall of Constantinople in 1453 but without any reference to the revival of the ancient Greek writings. In fact, the event does not seem to merit more than passing mention for in the very next sentence he states, “Most significant in the long run was the rise of Europe as a world power.”12 There is no mention of the consequences for Western music of the imminent presence of Turks in a very large sector of southeastern Europe. Again, we need a broad understanding of world history in order to understand the course of events in music history.
In the years after the conquest of the Byzantine Empire, the Ottoman Turks proceeded in their expansion. They quickly took over the Balkans and Greece, took the Italian port of Otranto, and defeated the Hungarians in 1526. During the time of Martin Luther and the Reformation, the Ottomans proved to be an important factor in forming alliances with Protestant German princes, and thus influencing the Peace of Augsburg in 1555, which officially recognized Lutheran Protestants. Adding this knowledge to music history, we can see that this alliance indirectly contributed to the development of the great body of Lutheran church music, especially that of Johann Sebastian Bach in the eighteenth century. The Ottomans, and Muslim Arabs as well, also directly influenced musical developments. In musical drama, stereotypes of Turks and Moors colored the subject matter and characters of works such as Mozart’s The Abduction from the Harem and The Magic Flute. The music of janissary troops, the Ottomans’ elite military, became well known and was incorporated into the classical music of Mozart, Beethoven, and others as colorful exoticism. Mozart’s “Rondo alla turca,” in the Piano Sonata in A Major, K. 311, may be the most famous of all, but Beethoven’s insertion of a Turkish march into his finale of the Ninth Symphony, may be the most telling and may offer an extramusical association that requires a broader knowledge of the Ottomans’ position in world history at this time.
Beethoven’s awareness of and passion for politics and world order is well documented in his famous dedication (and its subsequent removal) of his Third Symphony to Napoleon Bonaparte. Formerly his hero of revolutionary ideals, Napoleon became a curse to Beethoven when he realized that his goals were to rule as a despot of a French Empire that would stretch all across Europe. All three of the music history textbooks point out the famous scribbled out dedication page of the Eroica Symphony, and two of them have illustrations of it, each taking up nearly a half page. The story of the Turkish march in the Ninth Symphony, however, receives much less attention. Consider the following matters, however. First, Beethoven wrote his Ninth Symphony in his late period, one known for, among other things, intense reflection in his music. Second, the fourth movement of this symphony contains, for the first time in symphonic history, a chorus. The choir sings stanzas from Schiller’s Ode to Joy, a poem about universal love, joy, and brotherhood. This adds an unavoidable extra-musical meaning to the symphony and seems to demand a reading of the musical elements in the light of this text. Third, the Turkish March appears here, in the fourth movement. Although Burkholder states in another place that “Turkish style sounds and instruments were all the rage in the late 1700s,”13 I cannot so easily dismiss its insertion here as colorful exoticism. I do think, based on Beethoven’s passionate repudiation of Napoleon, and the fact that his music of this period shows reflection, that there is a message for mankind here, perhaps based on the theme of the Schiller poem.
Beyond Beethoven, what was Vienna’s position with the Turks in 1824, the year of the Ninth Symphony’s premiere? The Turks had tried to take over Vienna several times, but had failed each time, the last attempt being in 1683. After Napoleon’s occupation of Vienna in 1805 and after the Congress of Vienna in 1815 attempted to erase the marks of the “Corsican upstart” and re-establish a conservative Europe after near destruction by Napoleon’s forces, The Habsburgs renewed their vengeance against all threats to the old regime, denouncing in the same breath the declining Ottoman Empire as the “sick old man of Europe,” urging Christian nations to rid themselves of its presence in Europe. It was in this situation of political retrenchment that Beethoven composed the Ninth Symphony. Surely he must have considered the political implications of the janissary insertion. After the movement comes to a particularly glorious cadence, it pauses in complete silence for what seems like a very long time. As the march begins slowly, haltingly, awkwardly, missing the downbeat and sounding only every second measure for the next five measures, what was Beethoven thinking? Am I embracing the Turks in my theme of universal brotherhood, or am I ridiculing them, scorning them as I had done with Napoleon when I discovered that he was a ruthless dictator and not the embodiment of revolutionary ideals that I had originally thought? Was his message one of a love and brotherhood so universal that the Ottomans should be included under its banner? Was it in sympathy with the prevailing feeling that the “sick old man” needs to die, for the music itself can be seen as a stylistic mockery, with its regular rhythms and simple harmonies of the Turkish “band” juxtaposed with the most complex symphonic music European ears had ever heard? Or, was it just one more example of trendy exoticism? For these questions and others like them to become discourse in music history courses, we need the broader context of world history.
To repeat, developments in Western music were greatly affected, either directly or indirectly, by the interactions between European and non-European peoples. The knowledge of Europe’s relationship to the rest of the world at this time is of extreme importance in understanding the western musical tradition. Questions like the ones I have examined through this cross-disciplinary study can be used to generate lively discourse in the classroom, to understand the relevance of historical issues in today’s diverse society, and to encourage students on their own to seek out answers. Based on my findings and past experience, I propose an improvement in the way the Western tradition is taught, one that incorporates an expanded, more accurate view of Europe’s musical traditions in the light of all of the world’s cultures that would have had an impact on its development. I recommend that instructors who are teaching courses in the Western classical tradition be well versed in world history, especially the history that directly affects Europe. Europe was not in a shell or a bubble, or its own microcosm; Europe was and still is part of the world as a whole. I further recommend that music majors take at least a few survey courses in World History and that the curriculum for Music History courses be enlarged to include views of history that provide the context for the music under study. Again, a proper study of the Western tradition in music history must be supported by adequate college level courses in World History and other supporting disciplines.
Bentley, Jeremy, and Herbert Ziegler. Traditions and Encounters: A Global Perspective on the Past. 2nd ed. Boston: McGraw-Hill, 2003.
Bonds, Mark Evan. A History of Music in Western Culture. 2nd ed. Upper Saddle River, NJ: Pearson-Prentice Hall, 2006.
Burkholder, J. Peter, Donald Grout, and Claude Palisca. A History of Western Music. 7th ed. New York: W. W. Norton, 2006.
McKay, John P., Bennett D. Hill, and John Buckler. A History of World Societies. 7th ed. Boston: Houghton Mifflin, 2007.
Rosenstiel, Léonie, ed. Schirmer History of Music. New York: Schirmer, 1982.
Spodek, Howard. The World’s History. Upper Saddle River, NJ: Prentice-Hall, 1998.
1Charlotte Roederer wrote on the Middle Ages, Lowell Lindgren on the Baroque, and L. Michael Griffel on the Romantic periods. These sections in particular were consulted for this paper.
5Bonds, A History, 31, 34.
9Bentley and Ziegler, Traditions and Encounters, 363; Spodek, The World’s History, 348.
10Spodek, The World’s History, 349.
11Although it seems here that I am no longer arguing for Islamic influence, remember that I am speaking of the Turkish military conquest that caused rippling effects in European culture.


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I’m reposting this because it fits in with my State of the Biz Series.
The following is a spoof, my friends, meant to send up the absurdities of Big Publishing’s marketing strategies. Apparently this hit so close to home, though, that when I posted it on Facebook back in August 2013, people actually took it seriously and made many exasperated comments. If you’re an author, I sincerely hope you get a chuckle, not a fit of weeping.
As we all know, Big Publishing (BP) categorizes fiction according to the age of the main characters, who are meant to appeal to readers of the same age since everyone is so self-centered these days they only want to read about characters just like them (only much, much better or much, much worse). BP formulates its book marketing strategy according to these categories so you, the author, ignore them at your peril.
BP begins with Picture Books aimed at 3—5.5 years old (YO) with goofy illustrations that look as if they could have been drawn by a slightly slow 5 YO but in fact are drawn by cunning adults. BP moves on to Middle Grade, which has trended out to New Middle Grade (5.5—8). Middle Middle Grade (8—10), and Old Middle Grade (10—12.5).
From there BP leaps into the now somewhat dated but still hot Young Adult (YA), subdividing the category into Experimenting With Orgasms New Young Adult (12.5—14.5), Madly In Love With A Jerk Middle Young Adult (14.5—16.5), and Older and Wiser Old Young Adult (16.5—18.5), including the important subcategory Learning Archery, Watch Out Jerk Old Young Adult.
Now comes the hotter than hot, not dated yet but getting there fast, category New Adult (NA). BP is scrambling to subdivide NA into I’m So Troubled New New Adult (18.5—20.5), Crap, I’m Getting Old Middle New Adult (20.5—23.5), and I’m Supposed To Be Mature But I Still Ride A Skateboard Old New Adult (23.5—29.5).
The marketing demographic get dicey with I Felt Like Killing Myself When I Turned Thirty New-Thirtysomething Adult (29.5—32.5), Damn I Hate This Job Middle-Thirtysomething Adult (32.5—35.5), and I’m Divorcing That Jerk Old Thirtysomething Adult (35.5—39.5).
Dicier still are the Fortysomething Books–I Got Bifocals and My First Nose Ring New Forty (39.5—42.5), Having My Last Fling Middle Forty (42.5—46.5), and Having a Midlife Crisis Old Forty (46.5—49.5).
BP is puzzled how to market New Fifty (49.5—52.5) (dark, problematic downers), Mom Died And Left Me A Bunch Of Bills Middle Fifty (52.5—56.5). More saleable is the Still Flirty At Fifty Old Fifty Books (56.5—59.5).
It remains to be seen whether the readership will still be alive and solvent to buy I’m Still A Sixties Hippie at Sixty New Sixty books (59.5—62.5), let alone I Can’t Afford to Retire Middle Sixty books (62.5—65.5) or One Foot in the Grave Old Sixty books (65.5—69.5).
Book marketing is so difficult!
Celestial Girl, The Omnibus Edition (A Lily Modjeska Mystery) includes all four books. Five-star rated! On Nook, US Kindle, Canada Kindle, UK Kindle, Smashwords, Apple, Kobo, and Sony; Celestial Girl, The Omnibus Edition (A Lily Modjeska Mystery) is also on Amazon.com in France, Germany, Italy, Spain, Brazil, Japan, and India.
Strange Ladies: 7 Stories, five-star pro and reader reviews, on Nook, US Kindle, Canada Kindle, UK Kindle, Smashwords, Apple, Kobo, and Sony. Strange Ladies: 7 Stories is also on Amazon.com in France, Germany, Italy, Spain, Brazil, Japan, and India.
‘Thank you for your readership!


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Associate Position at LPA Law Firm!
LPA Law Firm is pleased to announce opening for the position of Associate.
** Good MS Office skills.
Interested candidates are welcome to submit their CV to vacancy@lpa.ge no later than January 20, 2018. Only shortlisted candidates shall be contacted and invited for the interview.

industry_corpus2: Law & Justice


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Explore Senior Housing options in Berlin, VT, and nearby cities. Use the advanced filters to search specific care types such as Nursing Care, 55+ Living, Independent Living, Alzheimer’s Care, Assisted Living, Continuing Care, Adult Day Care, Low-Income Affordable, Respite Care and/ or Home Care.
There are 1 senior living communities, including Independent Living, Assisted Living, Continuing Care(CCRC) and more in Berlin, VT. Find Berlin senior housing options with a variety of offerings that match your needs.

industry_corpus2: Health & Medicine


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3 wins from 3 now as Cambridge City Ladies Development continue their excellent start to the season to lead the Cambridgeshire Women’s Premiership. Away this Sunday were taking on ICA Sports Ladies. A first goal of the season for Rachael Littlewood along with another 2 goals for Megan Tonks now 13 for the season from just 5 appearances seeing the visitors continue their 100% winning start with a 3-0 win.
Hot on their heels though are Cambridge University Women, late starters in the Premiership built on their opening game 5-2 win over Fulbourn Institute Bluebirds with a 7-1 win over another of the promoted sides, Histon Ladies Reserves. Their goal scored by Philippa Hayden-Evans. 2 wins from 2 moving Cambridge University up into 2nd spot.
Fulbourn Institute Bluebirds are off the mark at last in the Premiership clocking up their 1st league win at this level since winning promotion last term. At home were playing last season’s Championship North Champions, Riverside Ladies. Annie Posnett scoring a brace for the visitors, Fulbourn were celebrating victory with 5 different players on target for a goal in the match, Emma Clark, Katie Luddy, Amy Smith, Marie Stubbings and Kirsty Geal. Fulbourn winning the game 5-2.
Everyone in the Premiership now clocking up a win with March Town United Ladies also getting off the mark this Sunday at home playing Netherton United Ladies. Holly Barber scoring in the first half for Netherton, March also finding the back of the net to see the sides drawing 1-1 at half-time the winning goal coming 2nd half going March’s way the 2-1 taking them off the foot of the Premiership table. Louise Barbour and Naomi McGarvie scoring the goals for March.
Both with 3 wins from 3 at the top of the Cambridgeshire Women’s Championship North, Wisbech Town Ladies and Ketton Ladies look like they will be slugging it out for the title even at this early stage of the season. Wisbech Town keeping up their 100% start to the season with victory away to Hungate Rovers Ladies on Sunday. Last season’s top scorer, Sophie Swinden leading the goal scoring charts for Wisbech Town already this time around scoring a brace on Sunday to move her onto 6 goals from 3 appearances. Leah Hall, Chelsea King and Rachael Simpson all getting on the scoresheet too for Wisbech Town with their first goals of the season in a 5-0 win.
Ketton Ladies too continuing their 100% winning start to the season winning away to Wisbech St Mary Ladies this Sunday. A much closer result, Wisbech St Mary will likely have a say in the title race too. Nicole Saunders getting a goal for Wisbech St Mary, Ketton edging the win getting 2 goals up the other end to win the 3 points.
Cardea Ladies a new name in the Championship North this season are largely made up of the old Orton Rangers Ladies squad. Earned their first 3 point haul at the weekend under their new name in only their 2nd league game together bouncing back from a 6-0 defeat at home to Ketton Ladies to win 5-2 away from home against Pinchbeck United Ladies this Sunday. Their captain Laura Rudd scoring 4 goals with Jessica O’Sullivan also getting a goal. Chloe Gray and Anete Murniece on the scoresheet for Pinchbeck.
Haverhill Rovers Ladies strong start to the season in the Cambridgeshire Women’s Championship South continued this Sunday as the newly formed side made it 4 wins from 4 in the league at the start of the campaign. Were away on Sunday playing Burwell Tigers Ladies whom they beat 5-0 in the League Cup 3 weeks ago. An even bigger result this time around, Pavlina Beasley, Hayley Turner and Joeli Kirby all getting two goals a piece, Abbi Griffin and Emma Barnes also getting a goal as did Amy Evans and Kayleigh Steed, their 1st goals for Haverhill. A six point lead already at the top of the Championship South.
St Ives Town Ladies Development are 2nd in the Championship South table their 2nd win of the season coming away from home this Sunday. Were taking on Park Ladies the 3 points coming courtesy of a 5-1 win.
For the 2nd game in a row Isleham United Ladies were involved in a 6-4 result. It was victory the first time around against Burwell Tigers. Not the case this time however as it was visitors Cambridge Ranger Women who emerged as the winners during the 10 goal encounter. Melanie Findlater and Emily Ingle both scoring a brace for Isleham United. Erika Balskute making her 1st start for Cambridge Rangers netting a hat-trick. Sharne Southgate moving onto 6 goals for the season also adding two goals to the total with Robyn Barlow also in the scoresheet Cambridge Rangers in 3rd position winning their 2nd league game of the season.
This entry was posted in Cambridgeshire Women's Championship North, Cambridgeshire Women's Championship South, Cambridgeshire Women's Premiership, The Round-Up and tagged Cambridgeshire Women's Championship North, Cambridgeshire Women's Championship South, Cambridgeshire Women's Premiership, The Round-Up on October 10, 2018 by WFEast.

industry_corpus2: Sports


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Applications are being accepted for the 2019 Dr. John Richter Memorial Scholarship for $1000.
We live in a truly unique location and the Jordan River is one-of-a-kind. That is why we host a photo competition each year to create a calendar sharing the visions of this magnificent location. We have also collected historic photos of the River.
View our collection of historical images from the Jordan River.
Our Mission Conserve the natural resources and protect the environmental quality of the Jordan River and its watershed.
Learn about our visions for the future and our stewardship plans.
Find out how to rent this beautiful location for your special event, and learn about the fun history of our unique building!
Over the years, the FOJ team has been recognized repeatedly for their conservation efforts. Find out more about these awards and recognitions.
Read archived newsletters back to 2004, historic newspaper clippings, and stories from over the years.
Learn more about our Watershed and environmental issues.


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When we asked health care support workers for their top tips on how to do a great job, many mentioned the importance of having the right attitude. From smiling to being clear about your responsibilities, a professional approach makes all the difference.
Never think of yourself as just an HCA or AP. We are gaining more clinical skills with training, and have become vital members of nursing teams.
From the admin assistant making the appointment, to the HCA taking the blood test, to the doctor giving the blood test results, each and every one of us has an important role to play. We are each a cog in the wheel, running the machine smoothly.
Start the morning by greeting everyone with a GREAT smile. We all know that some days can be panic days, but if you start your morning with a big smile, all the others will follow suit.
Know your environment, your responsibilities, and what is expected of you within your working limitations.
Always expect the unexpected – don't just rely on word of mouth and paperwork. Patients are all unique.
Acknowledge and recognise the different clinical team members but remember you are of equal value.
Be proud, be diligent and be professional: prove that HCAs are special people and not everyone can do this job.
Everything you say needs to meet three criteria: honest, kind, and necessary. If it meets these three then you can say it (test me!).
Be confident and professional at all times: these two things gives patients confidence in their care.
Remember – everything you do will have your signature and character stamped on it. Be a role model.


text: If you have any problems,such as the wrong delivery or damage,please contact us timely,we will make a good solution for you! Thank you!!


text: Viladecans (Catalan pronunciation: [ˌbiɫəðəˈkans]) is a large town very close to Barcelona, Spain. It is located between Sant Boi de Llobregat and Sant Climent de Llobregat, and is on the coast of the Mediterranean Sea between El Prat de Llobregat and Gavà. Viladecans is basically a service town. It has a hospital, which serves the surrounding towns.


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On in 5 Productions and Little London Theatre Company productions present Constellations by Nick Payne. First performed in London in 2012, winning the Evening Standard's Best Play Award, it transferred to Broadway in 2015 and was nominated for Tony and Drama League Awards for Best Play, Actor and Actress. It has toured the UK, but has never been performed in Wales.
The play tells the story of Roland and Marianne - one relationship, infinite possibilities. Touching and funny, Constellations is a play about free will, friendship, quantum multiverse theory, love and honey.
With Alexander McConnell as Roland and Victoria Pugh as Marianne.
Performance times: June 8, 9, 10 7.30pm.


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I'm hitting problems all over the place in just a few minutes of testing. Image viewer template blows up.
I think we need to start testing again, from the beginning, properly. I think we need to create new content using every template, and hit as many options in each as possible, and test every piece of functionality in the tools. I don't recommend anyone deploys it in anger yet - I would still like to do this next week, but I'm sensing there is a lot of work to do to get these things addressed.

industry_corpus2: Computing & Telecommunications


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PERFECT57 MEDSPA HAS CUSTOMIZED COOLSCULPTING TREATMENT PLANS AND A COMPLIMENTARY CONSULTATION TO DISCUSS YOUR FAT REDUCTION GOALS AND COST.
CoolSculpting is a great option for patients who are interested in slimming their appearance without surgical intervention or downtime. At Perfect57 Med Spa in NYC, our clinicians are highly-trained and dedicated to providing you with the exceptional benefits that CoolSculpting has to offer with a treatment plan that is designed to address your unique needs, so you can achieve your personal goals. If you are looking for a med spa in New York, NY with experienced and professional staff who can provide you with the very best CoolSculpting treatments available, look no further than Perfect57.
As with all aesthetic procedures, many of our clients are curious about the cost of CoolSculpting in NYC. Of course, the cost of a CoolSculpting treatment will vary depending on a multitude of factors including the desired treatment areas, the number of treatments required to attain full results, and where the procedure is performed. On average, a person could spend anywhere from $750-$3500 for their CoolSculpting cost in NYC. At Perfect57 Med Spa, we believe that cost should be only one factor in your treatment decision.
How Much is CoolSculpting NYC?
At Perfect57 Med Spa, your satisfaction and comfort are our priority. We believe in providing each of our clients with exceptional service and personalized attention, so they can achieve their goals. We strive to offer our CoolSculpting procedures at a competitive cost. In the NYC area, the average cost of a CoolSculpting treatment plan is approximately $1650. That estimate is based on the fact that most clients will be treated with multiple application points simultaneously. Of course, the cost of your individualized CoolSculpting treatment will depend in part on the areas you are interested in targeting. CoolSculpting can provide slimming over the back, buttocks, legs, chin, arms, and midsection.
The experienced clinicians at Perfect57 Med Spa want to make sure that you are totally comfortable with your CoolSculpting procedure, which is why we offer free consultations to patients who are interested in cryolipolysis as a potential fat reduction method. During your consultation, an experienced CoolSculpting technician will be able to help you better understand your treatment options and the potential costs of your treatment. We know that every body is different and that getting to know our clients on a one-to-one basis is an integral part of being able to provide the exceptional treatments they deserve to reach their goals as quickly as possible.
When it comes to attaining the body of your dreams, non-invasive CoolSculpting may be the right treatment choice for you. If you are interested in a permanent, safe, comfortable, and effective fat reduction method in the New York, NY area, call Perfect57 Med Spa today to schedule your free CoolSculpting consultation. We are a CoolSculpting Certified Practice, meaning our technicians can answer all of your questions and provide you with the very best CoolSculpting service possible.
Perfect57 Med Spa is conveniently located in the heart of NYC and can provide you with a wide range of treatment options that will help reveal your natural beauty and unlock your confidence. We are proud to offer CoolSculpting to our patients at a competitive cost, so they can achieve the body of their dreams without invasive plastic surgery.


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Our friends at the Prison Policy Initiative worked tirelessly last year for a legislative end to prison-based gerrymandering in New York State. To put the problem in perspective, upstate New York has seven State Senate districts that would not meet minimum population requirements without claiming incarcerated people as residents. The good news is the legislation passed, but now a group of (surprise!) upstate state senators has filed suit seeking to block implementation.
What if I told you your vote counts more depending on where you live in New York? Should a resident of Wyoming or Cayuga County gets more say in who is elected than a resident of Brooklyn or the Bronx?
Of course, prison-based gerrymandering does dilute the vote of residents of Brooklyn and the Bronx, but it also dilutes the vote of Manhattan and Staten Island and Long Island, of parts of upstate New York that aren’t near a prison — basically, it dilutes the vote of anyone who doesn’t live in a district with a prison. The Prison Policy Initiative also has a round-up of news coverage and a copy of the senators’ complaint (PDF).
How the incarcerated are counted in Montana is of critical importance to an accurate count of Native American communities. While Native Americans are 6% of the Montana population, more than 20% the incarcerated people in the state are Native American. Native American women are the same 6% of Montana women, but are 32% of the incarcerated women in the state. Native Americans in Montana are incarcerated at a rate more than 4 times higher than the White residents of the state.
Many critics of prison-based gerrymandering focus (rightly) on the practice’s effects on African-American communities, but it’s worth noting that prison-based gerrymandering (especially when combined with felon voting bans, although that’s a separate issue) dilutes the political power of any group that is disproportionately incarcerated. For that matter, prison-based gerrymandering also dilutes the political power of anyone who doesn’t live near a prison. As always, the Prisoners of the Census blog offers a wealth of resources on this topic.
Yesterday, the New York State Senate passed a bill to count prisoners in their home communities during next year’s legislative redistricting process — rather than counting prisoners where they are incarcerated, which inflates the districts in which prisons are located at the expense of other districts. The bill had already passed in the State Assembly and now goes to Gov. David Paterson for his signature. New York is the third state to pass legislation this year addressing prison-based gerrymandering, after Maryland and Delaware.
Seven of the current New York State Senate districts meet minimum population requirements only by claiming incarcerated people as residents.
Delaware’s Senate and House have passed legislation that would count prisoners at home for redistricting purposes. Now, the signature of Governor Jack Markell is the only remaining step to turn Delaware’s HB384 into law. Delaware will become, after Maryland, the second state in the nation to address the democracy-distorting practice of using prison populations to artificially inflate electoral districts. The Delaware law only applies to redistricting, and will not affect state or federal funding allocations.
“Delaware’s legislation recognizes that prison-based gerrymandering is a problem of fairness in redistricting. All districts — some far more than others — send people to prison, but only some districts have large prisons. Counting incarcerated people as residents of the prison distorts the principle of one person, one vote, and we applaud the Delaware General Assembly for enacting this common-sense solution,” said Peter Wagner, Executive Director of the Prison Policy Initiative.
The problem is national as well. One state assembly district in New York includes 7% prisoners; a state house district in Texas includes 12% prisoners; and 15% of one Montana state house district consists of prisoners imported from other parts of the state. Prison-based gerrymandering was not a serious problem when the prison population was tiny, but the 2010 Census will find five times as many people in prison as it did just three decades ago.
2010 Census and Redistricting — perhaps the discussion will touch on prison-based gerrymandering?


text: Explanation: Undoubtedly, some portion of the invalid click activity is not detected by Google’s proactive systems and processes. However, Google is able to effectively minimize that proportion through its proactive monitoring of both advertiser and publisher networks. Google’s belief in the quality of the sites in its network and the accuracy of its automated filtering is supported by the reactive investigations Google undertake on behalf of advertisers who contact with concerns.


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The Play it Forward! Human Foosball Tournament is a bracket style tournament. Each game is 12 minutes with a short break at the half. That may not sound like a long time, but trust us – it’s a good work out! You’ll be ready for a cold beverage between games.
Each team will have the chance to play at least three games. Those with the best records will advance to the playoffs for the opportunity to Go. All. The. Way! and win the prestigious CHiP Cup.
Six players are in play during a game, however you will have the opportunity to make substitutions. So you can keep those legs fresh and the cost per player low by adding more people to your team.
How old to you have to be to play?
We want this to be a fun, family-friendly event, so we welcome teams with kids and teens. However, players should be at least 48″ tall to play safely. We have divided the teams into two leagues: The Premier league is for the most serious competitors, and limited to ages 14 and up. the Just for Kicks league is a little more relaxed and appropriate for family groups. You will be able to choose your preference in the registration process.
How should I train for this event?
Fitness and skill are irrelevant. However, you can prepare by practicing a firm grip, kicking stuff out of the way, and taunting others from a safe distance.
What if I feel faint from hunger?
No worries! There will be food and beverages for sale to help you keep your strength up. You are also welcome to bring your own coolers and game day provisions.
But will there be hula hoops?
Chances are very good that there will be hula hoops, corn hole, face painting, and other fun distractions.
Will there be someplace to sit?
There will be picnic tables on site, but we encourage you to bring chairs and pop up tents/canopies for resting up between rounds.
We have a Rain Date scheduled for 4/29 – same time and place – in the unfortunate event we need to cancel due to inclement weather. This is an outdoor event, so watch the weather and dress accordingly.
And finally, if you are like me, the most important questions you will have are: Is there convenient parking? Are there bathrooms?
Yes and yes. Woo hoo!
I don’t see my question here. Who can I speak to about this oversight?
Email molly.fulton@jachip.org. She thinks she knows everything.


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These are available in 4, 8, 12 and 24 packs.
Allow 1 week for delivery. Order NOW! Shipping included in the price.


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"For many people, the primary reason they drive rather than bike short distances is because they feel cycling is too dangerous. We can change that. We must change that."
Tara Servatius' June 26 column "Why does the government continue to promote biking?" did exactly what Servatius does best — piss a lot of folks off. She's excellent at raising the volume rather than elevating the discourse, and her particular tone of shrill seems to be effective at one thing — driving traffic to the City Paper website. Unfortunately, it does nothing to help traffic flow around Charleston, which was the alleged subject matter of her rant against making the West Ashley Legare Bridge safer for bicyclists and pedestrians.
While many incensed readers were asking why the City Paper continues to promote Servatius, I'm glad for the fodder. Despite Servatius' flimsy logic and blatant rehash of a column published in 2010, she makes some valid points. Yes, bicycling in busy, high-traffic areas is risky and can be dangerous. Yes, bicyclists and pedestrians are likely to be hurt — or worse — by inattentive, reckless drivers. And true, not all roads are designed to accommodate bikes. But Servatius' argument that bicycling and walking are dangerous, ergo government should not encourage these activities, is as slippery as the Legare Bridge grating in the rain. By this reasoning, the government should not support space exploration, the police department, or the armed services — all of which are inherently dangerous.
Yet while Servatius' column is racking up hits on the web, bicyclists remain more likely to be hit on our roads, 12.7 times more often than motorists, according to the dated study cited by Servatius. Which is exactly why government should be taking action to make our roadways safer and more accessible to those who by choice or economic necessity opt for two wheels rather than four. And that's exactly what Charleston County Council has done regarding the Legare Bridge.
There are so many public and personal benefits to bicycling that it's difficult to list them here, and too obvious, really, in this day and age, to need to. Briefly, the list includes improved air quality, fewer carbon emissions, less traffic, improved economic growth, reduced healthcare costs related to diabetes and cardiovascular disease, and dare I say, lower rates of obesity? Plus the harder-to-quantify benefits of happier campers, more energetic workers, and a more connected, more livable community.
But as my fellow Charleston Moves board member Don Sparks has said, the real absurdity is not that people have to justify the need for bike lanes, it's that people have to fire up a car engine to go less than a mile to run an errand. For many people, the primary reason they drive rather than bike short distances is because they feel cycling is too dangerous. We can change that. We must change that. And as a traffic engineering study has determined for the Legare Bridge, we can do so without undue detriment to automotive traffic flow. And without huge expense.
Besides the safety factor, some people — women especially — say they are reluctant to bike because they don't know how to change a flat — I'd be happy to show you, Tara, if you don't know how — or they don't want to get sweaty, but Servatius seems all hot and bothered already, so no matter. Anyway, when it's a torrid 95 degrees, I opt for my car and its air conditioning. I, and almost all cyclists I know, are reasonable adults, and we also drive cars. We pay road taxes and care about efficient traffic flow. As drivers we cringe when other bicyclists don't obey traffic laws. But we also want options, and roads that are safe for all users — cars, bikes, and pedestrians.
We want intelligent, forward-thinking, environmentally responsible, economically sound transportation policies that plan for Charleston's future, a future that will have more people and more traffic and will need more options for getting around. We can't pave our way into that future only by building more roads and more parking garages on our limited and valuable Lowcountry real estate. Making it easier and safer for people to use bicycles is one step in the right direction.
Servatius is certainly not the only one who believes bikes don't belong on roads, that roads are for cars alone and that government dollars should not be spent to appease politically correct, skintight spandex-wearing bicyclists. I get that. But Servatius' argument that cycling doesn't merit our support because it may be dangerous is laughable in the 21st century, when every other forward-thinking metropolitan area — Chattanooga, Austin, Chicago, New York, Madison, and even the politically incorrect conservative bastions of Greenville and Spartanburg, to name a few — is making headway toward becoming more bicycle-friendly and thus less dangerous. If Charleston wants to retain its sheen as a top travel destination, a burgeoning Silicon Harbor, a growing economic region that can attract Generation Next talent, then it must continue the bike/ped-friendly momentum that County Council is currently supporting.
Servatius' column was called out by many readers as "trolling." Before the internet, trolls lurked under bridges. They preyed upon travelers just as Servatius preys upon readers and listeners. Forward-thinking policy makers see our bridges as connectors for everyone, as pathways to a brighter, healthier, more prosperous future. Let's keep the trolls away from the Legare Bridge. Join me and Charleston Moves in advocating for a more bicycle-friendly, safer region.
Stephanie Hunt is a freelance writer and chair of the board of Charleston Moves, a nonprofit bike/ped advocacy organization.
Why does the government continue to promote biking?

industry_corpus2: Transportation


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Born in Brooklyn, New York, to working-class Jewish parents of Eastern European descent, Leonard Freed (1929-2006) began making photographs while in the Netherlands in 1953. Photography became Freed's method of exploring societal violence and racial discrimination, and his coverage of the American civil rights movement brought him initial distinction. In 1972, Freed became an early member of Magnum.
Black in White America was first published in 1968, following a lengthy examination by Freed of the plight of African Americans in the United States. The book is a moving collection of photographs and telling captions that document the African American struggle for self-definition in mid-20th century America. Freed traveled to New York, Washington, D.C. and all throughout the South, capturing images of a segregated and racially-entrenched society. Freed's sensitive and informative black-and-white photographs of 1960s African American living throughout America investigates the politics of the country, and articulates the anxiety of an under-represented and discriminated people.
In his ground-breaking and controversial Police Work, Leonard Freed worked alongside the policemen of New York in order to see what life 'on the beat' was really like. What he photographed was an elegant yet grittily realistic portrait of ordinary people doing a "sometimes boring, sometimes corrupting, sometimes dangerous and ugly and unhealthy job." Freed shows the isolation, the complexity, the harshness and the camaraderie of the men and women hired as public servants, and the people they are required to protect. Police Work is a sharply tragic and compassionate view of police work and life.
For this collection, Brooklyn-born photographer Leonard Freed chose his most powerful images taken during a period of over thirty years spent traveling across continents. The 170 black and white pictures collected here are well worth the wait: the subject matter is sometimes violent and the images often startling, but a deep compassion and lively interest in seemingly every aspect of the human condition are evident in each shot. It is around the theme of 'life and all its emotions' that Freed conceived this anthology, and it balances his commissioned worked with images reflecting a more personal quality.
Freed's images are, like those of Boubat, Doisneau, and Cartier-Bresson, full of irony, humor, and pathos. They document black America, neo-Nazis, the Arab-Israeli war, the Romanian revolution, and many other subjects. Stefanie Rosenkranz, a journalist from "Stern" magazine who has worked with Freed on assignment, contributes a highly personal anecdotal essay.


text: Dr. Crystal and staff are dedicated to providing you with a pleasant visit and results that you’re proud to show off. Our administrative staff is ready to help you with questions about scheduling, financial policy and insurance, to make that part of the process as simple as possible.


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All the information and material provided on this web site is solely for illustrative purposes. It is not intended to, and does not create any business, contractual or employment relationship with Ryder & Amies. All the information, content, text, images, html code, photography and graphics are the property of Ryder & Amies, and may not be copied, reproduced, republished, posted, transmitted, or distributed in any way without our express, advance, written consent. All trademarks used or referred to in this site are the property of their respective owners.
Links on this site may lead to services or external websites not operated by Ryder & Amies. No judgement or warranty is made with respect to such other services or sites and Ryder & Amies takes no responsibility for such other sites or services. A link to another site or service is not an endorsement of that site or service. Any use you make of the information provided on this site, or any site or service linked to by this site, is at your own risk. This site is provided “as is” and Ryder & Amies expressly disclaims all warranties of any kind, whether express or implied, including the warranties of merchantability and fitness for a particular purpose.
In no event shall Ryder & Amies, or any of its employees or contractors, be liable for any damages whatsoever in connection with the information or material on this web site, including but not limited to actual, consequential, direct, exemplary, incidental, indirect, punitive or special damages.


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Dimensions: 26" L; less than 1 lb.
At 26 inches long, this poker will allow you to move logs within your fire at a safe distance so you do not have to worry about getting burned by embers or sparks. With a simple yet durable design, this is a useful tool to own for your outdoor and indoor fireside needs.
Poker design allows it to more easily move firewood or spark screens, so you don't have to risk burning your hands.

industry_corpus2: Safety Management


text: Had a great time with friends. Kayaked, swam, fished. Gorgeous days at the lake. Smores and campfires too.


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The introduction of next-generation sequencing (NGS) in the field of cancer research has boosted worldwide efforts of genome-wide personalized oncology aiming at identifying predictive biomarkers and novel actionable targets. Despite considerable progress in understanding the molecular biology of distinct cancer entities by the use of this revolutionary technology and despite contemporaneous innovations in drug development, translation of NGS findings into improved concepts for cancer treatment remains a challenge. The aim of this article is to describe shortly the NGS platforms for DNA sequencing and in more detail key achievements and unresolved hurdles. A special focus will be given on potential clinical applications of this innovative technique in the field of radiation oncology.
Recent technological advances in DNA sequencing with greater speed and resolution at lower costs has provided new insights in cancer genetics. The next-generation sequencing (NGS) technology is tremendously facilitating the in-depth genome-wide search for genetic alterations which might significantly contribute to aggressive and/or treatment-resistant phenotypes of cancers, thereby establishing the basis for the development of molecularly targeted therapy. High-throughput sequencing of distinct cancer entities in large-scale projects has improved our understanding of the disease-specific mutational patterns [1–4] and the ‘Darwinian’ selection forces involved in subclonal tumor evolution resulting in highly heterogeneous tumors. Initially, NGS has been developed for detection of DNA-based alterations. However, it can also assess other molecular aberrations, including those in the epigenome [5, 6], transcriptome [7, 8] or RNAome . In this review we will only briefly discuss the technical principle of NGS for DNA sequence analysis. For more detailed information we would like to refer the reader to the excellent reviews of Metzker et al. , Meyerson et al.  and Wong et al. . We will instead focus on key achievements in cancer genetics and potential clinical applications of this innovative technique in the field of radiation oncology.
Next-generation sequencing has rapidly been evolving within the last decade . This high-throughput method offers several advantages over classical capillary electrophoresis-based ‘Sanger’ sequencing including increased speed and resolution at dramatically lower costs compared to the older sequencing technologies. To illustrate the remarkable progress achieved by NGS, the Human Genome Project which used first-generation ‘Sanger’ sequencing technology to sequence the human genome took over 10 years and nearly 3 billion USD to achieve its goal [12–14]. By next-generation sequencing an individual human genome can now be sequenced in less than 2 weeks for approximately 5000 USD .
In theory, the whole genome does not need to be sequenced to identify genetic alterations in most human cancer-associated genes. More than 85 % of pathogenic mutations are found within the protein-coding regions of the genome , which collectively are referred to as the “human exome”. This already dramatically reduces the regions that need to be sequenced for personalized oncology, thereby decreasing costs and time for whole exome sequencing of one sample to approximately 1,500 USD and 48 h (the exact prices mainly depend on the NGS platform, the required sequencing depth and are exclusive of the costs for bioinformatics). Furthermore and probably even more relevant for integration into clinical trials  or routine diagnostic applications , focusing on a selected panel of genes with established impact in cancer progression and/or a proven role in treatment resistance is possible which offers the opportunity for detection of rare genetic variants at very high sensitivity [2, 17] in all types of samples including archival formalin-fixed, paraffin-embedded (FFPE) tissue [18, 19] and plasma cell-free circulating tumor DNA .
DNA sequencing was initially developed in 1975 by Sanger and Coulson  and these techniques are still used widely today. ‘Sanger’ sequencing is based on the use of oligonucleotide primers specifically binding to either side of the target DNA region which is then amplified in a polymerase chain reaction (PCR). The use of chain-terminating nucleotides in the DNA synthesis process allows the generation of different copies of the original DNA template at all possible lengths, which are separated by capillary electrophoresis. By using specifically labelled chain-terminating nucleotides (A, C, T or G) the original DNA sequence can be assembled.
NGS is based on the principle of sequencing in a massively parallel fashion. This means that up to millions of DNA fragments can be sequenced at the same time. Initially, DNA is fragmented into short segments called a shotgun library. Adaptors are ligated to the ends of each fragment. These adaptors are themselves short sequences of DNA which have primer binding sites for subsequent amplification. The shotgun library can subsequently be enriched for the sequences of interest, using different approaches [22, 23]. As one example, probes which correspond to the target regions, e.g. the human exome, and which are immobilized on beads or a solid plate can be used in order to physically separate the target DNA fragments from the remaining DNA. Alternatively, custom arrays can be designed to enrich for specific groups of genes of interest (cancer gene panels). Following enrichment, the fragment library can be sequenced on next-generation sequencing platforms from several manufacturers (for a comprehensive review of the differing platform techniques see Metzker et al. . Recording of the captured sequences occurs at live mode in a massively parallel fashion when the fluorescent signals from dye-labelled nucleotides in the nascent DNA strands on each bead, channel or cluster are detected during DNA synthesis.
Whilst large amounts of sequencing data can be generated relatively quickly, data analysis can be time-consuming and difficult. The first problem is the large size of NGS raw data files, especially for results from WES or WGS. For example, non-compressed FASTQ files from human WGS with a mean coverage of 30x requires up to 200 gigabytes, making data transfer and storage of even small WGS projects a real challenge. These estimates do not include the disk space required for any downstream analysis. Development of streamlined, highly automated pipelines for pre-processing of raw data, alignment or de novo assembly of reads, quality control, copy number variation (CNV) and/or SNP calling is essential and high-capacity server solutions are mandatory. The key first step of data processing is the alignment of the sequence reads to a reference genome. Three characteristics of NGS data complicate this task. First, read lengths are relatively short (in average 26–330 bp)  compared to capillary-based ‘Sanger’ sequencing, which decreases the likelihood that a read can be mapped to one unique location. Second, reads from NGS platforms contain higher rates of sequencing errors, especially in regions of homopolymer repeats . Subsequent validation of novel variants by ‘Sanger’ sequencing to exclude technical sequencing errors is therefore highly recommended. This technical limitation of NGS is also underlined by the results from a recent study which revealed a higher rate of false-positive single nucleotide variations detected by WES compared to WGS and a considerable fraction of insertions and deletions detected by both WES and WGS which could not be confirmed by subsequent Sanger sequencing .
By all means, in each individual case most of the identified variants will represent single nucleotide polymorphisms (SNPs) of no pathogenic relevance . These can be removed either by filtering against sequencing results from ‘control’ DNA of the same patient’s normal tissue or, if such control is not available, against data sets from public databases such as the NCBI dbSNP and the ‘1000-genomes’ project . The remaining variants can be filtered against public collections of genetic alterations in cancer, such as the Catalogue Of Somatic Mutations In Cancer (COSMIC) database (http://cancer.sanger.ac.uk) which as of August 2014 contained over 2 million coding mutations, more than 70,000 gene fusions or genome rearrangements and almost 700,000 abnormal copy number variants . By such an approach, genetic variants with known/potential oncogenic function can be identified.
An additional approach to separate biologically relevant from irrelevant variants often utilizes new software tools (SIFT [27, 28], PolyPhen-2 , mutation-assessor ) which are now widely available and help to determine which mutations may have a functional impact on the encoded protein, which are likely to be pathogenic, or which are rather neutral variants without biological effect. These methods are generally based on the assumption that important amino acids will be conserved in the protein family, and that changes at well-conserved positions are likely to be deleterious . For example, given a protein sequence SIFT chooses related proteins and obtains an alignment of these proteins with the query. Based on the amino acids appearing at each position in the alignment, SIFT calculates the probability that an amino acid at a position is tolerated or deleterious .
MutSig is another algorithm which has been developed at the Broad Institute of Harvard and MIT in 2007 . MutSig is currently broadly used to identify driver mutations among large numbers of passenger mutations. In contrast to the above mentioned methods, MutSig takes into account that background mutation processes occurred during formation of tumors and it considers the mutations of each gene to identify genes that were mutated more often than expected by chance . Besides looking for abundance above background, MutSig looks for positive selection in genes, i.e. increased numbers of non-synonymous vs. silent mutations or mutation clusters at hotspots. Its advanced version (MutSigv2.0) takes also into account the functional impact of mutations (as estimated by the above mentioned tools SIFT, PolypPhen-2, Mutation Assessor, etc). In addition, incorporation of the covariates DNA replication time, chromatin state (open/closed), and general level of transcription activity into the background model has been shown to substantially reduce the number of false-positive findings .
These in-silico methods certainly assist in the filtering process, however their results still need to be cautiously interpreted in conjunction with the involved gene and certainly have their limitations. Methods like MutSig identifying driver gene mutations based on background mutation rates rely on a correct estimation of this background rate in a given tumor type and at a defined genomic region in order to keep the number of false positives to a minimum . Other algorithms underestimate functional changes in poorly conserved positions . As a result, frequency-based methods with loose background mutation rates will detect driver candidates with a probably high rate of false positives. On the other hand, methods implementing stricter models will identify more specific candidate lists but might miss some true cancer driver genes. Combination of complementary methods might overcome these limitations  and will certainly increase the knowledge gain from NGS studies. Last but not least, functional studies in preclinical models for elucidation of the mode of interaction of genetic variants with biological processes in tumor cells are indispensable for validation of NGS findings and are certainly mandatory before NGS technologies should move into clinical applications . Translation into clinical practice can certainly only be achieved by multidisciplinary research approaches in order to extract meaningful diagnostic interpretation from large NGS datasets.
Over the last two decades, technological advances in treatment planning and delivery have improved the quality of radiotherapy in terms of precise dose application to the target volume together with minimal dose to normal tissue. Despite these achievements, a fundamental question that remains unresolved is whether based on the molecular profile of their tumors it is possible to prospectively identify patients who are more likely to benefit from radiotherapy. Personalized radiotherapy could be achieved by establishing biomarkers which can classify radiosensitive/-resistant tumors and/or tumor-surrounding normal tissue before initiation of treatment. To achieve such goal, previous studies have mostly evaluated single biomarkers or functional assays of DNA damage repair as predictor of intrinsic cellular radiosensitivity. Among others, assessment of the cell survival fraction  or the number of residual DNA double strand breaks after ex vivo irradiation of tumor cells  or normal tissue [36, 37] as well as in vivo determination of the extent of tumor hypoxia  have been evaluated extensively. Although promising according to preliminary clinical data, none of them have become routine yet which might be due to low robustness of some of these in-vivo assays .
The generation of high-throughput data sets in the omics era has provided a novel and complementary opportunity in biomarker discovery. Using high-throughput transcriptome analysis, it has been previously shown that prediction of cellular radiosensitivity of tumor cell lines by expression analysis of a defined set of genes clearly outperformed assays of single gene analysis . The value of this molecular signature as predictive biomarker for radiosensitivity was already confirmed in a large clinical cohort  speaking for its clinical potential. Another interesting approach is the use of hypoxia gene expression signatures for selecting patients who likely benefit from the inclusion of hypoxia-modifying drugs in regimens of radio-  or radiochemotherapy .
Beside the influence of gene expression levels, individual differences in cellular radiosensitivity are thought to be at least partly determined by germ-line genetic variants. Rare variants which are likely to be functional can only be detected by high-throughput DNA sequencing, made now affordable by the NGS technology. Up to date, only few studies used NGS for assessment of the exact role of SNPs for treatment outcome after radiotherapy. Recently, the role of germ-line SNPs and rare variants in MRE11A as predictive biomarkers of both tumor response and toxicity following definitive radiotherapy of muscle-invasive bladder cancer was analyzed by this technology . Carriers of at least one of six rare MRE11A variants had a significantly higher risk of local failure in the radiotherapy arm, whereas no such association was seen in the surgically treated patient cohort . It will certainly be interesting to expand such type of analysis to a broader spectrum of cancer types.
For elucidating the role of somatic mutations in radioresistance NGS has first been applied in bacteria . In a model of cellular adaption to irradiation, extremely radioresistant E.coli strains were generated from the respective founder cells by repetitive cycles of increasing irradiation doses. Whole genome sequencing revealed a large number of genomic alterations in the radioresistant descendants of which only few were recurrent mutations, suggesting that multiple mechanisms can contribute to radiation resistance and distinct evolutionary pathways leading to this phenotype. Intriguingly, despite this heterogeneity, clear genetic patterns also emerged. Not unexpectedly, mutations clustered more frequently in genes of DNA double strand break repair.
In two recent NGS studies in locally advanced squamous cell carcinoma of the head and neck (HNSCC) our group has evaluated the role of somatic mutations in a set of cancer-related genes for the efficacy of definitive  and adjuvant chemoradiation . Our studies could confirm previous reports of poor efficacy of radiotherapy in HNSCC tumors harboring disruptive TP53 mutations [47, 48]. For the first time, we demonstrated a possible role of mutations in NOTCH1 and key driver genes (PIK3CA, KRAS, NRAS and HRAS) as predictive biomarkers of outcome after chemoradiation. Moreover, our studies also confirmed that archival formalin-fixed paraffin-embedded (FFPE) specimens are indeed suitable for targeted NGS although in series older than 8–10 years a considerable portion of samples (up to 30 %) might fail due to the high extent of DNA fragmentation (IT, ms in preparation, July 2015).
NGS is also increasingly being used for the dissection of the mechanisms involved in treatment-induced clonal selection in the course of acquired treatment resistance. To our knowledge, only one study so far has addressed this question in a model of radioresistance . In this study, DNA-targeted sequencing was performed on pre- and post-treatment tumor tissues from rectal cancer patients who failed to respond to neoadjuvant chemoradiation. Mutant variants previously associated with radioresistance including TP53 were detected in post-treatment residual tumor tissue from non-responders. In line with an important role of TP53 mutation in radioresistance, an increase in allele frequency of aberrant TP53 variants as well as an increase in mutant p53 expression levels was observed in all cases in which the tumor harbored a hotspot missense mutation in the DNA-binding domain of p53. These data strongly suggest that chemoradiation exerts a selection pressure that leads to the increase in the relative portion of tumor cells expressing mutant p53 protein . Strategies of downregulating mutant p53  or refolding it into its wild-type confirmation  might prove effective in sensitizing tumor cells to chemoradiation in this scenario.
Another interesting approach with potential impact in radiooncology which makes use of NGS represents a novel method named XR-seq. This technique can be applied for genome-wide mapping of DNA excision repair . The underlying principle is that human nucleotide excision repair generates two incisions surrounding the site of damage, creating fragments of approximately 30 nucleotides. In XR-seq, these fragments are enriched by immunoprecipitation of specific repair proteins which are tightly bound to the excised DNA fragments. By subjecting this fragment library to NGS maps of global and transcription-coupled DNA repair can be generated. This novel method will allow uncovering repair characteristics and sequence preferences of treatment-induced DNA damage and as such might facilitate studies of the effects of mutational patterns on transcriptional activity on DNA repair in human tumor cells. This method should also prove useful in determining the effects of drugs like histone-modifying therapeutics or poly ADP ribose polymerase (PARP) inhibitors on nucleotide excision repair, and how they eventually interfere with radio- or chemosensitivity of tumor cells.
The immunomodulatory effects of radiation have been widely documented (for review see Burnette & Weichselbaum ) and immunogenic cell death was identified as key component not only of targeted therapies but also conventional treatment modalities including radiation . It could thus be speculated that radiation of tumors with large numbers of genetic alterations, with a portion of them serving as putative neo-antigens, is more likely to induce anti-tumor immunity compared to radiation of tumors with low number of alterations. In support of this assumption, the total number of immunogenic mutations per se (identified by WES) was positively correlated with overall survival of cancer patients treated with standard regimens . Combining radiation and immune checkpoint blockade which already demonstrated synergistic anti-tumor responses in animal models  are promising strategies which are based on the above-mentioned principles. Integration of NGS-based mutational profiling in upcoming clinical trials of such combinatory treatment are anticipated and will determine the predictive value of the mutational load and/or the number of immunogenic mutations in this setting.
As stated above, the technological advances coming along with NGS have permitted rapid analysis of individual cancer genomes at high resolution on single-nucleotide level. By this technical advancement, an astonishing heterogeneity between individual tumors has been revealed, with only a limited number of somatic alterations shared between tumors of the same histopathologic subtype. This large genetic heterogeneity can be illustrated in the model of HNSCC. Cases in this disease entity with a history of heavy smoking and alcohol consumption belong to the group of highly genetically instable tumors , most likely resulting from the extensive DNA damage that has been caused by tobacco carcinogen exposure for years. As of December 2014, preprocessed and preanalysed mutational data from 3 independent whole exome NGS studies in HNSCC [58–60] in total reporting on 412 HNSCC cases were available at cbioportal (http://www.cbioportal.org). We used these data which have been filtered using tissue-matched control sequences to exclude germ-line variants for a more detailed assessment of the extent of genetic heterogeneity in HNSCC. Overall, somatic non-synonymous mutations were detected in 15,293 genes. However, only 357 (2.3 %) of these genes were altered by mutation in >3 % of the tumors. In 127 (36 %) of the more frequently affected genes the mutation occurred within hotspot regions but for only 75 genes (15 %) the same base position was involved in more than one tumors. This means that recurrent mutations at hotspot regions were detected in only 0.5 % of all genes altered by mutations (Fig. 1). Alternatively, when the non-synonymous mutations were filtered using the MutSigv2.0 algorithm according to the background mutational rate per gene rather than their prevalence in HNSCC, only 51 genes (0.3 % of all affected genes) were identified as significantly mutated genes.
A second example for tumors of very high genetic heterogeneity is cutaneous melanoma . In a landmark WES study on paired tumor and normal genomic DNA from 135 patients with melanoma an overall number of 86,813 coding mutations were detected at a 2:1 ratio of non-synonymous to synonymous events, suggestive for a high passenger mutation load . Filtering against the basal mutation rates using MutSig  produced a list of 544 significantly mutated genes. By refining the algorithm to select for non-synonymous mutations of predicted functional consequence the authors reduced the list of candidate drivers to eleven genes harboring significant functional mutation burden. Interestingly, these genes included six well-known cancer genes (BRAF, NRAS, PTEN, TP53, CDKN2A, MAP2K1) and five new candidates (PPP6C, RAC1, SNX31, TACC1, and STK19) .
The huge genetic heterogeneity in these types of cancer underlines the need for advanced bioinformatics models for data analysis. It also impressively illustrates the need of identifying key oncogenic driver pathways rather than individual genes as targets of precision medicine. This assumption is also supported by the observation that many low-frequency mutations in breast and colorectal tumors, each of them having small effects on cell survival . It is thus rather unlikely that genome sequencing will uncover a single target as the “Achilles heel” of a tumor.
Exacerbating the complexity of the genetic landscape of tumors, intratumoral heterogeneity in terms of spatial and temporal differences in the mutational patterns of key driver genes has recently been demonstrated for renal [63, 64], lung , colorectal [66, 67] and breast cancer . Beyond etiologic, microenvironmental and tumor-specific factors which all might contribute to such genetic heterogeneity, therapy may act as further exogenous source of genome instability. Consistent with this, in a recent study using the genetic model system Caenorhabditis elegans cisplatin treatment has been found to lead to a striking increase in base substitutions as well as an elevated rate of larger structural alterations . Importantly, among the mutations found to be induced by cisplatin in the human model some variants have been linked to tumor progression and drug resistance like activating HRAS mutations at codons 12 and 13 [70, 71]. Temozolomide which is broadly used as radiosensitizer in brain tumors and sarcomas has been found to leave an imprint in the cancer genome in the form of an elevated rate of C > T transitions . Concerning potential mutagenicity of radiotherapy, TP53  as well as c-MYC among others were identified as radiosensitive gene loci .
In the light of accumulating evidence for high inter- and intratumoral genomic heterogeneity the identification of the relevant driver mutation(s) among passengers in an individual cancer biopsy at a defined stage of disease represents a significant hurdle in the development of NGS-based molecular diagnostics and personalized treatment. One approach to overcome such hurdle might represent deep sequencing of cell-free circulating tumor DNA derived from blood plasma for personalized cancer genomic profiling [20, 74–78], assuming that genetic variants which are present in tumors only at subclonal level (and which are probably not captured by the diagnostic biopsy) are finally and inevitably released by dying tumor cells to this common reservoir.
Exciting new data from a continuously growing number of NGS cancer studies nourish the hope that this technology will also significantly contribute to increasing our understanding of the molecular mechanisms of radioresistance. However, many more studies will certainly be needed to determine the functional consequences of individual mutations or distinct mutational patterns for cellular radiosensitivity and the individual tumor’s response to radiotherapy. Proteomics is expected to provide additional important information that will guide candidate drug selection and recent advances in proteomic techniques [79, 80] have opened new avenues for optimized cancer treatment. The application of these techniques will not only allow the monitoring of protein-protein interactions, posttranslational modification and drug-target engagement directly in cells or tissues but will also represent a valuable tool for identifying off-target drug effects . The latter feature will certainly also foster attempts to develop less toxic protocols of radiotherapy combined with molecularly targeted radiosensitizing agents.
The future of personalized radiation therapy will most likely not only include DNA-based NGS. It will also apply other high-throughput technologies such as RNA sequencing that in parallel provides quantitative gene expression as well as mutational status. Overall, it can be reasoned that integration of mutational patterns from NGS analysis and other omics data together with functional measures of cellular radiosensitivity in systems biology models will strongly improve the power of outcome prediction and optimize current treatment selection algorithms for individual patients.
IT, FN, RK, SL, MM, performed the data analysis of public NGS data in HNSCC described in the manuscript. IT, RK, AS, WW, UK and VB jointly developed the structure and arguments for the paper. All authors performed a literature research. IT wrote the manuscript. All authors discussed, made critical revisions and approved the final manuscript.
Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP) Available at: www.genome.gov/sequencingcosts. Accessed .

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