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0.999989	Who can I talk to about my psychosis? Psychosis can feel confusing and scary enough on its own. Misconceptions about and media portrayals of psychosis might make us afraid to share this part of ourselves with other people. Having to talk to someone about it when you may not even understand it yourself can feel impossible. Even if it feels like you are the only person you know who struggles psychosis, millions of people all over the world experience or have experienced psychosis, too. Many more than that are willing to listen or want to understand. There will be some people who just won’t get it, but it’s not your job to convince them. Even though it’s scary to reach out, you’d be surprised how many people around you now may have experienced it or would care enough to listen. You can talk to family members, friends, coaches, teachers, or religious leaders in your life. If you are unsure of what to say, you could write a letter or be prepared with research about psychosis to help you explain what you are going through. There are also many different types of mental health professionals who are available to discuss how you feel and to strategize around how to feel better. It’s important to reach out to a mental health professional as soon as possible. The earlier you get help, the better. Finding a professional can take some research and will come with costs, depending on your health insurance, but it could be worth it if it can make you feel better. Hotlines, warmlines, online support, or text lines can help, too. These are typically run by trained volunteers or employees whose job it is to listen to those who reach out. Talking to a stranger can help you feel safer about what you’re sharing, and strangers may be able to offer more objective feedback than the people involved in our lives. Getting what we’re feeling out, whether it’s talking, typing, or texting, often feels good. A great option is finding other people who share your experience in support groups or communities. These can be in-person or online and are made up of people who have experienced similar things. They talk about their daily lives, struggles, and strategies they’ve used to cope and thrive. It can be transformational to feel like you belong in a community or to find people sharing things you thought only impacts you. Whichever of these you choose, it’s important to reach out. Psychosis often makes us want to isolate and makes it hard to trust other people. Connecting and asking for support, even when it’s hard or scary, is a key part of recovery.
0.99793	List of famous people who died in France, with photos when available. These notable France deaths are loosely ordered by how famous each person was, meaning the most well-known people are at the top of the list. Some of the people mentioned below were celebrities who died in France, while others were just renowned in their line of work. Either way everyone on this list has France listed as their official place of death in any public records. Each prominent person who passed away in France has information about them next to their names, including the year they were born and their place of birth. This list is made up of a variety of people, including Georges Carpentier and André Gill. If you're trying to answer the questions, "Which famous people died in France?" and "Which celebrities died in France?" then this list will have you covered. This list of historic deaths in France includes athletes, musicians, celebrities and notable local figures.
0.941816	Seldom have I enjoyed a biography as much as I did with Ron Chernow's brilliant book about the first Treasury Secretary of the United States - Alexander Hamilton. Most will know of him from the $10 bill (a recent plan to replace his image with one of Harriet Tubman has been reversed - she will replace the slave owner Andrew Jackson on the $20 bill instead). There are two reasons in the main why I enjoyed this book: first, it is very well written and easy to read, secondly, Hamilton was a fascinating character who crammed in so much into his short 49-year life. Much is made of his rise from being an orphan born out of wedlock on the island of Nevis in the West Indies to being one of the founding fathers of the United States. He certainly was a self-made man who used his own initiative and brilliant brain to climb the political ladder. Inevitably he made enemies along the way like Thomas Jefferson, John Adams, and Aaron Burr. He was a brave soldier during the Revolutionary War seeking to command as well as provide George Washington with advice that he both needed and valued. His setting up of banks and his steady hand at the helm of the Treasury Department ensured that the early days of the United States were successful. An abolitionist, slavery was always at the back of policy - he predicted 60 years before it eventually happened would end up causing a Civil War. His needless death at the hands of Aaron Burr in a duel cut short the life of one of the greatest Americans. The award-winning musical "Hamilton" (based on Chernow's book) has also renewed interest in Alexander Hamilton. Is has been one of the most successful musicals ever on Broadway, and also one of the hottest tickets in New York. Some are available for next year - one seat will cost you $849 on Ticketmaster. What stands out for me about Alexander Hamilton is his honesty and integrity - he never sought to benefit financially from his Government work, frequently going pro bono. His enemies accused him many times of corruption, but he died in debt and never had the riches he could have taken. Compare this to our politicians today and the candidates for the Presidency of the United States - a man like Hamilton would be a shining stand-out beacon of honesty and hope who would have always put his country first.
0.999944	This week I thought I would highlight the role of a home health aide. A home health aide has a significant role in ensuring a patient’s well-being, while allowing a patient to reside in their own home, instead of moving into an assisted facility. A home health aide is a certified nurse’s aide who specializes at in-home personal care assistance. After gaining the foundation of medical training as a certified nurse’s aide, a home health aide can then utilize their skills to provide care to patients in their home. A home health aide provides care to the elderly and disabled and allows patients to remain in the comfort of their own residence. Home health aides may assist with activities of daily living such as bathing, dressing, hair care, changing adult diapers or brushing teeth. They can also assist with a patient’s exercise, administer medications in some situations, assist with wound care, monitor vitals and/or complete light housework. These job duties can vary from person to person depending on the patient’s medical needs or other lifestyle needs. A home health aide may be responsible for communicating the patient’s needs between caregivers, family members, doctors and other medical professionals. Some necessary skills of a home health aide include communication, compassion, patience, job flexibility, reliability, job knowledge and active listening. If you are interested in working one on one with a patient to help improve their lifestyle needs, this may be the career choice for you!
0.923041	The Grid plugin can be bound to multiple types of data collections including arrays, xml, json, tsv, csv or remote data. To data bind the Grid to a data source you need to set its source property to point to an instance of jqxDataAdapter. The source object represents a set of key/value pairs. localdata: data array or data string pointing to a local data source. datatype: the data's type. Possible values: 'xml', 'json', 'jsonp', 'tsv', 'csv', 'local', 'array', 'observablearray'. type: The type of request to make ("POST" or "GET"), default is "GET". id: A string containing the Id data field. root: A string describing where the data begins and all other loops begin from this element. record: A string describing the information for a particular record. name - A string containing the data field's name. type - A string containing the data field's type. Possible values: 'string', 'date', 'number', 'float', 'int', 'bool'. format(optional) - Sets the data formatting. By setting the format, the jqxDataAdapter plug-in will try to format the data before loading it. map(optional) - A mapping to the data field. Example with nested JSON data. Example #2 with XML Attributes Let's load the following data into the Grid from a file named customers.xml. Example #3 with nested JSON data. values - determines the foreign collection associated to the data field. Example with "values" This functionality allows you to join two or more data sources. // update the loaded records. Dynamically add EmployeeName and EmployeeID fields. // values - specifies the field's values. // values.value - specifies the field's name in the foreign source. // values.name - specifies the field's value in the foreign source. // callback called when a page or page size is changed. pagenum - determines the initial page number when paging is enabled. pagesize - determines the page size when paging is enabled. pager - callback function called when the current page or page size is changed. sortcolumn - determines the initial sort column. The expected value is a data field name. sortdirection - determines the sort order. The expected value is 'asc' for (A to Z) sorting or 'desc' for (Z to A) sorting. sort - callback function called when the sort column or sort order is changed. filter - callback function called when a filter is applied or removed. addrow - callback function, called when a new row is/are added. If multiple rows are added, the rowid and rowdata parameters are arrays of row ids and rows. //and with parameter false if the synchronization failed. deleterow - callback function, called when a row is deleted. If multiple rows are deleted, the rowid parameter is an array of row ids. updaterow - callback function, called when a row is updated. If multiple rows are added, the rowid and rowdata parameters are arrays of row ids and rows. processdata - extend the default data object sent to the server. formatdata - Before the data is sent to the server, you can fully override it by using the 'formatdata' function of the source object. The result that the 'formatdata' function returns is actually what will be sent to the server. contenttype: Use this option, If you want to explicitly pass in a content-type. Default is "application/x-www-form-urlencoded". The example code below illustrates how to create jqxDataAdapter from a source object. // data is not loaded. If you bind the Grid to remote data source using asynchronous requests( that is by default when you specify url in the source object and you didn't set the async field to false), then make sure that you call any method or set a property once the data is loaded. To ensure that you call your code when the Grid is loaded with data, use the Grid's ready callback function or bind to the 'bindingcomplete' event before the Grid's initialization and call your code inside the event handler. Initialize a Grid with the source property specified. Bind the Grid to an array. The data member is array. The datatype member is set to "array". What happens when the data source is changed? How to refresh the Grid? To refresh the Grid, you need to simply set its 'source' property again. Bind the Grid to XML data. - url of a xml file. - record - this is the data record which will be displayed as a row in the Grid. - datafields - the record's member names. You can also specify the mapping to the member's data. You can also set the datafield's type in the source object initialization. The sortcolumn and sortdirection properties in the above code apply a sorting and a sort order to a Grid column. Bind the Grid to JSON data. When you bind the Grid to JSON data, you need to set the source object's datatype to 'json'. If you want to bind the Grid to JSONP data, then you need to set the source object's datatype to 'jsonp'. Bind the Grid to tab-separated values (TSV). When you bind the Grid to TSV data, you need to set the source object's datatype to 'tab'. Bind the Grid to comma-separated values (CSV). When you bind the Grid to CSV data, you need to set the source object's datatype to 'csv'. mapChar - specifies the mapping char. By default it is '>'. In the following code, if the mapChar was set to '.', we should use '.' instead of '>' to specify the fields map. columnDelimiter - specifies the column delimiter when the data source is 'tab' or 'csv'. The default value for 'tab' is '\t' and the default value for 'csv' is ','. rowDelimiter - specifies the rows delimiter when the data source is 'tab' or 'csv'. The default value is '\n'.
0.999987	Suppose I have a data set on which I'm training a neural network. I'm using four-fold validation, meaning that I train four models, one for each fold. Two of the folds are used for training, one for testing and one for validation so that no model is trained on its testing data. The result of this process is four trained models (obviously). My question is what is the correct way of reporting the performance for my network? Should I report the arithmetic mean of these four models on their respective folds or something else? Do I include the validation set in final training?
0.999996	This is your personal text. Life with a group of strangers was proving to be not as scary as Kesa had first thought. Once she had passed her acceptance into the pride she immediately began to make the land known to her. The last thing she needed to do was get lost or tread in places best left alone. There was a lot that was new to her. The strangest though had to be the 'human' lodgings. Kesa had never seen a human but her parents had told her many tales of the strange creatures that walked on two legs and fought with sharp sticks and other weapons. At first, and she feared, that the pride lived among them. The stories had left her with an uneasy feeling towards them. Thankfully she found no humans nor heard talk of them. The lodgings were merely shells of what once existed in this land. Sometimes she would pass another member and would greet them enthusiastically, introducing herself before being distracted and finding something to engage herself in. Honestly, she loved it! There was always someone around who might talk to her, a huge change from only being surrounded by her two aging parents who soon tired of her talk. Perhaps that is why they encouraged her to seek out a pride; they needed the break. She laughed at that thought. They had often told her she was talkative and never knew when was a good time to shut her maw. Sometimes she missed them, especially moments when she relived some memories of home. However, the feeling would soon be pushed aside as she found something else in her new home that amazed her. The one thing that she was interested in the most was the ranks the pride provided. Upon her arrival, an old grey saber had spoken to her about the variety of jobs the pride expected their members to partake in. Some sounded interesting and others made her feel slightly uneasy. She was not a fighter, she had never fought in her life and feared the day she would be expected to. She was not a huge saber but she was fast. The old saber had mentioned the rank, fletcher. After finding out what it was she thought it was best suited to her personality. She loved talking to others which is what she would be expected to do if she acquired that rank. Of course there were other things she needed to consider such as invaders and stuff. Perhaps a few more days of thinking it through would do her good. Kesa eventually found herself at the base of the tree houses. She had yet to gain the courage to venture up to them. These new things frightened her slightly. Walking around was beginning to bore her. She wanted to find someone to have an actual conversation with. There was no one in sight and she turned her head first to the right and then to the left. With a sigh she lowered her head to the body of water in front of her. The water was cool and while she drank she gazed down at her reflection, spotting something below the water. It was a tooth. What kind of tooth she did not know. It was not of a cat or even a wolf. This could be a great conversation starter for her. Excitedly, she pulled the tooth out the water and placed it on the ground in front of her. All she needed was someone to actually come along. Stoneclaw had been his refuge. His sanctuary. The cubs that had accompanied him into the pride lands didn't need him anymore and as there were no more cubs for him to take care of. Not now anyway. At least they had escaped Mother. The thought of Conchita stopped the mint colored saber dead in his tracks. Flashes of his life with her rushed back all at once and the male couldn't help but choke back a whimper, lavender eyes closing tight. His claws dug into the soft earth of the forest floor, trying to cling to anything that would keep him grounded. How could she have done such wicked things to children? He simply couldn't comprehend her specific brand of evil. Nikolai needed water. He smelled the air, needing to find the nearest water source to swallow back the bile that had risen in his throat at the memory of cubs, mauled, being consumed. Before he knew it, he was running, tearing through the brush to get to the water. He didn't even see the female by the water's edge as he plunged right in. The shock of the cold water was enough to distract him, if even for right now. It wasn't until he broke the water's surface, gasping for breath, that he saw he wasn't alone. His face burned with embarrassment, eyes darting away from her. How foolish he had been. Slowly Nikolai swam back over to the bank, pulling himself up from the muddied water. A small sound escaped him and he hung his head in apology. Kesa found herself amazed at her discovery. She lay on the ground to allow herself a closer look at the tooth. "where are you from..." she thought out loud. In fact, Kesa was so distracted by the small object on the ground that she did not hear the visitor come bounded through the bushes. It was the splash that made her aware. The sound startled her making her jump up onto her feet. "What was that??" she yelled out, not to anyone in particular but more to herself. She looked around before spotting the feline in the water. A saber with the most beautiful coat she had ever seen walked out covered in water and a bit of mud. She heard what he thought was him saying something but it was too soft. His head was hung low and she couldn't make eye contact with him. "Your fur is beautiful!" Kesa heard herself blurt out. She often said things without thinking it all through. This moment was one of them. No 'hello, my name is Kesa!", nothing. She always had to say what was on her mind. First she took a deep breath, then she tried again, "What I meant to say is, hi there! My name is Kesa." She would sit on the bank of the lake watching him. "Today is a very good day for a swim. Before I forget to ask, what is your name?". He was the first member she had met since she joined. She finally had someone to ask about the tooth! "By the way, I saw this lying near the waters edge. It is tooth of some kind but I am not sure from what it comes from. Do you maybe have an idea?" There! She had done it. She had begun her plan to make friends. The first step was complete, meet someone! The second step was complete, initiate a conversation. Now on to step 3, maintain eagerness to socialise in order to not scare potential friends away. He parents had always told she had what was known as a bubbly personality. They warned her to introduce people to her personality slowly as not everyone would welcome it straight away. Let's see how well she can do that now. Nikolai's lavender eyes grew wide and his face burned even hotter than before. He shuffled his paws and made another strange noise. She was very pretty herself but how could he possibly convey that without words? Most here didn't even know his unique hieroglyphics. Even if they did, there was no way for him to convey how to say his name. There was no symbol for himself. "What I meant to say is, hi there! My name is Kesa. Today is a very good day for a swim. Before I forget to ask, what is your name?". This time he whistled out of his nose, face twisted in sorrow. He couldn't tell her his name. His paws flexed nervously, as his eyes cast down in shame. If only he could speak... if only he could make his tongue form the words. Every time he did, the horrors of Conchita flooded back to him and the words were choked down once more. "By the way, I saw this lying near the waters edge. It is tooth of some kind but I am not sure from what it comes from. Do you maybe have an idea?" Finally something he could respond to! His ears perked up and he nodded vigorously. He'd seen plenty of these things since moving into the forest. Nikolai quickly went to the waters edge where the soil was soft enough for him to draw a symbol. First he thought he would try to explain why he didn't speak so he drew out the shape of an open mouth with a line through it, then opened his own mouth and pointed into it, making a strange noise as he did. Then he quickly pointed to the tooth she had asked about and drew a new symbol in the soil. Croc. He opened his mouth wide and snapped a couple of times, then waited to see if she got the point.
0.999975	If you need to extract only a specific part of your input, you'll need to use the seeking option to get to that specific part in the input first. The parameter -ss is used to seek into the input and it can be used in several ways. This example will produce 1 image frame (out1.jpg) somewhere around 3rd minute from the beginning of the movie. The input will be parsed using keyframes, which is very fast. The drawback is that it will also finish the seeking at some keyframe, not necessarily located at specified time (00:03:00), so the seeking will not be as accurate as expected. This example will also produce 1 image frame (out2.jpg) precisely at 3rd minute from the beginning of the movie. Note the time difference on the clocks between the images out1.jpg and out2.jpg. The first one shows "00:02:05:05" and the second shows "00:02:05:06". The input is parsed very slowly, frame by frame. The advantage is that you'll get the frame at exactly 3rd minute, but the drawback is that it will take a lot of time until it finally reaches that time point. The bigger the seeking time is, the longer you will have to wait. This approach is combining the best characteristics of both fast and accurate ways of seeking in FFmpeg. Shortly, we first seek very fast somewhere before the 3rd minute and then we slow down and seek frame by frame to the 3rd minute. This works because FFmpeg will first seek by keyframes, until it reaches at 00:02:30, when it will stop at the last keyframe found (somewhat before 00:02:30, depending on the gop size/keyframes interval of the input) and then it will slowly seek the next 00:00:30 seconds to the desired time point. The result should be the same as in "Accurate seeking" section, only a lot faster. Note that both out2.jpg and out3.jpg show the same time on the clock "00:02:05:06" There is no general rule how to correctly set both time points for -ss options, because those depend on the keyframe interval used when the input was encoded. But, just for the purpose of some orientation, the x264 encoder uses the gop size of 250 (which means 1 keyframe each 10 seconds if the input frame rate is 25 fps). out1.jpg (34.9 KB) - added by burek 7 years ago. out2.jpg (39.6 KB) - added by burek 7 years ago. out3.jpg (39.6 KB) - added by burek 7 years ago. out.jpg (84.8 KB) - added by c-14 5 years ago. Example output for "Seeking with FFmpeg".
0.999971	Henri II of France issued the Edict of Compiègne on 24 July 1557. The Edict of Compiègne (French: Édit de Compiègne), issued from his Château de Compiègne by Henry II of France, 24 July 1557, applied the death penalty for all convictions of relapsed and obstinate "sacramentarians", for those who went to Geneva or published books there, for iconoclast blasphemers against images, and even for illegal preaching or participation in religious gatherings, whether public or private. It was the third in a series of increasingly severe punishments for expressions of Protestantism in France, which had for an aim the extirpation of the Reformation. By raising the stakes, which now literally became matters of life and death, the Edict had the result of precipitating the long religious crisis in France and hastening the onset of armed civil war between armies mustered on the basis of religion, the series of French Wars of Religion, which were not settled until Henri IV's edict of toleration, the Edict of Nantes (1598). The source of the "contagion", as court pamphleteers put it, was Geneva, where the French-born John Calvin achieved undisputed religious supremacy in 1555, the same year that the French Reformed Church organized itself at a synod in Paris, not far from the royal residence at the Louvre. At the Peace of Augsburg signed that same year in Germany, the essential concept was cuius regio eius religio, "Whose region, his religion". In other words, the religion of the king or other ruler would be the religion of the people. The petty princes of Germany were enabled to dictate the religion of their subjects, and it came to be sensed as a mark of weakness that the King of France could not do so: "One King, One Faith" would become the rallying cry of the ultra-Catholic party of the Guise faction. The Parlement de Paris was deeply divided on the issues. When the King approached the Parlement for its formal advice beforehand on the best means of punishing and stamping out heresy, the moderate voices of président Séguier and conseiller du Drac urged against the proposed new edict (as unnecessary) and specifically opposed the introduction of an Inquisition into France, an innovation that would appear to circumvent the king's justice, vested in the parlement. The preamble of the Edict of Compiègne, like earlier ones, remarked on the ineffectiveness of the courts in acting against "heretics", because of the malice or lenience of judges. The Edict sanctioned a papal brief that established a court of Inquisition in France, though the Parlement delayed in acting upon it, and it was rescinded in April 1558. For now it hesitated even to take up the edict: "On the last day of 1557, the gens du roi complained again that the court had still not deliberated the king's latest edict (Compiègne), "presented four months ago." They understated the case: the edict had been presented on July 24, 1557, and was registered in January 1558." But the first effects of the Edict had already transpired. On 4 September 1557 an angry mob had broken into a Calvinist meeting being held in a private house in the rue Saint-Jacques. They found nobles and royal officials, respected artisans, women and children. About 132 people were arrested and thrown into prison. On 14 September, three, including a noble widow, were publicly burned in the place Maubert. ^ A second Edict of Compiègne issued from the same château in August 1765, in the name of Louis XV, aimed at a minor adjustment of the process of electing mayors. ^ This meant Calvinists not Lutherans. ^ Robert Jean Knecht, The Rise and Fall of Renaissance France: 1483-1610 (rev. ed., Blackwell, 2001:241. ^ The first punitive code, the Edict of Fontainebleau (1540), had been issued in 1540. The second, more severe, was the Edict of Châteaubriant of 1551. The Edict of Écouen was issued in 1559, the year of the king's death. Roelker, Nancy Lyman, One King, One Faith: The Parlement of Paris and the Religious Reformations of the Sixteenth Century (Berkeley: University of California Press) 1996 "The Road to Civil War (1): 1555-1561"
0.999997	Dress that normally costs $69.50 is on sale for 45% off. The sale price of the dress is $38.23. Solution: 69.50 x 45% = 31.275; 69.50 - 31.275 = 38.225 or $38.23.
0.940475	For the 1978 Rajesh Khanna film, see Chakravyuha (1978 film). For the military formation mentioned in Mahabharata, see Padmavyuha. Chakravyuh (transl. Wheel formation) is a 2012 Indian action political thriller film directed by Prakash Jha starring Arjun Rampal in the lead role with Abhay Deol, Esha Gupta, Manoj Bajpayee and Anjali Patil in supporting roles. Chakravyuh aims to be a social commentary on the issue of Naxalites. The first theatrical trailer of Chakravyuh was released at midnight on 16–17 August 2012. The film released on Durga Puja. Chakravyuh released in 1100 cinemas in India. Despite being well-praised and really close to reality, the movie failed to attract an audience. The plot is inspired by 1973 Hindi film Namak Haraam, and the 1997 Telugu film Sindhooram. Adil Khan (Arjun Rampal), a highly decorated police officer is posted to Nandighat, after martyrdom of 84 policemen and CRPF soldiers. Within days, he discovers that the Maoists, led by the ruthless Rajan (Manoj Bajpayee), effectively control the area. They are able to swiftly thwart Adil's most determined efforts. Despite holding a position of enormous power as the SSP of Nandighat, Adil has never felt so helpless in his career. But then, into his life, re-enters his friend Kabir (Abhay Deol). Rootless, aimless, the quintessential rolling stone. His only anchor in life has always been his friendship with and his loyalty for Adil. The maverick proposes an outrageous plan: He will infiltrate Rajan's group and be Adil's informer, and together they will smash the Maoist organization in Nandighat. In spite of his apprehensions, Adil agrees. Sure enough, Kabir gets in and craftily wins their confidence, as only he can. He secretly begins informing Adil, who starts attacking the Naxals with great success. An enormous cache of arms is raided; two top national leaders and 63 Naxals are killed at an arms-training camp, and Rajan himself is captured. Within weeks, Adil-Kabir turn the game, pushing the Maoists onto the back foot. But Kabir also begins sympathising with abject helplessness of the rural poor, brutally displaced in the name of development, the fruits of which never reach them; their land, their forest, their water has been snatched to allow big business to exploit the area and its people further. Kabir begins identifying with Naxals. Juhi (Anjali Patil), a dedicated Naxal with a tender heart, who has seen pain like none other. She begins to fall in love with Kabir. The confusion in Kabir's heart intensifies dangerously until he is on the horns of a ghastly dilemma: Who does he support now? Who does he fight? He finds himself in a chakravyuh from which there is no retreat now. And yet, before Kabir can make one last desperate attempt to resolve this with his friend Adil, events hurtle him into making choices that would put him at war with him. A war that would change the future of the region. A war that can end only when one of them destroys the other. Arjun Rampal as Adil Khan (Senior SP Nandighat). He is the protagonist of the movie. He is a police officer and is on a mission to target the Naxals and capture their leader Rajan and ideologue Govind Suryavanshi. He sends his friend Kabir as an informer to get their information and foil their plans. She is an IPS officer and Adil's wife. He is Adil's best friend who infiltrates the Naxal movement as an informer. He initially supports Adil in the mission but slowly starts getting impressed with the Naxals and becomes their leader, thus entering a stand-off with Adil. She is a Naxalite commander, playing a key role in the argument. She also develops romantic feelings towards Kabir. He is the leader of Naxalites. He is the chief Marxist ideologue. Om Puri role is said to be inspired from Kobad Ghandy. He is an industrialist and negotiator for the government. Mukesh Tiwari as Inspector General of Police (IGP). Murli Sharma as Naxalite area commander Naga. Chetan Pandit as Inspector Madhav Rao. Daya Shankar Pandey as Inspector Raja Ram. Kiran Karmarkar as Home Minister. Radhakrishna Dutta as Chief Minister. Chakravyuh is shot in Panchmarhi and Bhopal. The movie was shot at Trinity Institute of Technology And Research, Bhopal and some scenes were shot at IES and MLB college. The entire schedule of shooting was wrapped up in about 57 days. The Madhya Zonal Committee of the CPI Maoists, has expressed gratitude for the film has, however, pointed out a few facts which are not in consonance with "their world". Maoists have given full credit to the film for being close to reality. Jha on his turn has said it was possible because of intense research in finalising the script, costumes and the plot. Prakash Jha has come up with a unique way to promote his upcoming socio-political thriller Chakravyuh by launching an online comic series. The first episode of the series, 'The Sohble Encounters', starts with a bunch of youngsters rounded up from a party by Inspector Sohble (needless to say a clear dig at Inspector Dhoble). Jha has managed to pitch it cleverly in the backdrop of his film. The first instalment of the series went online. Music for this film is composed by Salim-Sulaiman, Aadesh Shrivastava, Shantanu Moitra, Sandesh Shandilya, Vijay Verma, lyrics by Irshad Kamil, Panchhi Jalonvi, Ashish Sahu, A. M. Turaz. One song Tata, Birla, Ambani aur Bata had run into trouble with the Censor Board but was passed after a disclaimer saying these names have been used symbolically and it does not mean any harm or disrespect to any individual or brand. One song Kunda Khol is picturised on Sameera Reddy and Murali sharma. There is item song Tambai Rang Tera in the film, choreographed by Ganesh Acharya. Musicperk.com rated the album 6/10 quoting "This formation doesn’t work". Upon release,Chakravyuh received mixed to positive reviews from critics. The Times of India gave 3.5 stars out of 5. According to TOI, "Chakravyuh is a hard film to make and marks must be given to Jha for sticking his neck out. Staying true to the subject, he gives us an insight into uncomfortable truths unfolding in our backyard. He is one of the few filmmakers with such audacious work to his credit." Subhash K. Jha of Indo-Asian News Service gave the movie 4/5 stars and called it a "resolutely etched, firmly grounded drama". Bikas Bhagat of Zeenews gave the movie 4/5 and wrote in their review, "Here’s a fight which we have heard about and seen through the ages – the fight between the Capitalists and the Communists. Prakash Jha presents it in his own way; and going by illustrious line of work, it would be a big mistake on your part if you happen to give ‘Chakravyuh’ a miss." Gautam Batra & Roma Heer of Wassupbollywood gave the movie 2/5 saying, "Chakravyuh is surely a great concept but fails drastically on screen. Watch Prakash Jha’s past flicks on CD/DVD instead of wasting your time & money on it. Not Recommended." Sukanya Verma of Rediff gave the movie 2.5/5 stars and wrote, "Chakravyuh maintains an aggressive cinematic tone with sufficient stock of blood and action to dole, but is nothing more than an average action flick in the garb of relevant cinema". According to Hindustan times, Chakravyuh is, ultimately, a victim of typical Bollywood excesses and gave 2.5 out of 5 stars. Bollywood portal Films of India said, "Shot flawlessly the movie is raw, gritty, with no frills. Watch Chakravyuh for its performances and high intense drama. If you’re a person who likes to use their mind, then the 3 and a half star Chakravyuh is definitely the movie for you." Chakravyuh had an opening of ₹15 million (US$210,000) in first three days in India Chakravyuh had low first week than expectations where it raked ₹158.8 million (US$2.2 million) nett. Chakravyuh grossed $300,000 in extended 5-day weekend in overseas. ^ a b Box Office India (27 July 2012). "Prakash Jha's Chakravyuh to premiere at London Film Festival". DNA. Retrieved 22 July 2012. ^ "Box Office Earnings 16/11/12 – 23/11/122 (Nett Collections in Ind Rs)". boxofficeindia. Retrieved 24 October 2012. ^ a b "Chakravyuh Week One Territorial Breakdown". boxofficeindia. Archived from the original on 8 November 2012. Retrieved 5 November 2012. ^ "Chakravyuh's shoot begins in city". Articles.timesofindia.indiatimes.com. 30 March 2012. Retrieved 22 July 2012. ^ "Arjun to enter 'Chakravyuh' next week". Supergoodmovies.com. 30 March 2012. Retrieved 22 July 2012. ^ "Prakash Jha ties up with Eros International Media". Articles.economictimes.indiatimes.com. 15 March 2012. Archived from the original on 13 July 2012. Retrieved 22 July 2012. ^ "WATCH: Prakash Jha's 'Chakravyuh' trailer hits the web". Zeenews.com. 17 August 2012. Retrieved 17 August 2012. ^ "'Chakravyuha' has nothing to do with 'Ko': Prakash Jha". Ibnlive.in.com. 3 February 2012. Retrieved 22 July 2012. ^ "Arjun turns cop for Prakash Jha's Chakravyuh". The Times of India. Retrieved 1 April 2015. ^ Bollywood Hungama. "Arjun shoots intimate scenes with Esha Gupta - Latest Movie Features - Bollywood Hungama". Retrieved 1 April 2015. ^ "NDTVMovies.com : Bollywood News, Reviews, Celebrity News, Hollywood news, Entertainment News, Videos & Photos". Retrieved 1 April 2015. ^ "Entertainment News - Latest Stories, Headlines, Events, Happenings - Hindustan Times". hindustantimes.com/. Retrieved 1 April 2015. ^ "From the very first meeting, Prakash Sir had faith in me: Anjali Patil – Times Of India". Articles.timesofindia.indiatimes.com. 2 October 2012. Retrieved 2 October 2012. ^ "Anjali Patil is a great actor: Esha Gupta- Times Of India". Articles.timesofindia.indiatimes.com. 2 October 2012. Archived from the original on 27 September 2012. Retrieved 2012-10-02. ^ "Prakash Jha shoots a raunchy item song". The Times of India. Retrieved 1 April 2015. ^ "Om Puri plays Maoist Kobad Ghandy". The Times of India. Retrieved 1 April 2015. ^ "Page:". Retrieved 1 April 2015. ^ "I'm known as Wasooli uncle: Mukesh Tiwari". The Times of India. Retrieved 1 April 2015. ^ Priyanka Dasgupta (18 May 2012). "Celebrities face tough time in summer". Timesofindia.indiatimes.com. Retrieved 22 July 2012. ^ "Prakash Jha apologises, pays Rs 25,000 to Baiga troupes". Timesofindia.indiatimes.com. 13 April 2012. Retrieved 22 July 2012. ^ "I have met Naxalites, says Prakash Jha – Times Of India". The Times Of India. ^ "Maoists give 4 stars to 'Chakravyuh' - The Times of India". The Times Of India. 11 November 2012. ^ Bollywood Hungama. "Chakravyuh comic-series to highlight youth issues - Latest Movie Features - Bollywood Hungama". Retrieved 1 April 2015. ^ "The naxal chakravyu - The Times of India". The Times Of India. 17 August 2012. ^ "Chakravyuh in censor trouble - The Times of India". The Times Of India. 7 September 2012. ^ "Item song pulls Praksh Jha back to Bhopal". Hindustan Times. 20 September 2012. Retrieved 20 September 2012. ^ Upala KBR (24 April 2012). "Abhay's not comfortable with dancing: Prakash Jha – Times Of India". Articles.timesofindia.indiatimes.com. Retrieved 22 July 2012. ^ "Chakravyuh". Retrieved 1 April 2015. ^ "CHAKRAVYUH MOVIE REVIEW". Reviewgang. ^ "Chakravyuh - The Times of India". The Times Of India. ^ "'Chakravyuh' resolutely etched, firmly grounded drama (IANS Movie Review - Rating: ****)". Yahoo Celebrity India. 24 October 2012. Retrieved 1 April 2015. ^ "'Chakravyuh' review: Naxalism decoded by Prakash Jha". Zee News. Retrieved 1 April 2015. ^ "Chakravyuh Movie Analysis – Gautam Batra & Roma Heer". Retrieved 1 April 2015. ^ "Review: Chakravyuh is just your average action flick". Rediff. 24 October 2012. Retrieved 1 April 2015. ^ "Suprateek Chatterjee's review: Chakravyuh". hindustantimes.com/. Retrieved 1 April 2015. ^ "Chakravyuh Daily Three Day Business". Retrieved 27 October 2012. ^ "Chakravyuh and Ajab Gazabb Love Have No Takers". BOXOFFICEINDIA. Retrieved 31 October 2012.
0.999201	Write a fictional piece of no more than 300 words based on the picture above. You pick your poison, poetry or story. Please don’t forget to, mention this post of yours, and link back here. In was early morning, dawn had just broken, I was having a quick look through my binoculars from the top of the building before having a shower. All of a sudden something caught my eye, was I dreaming, over the top of another building was this strange looking cricket insect which had what looked like an antenna strapped to his body. What was this a new way to correspond with aliens by unsuspecting apparatus strapped to an insect, spying on Government buildings with protected information, sending it back to mars? Who would have thought of this strange way of getting information, or even to go so low to train insects to locate important guarded ideas on computers this way instead of tapping into personal emails? When I focus the binoculars again there was no insect to be seen, perhaps I was dreaming, let’s hope so, amazing what a half awake mind can dream.
0.987504	Familial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16–40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature. In the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation. Nineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53. In this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population. Breast cancer (BC) is the most common cancer in women, accounting for around 25% of all new cases of cancer . Most BC cases are sporadic, while 5 to 10% of all BC cases are inherited and cluster in families . While mutations in BRCA1 and BRCA2 genes explain 16–40% of all familial BC cases [1–3], other genes have also been found to increase BC susceptibility, which highlights the polygenic nature of many BC cases . Some of these genes including CDH1, TP53, PTEN and STK11, although less frequently altered compared to the BRCA1/2 genes, they have been linked to high-penetrance autosomal dominant BC [5–7]. Moderate penetrance genes are implicated in around 5% of familial BC. These genes include the Fanconi anemia pathway genes: FANCA, PALB2, BRIP1, RAD51C and XRCC2 [8–10] and non-Fanconi anemia genes: ATM, CHEK2, NBN, RAD50, RAD51B, and RAD51D [11–15]. In Lebanon, BC is the most common cancer type in females and it constitutes one-third of all reported cancer cases. BC incidence rates are expected to reach 137 per 100,000 by 2018 . Yet, to date, only two studies have investigated the role of BRCA1 and BRCA2 mutations in the Lebanese population. These studies reported varied prevalence of pathogenic BRCA mutations ranging between 5.6 to 12.5% in BC cases [17, 18]. The reported prevalences of both BRCA1 and BRCA2 deleterious mutations were lower than those reported for the Western populations, which suggest the involvement of other genes in the pathogenesis of BC cases . The reported low prevalence does not support the hypothesis that BRCA1 and BRCA2 mutations alone are responsible for the majority of the observed Lebanese women with early-onset BC. This finding could well explain the fact that BC is a disease with a high level of genetic heterogeneity and that monogenic and polygenic models of inheritance may exist. Since the completion of the human genome project, massive leaps have reshaped the field of clinical genomics. The development of Next-generation sequencing (NGS) platforms allowed a more robust, fast and accurate analysis of diseases and syndromes with polygenic nature. NGS platforms including WES are believed to enhance and improve diagnosis and therapy development of many diseases including BC [20–23]. In the presented study, we utilized WES to investigate germline genetic variations in 45 Lebanese cases diagnosed with familial BC and unknown BRCA1 or BRCA2 status. We found several rare variants that can potentially explain BC susceptibility in the analyzed cases. From 2012 to 2015, 45 unrelated patients with inherited BC were selected to undergo DNA testing. They were referred from a wide variety of settings from all over the country, ranging from private physicians’ clinics to major academic medical centers because of hereditary BC. The patients fulfilled a personal history of invasive BC and at least one of the following criteria: A) diagnosis at age ≤ 40 years, B) BC at any age at onset with at least 2 first- and/or second-degree relatives, C) BC < 50 years in a first- or second-degree relative, D) ovarian cancer in at least 2 first- and/or second-degree relatives, E) breast and ovarian cancer in at least 2 first- and/or second-degree relatives, F) both breast and ovarian cancer in a single first- or second-degree relative. Approval to conduct the study was obtained from the Ethics Committee of Saint-Joseph University-Lebanon. After an informed consent was signed and all ethical requirements were fulfilled, a 10 ml of peripheral blood was isolated from each individual enrolled and the DNA was extracted using the salting out methods . All patients signed the informed consent and agreed to share their variant data. Exon capture and sequencing: Samples were prepared for whole Exome sequencing and enriched according to the manufacturer’s standard protocol. The concentration of each library was determined using Agilent’s QPCR NGS Library Quantification Kit (G4880A). Samples were pooled prior to sequencing with each sample at a final concentration of 10nM. Sequencing was performed on the Illumina HiSeq2000 platform using TruSeq v3 chemistry. Mapping and alignment: Reads files (FASTQ) were generated from the sequencing platform via the manufacturer’s proprietary software. Reads were aligned to the hg19/b37 reference genome using the Burrows-Wheeler Aligner (BWA) package v0.6.1 . Local realignment of the mapped reads around potential insertion/deletion (Indel) sites was carried out with the Genome Analysis Tool Kit (GATK) v1.6 . Duplicate reads were marked using Picard v1.62. Additional BAM file manipulations were performed with Samtools 0.1.18 . Base quality (Phred scale) scores were recalibrated using GATK’s covariance recalibration. SNP and Indel variants called using the GATK Unified Genotyper for each sample . SNP novelty is determined against dbSNP. A list of 134 genes known to be associated with hereditary BC and other cancers were studied (Additional file 1). Variants obtained were reported using five categories according to the Human Genome Mutation Database (HGMD Professional) . These categories are listed in Table 1. The first variant category consists of alleles labeled as disease causing mutations (DM) in HGMD Professional. These alleles must be rare: <1% allele frequency in 6,500 exomes from the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (“Exome Variant Server” 2015) and the 1,000 Genomes Project Genomes . The BRCA gene variants identified were checked for pathogenicity in 4 databases: Breast Cancer Information Core (BIC) , Leiden Open Variation Database (LOVD) , the Catalogue of Somatic Mutations in Cancer database (COSMIC) and BRCA Exchange website (http://brcaexchange.org) providing data from the ENIGMA consortium . Sanger’s sequencing was utilized to confirm the relevant variants identified by WES and to study the segregation of these variants with the disease phenotype in members of families included in the study. PCR reactions were run in final volumes of 50 μl containing 100 ng DNA, 0.25 mM dNTPs, 100 ng of each primer and 0.02 unit of Taq polymerase (Invitrogen Life Technologies, Carlsbad, CA, USA). PCR was performed in an ABI9700 thermocycler (Applied Biosystems, Foster City, CA) with initial denaturation at 94 °C for 5 min, followed by 35 cycles of 95 °C for 30s, specific annealing temperature for 30s, 72 °C for 30s. Primer sequences are available on request as well as annealing temperatures of each exon. PCR products were purified using the illustraTM GFX PCR DNA and Gel Band Purification Kit (GE Healthcare, Buckinghamshire, UK). Both strands of the products were sequenced using the BigDyeW Terminator v1.1 Cycle Sequencing Kit (Applied Biosystems, Foster City, CA) under standard conditions. The labeled products were subjected to electrophoresis on an ABI3130 and ABI3500 Genetic Analyzer sequencing system (Applied Biosystems, Foster City, CA, USA). Electropherograms were analyzed using Sequence Analysis Software v5.2 (Applied Biosystems, Foster City, CA, USA) and compared to reference sequences using ChromasPro v1.7.6.1 (Technelysium, Queensland, Australia). The mean age at diagnosis of BC for the 45 patients was 44 years (range 29–79). Sixteen patients provided us with their histopathological results. Seven BC were estrogen-receptor (ER) and progesterone-receptor (PR) positive, 5 patients had negative ER and PR disease and 2 patients had negative ER and positive PR disease. Two patients had triple negative disease from which one patient (Family 30) carried p.C44F mutation in BRCA1 (Fig. 1). We obtained an average of 44 million reads per sample, with a mean coverage of 94% at a mean X coverage of 20X. Within this cohort, a total of 126 variants were detected by WES and these are listed in Table 2. In 7 of the 45 patients, not listed in Table 2, no variants in cancer predisposing genes (Additional file 1) were identified. We were able to detect 19 HGMD DM variations of which 9 are specifically associated with breast cancer (Table 2). The distribution of the remaining variants in the HGMD categories was: 11 DM?, 11 DP, 1 FP, and 9 DFP. In addition, 75 novel variations were detected in this study (Table 2). Six BRCA1 and BRCA2 DM mutations were detected in 5 and 2 patients, respectively in a total prevalence of 15.5% (Table 2). Nine truncating mutations were detected in 9 different patients (Table 2). Three of these mutations were DM in HGMD: The first woman carried p.R1443* in BRCA1, the second one carried p.V220I* in BRCA2 and the third one carried p.G164X in ABCC12 (Table 2). The six remaining truncating mutations were not found in HGMD: p.Q613X in SLX4, p.R170X in ERCC3, p.Q117X in EZH2, p.P742fs in NSD1, p.357_364del in BARD1 and p.L1697fs in BRCA1 (Table 2). Three DM mutations were found, each one, in 2 different patients: p.C44F in BRCA1 (Families 13 and 30), p.P349A in MSH2 (Families 7 and 24) and p.G141W in SLX4 (Fig. 1 and Table 2). In some families where different variants were found, in order to consider, which variant is pathogenic, we analyzed the co-segregation of the variations found with the cancer phenotype within 3 families 12, 13, and 32 (Figs. 1 and 2). Two members of family 12 were diagnosed with BC, their mother and maternal uncle were diagnosed with primary lung cancer and bone cancer, respectively. The nonsmoking mother was affected at the age of 63 but the age of the maternal uncle at diagnostic was not accessible. WES, in proband 12/B35 diagnosed with BC at the age of 42, identified 2 variants including one DM? p.I94L in RAD50, according to HGMD Professional database, and one novel variation p.G191R in ARL11 (data not shown). Prediction tool Polyphen2 indicated that both changes are benign and SIFT prediction tool indicated that p.I94L in RAD50 is tolerated and that p.G191R in ARL11 is damaging. Only p.I94L in RAD50 segregated in the affected sisters, diagnosed with BC at the age of 48, but it was also found in their third youngest 51 years old unaffected sister. Three members of Family 13 were diagnosed with BC. WES identified 3 DM according to HGMD Professional database, including p.C44F in BRCA1, p.G141W in SLX4 and p.S404F in STK11 (Table 2). Leiden Open Variation Database indicated that p.C44F in BRCA1 affects protein function and it segregated with the disease (Table 3) (Fig. 1). Six members of family 32 were diagnosed with BC (Fig. 2). Members III-3, III-4 and III-6 were diagnosed with BC at the age of 56, 48 and 50, respectively. WES in proband III-4 identified 2 relevant variants including p.M1I in CDH1 and p.T1354M in BRCA2. Prediction tool SIFT indicated that both changes are damaging and are DM according to HGMD Professional database (Table 2 and Fig. 2). The analysis of this family showed that these variations were carried by affected and siblings that are not affected to date (Fig. 2). However, they were advised to join our screening program. We have noted that the most frequently altered genes involved in our familial cases are DNA repair genes (Fig. 3a) and that some variants were recurrent in our cohort: p.W149X in ARL11, p.S836S in RET, p.A126T in RAD51C, p.T241M in XRCC3, p.G998E in PALB2 and c.673-36G > C in TP53 (Table 2 and Fig. 3b). In four cases, like the 4 families shown in Fig. 1, individuals appear to co-inherit multiple cancer causing or predisposing gene mutations. Unlike, the old strategy where one stops the investigation once a pathogenic mutation was identified, NGS gives us the capability of collating all known mutations/variants in a sample, which may permit a more comprehensive understanding of the polygenic landscape model of cancer. An important question to be answered is: Does an individual in Family 13 harboring all three DM mutation have different penetrance, genotype to phenotype correlation, type or age of onset of cancer than a sibling with only one DM variant? This critical question can only be answered when we start to combine all germline variant data of cancer patients and their comprehensive phenotypes from around the world in well-curated databases. We identified, in 45 patients with familial BC, 19 pathogenic mutations that are DM mutations according to the HGMD Professional database (Table 2). These 19 mutations were found in 13 different genes including ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11, and TP53. Six mutations were found in BRCA1 and BRCA2 presenting a lower prevalence (15.5%) of deleterious BRCA mutations compared to the published literature [21–23]. In the Lebanese population, p.C44F mutation in the BRCA1 gene was found twice in this study and 5 times in previous studies [17, 18] in a total of 7 from 367 cases studied (1.9%). In fact, 2 of 9 patients carried a deleterious BRCA mutation in a cohort of 72 patients and 3 of 14 patients carried a deleterious BRCA mutation in a cohort of 250 patients. Our findings suggest it is the most recurrent mutation in the Lebanese population. In families 23 and 35, we identified the truncating mutation p.357_364del in BARD1 (Table 2). A previous study, on this variation, showed the absence of co-segregation with the disease and it was considered as neutral polymorphisms . We have observed this variant in our population and breast cancer patients and it is recommended that a more thorough and functional examination of this variant be conducted in the future. In families 12, 13 and 32, we identified 7 variants in ARL11, BRCA1, BRCA2, CDH1, RAD50, SLX4, and STK11. The association of which variation towards increasing predisposition to BC remains unknown. Therefore, we analyzed the segregation of these variations and BC within the families. In family 13, only p.C44F in BRCA1 segregated with BC in the family. In family 12, p.I94L in RAD50 (a DM? mutation) was found in affected and healthy sisters and could therefore not lead to a conclusion regarding predisposition to BC. In family 32, p.M1I in CDH1 and p.T1354M in BRCA2 are implicated in gastric cancer and BC respectively and knowing that the family presented with only BC, two hypothesis can be formulated. First, III-6 can be considered as phenocopy and second healthy, till now, sisters III-5, III-7 and III-9 are at high risk (Fig. 2). In fact, in high-risk families, women testing negative for the familial BRCA mutation have an increased risk of BC and should be considered for continued surveillance . Interestingly, two members of this family, III-4 and III-6 presented with invasive lobular breast cancer (Fig. 2). The association between CDH1 gene mutation and lobular cancer has been well established previously , and it is not unrealistic to suggest that this CDH1 variant may be the cause of lobular breast cancer in this family. The pathogenic status of the majority of novel substitutions found and the 6 variations considered as DM? according to HGMD professional, remains problematic (Table 2). In fact, HGMD professional reports DM? as likely pathological mutation reported to be disease causing in the corresponding report, but the author has indicated that there may be some degree of doubt, or subsequent evidence has come to light in the literature, calling the deleterious nature of the variant into question . Further studies are needed to define the pathogenic status of the novel substitutions and the DM? variations that have been found in our cohort of patients with BC. These future studies have to be analyzed in a larger number of affected families and control population samples. NGS and traditional sequencing methods are not proficient in detecting BRCA genomic rearrangements including large deletions or duplications. Deletion and duplication genomic rearrangements vary significantly among countries and within ethnic groups . We admit, therefore, that our reported BRCA mutation prevalence is underestimated. Among the DM mutations found, several were associated with syndromes (Peutz-Jeghers), different cancer types (renal cell carcinoma, gastric cancer) and with diseases (Xeroderma pigmentosa, ataxia telangiectasia) (Table 2). Clinically, none of the symptoms found in these diseases were manifested in the different studied families except for family 24. In this family, proband 24/B49 carried the mutation p.R1443* in BRCA1 and two MSH2 variants (Fig. 1). Her mother had ovarian cancer and her sister uterine cancer, both are deceased and could not consequently be tested for these variants. MSH2 mutation is reported in families with endometrial cancer (Lynch syndrome) and breast cancer from Kuwait . This is the first application of NGS on BC in Lebanon. In this study, we showed that the prevalence of deleterious BRCA mutations (15.5%) is lower than expected [17, 18] and that the overall mutation prevalence is equal to 40%, justifying the urgent need for the adoption of high-throughput NGS technologies to identify genes responsible for familial BC in the Lebanese population. Indeed, additional to BRCA mutations, highly penetrant mutations in genes associated with various hereditary cancer syndromes, such as CDH1, TP53, MSH2, ATM and POLH were found in the Lebanese population. Finally, we cannot rule out that some of these families shift a putative explanation towards a polygenic model where moderate and low penetrance alleles, acting together, may play a predominant role [20, 40, 41]. Our findings support the eligibility of performing genetic testing by massively parallel sequencing on Lebanese familial BC cases. Moreover, we would like to use this technology for tumor genome sequencing, in order to identify somatic alterations, which would be a valuable guidance towards individualized cancer therapy of Lebanese patients with BC. However, it is worthy of note that our study reports a small number of variants that are clinically actionable. Given the high rate of novel variants identified in BRCA1/2 and other breast cancer-associated genes, the clinical usefulness of the data is currently limited. Unless larger and rigorous studies are committed in this area of the world to correctly classify variants identified here or in other studies, the diagnosis and treatment of breast cancer will remain suboptimal. This is the first study that utilized NGS technology to study genetic variants in 45 patients with familial breast cancer from Lebanon. Our deleterious mutation prevalence was 40% with only 15.5% accounted for by the BRCA1 and BRCA2 genes. This data should encourage a different strategy for familial breast cancer genetic screening in Lebanon, one that is based on WES rather than the initial screening of BRCA1/2 genes. We report here novel and rare variants in breast cancer predisposing genes, which will be valuable to researchers and clinicians around the world for variants’ classification and patients’ care in general. We would like to thank all the patients and their family members who contributed their samples and information for this study. This work was supported by a grant from the Kuwait Foundation for the Advancement of Sciences (KFAS No. 2011-1302-06) given to Prof. Fahd Al-Mulla and by grants from the Saint Joseph University and the Mohamad Cheaib Foundation. Data generated or analyzed during this study are included in this published article and its Additional file. The link to the compiled data will be shared on our website http://www.al-mulla.org, which will be made available once it is connected to international databases in the near future. Meanwhile, data supporting the manuscript can be requested from the any of the two corresponding authors. NJ, FM, AM: drafted the manuscript. NJ, EC, ZH, HA, FM, MRM: carried out the molecular genetic studies and participated in the sequence alignment. CK, DA, MJM: acquisition of data. FM, HA, MRM, NJ: performed statistical analysis and interpretation of data. FM, AM conceived of the study, participated in the design of the study, and in its design and coordination. All authors read and approved the final manuscript. All patients signed the informed consent during the counseling sessions and agreed to share their variant data in a reputable scientific journal. Approval to conduct the study was obtained from the Ethics Committee of Saint-Joseph University-Lebanon. Written informed consent was obtained at the time of enrollment for genetic sample collection.
0.956382	Light gathering power of binocular Vs refractor? Is the effective combined aperture of your binocular additive? To put it another way, do the two 50mm objectives in your 7X50 have the same light gathering power and resolution as single lens, 100mm refractor? With microwave dish, receiving antennas, placing two of them side by side, increases the effective aperture and resolution, over that of a single dish. The only difference between a optical lens, and a microwave( parabolic lens), dish antenna, is the frequency of the electro magnetic spectrum that they deal with! I don't recall the math involved, but the equation is not that simple. So the short answer to your question is no. EdZ has authored several definitive threads on "binocular summation" - do a CN search for that phrase in quotes for the binocular forum. 1. A 100 mm refractor has four times the light gathering power of a 50 mm refractor. Clearly if the effect were perfectly additive, which I doubt, the result of using two 50 mm. objectives would be that of a 71 mm. objective. 2. I think that the use of two parabolic dish antennae may require some sophisticated engineering and software to increase resolution. Also the distance between the dishes, as well as the size of the dishes determines the increased resolution. Baselines of thousands of kilometers are being used. Doing the same thing with optical telescopes is in its infancy as I do recall reading about this. 3. This subject has been discussed in this forum before and my recollection is that the increased limiting magnitude was marginal, but not insiginificant, but I cannot find the posts. The reason that I was wondering is because I hadn't heard this mentioned before. I will have to look up the threads that have been mentioned, and also see what I can learn from a Google search of the subject. Actually, with just two lenses or dishes, the method is quite simple,and does not require any computer programs or complicated formulae. In fact, I do this here, with some of my dishes. Spacing two parabolic lens dishes, several wavelengths, and in phase, represents an increase over one, of Approx. 6dB or a power factor of 4X! As the spacing increases, the power gain increases! If you could focus the Sunlight from two binocular lenses into ONE Single Point, onto a piece of paper, would it not be more intense(in burning power) than a single lens? It will be interesting to research this, and learn why the two should differ since they both deal with focusing electro magnetic energy! That's only because you haven't been on this forum that long. The subject seems to get beaten to death every few months. Edz's Binocular Summation article has it all, but in a nutshell, the light from the two objectives is not simply summed. You may get the equivalent of 10%-20% increase in light gathering power and a 20%-40% increase in contrast. This is simply because the brain is more effective in processing light coming to both eyes. For the same reason, you will get a small but significant increase in resolution when using two eyes. However, this is different from the why that long-baseline radio telescopes get increased resolution -- increased synthetic aperture. With binoculars, the magnifications are generally too low to see the resolution limits caused by aperture-controlled diffraction effects. Now that makes sense Bill, thank's for that Info! If I understand this correctly, each dish has the same sensitivity but synthetic aperture, the distance between the dishes provides the greater resolution. As Bill wrote, this is not the radio wave equivalent of binouclars. No. Even if not using binoculars, two 50mm lenses do not have the light gathering power of a 100mm lens. LG is based on the area of the circle. As Aurthur pointed out a 100mm has four times the area of a 50. But it's more involved when comparing the light from one lens to one eye vs the binocular summation of two lenses to two eyes. You would need an 85mm binocular to get the equivalent of LG delivered to one eye from a 100mm refractor. This (second sentence) can be misleading if not understood properly, and is incorrect if referring to binocular summation. Aurthur has good reason to doubt. So if I may, let me reword this. If the effect were additive then the result of using two 50s would be that of a 71, ONLY IF the two 50s were delivering all of their combined light to ONE EYE. There are no common optical use instruments that do that. Also, that does not represent binocular summation. Binocular summation, the effect of observing thru two 50s using two eyes, is measured as a 40% gain (by area) over that of one 50mm lens to one eye. Therefore, a 50mm binocular provides the light gathering equivalent of a single 59mm lens delivering light to one eye. The percentage binocular summation gain varies from 20% to 40% for light gathering, contrast, brightness and resolution. I have used the maximum gain here. See the Best Of Link to Binocular Summation - Two Eyes vs One Eyed Viewing. Thank's for the feedback guys! There's more to this than meets the eye( no pun intended) as it envolves the brighteness perception of one eye Vs two eyes! spectrum, theory shows that both will exhibit a power gain, over the single lens by itself! Another example which came to my attention envolved this experiment. Hold a simple magnifying lens of say, three inches in diameter,in one hand, and focus the Sun's image on a themocouple, and measure the maximum temperature produced. Now take another three inch lens, and holding it in your other hand, spaced one foot apart, focus the Sun's image on the same thermocouple, so that you now have two focused solar images superimposed on each other. The increase of light energy gathered by the addition of the second lenses will result in a higher measured temperature than with the one lens alone! Very interesting, but it obviously doesn't apply to a comparison between a 50mm binocular, and a 100mm refractor . As far as I'm concerned, the diameter squared law still holds...to wit... the 100mm lens will gather four times as much light as either 50mm binocular lens! I'm missing something here, in the theory, and "coping out", but thats OK! I don't think anyone here is denying that. Bob needs to recognize that two 50mm diameters does not equal a 100mm diameter.
0.980678	从上图的虚线指向可以看出, event_base 是绝对的核心,它包含了定时器事件最小堆结构 min_heap ,信号事件队列结构 evsignal_info 和I/O事件队列结构 eventqueue ,也就是说,libevent把定时器,I/O,信号这些事件都统一到event_base管理.另外,既然libevent是事件驱动的,那么事件属性也很自然的自成一个结构体了,就是 event . A tail queue is headed by a pair of pointers, one to the head of the list and the other to the tail of the list. The elements are doubly linked so that an arbitrary element can be removed without a need to traverse the list. New elements can be added to the list before or after an existing element, at the head of the list, or at the end of the list. A tail queue may be traversed in either direction. 可以看到,一个事件是可以插入到多个队列的,当它与一个反应堆实例(event_base)关联时,这个事件被插入到反应堆实例下的已注册事件队列 event_base -> eventqueue ,当它处于就绪状态时,会被插入到反应堆实例下的已激活事件队列 event_base -> activequeues[id], id = event -> ev_pri .同时,如果此事件是信号事件,那么它会被插入到反应堆结构体下的信号事件结构体下的信号队列 event_base -> evsignal_info -> evsigevents[id], id = event -> ev_fd . 需要指出的,每个事件都保持了一个成员 struct event_base *ev_base; ,它表示该事件属于哪个反应堆实例. 还有一个成员需要注意, short ev_events; ,它表明此事件的事件类型,libevent正是基于此实现对I/O,信号,定时 3种事件的封装的. unsigned n, a; // n表示目前保存了多少元素,a表示p指向的内存能够存储event指针的个数. eventop实现了对系统I/O多路复用机制的封装,这些机制包括 select poll epoll evport kqueue devpoll (别忘了libevent是跨平台的). 其中, struct event_list evsigevents[NSIG]; 成员是一个数组,它的元素 evsigevents[id] 表示注册到信号id的事件链表.
0.953868	Are pauses followed by surges? The slower warming of global temperatures in the early 2000s has motivated many papers examining the modulation of global trends by climate variability. One question that has emerged is: what happens after a pause? Observed global temperatures showed a 10-year trend of near-zero in the early 2000s, which is likely due to a combination of internal variability and natural forcings (solar & volcanic activity) temporarily offsetting the warming from greenhouse gases. When these temporary cooling influences are removed, what happens to global temperatures? The figure (top row) shows the distribution of all 10, 15 & 20 year trends in a large ensemble (230 members) of simulations with the FAMOUS GCM with CO2 increasing at 1%/year. The mean trend is clearly positive, but there are also many periods of cooling, including several lasting 20+ years. The black curve shows the expected distribution using the control simulation, offset by the mean warming, highlighting that the control simulation alone provides a good estimate of the spread in possible trends. If we then select all periods of the same length which occur immediately after periods which show a cooling then the distributions are shifted towards larger warming by around 20% (bottom row). In FAMOUS there is an increased likelihood of a faster than expected warming period (or ‘surge’) following a pause and this not just simply due to the removal of the cooling periods from the distributions. So, will the real world similarly exhibit a ‘surge’? Top row: histograms of global temperature trends in a large ensemble of FAMOUS simulations with CO2 increasing at 1%/year. The black curve shows the expected distribution from the control simulation. THe percentages give the fraction of periods with a negative trend (and those inferred from the control simulation). Bottow row: Same, but for periods after a previous period of cooling of the same length. Percentages indicate the shift in the mean. I think we are at a sort of crossroads. The general talk about the pause is that it is temporary and warming will resume, perhaps at an accelerated rate as claimed in this paper, i.e. a “surge”. There is a presumption as well that if warming has been indeed going into the oceans for the past 15 years then its release might be the mechanism for warming returning with a vengeance. On the other had, several solar physicists have projected the Sun is entering a prolonged period of very low activity, comparable perhaps to the Dalton or even Maunder minimums. Climate scientists have claimed however that the effect of CO2 forcing will overwhelm reduced solar forcings and the warming will only be slowed by a minuscule amount (IIRC the number is in the range of 0.1C/decade). If by chance the pause extends for another 10 or 20 years or the surface temperatures begin to drop, what is the expected scientific response? yea, co2 clogs the heat exhaust of oceanic warming, so some larger than normal back pressure hits are pretty inevitable. It’ll not be interesting which part of the engine, ocean (exhaust manifold) or atmosphere (the pipe), will blow up first. Maybe the exhaust even gets totally blocked (CO2 will saturate like in Venus) and we can kiss our engine (earth) goodbye. It had occurred to me that you could actually reverse the question and possibly come to an alternative answer. Presumably there are surges where the warming trend exceeds the ‘expected’ trend from forcing. How often are these followed by slowdowns? If we applied this to the real world then 1970s-1990s could be the surge (overwarming) followed by a correction during the early 21st century hiatus. The answer is in the question: ‘Does the climate system have a memory short-term memory’ – perhaps the oceans wouldn’t even ‘feel’ a short-term climate blip less than 30 years if it (which is probably is) super-efficient at distributing heat and the radiation budget re-adjusting itself. I’m inclined to say that its like a loaded dice. Throw lots of sixes in a gamble, and you don’t play catch up in the second game. I think it’s independent of the past.
0.94677	Book Of Common Prayer, the formulary of public worship of churches of the Anglican communion. The early British church appears to have adopted, many years previous to the departure of the Romans from Britain, a liturgy almost identical with that of the Gallican churches, and which, like the latter, was derived from the Ephesine liturgy of St. John. To this the remnant of native Christians in the west and southwest, who had escaped the fury of the Saxon invaders, clung with great tenacity, and Augustin upon his arrival in England in 596, on his mission to convert the Saxons, found it in common use wherever Christian worship was tolerated. Being desirous of establishing the Roman ritual, to which the British bishops strongly objected, he applied for instructions to Pope Gregory the Great, who authorized him to choose either the Gallican or the Roman services, or selections from various forms, as he might find most suitable. The result was a species of amalgamation of liturgies. Different dioceses or districts adopted different modifications of the forms of public worship, in all of which, however, the influence of the early English liturgy was more or less perceptible. After the Norman conquest a vigorous effort was made to secure uniformity in the performance of divine service, and about 1085 Osmond, bishop of Salisbury, compiled the "Sarum Use," or prayer book of the diocese of Salisbury, which eventually became the principal devotional rule of the Anglican church for nearly four centuries and a half. Other local uses, however, prevailed, such as those of Bangor, Hereford, York, and Lincoln; and the Roman system was recognized in most of the monasteries. The service books of the several English uses were in the Latin language; but long before the period of the reformation books of private devotion in the vernacular, called "Prymers," had been introduced, of which three, containing the Lord's prayer, the creed, the ten commandments, and other offices of worship, were put forth between 1535 and 1545. Early in the reign of Henry VIII. amended editions of the Salisbury breviary and missal appeared, and subsequent to 1538 many editions of the Epistles and Gospels in English were published. In 1544 the litany was translated, with the omission of the names of saints which had accumulated in the Latin litanies. These publications were but the preliminary steps toward the introduction of a reformed prayer book. In 1542 a committee of convocation was appointed, with the sanction of Henry VIII., to consider what revision should be made in the existing service books. The committee sat for several years, and during the life of Henry were compelled to act with extreme caution, as the " statute of six articles," passed through his personal influence, made their labors penal. After his death in 1547 their number was enlarged, and, the obnoxious statute having been repealed, they produced at the close of the year "a form of a certain ordinance for the receiving of the body of our Lord in both kinds, viz., of bread and wine," which was ratified by parliament in March, 1548, and was authorized to be used until the whole of the projected service book should be prepared. In the following December they laid before parliament a reformed book of common prayer, which, together with an "act for uniformity of service," was adopted by that body in January, 1549, and came into general use on Whitsunday, June 9. This book, known as the first service book of Edward VI., was the result of six years of diligent labor on the part of the revisers, who endeavored to reduce the different uses prevalent in England to one, the reformed Salisbury use of 1516 and 1541 forming their basis, and to make their work simple and intelligible. They translated into English from the existing service books the prayers, psalms, hymns, epistles, and gospels, omitting what appeared to them to have been derived from other sources than Scripture or primitive practice, and expunging, especially from the communion service, the prayers of invocation to the Virgin Mary and the saints. Where new elements of thought are visible, the sources which supplied them were the reformed breviary of Cardinal Quignones, recommended by Pope Paul III., and especially the "Consultation" of Hermann, archbishop of Cologne, compiled in 1543 with the aid of Bucer and Melanchthon. To the latter formulary the baptismal office was largely indebted, and through it to one of Luther's compilations, made as early as 1523. The new book comprised the order for matins and even song, corresponding with morning prayer and evening prayer in the modernized prayer book, and which were a condensation of the "seven hours of prayer" in the breviary; the introits, collects, epistles, and gospels used at the celebration of the holy communion; the office of the communion; the litany; the rite of baptism; confirmation, which included the catechism; matrimony; the visitation and communion of the sick; the burial of the dead; the purification of women; and a form of service for Ash Wednesday. The psalms appointed to be sung at matins and even song were taken from the " Great English Bible" of Cranmer, and this version is used in the "Book of Common Prayer" to the present day in preference to that contained in the authorized version of the Scriptures. This service book did not require absolute uniformity in outward observances, but allowed the practice in minor details of public worship to be guided by individual tastes and preferences. But a statute passed both houses of parliament in January, 1549, enjoining under the severest penalties that after the feast of Pentecost following, all ministers of the church within the realm of England should be bound to use the form of the said book and no other. In 1550 a "Form for the Ordering of Bishops, Priests, and Deacons" was drawn up, which was subsequently incorporated with the prayer book. - Scarcely had the new book come into use when it encountered opposition from the more radical school of reformers, headed by Hooper, bishop of Gloucester, and several continental Protestants, of whom the most eminent were Peter Martyr, Martin Bucer, and John a Lasco, who had come to England after the accession of Edward VI., and made their way to important posts. Calvin also urged upon the protector Somerset the necessity of pushing the reformation in England further than it had gone. The court yielded to these influences, and the young king declared himself in favor of a more thorough revision of the prayer hook. Cranmer, archbishop of Canterbury, one of the framers of the first book, was induced to give his consent to the undertaking, and another committee of divines, who are conjectured to have been the same who prepared the ordinal of 1550, undertook the preparation of a second prayer book, which was duly ratified by parliament, and came into use on All Saints' day, 1552. This is substantially the "Book of Common Prayer" in use at the present day. The difference between this book and that of 1549 consists chiefly in the following particulars: To the offices of matins and even song, which began with the Lord's prayer, were prefixed the sentences, exhortations, confession, and absolution. In the communion service the ten commandments were added, the title of the prayer "for the whole state of Christ's church " was changed to that of a prayer "for the whole state of Christ's church militant here on earth," and the commendation of the departed to divine mercy was omitted. In the prayer of consecration the invocation of the Holy Spirit to sanctify the elements was omitted, and in the administration of the elements a different form of words was used. In the office of baptism the practices of exorcism, anointing, putting on the chrisome, and trine immersion, prescribed in the first book, were abolished in the second. In the burial service the prayers for the dead were changed into thanksgiving, and the service for Ash Wednesday was entitled "A Commination against Sinners." Certain changes were also made in the vestments of the clergy. A few months after this book came into use Edward VI. died, and the first parliament of his successor, Mary, by an act passed in October, 1553, restored the services to the condition in which they were in the last year of Henry VIII. In November, 1558, Elizabeth succeeded to the throne; and early in April, 1559, the second, book of Edward VI. was restored to use, with certain slight modifications, prominent among which was the omission of the litany clause, "from the tyranny of the bishop of Rome, and all his detestable enormities." The "ornaments " of the church and the ministers which had been in use under the first book of Edward VI., but had been curtailed by the second, were also restored. The prayer book thus modified, of which a Latin version was also published, was at length acquiesced in by the great body of the English people, and, according to Sir Edward Coke, was even approved by Pope Pius IV., who offered to give it his full sanction " so as her majesty would acknowledge to receive it from the pope, and by his allowance." This statement of Coke's, however, is not accepted as authentic by Catholic authorities. With the exception of a revision of the calendar, no further changes were made in the prayer book until the accession of James I. in 1603. The Puritan or nonconformist party had meanwhile gathered strength, and soon after the arrival of the new sovereign in London they presented to him a petition in favor of a further revision and purification of the liturgy. The result was the so-called Hampton Court conference, participated in by eminent clergy of the established church and of the nonconformist bodies, and which met on Jan. 14, 1604, in presence of the king and the privy council. The king considered the demands of the Puritans untenable, and broke up the conference on the third day; but under the clause of the act of uniformity by which Elizabeth had authorized a revision of the calendar, he directed a few changes to be made in the prayer book, of which the most important seem to have been the questions and answers concerning the sacraments subjoined to the catechism, and the restriction of the administration of baptism to regularly ordained ministers. With the triumph of parliament in the reign of Charles I. the opponents of the prayer book succeeded in 1645 in getting it entirely suppressed, and for fifteen years it passed almost out of sight. The restoration of the royal family brought it again into favor, and subsequent to July, 1660, as Evelyn records, it was publicly used in the churches. In March, 1661, Charles II. summoned a number of divines, representing equally the established church and the nonconformists, to meet in London and review the "liturgy of the church of England, contained in the Book of Common Prayer, and by law established." This assembly, called from its place of meeting the "Savoy conference," was the last official attempt to reconcile the differences of opinion between the advocates and the opponents of the prayer book. Its sessions extended from April 15 to July 24, 1661, and were barren of any practical result. A strong reaction had taken place in favor of the church party, and the nonconformists, though represented by such men as Baxter and Calamy, were not sufficiently united in their plan of opposition to accomplish their object. Baxter even drew up a substitute for the prayer book, which failed to meet the approval of his friends. The work of revision was then committed to the convocations of the provinces of Canterbury and York, by which a number of slight changes were made, which seem to have been in the opposite direction from that desired by the nonconformists. A service was also provided for the baptism of those of riper years, and a form of prayer to be used at sea. The prayer book thus revised, together with an act for uniformity of public worship, was approved by parliament in 1662, and went into immediate use. A further attempt in the reign of William III. to revise it proved unsuccessful, and the prayer book of 1662 remained unaltered till 1872, when a new lectionary or course of lessons from the Scriptures was introduced, which is made optional till 1879. In the new lection-ary many chapters from the Apocrypha are omitted. Previous to 1859 it was customary to include in modern editions of the Book of Common Prayer four services for special days of the year, known as "state services," which, however, properly formed no part of the book. Three of these services, being forms of prayer for the 5th of November, in commemoration of the discovery of the gunpowder plot of 1605; the 30th of January, the anniversary of the execution of Charles I.; and the 29th of May, the birthday of Charles II. and the anniversary of the restoration of the royal family, were in the year above mentioned abolished by act of parliament. The fourth, a form of prayer for the accession of the reigning sovereign, has been retained. - For many years after the reformation no attempt was made to introduce a uniform system of worship in Scotland, although Knox's "Book of Common Order " was very generally used. In deference to the wishes of James I. the general assembly in 1616 decided in favor of a uniform order of liturgy; but nothing was done in the matter till after the accession of Charles I., who was very desirous of having the English prayer book adopted by the church of Scotland. The Scottish bishops, however, preferred to frame a liturgy of their own, and eventually an episcopal committee was appointed to carry this design into execution. The committee after several years' labor, in which they were aided by suggestions from Archbishop Laud, completed their prayer book in 1636, and in 1637 it was imposed upon the church of Scotland by letters patent and the authority of the bishops, without having been submitted to the general assembly. It was modelled after the English prayer book of the time, with a number of slight variations; but the communion office rather followed the form in the first book of Edward VI. The book encountered vehement opposition, and was almost immediately suppressed. From that time until the close of the 18th century the Scottish Episcopal church and its liturgy remained in comparative obscurity, being for many years under the operation of penal laws. The prayer book was several times revised, notably in 1765, and is now in most respects identical with that of the church of England. The communion office, however, retains many features peculiar to the first book of Edward VI.; and certain ancient usages, such as the sign of the cross at confirmation, the mixture of water with wine at the eucharist, and the dismissal previous to the consecration of the elements of those' not intending to communicate, are still enjoined by rubric. - Until the disestablishment of the Irish Episcopal church on Jan. 1, 1871, its prayer book was identical with that of the church of England, except that it contained a few additional services, such as a form for the visitation of prisoners, a form of consecration or dedication of churches and chapels, and a prayer for the lord lieutenant. One of the declarations prefixed to the constitution of the disestablished church enjoins the use of the Book of Common Prayer, "subject to such alterations only as may be made therein from time to time by the lawful authority of the church." In the first synod, which met in April, 1871, a number of attempts to alter the liturgy and formularies failed of success, and the subject of revision was referred to the bishops and to a mixed committee of clergy and laymen, who were directed to report in the succeeding year. The synod of 1872 declared the word priest to be synonymous with presbyter, and authorized the shortening of the services on week days and the dividing of them. It also approved of a recommendation for the omission of the rubric on ornaments. Propositions to remove the damnatory clauses from the Athanasian creed, and to allow deacons to pronounce absolution, were defeated, which was declared to be equivalent to a withdrawal of those subjects from further consideration by the synod. The committee was then reappointed and directed to report in 1873. - Previous to the American war of independence members of the church of England in the British North American colonies were under the episcopal supervision of the bishop of London, and used the English Book of Common Prayer. Immediately upon the acknowledgment by Great Britain of the political independence of the United States, measures were taken to establish an American Episcopal church, and to compile a service book for its use. The initiatory step was taken by Connecticut, where in March, 1783, a convention of Episcopal clergy recommended Dr. Samuel Seabury to the English bishops for consecration to the episcopate. Owing to certain technical legal difficulties, this could not at once be effected, and Dr. Seabury went by advice to Scotland, where on Nov. 14, 1784, he was consecrated at Aberdeen by the bishops of the Scottish. Episcopal church. Meanwhile a convention, participated in by Episcopalians from various states, had met in New York in October, 1784, and adopted a series of articles, one of which provided "That the said (American) church shall maintain the doctrines of the gospel as now held by the church of England; and shall adhere to the liturgy of the said church, as far as shall be consistent with the American revolution, and the constitutions of the respective states." Pursuant to the recommendations of this body, another convention assembled in Philadelphia in September, 1785, which put forth a volume known as "the proposed book," embodying many important variations from the English Book of Common Prayer. These were of two kinds, political and doctrinal. Under the former head all passages referring to the royal family and government of Great Britain were either entirely omitted or adapted to the new political relations of the country, and the so-called "state services" of the English prayer book were stricken out. The chief changes under the second head were the rejection of the Nicene and Athanasian creeds, and the omission of the words "He descended into Hell" from the apostles' creed. The convention of 1785 also recommended to the English church for consecration as bishops Dr. William White of Philadelphia and Dr. Samuel Provoost of New York. But before this act was consummated a copy of the "proposed book" reached England, and elicited from the archbishops of Canterbury and York an expression of disapprobation, not only at various verbal alterations that seemed uncalled for, but at the radical changes made in the three ancient confessions of faith which had always been accepted by the church of England. Whether or not in consequence of this remonstrance, the American Episcopal convention which met at Wilmington, Del., in October, 1786, restored to the prayer book the Nicene creed, allowing it to be used as an alternative instead of the apostles' creed both in the communion and daily offices. The clause "He descended into Hell" was also restored to the apostles' creed, with the rubrical provision that "any churches may omit the words, ' He descended into Hell,' or may instead of them use the words, ' He went into the place of departed spirits,' which are considered as words of the same meaning in the creed." No change, however, was made in the resolution of the convention to discontinue the use of the Athanasian creed in divine service. These concessions having removed the scruples of the English prelates, Drs. White and Provoost were consecrated bishops of Pennsylvania and New York in February, 1787. The general convention which met at Philadelphia in September, 1789, undertook the final revision of the liturgy. A house of bishops was now for the first time organized as a distinct branch of the convention; and although but two of the three members composing it, Bishops Seabury and White, were present, the influence which they exerted prevented any such radical alteration of the prayer book as was desired by a strong party in the house of clerical and lay deputies. The bishops were determined to hold the English prayer book as the basis of their work, and to avoid as far as they could all unnecessary changes; and to their tenacity of purpose and ready cooperation is due the fact that in all their main features the liturgies of the Anglican church in the United States and the mother country are identical. Apart from the changes above noticed, the chief differences between the English and the American Book of Common Prayer, as the latter was settled by this and subsequent conventions, are the following: Many changes of words and phrases have been made with a view to the removal of what was obsolete, or in order to attain greater correctness of expression. In morning prayer and evening prayer the Lord's prayer is directed to be said but once; in both offices the versicles and responses have been abridged; and from evening prayer the Magnificat or song of the Virgin and the Nunc dimittis have been excluded. The lectionary, or lessons from the Bible, has been in part remodelled, the portions from the Apocrypha being omitted. A "Selection from the Psalms," instead of the portion of the Psalms appointed for the day, is allowed to be used at the discretion of the minister. The Gloria in excelsis, found only in the communion service in the English book, is allowed in morning and evening prayer as an alternative with the Gloria Patri; and the form of absolution peculiar to the communion service is similarly introduced into morning and evening prayer. The communion service, owing to the influence of Bishop Seabury, was borrowed from the Scottish office, although the order of the English office is generally retained; the distinguishing feature consisting in the incorporation into the prayer of consecration in the American book of the oblation and invocation according to the new Scottish office as revised in 1765. In the baptismal office the minister is permitted to dispense with the sign of the cross after sprinkling the candidate. In the office for the visitation of the sick the rubric directing the minister to advise sick persons to confess their sins, and also the form of absolution, are stricken out. The marriage service is considerably abridged, and the commination service for Ash Wednesday is omitted. From the calendar all names of saints not commemorative of persons and facts of Scripture history have been excluded; and services for the visitation of prisoners, for the consecration of a church or chapel, and for the institution of ministers have been added. Finally, to show their desire to adhere substantially to the English liturgy, the American revisers state in the preface to their Book of Common Prayer that "this (American) church is far from intending to depart from the church of England in any essential point of doctrine, discipline, or worship; or further than local circumstances require." It is customary to include in the English and the American Book of Common Prayer the " Articles of Religion " adopted by the churches of the Anglican communion; also metrical versions of the Psalms and a collection of hymns to be used in divine service. These, however, are not properly a portion of the book, the standard edition of which ends with "The Psalter or Psalms of David." The American prayer book came into general use on Oct. 1, 1790, and in its essential features has remained unchanged to the present day.
0.999999	Compare the structure and function of organs in the digestive system. Activity: Constructing a Digestive System Model - Follow the instructions to create a model of the system. Also includes other worksheet activities to help understand the organs and functions of the digestive system. Body Basics Article: Digestive System - All you need to know about the digestive system, including an Interactive Diagram that provides information over the various structures as you roll your mouse over each one. Crossword Puzzle: Digestive System - Print off the puzzle for students to complete the crossword puzzle. Digestion - Function and structures of the digestive system. Digestive System - Learn about the anatomy, functions and more. Includes a self checking quiz as well. Digestive System Activities - Numerous interactive activities, quizzes, demonstrations, etc. Digestive System Lessons and Activities - A variety of handouts, activities, presentations, lessons and more. Food and the Digestive System - Lesson plan with a purpose "to learn about the digestive system. To begin to explore where nutrients come from, as well as their importance for particular tasks in the body." Functions of the Digestive System - Digestive system chapter that includes vocabulary, activities and questions to check that the objectives were learned. Introduction to Digestion and Nutrition - Module with a variety of lessons on the structure and function of the digestive system as well as other topics related to digestion. Learn the Structures - Free printable diagram for students to label and color the various structures of the digestive system. Lesson Plan: Digestive System - "The purpose of this lesson will be to help students understand the function of the digestive system and how it relates to the well-being of the body as a whole." Lesson Plan 2 - "This lesson is designed to help students learn the structure and function of the organs in the digestive system. They will use the Internet to research the information and do classroom experiments to solidify their knowledge. Organs of Digestion - Interactive animation explaining the function of the digestive system. A self checking quiz follows the animation to see that the concepts are understood. Organs of the Digestive System and their Functions - Find out about the organs that contribute to the breaking-down process of food. Practice Test: Digestive System - 57 question test on the organs, functions, etc. of the digestive system. Answers provided on the last pages. Structure and Function of Digestive System - Overview of the complex system known as the digestive system. The Digestive System - From WebMD. Find out what happens to food as it makes its way through the digestive system. Tour the Digestive System - Learn what each organ does one by one. Worksheets: Digestive System - Variety of worksheets for learning the various organs and functions of the digestive system. Contrast mechanical and chemical digestion. Chemical and Mechanical Digestion - The difference in how food is broken apart to be absorbed through the intestinal walls. Chemical vs. Mechanical Digestion - Difference between the two digestions. Digest This! - Numerous activities and lessons. Activity #1 topic is mechanical and chemical digestion. Digestion Lesson Plan - Objective is to learn how our food is broken down mechanically and chemically. Lesson: Mechanical and Chemical Digestion - Classroom activity examining both processes and observe how enzymes affect the rate of chemical digestion. Mechanical Digestion: The Initial Breakdown of Digestion - Class activity to see how mechanical digestion aids chemical digestion. Tales from the Tummy - Lesson involving creative writing by the student with an objective of describing each organ in the digestive system and its function as well as distinguishing between chemical and mechanical digestion. What is Mechanical and Chemical Digestion? - From eHow.com. Also includes information on the "Differences Between Chemical and Mechanical Digestion"as well as instructions on "How to Compare Chemical and Mechanical Digestion." Why is it Important to Chew? - Classroom activity to assist in learning why and how particle size aids in effective digestion. Trace a selected food through the alimentary canal. A Journey Through The Alimentary Canal - The journey of a chicken sandwich as it contains all the macro nutrients which will need to be digested. Diagrams included. Animated Digestion - Impressive interactive animation showing the digestion process. Pick a food to eat and click on each stage of the digestion process to see the explanations of what is occurring. Canal Movements - Description of the two movements, mixing and peristalsis, the alimentary canal makes to move food along. Digestion Lesson Plan - Objective includes tracing a piece of food through the alimentary canal. Digestive System Slides - PowerPoint slides outlining the general characteristics of the alimentary canal with detailed diagrams indicating the path which food travels. Quiz: Digestion - 45 question quiz plus 13 question for identifying structures of the digestive system. Quiz includes questions about the passage of food through the alimentary canal, answer key provided. Web Tutorial: Digestion and Absorption of Food - Explains the role of each part of the digestive system including the passage of food through the alimentary canal. The Alimentary Canal - PowerPoint from worldofteaching.com. The Bottomless Pit - Describes in detail the functional anatomy of the alimentary canal. The Digestion of Food - Detailed outline of the chemical breakdown of food. Identify the enzymes and biochemical reactions that facilitate digestion. Digestive Enzymes - Video providing detailed information on enzymes and different parts of the gut that produce enzymes. Video is interactive and students must click at various parts to continue hearing the information. Digestive Enzymes 2 - Biology lesson on enzymes and how they work. Digestive Enzymes Practice Test - Multiple choice questions; self checking. Enzymes - Description of the characteristics, uses and how enzymes work. Enzymes and Digestion - Information on enzymes: how they work, where they are produced and the various uses of them. Enzymes and Digestion - Interactive presentation describing enzymes. Enzymes and Digestion Activity - Interactive video detailing how enzymes help respiration and digestion. Enzymes and Digestion Quiz - Multiple choice quiz on enzymes and digestion. Self checking. Enzymes Involved in Digestion - Outlines the specific enzymes and also provides a summary chart for them. Explain how the products of digestion are absorbed. Absorption - The four mechanisms of absorption. Absorption of Food - Describes the GI process and the digestion of food. Digestion - Diagrams and descriptions of digestive process. Digestion and Absorption - Explanation of how food is absorbed. Practice Test - Multiple choice questions on digestion, absorption and transport. Self checking. The Digestion Process - How the normal digestive system works. Absorption in the small intestines. Includes quiz questions. The Human GI Tract - Very descriptive outline explaining the process of digesting food including absorption. Web Tutorial: The Digestion and Absorption of Food - Tutorial showing how carbs, proteins and fats are digested; how nutrients are absorbed from food; and how wastes are eliminated. Includes a lot of interactive activities including a pre and post test. Where Did That Sandwich Go? - Lesson plan explaining digestion and absorption. Includes quiz. Compare and contrast the male and female urinary systems. Genito-Urinary System - Interactive online practice of the upper and lower urinary tract. Has diagrams of both the male and female lower urinary tract; click on each label of the diagram to read more about the function of each body part. Label the Diagram - Interactive diagram. For each green dot, drag the correct label to identify the part. Lower Urinary System - Development of the male and female urethra. Male Urinary System - YouTube video with narration and diagrams describing the system. Male/Female Urethra - From Wikipedia. Urinary Anatomy - Description of what makes up the urinary system, including how it works. Urinary System Structure and Function - Video detailing the urinary system. Urinary System Unit - Lesson plans with outlined information on the urinary systems. Includes activities for students also, such as matching worksheets and diagrams that should be labeled. Explain how the kidneys act to maintain homeostasis. Excretion and Homeostasis - Lesson plan for teaching about the urinary system and the structures and function of the kidneys. Homeostasis: The Steady State - Lesson and activities. Kidneys and Homeostasis Lesson - Explains the functions of the kidney and includes activities and quizzes. Lesson: The Urinary System - Overview of lesson with a focus on the kidney and the main function of the kidney. Includes diagrams of the kidney and urinary tract as well as activities for students to do. Maintaining the Excretory System - Lesson, lab, interactive active and hand-in assignments. Quiz on Urinary System #1 - Focus is on kidneys. Click a question card and then click the answer choice card that best fits the question. Recommended for 7th - 12th grade. Quiz on Urinary System #2 - Click a question card and then click the answer choice card that best fits the question. Recommended for 7th - 12th grade. The Urinary System - Detailed information explaining the anatomy and role of the kidney. Urinary System - From Wikipedia. Emphasis on the kidneys and their role. Urinary Tract: Kidney - Slides detailing the function of the kidneys in the urinary system. Water and the Urinary System - The importance of water and the kidneys for our body to function. Your Kidneys - Everything you need to know about the kidneys, including an interactive diagram. Identify the parts of a nephron and describe how they assist in urine formation. Function of the Nephron - Video identifying the parts of the nephron and how it pertains to urine formation. Nephron - Description, diagram and details about the nephron and kidney. Structure of the Nephron - Worksheet for students to color the diagrams labeling the parts of the nephron. Also contains information explaining the function of the nephron and has questions at the end. The Nephron - YouTube video with detailed graphics and narration of the parts of a nephron as well as the role of the nephron. The Urinary System - Detailed information describing nephrons with a diagram identifying the parts. Urine Formation - Video detailing the formation of urine and begins with the nephron. Urine Formation in the Nephron - 5 page lesson with interactive activities. Includes a module with hand-in assignments. Describe the composition of urine. Describe a countercurrent mechanism and explain how it concentrates urine. Discuss the importance of water and electrolyte balance. Describe how body temperature is regulated.
0.975605	Not to be confused with Lefty Gomez. Robert Moses "Lefty" Grove (March 6, 1900 – May 22, 1975) was a professional baseball pitcher. After having success in the minor leagues during the early 1920s, Grove became a star in Major League Baseball with the American League's Philadelphia Athletics and Boston Red Sox, winning 300 games in his 17-year MLB career. He was elected to the National Baseball Hall of Fame in 1947. One of the greatest left-handed pitchers in major league history, Grove led the American League in wins in four separate seasons, in strikeouts seven years in a row, and had the league's lowest earned run average a record nine times. Over the course of the three years from 1929 to 1931 he twice won the pitcher's Triple Crown, leading the league in wins, strikeouts, and ERA, while amassing a 79-15 record as the ace for the Athletics' dynasty teams. Born in Lonaconing, Maryland to John Robert Grove, (1865–1957), and Emma Catherine Beeman, (1872–1959), Grove was a sandlot star in the Baltimore area during the 1910s. Grove didn't play organized baseball until he was 19 years old. In 1920, he made his professional debut with the Martinsburg Mountaineers of the class-D Blue Ridge League, where he appeared in six games. In 59 innings pitched, Grove gave up just 30 hits, and he had an earned run average (ERA) of 1.68. His performance attracted the attention of Jack Dunn, Sr. (1878–1928), the manager/owner of the minor league Baltimore Orioles, who also discovered George Herman ("Babe") Ruth (1895–1948). Grove joined the Baltimore Orioles in 1920, while they were playing a half-century in the minor leagues of first the old Eastern League (1903–1914) and then after 1916, in the reorganized International League of "Triple A" (AAA) ball. "Lefty" broke into the team's pitching rotation at midseason with a 12-2 record during their most famous winning championships sprint of 1919–1925, winning six straight titles. Over the next four seasons, he posted marks of 25-10, 18-8, 27-10 and 26-6, leading the International League in strikeouts each season. Grove remained in the minor leagues through 1924 because owner Jack Dunn, Sr. (1872–1928), refused several offers from the majors to acquire him. At the time, the Orioles were an independent operation with no major league affiliation and the International League had declared its players not subject to a major league draft. Since the reserve clause in all contracts was honored throughout organized baseball, this meant that Grove had no way to reach the majors until the Orioles became willing to trade or sell his contract. Finally, early in 1925, Dunn agreed to sell Grove's rights to Connie Mack (1862–1956), and his Philadelphia Athletics in the American League for $100,600, the highest amount ever paid for a player at the time. Grove battled injuries as a rookie and posted a 10-13 mark (which would prove his only losing record in 17 major league seasons), despite leading the league in strikeouts. Grove then settled down in 1926 and won the first of a record nine earned run average (ERA) titles with a mark of 2.51. In 1927, Grove won 20 games for the first time, and a year later he led the league in wins with 24. In 1928, Grove twice struck out the side on nine pitches. On August 23, he did it in the second inning of a 3-1 win over the Cleveland Indians to become the third American League pitcher and seventh pitcher in major league history to accomplish the feat. On September 27, he did it in the seventh inning of a 5-3 win over the Chicago White Sox, becoming the first pitcher in major league history to accomplish the feat twice in a career; since then, only Sandy Koufax, Randy Johnson and, Nolan Ryan, all Hall of Famers, have joined him. Grove, however, remains the only pitcher to do it twice in the same season. The sportswriter Arthur "Bugs" Baer wrote, "Lefty Grove could throw a lamb chop past a wolf." The Athletics won the pennant in three successive seasons (1929 to 1931), as well as consecutive World Series championships in 1929 and 1930. During the Athletics' championship run, Grove led the way as the league's top pitcher, posting records of 20-6, 28-5 and 31-4. In 1930, Grove led the league in wins, ERA (2.06), strikeouts (175), winning percentage, complete games, and shutouts. His 2.06 ERA was 2.32 runs below the league average. He was also chosen as league MVP in 1931, making him one of only a handful of pitchers to achieve this honor. His M.V.P. award is the only one not enshrined in the National Baseball Hall of Fame in Cooperstown, New York, instead being housed at the George's Creek Library of the Western Maryland Regional Library system in Lonaconing. The Athletics contended for the next two seasons, but finished second to the New York Yankees in 1932 and third behind the Washington Senators and Yankees in 1933. In 1933, Grove became the first player in Major League Baseball history to strike out five times in a nine-inning game. On December 12, 1933, team owner Connie Mack traded Grove, along with Max Bishop and Rube Walberg, to the Boston Red Sox for Bob Kline, Rabbit Warstler and $125,000. Grove was unable to contribute substantially during his first year in Boston, an arm injury holding him to an 8-8 record. In 1935, however, Grove returned to form with a 20-12 record and a league-leading 2.70 ERA. Grove won his eighth ERA title a year later, and also led the league in ERA and winning percentage in 1938. Grove continued to post outstanding records, including 14-4 in 1938 and 15-4 in 1939, as well as lead the AL in ERA 4 times between 1935 and 1939. In his last season, he won and lost 7 games, winning his 300th game on July 25 (giving up 6 runs on 12 hits, but winning 10-6), before losing his last three major league games, ending his career on September 28, pitching just one inning in the 2nd game of a doubleheader. Grove retired in 1941 with a career record of 300-141. His .680 lifetime winning percentage is eighth all-time; however, none of the seven men ahead of him won more than 236 games. His lifetime ERA of 3.06, when normalized to overall league ERA and adjusted for the parks in which Grove played during his career, is fourth all-time among pitchers with at least 1,000 innings pitched (behind Mariano Rivera, Jim Devlin, and Pedro Martínez) at 48 percent better than average. Grove was elected to the National Baseball Hall of Fame in 1947. He died in Norwalk, Ohio and was interred in the Frostburg Memorial Cemetery in Frostburg, Maryland. In 1969 Grove was voted starting pitcher for the 100th anniversary team. In 1999, Grove was ranked number 23 on The Sporting News list of Baseball's Greatest Players. He ranked second, behind only Warren Spahn, among left-handed pitchers (third when Babe Ruth is counted as a pitcher as well as an outfielder) although Babe Ruth never pitched long enough to be considered. That same year, Grove was elected to the Major League Baseball All-Century Team.
0.999974	This natural slate photo frame with a heart-shaped window cut into the stone to display your treasured keepsake photo. The engraved sentiment above photo insert: "i heart you". is fixed. The dimensions of the frame is 23 x 19cm.
0.946965	The oldest of the great painters of the Spanish Baroque, Jusepe de Ribera almost doesn't even qualify as a Spanish artist, given that he spent the majority of his life and his entire career in Italy. Nonetheless, the artist was fiercely proud of his Spanish roots, and furthermore lived in Naples, which during the 17th century was a Spanish territory. The artist thus had strong connections with his homeland and exerted an enormous influence on Baroque art, both in Spain as well as in the rest of Europe. Ribera was lucky to be working in Naples. After becoming part of the Spanish empire in 1501 (the city would remain under Spanish rule for two centuries), the city's population tripled in size, making it Europe's second largest urban center after Paris. During the 17th century, Naples was a hotbed of intellectual and artistic activity, home to the century's greatest artists, philosophers, writers and musicians, at least until the great plague of 1565 wiped out half the city's population. By living and working in Naples, Ribera was guaranteed to be surrounded by cutting-edge art and wealthy patrons. Virtually no documents exist that could shed some light on Ribera's childhood in Spain. It is known that he was born and baptized in the town of Játiva in the Valencia region, the second son of a successful shoemaker named Simón Ribera; he lost his mother when he was only about five or six years old. Although sons were usually trained to continue the same profession as their fathers, some art historians have speculated that Ribera's artistic pursuits could have been encouraged by other artists in his family. His paternal grandmother was named Juana Navarro of Tervel, and several painters with the surname Navarro were known in Valencia; this remains mere speculation, however. Ribera's biographer claims that as a boy, Ribera was apprenticed to the successful local artist Francisco Ribalta, although there is absolutely no evidence to support this claim. Whatever the facts of his childhood, Ribera was evidently displeased with the way things were going and left his hometown in pursuit of bigger and better things (popular belief holds that he left Spain over an argument with Ribalta concerning the master artist's daughter). Ribera was in Italy by 1611, stopping first in Parma, where documents reveal he executed a painting for the church of St. Prospero, and then ending up in Rome by 1613. Ribera stayed in Rome until 1616, studying at the Academy of St. Luke and living with his younger brother, Juan, as well as a whole flock of other fellow Spaniards in the house of a Flemish merchant on the Via Margutta. Contemporary sources suggest that during these early years in Rome, Ribera led a libertine existence, perhaps in imitation of Caravaggio, whose art Ribera so admired. He thus quickly ran out of money and, apparently to escape his creditors, fled to the Spanish-ruled Kingdom of Naples in 1616, where he would stay for the rest of his life. Fortunately for Ribera, as a Spaniard he was able to ally himself with the Spanish elite as well as the Flemish merchants who were in the upper echelons of Neapolitan society, and who were thus the primary patrons of art in Naples. Soon after his arrival Ribera made an advantageous marriage to Catalina Azzolino India, the daughter of the established and successful painter and art dealer, Giovanni Bernardino Azzolino (the haste of the marriage suggests that Ribera may in fact have arranged it before he even left Rome). It should be noted that as popular as Ribera was as an artist, as a man he was often reviled. The Italian Neapolitans often resented their Spanish oppressors and Ribera's proud demeanor and apparently tempestuous personality were far from ingratiating. Contemporary documents reveal that Ribera took a long time to learn Italian, and never learned it well, speaking with a heavy Spanish accent and making atrocious mistakes in spelling and grammar in his correspondence, yet another slap in the face to his Italian rivals. After arriving in Naples, seemingly nothing could stop Ribera. His reputation skyrocketed to the point that by 1618, Ribera was considered the most popular painter in town, garnering commissions from such elite patrons as Cosimo II de Medici, the grand duke of Tuscany, and the Viceroy of Naples. Overwhelmed with work, Ribera earned enough money to move into a larger house with a garden, just in time for the birth of his first three children in the late 1620s (son Anotonio Simone was born in January of 1627, followed by his little brother Jacinto Tomás in November, 1628, and finally little sister Margarita in April 1630). The 1630s proved to be even kinder to Ribera than the previous decade. In 1630 he received visits from Velázquez as well as the Spanish ambassador, who would later become the Viceroy of Naples and who commissioned several important works from the expatriate painter. In 1631, Ribera received the immense honor of becoming a knight of the Papal Order of the Vatican, one of the highest achievements any painter in Italy could hope for. Ribera's success continued throughout the 1630s to the point that by the 1640s, he was able to move himself and his family into a veritable palace (decadent digs complete with two gardens and an orchard) in the luxurious Chiaia district, near the church of St. Teresa degli Scalzi. By this time, Ribera had established a large, well-organized workshop to help him complete his plethora of commissions, which were far too numerous for one man to finish alone. In 1641, Ribera was lucky enough to be awarded the commission for the most important religious site in all of Naples, the chapel of St. Gennaro in the Naples Cathedral. Finally, as the icing on the cake, Ribera's prestige and social status would attain new heights when his daughter Margarita married a judge of the Tribunale della Vicaría named Giovanni Leonardo Sersale. Unfortunately for Ribera, what goes up must come down. The good times came to an end in the mid-1640s, when the artist fell seriously ill and his painting production came to a standstill. Just after Ribera finally recovered his health, the popular uprising against Spanish rule led by Tommasso Aniello Masaniello in July of 1647 forced Ribera and his family to take refuge in the Spanish Palazzo Reale, where Ribera would meet Philip IV's illegitimate son Don Juan of Austria. The uprising had major ramifications for Ribera: due to the repressive measures the Spaniards took against the revolting Italians, the artist and his family became completely ostracized by the city's Italian population. After the rebellion, the woes kept on accumulating just as fast as the accolades had a mere decade earlier. Ribera had a relapse of his illness in 1649, and as a result of his inability to work both due to his sickness and to the tumult of the rebellion, the Ribera family began to experience real financial trouble. The situation was worsened when Ribera had to take his daughter Margarita back into his household after her husband died only a few years after their wedding. Ribera's difficulties were such that in 1651, he wrote a petition to the King asking for some financial compensation for Margarita's widowhood. Ribera would never have the time to see if his petition would come to fruition, however. The next year, in July 1652, he moved into a smaller, quieter house in the Mergellina district and died shortly thereafter. Head of a Man Line and Finished Studies of Mouths and Noses Saint Albert Saint Jerome Hearing the Trumpet of the Last Judgment Seven Line Studies and Six Finished Studies of Eyes Silenus at the Wine Vat.
0.96981	The function of Epstein–Barr virus (EBV) stable intronic sequence (sis)RNAs, non-coding RNAs transcribed from a region required for EBV-mediated cellular transformation, remain unknown. To better understand the function of ebv-sisRNA-1 and ebv-sisRNA-2 from the internal repeat (IR)1 region of EBV, we used a combination of bioinformatics and biochemistry to identify associated RNA binding proteins. The findings reported here are part of ongoing studies to determine the functions of non-coding RNAs from the IR1 region of EBV. Human regulatory proteins HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPC, HNRNPL, HuR (human antigen R), and protein LIN28A (lin-28 homolog A) were predicted to bind ebv-sisRNA-1 and/or ebv-sisRNA-2; FUS (fused in sarcoma) was predicted to associate with ebv-sisRNA-2. Protein interactions were validated using a combination of RNA immunoprecipitation and biotin pulldown assays. Both sisRNAs also precipitated with HNRNPD and NONO (non-POU domain-containing octamer-binding protein). Interestingly, each of these interacting proteins also precipitated non-spliced non-coding RNA sequences transcribed from the IR1 region. Our findings suggest interesting roles for sisRNAs (through their interactions with regulatory proteins) and provide further evidence for the existence of non-spliced stable non-coding RNAs. Stable intronic sequences (sis)RNAs and long non-coding (lnc)RNAs are non-coding RNAs (nc)RNAs known to perform many functions that can regulate gene expression [1, 2]. Aberrant expression of lncRNAs is thought to contribute to disease states such as cancer . The impact of the relatively new category of sisRNAs are not well understood but could include roles in development or cancer [1, 4]. Rarely (if ever), is the function of these RNAs independent of the proteins that bind them. Numerous RNA binding proteins have been identified and many of their important functions have been discussed elsewhere in detail , including their implication in disease states such as cancer . Two abundant sisRNAs expressed from the internal repeat (IR)1 region, containing the W-repeats, of the Epstein–Barr virus (EBV; human herpes virus 4, HHV4) genome were identified previously . Their transcription is linked to that of the Epstein–Barr nuclear antigen leader protein (EBNA-LP), and occurs during cancer-associated latency III infection as well as in a rare latency program found in Burkitts lymphomas: Wp-restricted . Efficient transformation of B cells requires EBNA-LP expression . Indeed, the connection between EBV and cancer is well established [10, 11], but the role of the IR1 region stable introns in cellular transformation is not. Recently, a mutation in ebv-sisRNA-1 that inhibited EBV-mediated transformation of B cells was reported . Though the mutation did not occur in isolation, this maintains the idea that the ncRNA from this region is important for tumorigenesis. Here, we extend the understanding of the non-coding RNAs, ebv-sisRNA-1 and ebv-sisRNA-2, through the demonstration of their association with a number of human regulatory proteins. Further, we provide evidence that these intronic sequences are more likely to be found embedded within non-spliced transcripts that retain both exons of the IR1-region. Descriptions of cell lines and transductions, biotin precipitations and mass spectrometry, bioinformatics and data processing, RNA immunoprecipitation, RNA extraction, and PCR are in Additional file 1. The majority of ebv-sisRNA-1 is predicted to be unstructured (Fig. 1a), providing easier access to single-stranded RNA binding proteins. To identify proteins that bind ebv-sisRNA-1, biotin precipitation assays were performed using BJAB cell lysates (EBV negative) and either a wild-type or deletion mutant of the conserved CA-rich region (ΔCA). This region was speculated previously to be important for heterogeneous nuclear ribonucleoprotein (HNRNP)L binding . Silver staining revealed losses of several protein bands, prominently at both 60–65 kDa (size of HNRNPL) and 35–40 kDa (most intense band for wt) compared to ΔCA mutation (Fig. 1b). Mass spectrometry of these regions identified HNRNPL and HNRNPD/AUF1 as the most probable interactors (Additional file 2). HNRNPL binding is fully consistent with reported CA-rich consensus binding sequences [13, 14]. HNRNPD/AUF1 typically binds AU-rich elements (AREs) of RNA but has also been shown to interact with HNRNPL . RNA immunoprecipitation (RIP) for HNRNPL and HNRNPD/AUF1 on both Raji and BJAB-B1 cells, which harbor type 1 and type 2 EBV genomes, respectively, revealed an association with ebv-sisRNA-1 (Fig. 1c; Additional file 3). Ebv-sisRNA-1 is highly abundant and expressed at the same time as EBNA-LP , and recent genetic evidence suggests that EBNA-LP and possibly ebv-sisRNA-1 may be important for EBV-mediated B cell transformation ; thus, its interactions with two key regulatory proteins have interesting implications. HNRNPD/AUF1 is best known for its function in regulating mRNA abundance (e.g., binding to ARE-containing 3′ untranslated regions (UTRs) and destabilizing transcripts) . Overexpression of HNRNPD/AUF1 can promote oncogenesis and control translation [18, 19]. Interestingly, HNRNPD/AUF1 binds directly to EBER1 , another EBV ncRNA that is highly expressed throughout all stages of latent/lytic infection. The proposed function of this EBER1 interaction is to perturb the normal homeostasis between HNRNPD/AUF1 and target mRNAs in EBV-infected cells. Given that both ebv-sisRNA-1 and EBER1 are abundantly present during the initial patterning of B-cell gene expression (e.g., latency III), it is enticing to speculate that ebv-sisRNA-1 and EBER1 may coordinately contribute to disease-promoting functions of HNRNPD/AUF1. HNRNPL has a proposed role in various cancers and is known to affect the expression (e.g., alternative splicing) of a wide array of human genes [21–24]. HNRNPL shuttles between the cytoplasm and nucleus; thus, its interaction with a viral ncRNA that is abundantly present in the nucleus, suggests a potential role in disrupting HNRNPL localization/interactions. This could have a vast impact on the alternative splicing of many host genes; as well as, interestingly, in the regulation of the EBNA-LP gene from which ebv-sisRNA-1 is derived: e.g., through a competition between EBNA-LP pre-mRNA and the accumulating sisRNA that forms stable ribonucleoproteins (RNPs) with HNRNPL. These possibilities are being explored. To better understand the protein binding repertoire of ebv-sisRNA-1 and ebv-sisRNA-2, we used the program RBPmap to predict human host RNA binding proteins (RBPs) that might directly interact. Both type 1 (NC_007605) and type 2 (NC_009334) EBV sequences were analyzed using a sequence fragment of the IR1 W-repeat region from each genome, which contains exon W1, ebv-sisRNA-1, exon W2, and ebv-sisRNA-2 (Fig. 2a, W1s1W2s2). RBPmap compares these sequences to known consensus binding sites of human and mouse proteins and classifies/ranks hits based on their fit to the consensus motif. 81 unique proteins were identified that had significant binding site consensus throughout the region of interest (Fig. 2b; see Additional file 4 for binding region detailed information). The putative interacting proteins are known to be involved in biological processes of RNA processing, splicing, and gene expression (Fig. 2c; Additional files 3 and 5). Consistent with our findings above, ebv-sisRNA-1 contained predicted HNRNPL binding regions (Fig. 2b). Ebv-sisRNA-2 did as well, and this interaction was verified by RIP (Fig. 2d). Similar to ebv-sisRNA-1, ebv-sisRNA-2 precipitated with HNRNPD/AUF1. Multiple interaction sites for several RBPs throughout the sisRNAs suggest similar functions for potential regulation of EBNA-LP and sisRNA processing, as well as downstream effects on cellular homeostasis of RBP interactions with endogenously regulated host genes, which remains to be explored. Eight other predicted proteins (Fig. 2b, blue; Additional file 6) were tested for their ability to co-precipitate either ebv-sisRNA-1 (HuR/ELAVL1, IGF2BP2, IGF2BP3), ebv-sisRNA-2 (FUS, HNRNPA1, LIN28, MBNL1), or both (HNRNPC). Quantitative (q)PCR for both sisRNAs was performed for all RIPs (Fig. 3a; Additional file 3). HuR, HNRNPA1, LIN28, and HNRNPC precipitated both ebv-sisRNAs with at least twofold enrichment over normal IgG in two cell lines. FUS bound ebv-sisRNA-2 in both cell lines, but only precipitated ebv-sisRNA-1 in BJAB-B1 cells. IGF2BP2, IGF2BP3, and MBNL1 did not bind under these experimental conditions. Two RBPs not predicted by RBPmap were also tested. To determine if sisRNAs were potential targets of micro (mi)RNAs (e.g., acting as “sponges”), an antibody that targets multiple Argonaute proteins was used. Neither sisRNA was enriched in our experiments. This result challenges a previous in silico predicted interaction of ebv-sisRNA-1 and miR-142-3p (previously proposed to be targeted by another herpes virus ncRNA [26, 27]). Lytic EBV ncRNAs originating from the OriP region contain long hairpin stems similar in size/structure to ebv-sisRNA-2 [7, 26] and were found to interact with the paraspeckle-associated protein p54nrb/NONO . The OriP ncRNA was found to promote transcription/replication of EBV and to modulate host innate immunity through its interactions with paraspeckles. Likewise, NONO interacts with EBER2 and may bridge an interaction with host transcription factor PAX5, which supports EBV replication through recruitment by EBER2 to the viral genome . Similar to the OriP and EBER2 ncRNAs, NONO bound both ebv-sisRNAs by RIP. The common interaction of these viral ncRNAs with NONO suggests potential overlapping functions (e.g., replication or immune modulation) that need to be tested. Additionally, localization of the sisRNAs (and other viral ncRNAs) to paraspeckles remains to be shown. These results show binding—either direct or indirect—of the IR1 sisRNAs to HNRNPL, HNRNPD/AUF1, HuR, HNRNPA1, LIN28, NONO, and HNRNPC (Fig. 3a). Intriguingly, each of these proteins are implicated in pro-cancer-related phenotypes [6, 31]. Binding of these regulatory proteins to ebv-sisRNAs may play roles in the emergence of these phenotypes in EBV-associated diseases, which merits further investigation. Intrigued that both ebv-sisRNAs associated with HuR, HNRNPA1, FUS, and LIN28, when only one or the other was predicted to bind, a primer set that spanned the ebv-sisRNA-1 to W2 splice junction was tested (Figs. 2b, amplicon 3; 3b; Additional file 3). This RNA, containing an intact splice junction, precipitated with the majority of interacting proteins, suggesting that these RBPs also bound non-spliced RNA from the W-repeat region. To test for the relative abundance of spliced to non-spliced ebv-sisRNA-1, RT-PCR was performed using a forward primer targeting exon W1 and a reverse primer targeting exon W2 (Figs. 2b, amplicon 4; 3c). The overwhelming majority of RNA contained intact exon–intron junctions. The non-spliced form was also more abundant than the spliced form in EBV-free BJAB cells transduced to overexpress W1-sis1-W2. Likewise, amplification from the 3′ end of sisRNA-2 across W1-sisRNA-1-W2 to the 5′ end of the next sisRNA-2 intron (Fig. 2b, amplicon 5) demonstrated that the predominant form of RNA from the IR1 W-repeats retains intact exon–intron boundaries (Fig. 3d). There are several possible interpretations of these findings. Firstly, W-repeat intronic RNAs could be embedded within non-polyadenylated [poly(A)] lncRNAs arising from this region. Secondly, splicing may have resulted in excision of an entire stable sis2-exonW1-sis1-exonW2 region (~ 5.9 kb) or an exonW1-sis1-exonW2-sis2 (~ 3 kb) region; the stability of such products could possibly be conferred through circularization and back splicing . Both interpretations are made plausible by early work that found prominent Northern blot bands of poly(A)− RNA up to 13 kb in size. . Thirdly, splicing may be inhibited leading to the accumulation of intron-containing pre-mRNA from the EBV W-repeat region, which has been observed previously . HNRNPL and HNRNPA1 are known spicing repressors , which supports this hypothesis. Likewise, lncRNAs spanning the W-repeat intronic regions may be polyadenylated. Previous analyses of poly(A)+ samples [33, 36], showed Northern blot bands overlapping poly(A)− RNAs as well as larger ones (up to ~ 22 kb). These possibilities are not mutually exclusive and the exact architecture of the ncRNAs from this region is likely to be complex: consisting of multiple sized species of spliced/unspliced RNAs with and without poly(A) tails. Supporting this idea, recent analyses of RNA-Seq data from EBV-infected cells found extensive read coverage of the ebv-sisRNA regions in both ribosome-depleted and poly(A)-selected samples . We have shown that the ebv-sisRNAs exist within a complex milieu of non-coding transcripts. In addition to independent intronic units, sisRNAs are embedded within various sized ncRNAs that can arise from alternative splicing or initiation and that may be polyadenylated. Regardless of their transcript structure, sisRNAs are capable of interacting with a number of human regulatory proteins. We present a list of 81 proteins from in silico predictions and validate six highly interesting ones that associate with both ebv-sisRNA-1 and ebv-sisRNA-2 (FUS, HNRNPA1, HNRNPC, HNRNPL, HuR, LIN28). Furthermore, we identify additional interactions with HNRNPD/AUF1 and NONO, both of which interact with other EBV ncRNAs. Taken together, our results begin to unravel the RNP composition of this intriguing class of viral ncRNAs and suggest multiple leads for follow-up analyses into the functional consequences of deduced interactions: e.g., in EBV infection and the emergence of disease. Additional work is needed to confirm other predicted interactions as well as to determine if validated binding proteins are interacting directly or indirectly. Most importantly, the exciting implications of the identified/validated RBPs have yet to be explored. We hope this report will facilitate additional research required to understand the functions of these interesting EBV ncRNAs. VST—experimental design and execution, interpretation of results and primary authorship of the manuscript; DV executed experiments; WNM conceived of the work, oversaw its production, and contributed to the writing of the manuscript. All authors read and approved the final manuscript. We would like to thank Ashwanth Lalithaa-Padmanabhan (Iowa State University) and Nuwanthika D. Kumarashinghe (Iowa State University) for technical contributions, as well as Jacob Schwartz (University of Arizona), Joan Steitz (Yale University), and Siegfried Janz (University of Iowa) for kindly providing antibodies and cells. This work was supported by startup funds from the Iowa State University College of Agriculture and Life Sciences and the Roy J. Carver Charitable Trust, as well as Grant 4R00GM112877-02 from the NIH/NIGMS. 13104_2018_3250_MOESM1_ESM.docx Additional file 1. Methods and materials. Detailed description of methods and materials used to collect and analyze data. 13104_2018_3250_MOESM2_ESM.xlsx Additional file 2. Mass spectrometry results. List of proteins that bound biotinylated forms of ebv-sisRNA-1 after mass spectrometry from gel slices indicated in Fig. 1B. Hits resulting from either the top (60-65 kDa) or bottom (35-40 kDa) are indicated. 13104_2018_3250_MOESM3_ESM.xlsx Additional file 3. Fold enrichment individual experimental results from all RIPs. 13104_2018_3250_MOESM4_ESM.xlsx Additional file 4. RBPmap of EBV W1s1W2s2. Human or mouse proteins predicted (RBPmap) to bind W1s1W2s2 RNA (see Fig. 2A) from the IR1 region of EBV. Results from both EBV type 1 and type 2 sequences are included as well as a comparison. 13104_2018_3250_MOESM5_ESM.xlsx Additional file 5. STRING analyses of predicted RBPs. Results from STRING enrichment analyses of 81 RBPmap-identified proteins. Information includes annotations and enrichment data on biological processes, KEGG pathways, molecular functions, cellular components, InterPro, and Pfam. 13104_2018_3250_MOESM6_ESM.pdf Additional file 6. Map of predicted binding sites for proteins assessed by RIP. Szymula A, Palermo RD, Groves IJ, Ba abdullah M, Holder BS, White RE. Epstein-barr virus nuclear antigen ebna-lp is essential for transforming naive b cells, and facilitates recruitment of transcription factors to the viral genome. bioRxiv. 2017;176099. https://doi.org/10.1101/176099.
0.996124	In order to understand this article, I recommend you first read my blog entry from 2011. It will set the scene for the rant which you are about to read! The original Dark Hedges disaster blog entry. A lot has happened in my landscape photography world since late 2011 when this article was posted. I have purchased an entirely new camera and lens setup, taken landscape photographs in destinations I have never visited before like Cyprus, and created this new website to display my work! However, in that same time the Dark Hedges in County Antrim has encountered several problems and, in my opinion, is a classic case of a tourist location being a victim of its own success. For as long as I have been a landscape photographer I have been aware of this famous road. It has always been popular and I would have regularly seen a few other photographers when I was there with my camera. With the exception of a few rogue photographers, courtesy was generally the order of the day and visiting was a pleasant experience. However, the very popular HBO television series Game of Thrones used the road in one of their scenes a few years ago (I think 2010/11), sending the popularity of this simple little country road into the stratosphere. At this point I think it is important that I make clear my support for anything which increases tourism and creates jobs and other opportunities. There can be no doubt that the Game of Thrones has had a positive impact in this regard and all involved in securing its production in Northern Ireland should be applauded. However, in allowing the country's landscape to be used in this way, the various government bodies and other stakeholders who have a responsibility to protect said landscape must do so in a strategic and considered way, in partnership with each other. In the case of the Dark Hedges this has not happened and the results have not been pretty. The saga began with the horrible fence I talked about in my 2011 article. A bright green monstrosity which glowed like a cartoon nuclear rod, it fortunately had a shorter half-life than expected and the colour faded. Next came the cars and tourist coaches. At the weekends there was congestion that central London drivers would have been grumpy about, with people parking seemingly at random along the road, thinking nothing of sticking 2 wheels of their vehicles up into the root systems of the trees. If one wished to witness the potential for human stupidity and selfishness first hand, sending them to the Dark Hedges with a camera on a mission to capture the beautiful avenue of trees would almost certainly do the job. There isn't a car park worth talking about, discrete signs to discourage parking on the road itself, or any form of traffic management that I can find. It is a free-for-all. With this increase in traffic came the erosion of the grass verges which line the road and protect the tree roots to an extent. To call the trees fragile would be an understatement, in a recent storm several were felled and are gone forever. Hundreds of years of growth wiped out in seconds. Of course this would have happened even without the increase in tourist numbers, but let's give the trees a fighting chance. The photograph at the top of this page is the latest 'disaster' to be inflicted on this beautiful road. Not only is the white line down the middle of the road the visual equivalent of graffiti on a beautiful building, but look at how the new road surface encroaches on the base of the trees. It beggars belief that someone signed off on this decision. I know I'm not the only person thinking "what an idiot!" I realise that it is much easier to to critisise decisions from the sidelines than to make them whilst following rules and regulations, but is this really the best we can do? I'm not ashamed to say that I was upset when I first heard that these road markings had been laid. Upset with the person who made the decision, upset with the stakeholders in the Dark Hedges who allowed this to happen, and upset with the person putting the lines on the road for not thinking 'this doesn't look right.' I have known for a long time that most people don't care about the beauty around them, some pay lip-service to the idea of appreciating it, and very few really take the time to stop, stare and realise just how lucky they are. My intention is to email Mervyn Storey who is part of the Dark Hedges Preservation Trust in the morning and urge him to use his considerable influence to put a stop to this madness. The markings only extend along 25% of the road so far, so perhaps it can be stopped before the whole road is ruined. I would encourage anyone reading this blog who cares about the landscape around them to share this blog post or email Mr Storey to make your views known.
0.999982	The activities in a lake such as Lake Erie are controlled in part by what happens in the watershed. Losses from the land are gained by the lake, for better or for worse–often to the detriment of organisms living in the lake. Nutrients, such as nitrogen and phosphorus that contain compounds from agricultural and residential fertilizers, along with toxic materials such as industrial wastes (e.g., polychlorinated biphenyls, or PCBs) and human hygienic products (e.g., endocrine disrupting estrogen agonists and antagonists) enter lakes largely through riverine inputs, often exacerbated by rainstorms and snowmelt runoff. Also, ecosystem managers need to consider particulate materials, which consist largely of soil particles (i.e., sand, silts, and clays) carried along with flowing water and which may turn into sediment at the bottom of a lake when the flow decreases at the mouth of a river or after entry to a lake. Although point sources such as pipes from a sewage treatment plant or local industry can be feeders of pollutants to a river, much of point-source pollution is now regulated to prevent large inputs to receiving waters. The major source of pollutants now is from nonpoint sources such as runoff from residential yards and agricultural fields. When runoff occurs from these nonpoint sources, generally it comes as a mix of dissolved and particulate materials. Although most nutrients and many toxic materials are soluble in water, they often are attached to the surface of sediments when they enter a stream or river, complicating the management picture. Which sediments are worst for holding unwanted materials? Recall from geometry that as the radius of a sphere gets smaller, the ratio of surface area to volume gets larger. So the surfaces of smaller particles (e.g., clays) are proportionately much more coated with nutrient and toxic materials than the larger sand particles. This means that sediments of different sizes can be and need to be managed differently. Until recently, eroded sediments were treated as a nuisance, filling up harbors at the mouth of rivers and requiring dredging to keep those ports open for commerce. The Cuyahoga River fills its navigation channel with eight to ten feet of sediment each year, requiring the U.S. Army Corps of Engineers to dredge it to maintain shipping access up six miles to the ArcelorMittal steel company. To be exact, the corp dredges 225,000 cubic yards of sediment at great expense to public funds, whether state or federal. Recent advances in technology have begun to turn bane into bonanza. The Port of Cleveland in partnership with Kurtz Bros., Inc. has been harvesting sand five miles upstream of ArcelorMittal using a sand interceptor that collects sand from the river and deposits it along the riverbank, where it is delivered to trucks and sold for construction, soil conditioning, and stream and beach reconstruction. It is then dried and sorted by size. Because it is collected above most industrial activities, it is sufficiently clean for reuse. It is estimated that with expansion of its capabilities, the sand interceptor may be able to reduce sediment loads to the port by 20%. The interceptor was funded with $1.2 million by the Ohio Healthy Lake Erie Fund. Independent research conducted at the University of Akron and verified by the Ohio EPA found that the material met state and federal standards for cleanliness. But what about the sediments that are not collected by the sand interceptor? Aren’t those the materials most likely to have hazardous materials adhering to them? Sediments dredged from the mouth of the Cuyahoga River are now placed in a confined disposal facility (CDF) at the eastern end of Burke Lakefront Airport. This is a special experimental CDF that is administered by the Ohio Department of Natural Resources Office of Coastal Management. It is constructed as a series of pools through which sediment slurries pass. The sediment material gradually sinks to the bottom, leaving the water to pass back into the shipping channel in a process called dewatering the sediment. Over time, the sediment consolidates, with the larger, heavier materials settling in the first pond and lighter sediments settling in later pools. Bacterial and fungal activities gradually will decompose the toxic materials (e.g., PCBs and polyaromatic hydrocarbons, or PAHs). In the meantime, small amounts of these dewatered sediments can be combined with other materials and used in soil mixes. The Ohio EPA tests the mixes to ensure that they meet state and federal standards for safety. Once again, these soil mixes are made through the public-private partnership between the state and Kurtz Bros. Through these innovative measures, sediment no longer need to be considered something to be disposed of; instead, sediment can be considered to be a valuable resource that can be recycled and marketed. It is something to think about and to carefully consider as the next wave of environmental protection: making the environment safe by making it profitable. Time will tell whether this is a valuable direction, especially given the current political aversion to making sweeping environmental regulations.
0.980777	Integrating multimodal sensory signals is one of the fundamental operations performed by the brain. The midbrain and cerebral association cortex (Stein and Stanford, 2008), and the cerebellum receive and process sensory signals of various modalities (Snider and Stowell, 1944; Azizi and Woodward, 1990; Gao et al., 1996; Sobel et al., 1998). Although it is well known that each granule cell in the mammalian cerebellum receives excitatory synaptic inputs from on average four mossy fibers (Eccles et al., 1967; Jakab and Hamori, 1988), it is important to determine whether multisensory integration takes place already on the level of the granule cells, which form the input layer, or only in the downstream neurons, including Purkinje cells. A recent study using projection mapping has shown that some granule cells receive mossy fibers from two areas in the brainstem (the basilar pontine nucleus and the external cuneate nucleus), providing morphological evidence of multimodal convergence in single granule cells (Huang et al., 2013; see also Chabrol et al., 2015). However, in vivo single cerebellar granule cells in cats have been shown to only respond to stimulation of a single modality (Jörntell and Ekerot, 2006; Spanne and Jörntell, 2015). Therefore, to determine whether functional multimodal convergence is common we made whole-cell patch-clamp recordings in vivo from single granule cells and directly tested responsiveness to sensory stimulation of different modalities. We made patch-clamp recordings from single cerebellar granule cells of rats in vivo to examine their responses to auditory, visual and somatosensory stimulation. We selected crus I and II and the dorsal paraflocculus of the cerebellum because previous studies suggested that these areas might receive multisensory inputs (Azizi and Woodward, 1990; Huang et al., 2013). The high quality of voltage clamp recordings in granule cells in vivo enabled detection of individual sensory-evoked EPSCs (Chadderton et al., 2004; Rancz et al., 2007; Arenz et al., 2008), thus providing exquisite sensitivity for detection of responses to a sensory stimulus. 45% of granule cells (60/133 cells) in crus I and II and 10% of those (3/30 cells) in the dorsal paraflocculus responded to somatosensory stimulation with a burst of EPSCs (Figure 1A–E left column and Figure 1F–G), as described previously (Chadderton et al., 2004; Rancz et al., 2007). In contrast, auditory stimulation (white noise, 81–91 dB SPL, Figure 1A–E middle column) evoked EPSCs in 25% of granule cells in crus I and II (33/133 cells) and 10% (3/30 cells) of granule cells in the dorsal paraflocculus (Figure 1F–G). When different sound levels were systematically tested, the number of evoked EPSC events increased with increasing sound levels (from 75 dB to 94 dB), while the mean amplitude of evoked EPSCs remained constant (Figure 1—figure supplement 1). Finally, visual stimulation (binocular LED flash; Figure 1A–E right column) evoked EPSCs in 87% of granule cells (26/30 cells) in the dorsal paraflocculus, while visual responses in crus I and II were rare (Figure 1F–G). When visual stimulation was delivered monocularly, ipsilateral stimulation evoked the predominant response (Figure 1—figure supplement 2). In summary, auditory and visual stimulation evoked bursts of EPSCs in granule cells that were comparable to those evoked by somatosensory stimulation (Figure 1—figure supplement 3). EPSCs evoked by activation of different sensory modalities in cerebellar granule cells in vivo. (A–F) Representative recordings from three different granule cells are presented for each modality. EPSCs were evoked by somatosensory stimulation (air puff to whiskers), auditory stimulation (white noise 89 dB) or visual stimulation (white LED, ipsilateral eye) recorded under voltage clamp at -70 mV. The bars above the traces indicate the timing of stimulation and the vertical dotted lines indicate the onset of the stimulation. The timescale is common for all panels A–E and is indicated at the bottom of panel E. (A) Four consecutive traces for each type of stimulation. (B) Raster plots of EPSC events. (C) Time histograms of EPSCs; bin width is 25 ms. (D) Cumulative time histograms (baseline subtracted). (E) The amplitudes of all EPSCs are plotted. (F–G) Pie charts indicating the total numbers of multimodal, unimodal and nonresponsive cells recorded in the crus I and II area (133 cells) and the dorsal paraflocculus (30 cells). Characters indicate the types of stimulation (S, somatosensory; A, auditory; V, visual), to which the cells responded. Cells that responded to multiple sensory modalities were indicated by the combination of those characters (A & S, S & V, A & V and A & S & V). A subpopulation of granule cells responded to multiple sensory modalities (Figure 1F,G). In dorsal paraflocculus 20% (6/30 cells) of granule cells were multisensory, and in crus I and II 14% (18/133 cells) were multisensory. In both regions, we found individual granule cells that responded to stimulation of three separate sensory modalities. Figure 2 shows a representative granule cell in crus II that responded to auditory stimulation, somatosensory stimulation and a combination of these two stimuli. Single granule cells exhibit multi-sensory responses. EPSCs evoked by multi-sensory stimulation in a single cerebellar granule cell in crus II. EPSCs were evoked by somatosensory stimulation (air puff to whiskers), auditory stimulation (white noise, 91 dB) or a combination of the two. Trials were interleaved with an inter-trial interval of 3 s under voltage clamp at -70 mV. The color bars at the top indicate duration of stimuli, and the vertical dotted lines indicate the onset of the stimulation. The time scale is common for panels A–E and indicated at the bottom of E. (A) Four consecutive traces for each type of stimulation. (B) Raster plots of EPSC events. (C) Time histograms of EPSCs; bin width is 25 ms. The linearity index was calculated as the event number evoked by the combined stimulation divided by the sum of those evoked by the two unimodal stimulations. (D) Cumulative time histograms (baseline subtracted). (E) Amplitudes of all EPSCs. (F) Cumulative distribution of the amplitudes of the first events in a burst of evoked EPSCs. The amplitudes were significantly different between the two modalities (P < 0.05). Inset, average traces of first EPSCs. (G–H) Comparison of the amplitudes of EPSCs evoked by different sensory modalities. For each multimodal cell, the amplitudes of first-evoked EPSCs (mean ± s.e.m.) in response to two sensory modalities are plotted against each other. Eight out of 20 cells (16 in crus I and II [G] and 4 in dorsal paraflocculus [H]) had significantly different amplitudes (P < 0.05, indicated by red marks) and deviate from the unity line (dotted line). To examine if responses to different sensory stimuli in a single granule cell were mediated by the same or separate mossy fibers, we analyzed the amplitude and waveform of individual EPSCs, since these characteristics reflect unique properties of distinct synapses (Silver et al., 1996; Arenz et al., 2008). When comparing EPSC amplitudes, we focused on the first EPSC of a sensory-evoked burst because the second and subsequent events are likely to be affected by synaptic facilitation and depression. In the cell shown in Figure 2A–F, the amplitude of auditory-evoked EPSCs (16.6 ± 0.8 pA, n = 23 sweeps) was significantly larger than that of somatosensory-evoked EPSCs (8.6 ± 1.2 pA, n = 23, P < 0.05), indicating that those two groups of EPSCs originate from different synapses, i.e. the signals are conveyed by different mossy fibers (Figure 4A). Across the population, 40% (8/20) of multisensory cells showed significantly different (P < 0.05) first EPSC amplitudes in response to different modalities (Figure 2G–H and Figure 2—figure supplement 1). Additionally, one cell also showed a significant difference (P < 0.05) in EPSC rise time for the different modalities. For the remaining cells that did not exhibit a significant difference in EPSC amplitudes between modalities, it is not possible to determine if their multimodal input arises from a single mossy fiber (Figure 4B) or from two mossy fibers that have indistinguishable characteristics (Figure 4A). Multisensory integration can enhance granule cell output. (A–C) Action potentials in a representative granule cell evoked by multisensory stimulation. EPSPs and action potentials were evoked by somatosensory stimulation, auditory stimulation and combination of these two. Trials were interleaved with an inter-trial interval of 3 s. The granule cell was current-clamped with no bias current. The color bars at the top indicate the duration of stimulation and the vertical dotted lines indicate the onset of stimulation. (A) Representative traces are expanded to show evoked EPSPs and action potentials. Ten consecutive traces are overlaid. The peaks of action potentials are truncated. (B) All recorded traces are shown with the time scale indicated at the bottom of panel C. (C) Time histograms of evoked action potentials. The bin width is 25 ms. (D) Input-output relationships for 4 granule cells. The number of action potentials evoked in current-clamp mode was plotted against synaptic charge measured in voltage-clamp mode. The spike numbers are baseline-subtracted. Values from the same granule cell are connected by lines. Blue circles indicate the response to somatosensory stimulation, red circles auditory stimulation, purple circles combined somatosensory and auditory stimulation. The cell shown in A–C corresponds to Cell 1 in D. Functional configurations of multisensory integration at the mossy fiber–granule cell connection. Schematic diagrams showing potential anatomical substrates of the different multisensory integration scenarios described in the results. (A) Multimodal signals are transmitted by separate pathways and converge onto a single granule cell. (B) A single mossy fiber conveys mixed multi-modal signals. (C) Multimodal signals converge onto a granule cell, but the two pathways interact. In these schematics, the round cells represent pre-cerebellar neurons whose axons form mossy fibers. The triangular cells represent neurons projecting to the pre-cerebellar neurons (e.g. cortical neurons projecting to pontine neurons). Gray diamond-shaped neurons represent hypothetical interneurons. Another possibility for interaction between two separate pathways (not illustrated here) is presynaptic inhibition (Mitchell and Silver, 2000) or postsynaptic inhibition (Duguid et al., 2015) via Golgi cells. Combined stimulation of two modalities evoked responses that were approximately the sum of two unimodal responses (Figure 2). If the summation is perfectly linear, the linearity index (see Figure 2 legend) should fall on the unity line. For the cell shown in Figure 2, this index was close to, but slightly below unity (Figure 2C). Interestingly, the linearity index showed considerable variation across cells and indicated moderately sublinear summation on average (0.71 ± 0.23; mean ± s.d.) for 8 cells that received inputs from two separate mossy fibers ( Figure 4C, see Discussion). The same tendency was seen for cells that were not determined to have separate mossy fiber inputs for different modalities (0.70 ± 0.20, mean ± s.d., n = 12), which was confirmed when the synaptic charge was used instead of event number to calculate the linearity index. Finally, we examined how multisensory stimulation drives action potential output. We first identified granule cells receiving multisensory inputs via different mossy fibers using voltage-clamp recordings, and then we obtained recordings in the same neurons in current-clamp mode. The resting membrane potential and the action potential threshold were −55.0 ± 4.7 mV and −39.7 ± 3.0 mV (n = 4), respectively. In the granule cell shown in Figure 3A–C, combined stimulation with two sensory modalities evoked more action potentials than the sum of two unimodal stimuli, indicating supralinear summation. Two of four cells exhibited such supralinear summation (Cell 1 and 2 in Figure 3D), while the other two cells showed sublinear summation. These findings suggest that, although there exists diversity across the population, granule cells are capable of integrating multisensory signals to generate enhanced action potential output. We have taken advantage of the electrical compactness of cerebellar granule cells and their small number of synaptic inputs to probe how multisensory signals are integrated by single neurons at the input stage of the cerebellar cortex. Using high-resolution voltage-clamp recordings, we demonstrate directly that multisensory signals converge onto individual granule cells in vivo, and that multisensory input can enhance granule cell spike output. Granule cells receive excitatory input from only 4 mossy fibers on average (Eccles et al., 1967; Jakab and Hamori, 1988). Electrophysiological recordings have shown that somatosensory inputs to crus I and II (Chadderton et al., 2004; Rancz et al., 2007) and vestibular signals to the flocculus (Arenz et al., 2008) can be conveyed to individual granule cells by single mossy fibers. Therefore, it has been speculated that the other three mossy fibers (on average) could conduct signals of other sensory modalities. This conjecture has been supported by the recent anatomical (Huang et al., 2013) and in vitro electrophysiological (Chabrol et al., 2015) demonstration that single granule cells can receive mossy fibers of different origins (see also [Sawtell, 2010]). Our findings in vivo provide a direct functional demonstration that single granule cells can receive inputs from up to three separate sensory modalities. Furthermore, we show that combined stimulation of two sensory modalities can produce enhanced spike output from granule cells, indicating that the result of multisensory integration can be transmitted to downstream neurons in the cerebellar network. While the present study strongly supports the conclusions of Huang et al. (2013) regarding multimodal integration in single cerebellar granule cells, we could not directly prove the integration of sensory and motor signals in granule cells as proposed by their study, because we could test only integration of sensory modalities in anesthetized animals. Integration of sensory and motor inputs should to be tested in future studies using recordings from granule cells in awake behaving animals (Powell et al., 2015). When combining stimulation of two sensory modalities, we observed significant sublinear summation of synaptic currents in a subset of granule cells. Under the excellent voltage-clamp conditions that exist in granule cells, inputs from different synapses are expected to summate linearly. Thus, the observed sublinear summation of synaptic currents is likely to be due to inhibitory interactions between the two sensory pathways upstream from the granule cell (see Figure 4). Such interactions could occur at any point in upstream sensory pathways, including the brainstem, the thalamus and the cerebral cortex, particularly given that the relatively long latency (> 10 ms) of sensory responses in our recordings suggests that these sensory signals are mediated via the corticocerebellar pathway rather than direct projections from primary sensory neurons (Morissette and Bower, 1996). Further studies are required to understand the mechanism and significance of such inhibitory interactions. It should also be noted that our findings do not directly contradict the absence of multimodal integration observed in granule cells in decerebrate animals in which the corticocerebellar pathway is not preserved (Jörntell and Ekerot, 2006; Spanne and Jörntell, 2015). It is likely that granule cells represent a diverse population with respect to functional multisensory input (Figure 4), with some granule cells appearing to be unimodal, some with multisensory input delivered by separate mossy fibers, and some with multisensory input delivered by a single mossy fiber. The convergence of functionally distinct sensory signals in single granule cells at the input layer of the cerebellar cortex, predicted by Huang et al. (2013) and demonstrated directly here, is likely to be a crucial feature of cerebellar signal processing. Indeed, influential theories of cerebellar computation (Marr, 1969; Albus, 1971) have proposed that granule cells are not merely relaying signals but “recoding” multiple types of incoming signals. Our present study provides important in vivo functional evidence supporting this “recoding” hypothesis in the mammalian cerebellum. Moreover, it was hypothesized (Albus, 1971) that such “recoding” would expand the representation of population patterns because granule cells outnumber mossy fibers by a factor of 100 (due to the extensive branching of mossy fibers). Our observation that the linearity of summation (both in synaptic inputs and in spike outputs) varies across cells may reflect the diversity of coding patterns required for the computational role of the granule cell in expansion recoding. In future studies, it will be important to reveal how synaptic plasticity at the mossy fiber-granule cell synapse (Roggeri et al., 2008) may affect the representation of multiple sensory inputs at the level of a single granule cell. All experiments were carried out in accordance with UK Home Office regulations and the guidelines of the Animal Experiment Committee of Jikei University. Lister-hooded rats (19–24 days old) were anaesthetized with a ketamine (60 mg/kg) and xylazine (4.5 mg/kg) mixture. Rats were freely breathing during surgery and recording. A peripheral anticholinergic drug, glycopyrrolate bromide (0.02 mg/kg S.C.) was administered in most of the experiments. In some early experiments, atropine (0.06 mg/kg) was used instead of glycopyrrolate. A head-post was glued onto the skull and a small craniotomy was made over the cerebellar region to be targeted. After removal of the dura, saline was used to prevent drying of the exposed brain surface. Whole cell voltage-clamp (V-C) and current-clamp (I-C) recordings were made from granule cells in crus I and II and paraflocculus of the cerebellar cortex, using a Multiclamp 700B amplifier (Molecular Devices, Sunnyvale, CA). The internal solution contained: K-methanesulphonate 133 mM, KCl 7 mM, HEPES 10 mM, Mg-ATP 2 mM, Na2ATP 2 mM, Na2GTP 0.5 mM, EGTA 0.05 mM and biocytin 0.5%, pH 7.2, giving an estimated chloride reversal potential (ECl) of -69 mV. This allows excitatory synaptic currents to be observed in isolation by voltage clamping at −70 mV. Data were low-pass filtered at 6 kHz and acquired at 50 kHz using a Digidata interface and pClamp software (Molecular Devices). Offline box smoothing (up to 11 points) was applied for noise reduction. The animal was placed in a sound-attenuating light-proof box during the recording. Somatosensory stimulation was delivered using an air-puff (50 ms, 20–50 psi at source) timed by a Picospritzer and aimed at the ipsilateral whiskers, perioral skin or eye regions. Audible noise caused by the airpuff apparatus was carefully minimized and did not evoke cerebellar responses by itself. Auditory stimulation was delivered with a calibrated speaker driven by an RP2.1 processor and RPdvs software (Tucker-Davis Technologies, Alachua, FL). Gaussian white noise (up to 20 kHz) was presented for 350 ms with linear ramp rise and fall (5 ms). Visual stimulation was presented using two white LEDs (approximate intensity 200 mcd, one for each eye) each placed at 10 mm from the left or right eye. Each LED was light-shielded with a black cylinder, which also surrounds the eye, in order to deliver monocular stimulation. These LEDs diffusely illuminate a wide visual field because they are out of focus for the rat’s vision. In a subset of visual experiments, a computer screen placed at 12 cm from the animal head was used to deliver a wide-field visual presentation (from 10° contralateral to 60° ipsilateral) of full screen flickering from black to white (10 frames/s). The detection of EPSCs and action potentials was performed using a custom threshold-based algorithm programmed in Igor Pro (TaroTools: https://sites.google.com/site/tarotoolsregister/). The event number evoked by stimulation was counted (baseline-subtracted) in a time window adjusted for each cell to include all evoked events. Sensory responses were defined as positive when the post-stimulus histogram exceeded three times the standard deviation of the baseline. The synaptic charge was measured as the integral of the averaged current trace (baseline-subtracted and sign-reversed). Sensory response latency was defined as the time from the stimulus onset to the first EPSC event. In the analysis for Figure 3D, a granule cell that had an extremely large time difference (109 ms) between two unimodal responses compared to other cases (<35 ms) was excluded. Data are represented as mean ± s.e.m unless otherwise noted. Statistical significance was tested using the unpaired Student’s t-test unless otherwise noted. We are grateful to Charlotte Arlt, Beverley Clark, Dimitar Kostadinov, Arnd Roth, Greg Stuart and Christian Wilms for helpful discussions and for comments on the manuscript. We thank Toshihiko Momiyama for his support, Hysell Oviedo and Jennifer Linden for help with setting up auditory equipment and Arifa Naeem for technical assistance. This work was supported by grants from the Wellcome Trust and the Gatsby Charitable Foundation (to MH) and Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and grants from the Uehara Memorial Foundation and the Takeda Science Foundation (to TI). Proceedings of the National Academy of Sciences of the United States of America 112:13099–13104. The Journal of Physiology 202:437–470. The Journal of Physiology 494:231–250. Thank you for submitting your work entitled "Multimodal sensory integration in single cerebellar granule cells in vivo" for consideration by eLife. Your article has been reviewed by three peer reviewers, and the evaluation has been overseen by Eve Marder as the Senior Editor and Reviewing Editor. As you know, we usually provide a summary of the needed revisions, but instead I am providing you with the entire set of reviewer comments. The revisions needed are exclusively editorial, and many of them relatively minor, but it seems that the context provided by these full reviews will help you understand what is necessary for you to directly address. It has long been thought that cerebellar granule cells perform multimodal integration and that such integration represents an important step in cerebellar processing, however whether or not granule cells actually perform such integration has been debated until recently. An elegant anatomical study published in eLife provided clear evidence that individual granule cells in some cerebellar regions integrate mossy fiber input from different sources. A recent study (Chabrol et al.) provides clear evidence for multimodal integration in cerebellar granule cells using both anatomy and in vitro electrophysiology. Multimodal integration has also been shown in vivo in granule cells in a cerebellum-like structure in electric fish. The present study by Ishikawa et al. provides further support for multimodal integration in cerebellar granule cells using in vivo electrophysiological recordings. The central finding is that a subset of granule cells receive input about different sensory modalities and that in some cases these are conveyed by different mossy fibers (as indicated by distinct EPSC waveforms). This is a strong result with clear relevance to the field and provides in vivo physiological support for the results of Huang et al. (albeit in relation to different sets of inputs). The authors also make claims regarding the important functional question of how multimodal convergence affects spiking output and about the different possible functional connectivity patterns in granule cells (unimodal, multimodal input conveyed by a single anatomical input etc). These claims are less well supported. The analysis of spiking output involves only four neurons amongst which half were suppressed and the other half enhanced by multimodal stimulation. Discussion: …"Importantly, we show that granule cells represent a diverse population with respect to functional multisensory input, with some granule cells appearing to be unimodal, some with multisensory input delivered by separate mossy fibers, and some with multisensory input delivered by a single mossy fiber. These different anatomical and functional arrangements are illustrated schematically in Figure 3." I am not convinced that the authors have provided strong support for these claims. Some granule cells may be unimodal but the authors tested only a tiny fraction of the possible stimuli that could engage granule cells, so the appearance of unimodality does not count for much in my opinion. In the Results the authors say that for cases in which EPSCs don't differ significantly "it is not possible to determine if multimodal input arises from a single mossy fiber or from two mossy fibers that have indistinguishable characteristics." If this is true what is the support for the claim that some granule cells receive multisensory input delivered by a single mossy fiber? The statements made here need to be carefully qualified. While the present manuscript is clearly relevant to the Huang et al. paper, the relationship between the two including the similarities/differences and advantages/limitations of both approaches could be made more explicit. This seems to warrant a separate paragraph in Discussion. For example Huang et al. looked at integration of cuneate and pontine (sensory and motor inputs) while the present paper looks at convergence of various sensory inputs. Reviewer #2: In this manuscript, the authors accomplish the challenging task of making in vivo whole cell patch clamp recordings from cerebellar granule neurons in anesthetized rat. By doing so, they demonstrate conclusively that a subset of granule neurons can respond to two or more types of sensory stimulation (most frequently, auditory and somatosensory; 20% in the paraflocculus and14% in crus I & II). While this multisensory sensitivity is predicted from the anatomy, conflicting in vitro electrophysiological data make it important to demonstrate physiologically in an in vivo preparation. In fact, the result that the majority of cells were sensitive to just one modality (at least with the stimulus parameters tested) yet a significant minority were multisensory goes a long way toward resolving the discrepancy in the literature, although the authors (surprisingly?) don't emphasize this aspect of the work. The authors go on to show that in these multimodal cells, the EPSCs evoked by the two sensory stimuli applied together sum slightly sublinearly in voltage clamp, and evidence and reasoning are presented to suggest that this is indicative of upstream interactions in the two sensory pathways. The authors also demonstrate in current clamp that the sublinear EPSC summation can result in either more or fewer spikes than elicited by stimulation through a single modality, which is a useful additional piece of information, since it shows that multiple factors determine the nature of spike integration. The data are of high quality, and the manuscript is for the most part clearly written. It is hard not to wish for more manipulations, but given the technical difficulty of the recordings, it is not surprising that the work stops where it does. The manuscript seems well suited to eLife's description of a Research Advance, since the paper by Hantman and colleagues that precedes this study was anatomical, and the present work offers a (much needed) physiological confirmation. All my comments are stylistic. 1) Abstract: "These findings provide functional evidence for convergence of multimodal signals onto single granule cells." That is true but somehow this seems to go just beyond "providing evidence" for multimodal signals. The multimodal signals are actually measured. 2) Introduction, "Therefore, determining the extent to which multimodal convergence is functionally relevant in vivo requires direct recordings from single granule cells using sensory stimulation of different modalities." This sentence is likewise a bit oblique and off the point, as there is nothing about functional relevance here. Isn't the question that whether granule cells in the intact, functioning brain respond to multimodal inputs can only be assessed with direct in vivo measurements in the species of interest? 3) Please indicate species at the beginning of Results. 4) Suggestion if space permits: please give a hint in the results of why the sublinear summation might be interesting. On first reading, it seemed that non-linear summation of synaptic inputs would be expected, unless the idea was that the different modalities on the different dendrites would necessarily be so segregated that they would have to sum linearly. The Discussion cleared this up, but a little more extensive orienting of the reader earlier would be helpful. Reviewer #3: The manuscript describes powerful and straightforward measurements indicating that single cerebellar granule neurons receive multimodal sensory inputs; it also shows that such multimodal inputs are summed in a simple manner to generate spike output. These are striking results given that these neurons receive input from 3-5 mossy fiber presynaptic terminals. They are also important because they provide direct evidence for a hypothesized integrative role for granule cells in sensorimotor processing. In general the paper is clearly written and reports interesting findings that should be of interest to a general audience of neuroscientists. I have no substantive concerns and recommend that the paper be accepted with minimal revisions. Minor comment: The last sentence of the Introduction seems indirect. The authors might consider something like, "To determine whether multimodal convergence is common we made whole cell recordings in vivo from single granule cells and tested responsiveness to sensory stimulation of different modalities." "Importantly, we show that granule cells represent a diverse population with respect to functional multisensory input, with some granule cells appearing to be unimodal, some with multisensory input delivered by separate mossy fibers, and some with multisensory input delivered by a single mossy fiber. These different anatomical and functional arrangements are illustrated schematically in Figure 3." I am not convinced that the authors have provided strong support for these claims. Some granule cells may be unimodal but the authors tested only a tiny fraction of the possible stimuli that could engage granule cells, so the appearance of unimodality does not count for much in my opinion. In the Results the authors say that for cases in which EPSCs don't differ significantly "it is not possible to determine if multimodal input arises from a single mossy fiber or from two mossy fibers that have indistinguishable characteristics." If this is true what is the support for the claim that some granule cells receive multisensory input delivered by a single mossy fiber? The statements made here need to be carefully qualified. We agree that these conclusions are rather speculative. We have removed this section, and added a more carefully worded statement later in the Discussion. While the present manuscript is clearly relevant to the Huang et al. paper, the relationship between the two including the similarities/differences and advantages/limitations of both approaches could be made more explicit. This seems to warrant a separate paragraph in Discussion. For example Huang et al.looked at integration of cuneate and pontine (sensory and motor inputs) while the present paper looks at convergence of various sensory inputs. A separate paragraph has been added to the discussion as suggested. […] The manuscript seems well suited to eLife's description of a Research Advance, since the paper by Hantman and colleagues that precedes this study was anatomical, and the present work offers a (much needed) physiological confirmation. All my comments are stylistic. We are grateful for the positive assessment of our work. We have rephrased this to emphasize the actual measurement. This is a good suggestion – we have changed the last sentence of the introduction. This is an interesting suggestion, but such explanation would require significant description in the Results. Due to space limitations, we instead provide a pointer to the Discussion. The manuscript describes powerful and straightforward measurements indicating that single cerebellar granule neurons receive multimodal sensory inputs; it also shows that such multimodal inputs are summed in a simple manner to generate spike output. These are striking results given that these neurons receive input from 3-5 mossy fiber presynaptic terminals. They are also important because they provide direct evidence for a hypothesized integrative role for granule cells in sensorimotor processing. In general the paper is clearly written and reports interesting findings that should be of interest to a general audience of neuroscientists. I have no substantive concerns and recommend that the paper be accepted with minimal revisions. The last sentence of the Introduction seems indirect. The authors might consider something like, "To determine whether multimodal convergence is common we made whole cell recordings in vivo from single granule cells and tested responsiveness to sensory stimulation of different modalities." This is a great suggestion – we have adopted this almost verbatim. Animal experimentation: This study was performed in strict accordance with UK Home Office regulations and under approval and supervision of the Animal Experiment Committee of Jikei University. Experiments were carried out under Project Licence 70/7833 issued by the Home Office, which was issued following local ethical review, and under the relevant Personal Licences issued by the Home Office. All surgery was performed under ketamine/xylazine anesthesia, and every effort was made to minimize suffering. © 2015, Ishikawa et al.
0.982412	I want to calculate the net paying customers for each line of business for each month and for both the months put together: Basically, i want to calculate the total revenue for each LOB for the time period I'm interested in and then count(#customers with >0 total revenue) - count(#customers with <0 total revenue). More detail is available in the SQL queries at the bottom of this post. Let me explain my April + May numbers better. The total book revenue for User ID 1 is 6 during this period. Total Book revenue for User ID 2 is -1. I summed up the revenues in April and May here. As a result, the #Net paying customers = 1 (since User_id 1 has >0 revenue and we don't care about customers with revenue = 0). Similarly, User ID 1 has -1 net revenue in April + May. User ID 2 has +1 net revenue in April + May. As a result, #Net Paying customers = 1 (paying customer) - 1 (refund customer) = 0. Any help on this would be appreciated!! I've attached my current workbook and my efforts on this so far can be seen here. I'm not sure if I follow the expected output. Shouldn't book_rev for April + May be 1, not 0? user_id 1 showed revenue for both months. I've attached a workbook that might help the conversation get started... but if I've not understood the issue, you will want to follow Shawn's advice and post a packaged (twbx) workbook -- not a twb. Thanks for having a look at my post! I've attached my packaged workbook to this post. Let me know if this doesn't work for you. The total book revenue for User ID 1 is 6 during this period. Total Book revenue for User ID 2 is -1. I summed up the revenues in April and May here. As a result, the #Net paying customers = 1 (since User_id 1 has >0 revenue). Similarly, User ID 1 has -1 net revenue in April + May. User ID 2 has +1 net revenue in April + May. As a result, #Net Paying customers = 1 (paying customer) - 1 (refund customer) = 0. That makes sense now. I worked on this a bit and came up with a solution using sets (to determine whether the user is net paying/refund overall) and a custom grand total trick (see the blog posts starting with Part 1: Customizing Grand Totals – Part 1 \| Drawing with Numbers). I haven't included a lot of documentation, but I'd be happy to provide any explanation as needed! That sounds great!! However, I use Tableau 7 and it looks like you use Tableau 8. Is it possible to do the same thing in Tableau 7? If you're not sure, can you help me provide more explanation as to what you did here? Also, just to clarify: user_id cannot be a field in the tableau table. If your solution doesn't need to do this and can work in Tableau 7, it will definitely work for me! If it doesn't, I can still go back to my stakeholders and explain when and why this can't be done. This is helpful in any case. Ah! Well... how soon until you upgrade? I don't believe my approach will be possible in 7 as sets weren't really robust until 8. I'll have to give it some more thought to see if there is a good approach for 7. I had originally started down a table calculation rout and may return to that. Another possibility that might be much simpler would be to create two views. One by month and then another for the combined months. Then combine the two views in a dashboard. I'll try to get to that soon as well. But in the meantime, maybe there are some others in the community who'd like to take a swing at it? Swathi also requested assistance via Support so I am adding the solution provided by Support to this thread as this uses a Tableau version 7 workbook, calculated fields and a couple of Table Calculations to arrive at the same outcome. We create a calculated field that set the value to 1 or -1 depending on the sum of Revenue for each product line. We then Window_Sum that value to arrive at the totals across Months. User ID is left on the Level of detail since this field is used for each table calculation function in the view.
0.999998	What are the characteristics of 'normal' skin? Face Wash - dampen the face with luke warm water, lather a small amount in your hand and gently massage the face to remove dirt and makeup, then rinse with luke warm water. Gentle Peeling - to exfoliate dull surface cells and give skin a healthy glow. Use light circular movements to massage into damp skin and rinse off with luke warm water. Avoid eye area, surface blood vessels and active spots. 1-2 times per week. Clay Mask - for a deep cleanse to relax, balance and soften the skin. Apply thin layer and let it work for about 15 minutes and then rinse off with lukewarm water. Once per week.
0.991347	The LPGA Championship, currently known for sponsorship reasons as the LPGA Championship presented by Wegmans, is the second-longest running tournament in the history of the Ladies Professional Golf Association surpassed only by the U.S. Women's Open. It is one of four majors on the LPGA tour, but is not recognized as a major by the Ladies European Tour. With a purse exceeding $2 million, the winner of this tournament automatically qualifies for the season-ending LPGA Tour Championship. Prior to 2005, the LPGA Championship had a professionals only rule. This is in contrast to events such as the U.S. and British Opens, which have long had both amateur and professional entrants. The LPGA Championship is the LPGA's own event, and the LPGA was created specifically to provide opportunities for women in professional golf. In 2005 this rule was revoked, effectively to allow then-amateur Michelle Wie to compete in order to attract more media coverage and sell more tickets, though this was not publicly acknowledged by the LPGA. Some professionals objected to this move as they felt that places given to amateurs would come at the expense of the LPGA Tour's less successful professionals, who need to play regularly to make a living. One of the leading professionals, Laura Davies, stated objections to the change were shortsighted. In 2006, the LPGA Championship reverted to its professionals-only status, with only professionals in the field. Michelle Wie participated that year as a professional, having turned pro the previous October upon signing multi-million dollar endorsement contracts with Nike , Sony and other sponsors. This table lists the golfers who have won more than one LPGA Championship.
0.999568	i have made a 3v tesla coil,, please tell me how to ground the end of the secondary coil? According to an experienced Tesla builder I was speaking to about three weeks ago, you hammer a metal pole into the actual ground and connect a cable to that - using a domestic power-supply ground can cause unexpected, potentially dangerous or destructive, side effects. It goes to chassis ground. Here's an example https://www.instructables.com/id/How-to-build-a-Tesla-Coil/ so the metal on your grounded power supply will work.
0.999481	While booking a luxury cabin rental in the Smoky Mountains, I do recommend visiting the Biltmore Estate in Asheville, North Carolina. You can be there in a little over an hour. The Biltmore estate was built by the Vanderbilts in the 19th Century. It is truly a remarkable home with incredible gardens, wonderful dining, & intriguing American history. Feel free to plan your lodging in Gatlinburg or Pigeon Forge, while spending one day in Asheville at Biltmore. You'll want to stay in the Smoky Mountains because most of your other itenary will be completed in Gatlinburg or Pigeon Forge. Your family will want to travel to the Smoky Mountain National Park, Aquarium of the Smokies, Ober Gatlinburg, Dollywood, et cetera. Completed in 1895, George Vanderbilt's 250-room French château is a real life wonder. Enjoy a self-guided visit of Biltmore House that unveils a fresh look at how people lived and worked in America’s largest home. Also, explore the acres of beautiful gardens and grounds, designed by renowned landscape architect Frederick Law Olmsted, during your visit.
0.977274	From the “File” menu, choose “Place”. Select the AI file that will be imported. If the “Link” checkbox is checked, then uncheck this option. Click “Place” to import the file. Scale the template by 200%, and the finished the design at 1,000% for a combined scaling of 2,000%. This gives us an 1 inch = ten inches ratio when designing. Scale the template by 166.666%, and then output the finished design at 1,200% for a combined scaling of 2,000%. This gives us a 1 inch = 1 foot ratio when designing. Always measure the vehicle and check those measurements before printing your artwork.
0.999978	The best of watermelon can you consume in the summer. Summer is the best quality of watermelon because it is such kind of crunchy and quenching fruit. This fruit contains so many sources of vitamin as like vitamin A, vitamin B, thiamin, potassium, magnesium, and beta carotene. The red color means that this fruit contains anti-oxidant lycopene. Lycopene is able to reduce the heart disease risk for preventing cholesterol oxidation to deposit on the artery wall. So, benefits of watermelon are able to reduce the risk of getting prostate cancer, color cancer, and asthma.
0.985791	Literature Cited CA Hwy 127 is the southern gateway to Death Valley. Junction: Nevada Highway 373, north to US Highway 95 in Amargosa Valley. Junction: California Highway 190, west to Death Valley. Is this a landslide? Every time I drive by this canyon at the very southeastern tip of the Funeral Mountains, I wonder whether it might be a landslide. Of course, I'll also have to confess that I've not been sufficiently curious that I went to any effort to go look at it. Southeastern tip of the Funeral Mountains. Funeral mountains to the north. - Bradley, Dwight, LeeAnn Munk, Hillary Jochens, Scott Hynek, and Keigh Labay, 2013. - Pacific Imperial Mines, Inc., 2011. To the east is the Eagle Mountain Salina, not a name recognized by the GNIS. This salina has been prospected for lithium brines and claimed by Pacific Imperial Mines, Inc. (Pacific Imperial Mines, Inc., 2011). There is some concern that mining on this salina, specifically pumping of subsurface brines might affect the water table in Ash Meadows and further imperil the pupfish. Other articles: CA Hwy 178 near Shoshone Junction: California Highway 178, west over Salsberry Pass and Jubilee Pass to southern Death Valley. Nighthawks in Shoshone. On this warm May evening, there were nighthawks flying over the lights of the motel parking lot. Downtown Shoshone in the early morning. Other articles: CA Hwy 178 near Shoshone Junction: California Highway 178, east to Pahrump Nevada. Other articles: Furnace Creek Wash Road at CA Hwy 127 Junction: Furnace Creek Wash Road, northwest to Greenwater Valley. Other articles: Furnace Creek Road at CA Hwy 127 Junction: Furnace Creek Road, southeast to Tecopa. Highway 127 skirts Tecopa Valley. To the east you can see the town of Tecopa. You can read about the geology of Tecopa Valley in Geophysical constraints on the cessation of extension and thickness of basin fill in Tecopa Valley, California. Locations: Ibex Hills. Ibex Pass. Sperry Hills. Sperry Hills on the east; Ibex Hills on the west. Looking north toward the Ibex Hills and Ibex Pass from the Amargosa River. Locations: Amargosa River. Amargosa River. The Amargosa River where it crosses California Highway 127. Other articles: Harry Wade Road 18000 Junction: Harry Wade Road, west turning north into Death Valley. Locations: Avawatz Mountains. Avawatz Mountains to the southwest. Locations: Salt Creek. Salt Spring Hills. Salt Creek, looking upstream, to the southeast. Other articles: Eastern Mojave Geology Engel and Sharp (1958) In one of the early studies on desert varnish, Engel and Sharp (1958) performed wet chemical analyses on varnish, the underlying weathered rind, and fresh rock from ten locations in southeast California. One of the locations was near Salt Spring (sic), on a steep bedrock slope facing east about 300 yards west of the highway in the NW 1/4 of Sec. 32, T. 18 N., R. 7 E., at elevation 630 feet (Avawatz Pass quadrangle). Engel and Sharp found that (1) varnish on stones seated in soil or colluvium is derived largely from that material, (2) varnish on large bedrock esposures come from weathered parts of the rock, (3) air-borne material is probably a minor contributor. Silurian Hills in the late afternoon. Lower spillway from Silver Lake, with Avawatz Mountains in distance. Dave Miller leads field discussion of the outlet of Lake Mojave and the tectonics of the Silurian Valley and Avawatz Mountains. - Miller, David M., 2005. - Ore, H. Thomas, and Claude N. Warren, 1971. - Owen, Lewis A., et al., 2007. Lake Mojave, the name given to a large lake filling the present day Soda and Silver Lakes, overflowed at hills on the north side of Silver Lake, cascading down a narrow channel and thence to Death Valley. Full Lake Mojave and associated overflow to Death Valley occurred between 19 and 17 ka, and episodically from 14 to 9 ka. Since that time, there has been no fluvial communication between the Mojave River and points lower than Silver Lake, but episodic flow of the Mojave River from the San Bernardino Mountains to Silver Lake occurs regularly, including Winter 2005 (Miller, 2005). Foundations at Silver Lake (site). Silver Lake to Goodsprings, by way of Francis Spring and Ripley (present-day Sandy). Silver Lake to Nipton, by way of Halloran Spring and Valley Wells (through present-day Mountain Pass). Junction: Halloran Springs Road, east through the Halloran Hills to Halloran Springs at US Interstate 15. View west across Silver Lake from Silver Lake. Avawatz Mountains from CA Highway 127. View of the Avawatz Mountains to the northwest across Silver Lake. Kelbaker Road, south to Kelso, U. S. Interstate 40. U. S. Interstate 15, west to Los Angeles, east to Las Vegas. Bradley, Dwight, LeeAnn Munk, Hillary Jochens, Scott Hynek, and Keigh Labay. 2013. A Preliminary Deposit Model for Lithium Brines. U. S. Geological Survey Open-File Report 2013-1006. Owen, Lewis A., et al. 2007. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa. Quaternary International. 166(1):87-110.
0.99964	The coolest coding language to learn for the first time beginners is Python. Python is open source and free to use, even for commercial applications. It is usually referred to as a scripting language, allowing programmers to create out large numbers of easily readable and functional code in short periods of time. It’s also dynamic, and supports object-oriented, procedural, and functional programming styles, among others. Python is one of the most widely used high-level programming languages today. Ruby is simple, readable and for people who don’t have any kind of programming experience. Ruby is a dynamic, object-oriented scripting language that is used in the development of websites and mobile apps. It is the language that powers their framework, Ruby on Rails, which is behind websites such as Twitter, Groupon and GitHub. It is also mostly used for backend development, and popular sites such as Airbnb, Shopify, Bloomberg, Hulu, and Slideshare. It is easy to learn with a helpful 20 minute quick start guide on the official Ruby website. There are a lot of documentation available as well as great resources that will help you to understand Ruby from the very beginning. Java is one of the most popular and general purpose programming language in the world. It is a class-based, object-oriented language and designed to be portable, which means that you can find it on all platforms, operating systems and devices. Java is usually used to build Android apps, desktop apps, and video games. It is also commonly used as a server-side language for enterprise-level backend development. In addition, it adds to the capabilities of the C++ language. So, if you already have knowledge of C++, it will help with learning Java. C is often used to program system software and is the lingua franca of Operating Systems. C has influenced almost all programming languages, especially C++. So, if you know C well, you would probably have less difficulty picking up other popular languages. On the other hand, C++ is a powerful language based on C, which has added object-oriented features like classes to the language, along with virtual functions and templates. C++ is another of the world’s most popular programming languages and is designed for programming systems software. It is still widely used to build games/game engines, desktop apps, mobile apps, and web apps. C++ is powerful and fast, which has been used to build software such as Adobe Systems, Amazon, Paypal, Chrome, and more. Much like C, C++ is generally considered harder for beginners to learn on their own.
0.999999	How to say "Don't be so reserved" in Russian? 1. Не будь таким замкнутым.
0.999961	Lace running shoe Saucony is among the most respected names in running shoes. They offer a wide range of running and walking shoes, each with the Saucony trademark fit, feel, and performance. They've spent years studying the biomechanics of top athletes because the goal is to develop creatively engineered systems that maximize your performance, allowing you to focus on the activity instead of the equipment. From studies have come many innovative Saucony concepts. Advanced technologies like Grid, the first sole-based stability and cushioning system, provide an advantage to athletes of all types.
0.980429	During the Cold War, the Americans and the Soviets were relentless in their efforts to outdo each other. As a part of this effort, the CIA ran many experiments, some very pragmatic, others fanciful and in the realms of science fiction. Operation Acoustic Kitty was one such experiment. Let us learn how and why this project was conducted, and whether it was successful or not. According to a few media reports, the Iranian police department caught 14 squirrels in 2007, that were suspected of being spies. Allegedly, the foreign intelligence services found that the squirrels were attached with eavesdropping equipment. However a source from the Iran Foreign Office refuted these stories, by calling them completely bogus. The practice of using animals for espionage has been going on for years, and numerous fascinating tales about the ingenuity and partnership between man and animal can be found in the Revolutionary War, the Civil War, the World Wars, etc. At the height of the Cold War, around the time of the Cuban Missile Crisis, the United States of America was on edge, and was constantly on the look for an opportunity to get the upper hand over the Soviets. The Central Intelligence Agency (CIA) in particular was looking at all possible avenues of information gathering, including creating spy planes and satellites, and using psychics and clairvoyants to view Russian secrets and attempting mind control. Another bizarre project also aimed to turn cats into spies. Some imaginative people in the CIA reasoned that the Soviets would never suspect ordinary cats to be U.S. Agents. Also, the animal's natural stealth and agility made it a good potential spy. So, implanting the animal with audio receivers and transmitters, seemed like a good idea for getting close to the Soviet operatives and eavesdropping on them. Despite being skeptical of this plan, the project got the go ahead. The details of the operation were revealed in some declassified, but partially redacted, documents released in 2001, after the National Security Archives put in a Freedom of Information Act request. How Was Operation Acoustic Kitty Conducted? CIA's Acoustic Kitty Project was not a very easy project, and it took around 5 years to come to fruition. The technicians at the CIA had to make sure, that any implants designed by them did not interfere with the natural movements of the cat, so as to avoid suspicion from the enemy. The devices also had to be comfortable to the cat, so that the animals would not try to dislodge the equipment. The task was difficult, as the cats had to be installed with a microphone, a transmitter, an antenna, and a power source, that could handle the internal biological processes of the animal. Creating these technologies was estimated to have cost over USD 10 million. For the first test subject, an adult female, gray and white cat was chosen. The surgery to make the cat a super spy involved placing the microphone into the ear canal, and embedding a ¾-inch long antenna into the base of skull, which was wired through the fur along the spine, all the way to the tail. A small transmitter and set of batteries were embedded into the chest cavity of the cat. The setup was designed so that the cat could be directed by the use of ultrasonic sound. After managing to somehow survive this surgery, the feline was now ready for further testing. Once the surgery was completed and the cat woke up from the influence of anesthesia. The handlers tried to run the animal through test scenarios, all the while monitoring how the cat was reacting to the new additions to its body. However, they found this task very arduous, as cats are naturally averse to any kind of training, and they aren't interested in the security of the nation either. The test animal would constantly get bored, distracted, or hungry and run off. To counter this behavior, another surgery was conducted and additional training was provided. This extra effort is estimated to have shot the expenses up to USD 20 million. However, there were signs of success, as the handlers had a certain amount of control over the cat's actions. It was time for the first real-world field test. In the test, the cat was taken to the Soviet compound in a CIA reconnaissance van. The van parked across the street from the two men, who were the targets for this test. The cat was let out of the van, and the men waited with bated breath as the cat started to cross the road. However, as soon as it took the first few steps, the cat was hit and killed by a passing taxi cab. The project had ended, before it had even begun. The CIA agents collected the corpse, as they did not want the Soviets to find the audio equipment. Reasoning that using any agent which was so difficult to train and control as a bad idea, Project Acoustic Kitty was declared a complete failure and abandoned in 1967. The declassified documents, however, praised the work of the team, calling them 'scientific pioneers' for proving that cats can actually be trained to move according to instructions for short distances. During the Second World War, it was proposed to use pigeons to guide missiles towards their targets. The process involved putting the birds inside the missile and allowing it to peck on a video screen to direct the missile towards the intended target. The idea was scrapped because officials felt that the idea was just too ridiculous. During the 1960s, the U.S. military started training dolphins to detect naval mines and enemy swimmers and divers. Such aquatic agents are used even today. The CIA also trained ravens to drop listening devices in very specific locations. The U.S. army trained pigeons to fly ahead of the troops, and land if they spotted the enemy, acting as a warning. However, if the birds did not spot anything they kept flying and never returned. Honeybees are now being trained to detect the scent of bomb ingredients. When detecting such scents, the bees move their proboscis in unison, and a pattern recognition software alerts the authorities to the bees' actions. Gerbils were used by the United Kingdom to find terrorists at airports, by detecting high levels of adrenalin in a person. However, the project was abandoned after the animals got confused and reacted to regular passengers who were just afraid of flying. Homing pigeons were widely used by American and British forces during World War II to transport messages, maps, and reconnaissance photographs. In fact, many of these birds were given awards to honor their valor during the war. Similar to the dolphins, sea lions were also trained by the U.S. Navy to cuff suspicious divers and swimmers. Although, not successfully used, the U.S. military strapped small bombs to bats and planned to use them as an attack option in World War II. Although the Acoustic Kitty Project was a bust, it has inspired and lead to many animal-based inventions, such as insect-based flying surveillance drones, to pave the way of the future of international espionage.
0.954656	Have you come across a car that seemed like it was painted like a wall mural? Chances are they’re not actually painted, but covered with a vinyl wrap. Vinyl wraps are covers with graphics drawn on them that can be put on surfaces of vehicles. These can be put on walls and boats, as well. Vinyl wraps on cars are dependent on the desired graphics of the customer. This could be as simple as having a single color, like red or green, wrapped on the car. Some may prefer more detailed art, such as those with symbols or words on it. You can use vinyl wraps for a food truck’s logo and menu, for delivery trucks and their hotline numbers, and many more. Even boats can benefit from graphics made through vinyl wraps. The material for boats and jet skis are designed to withstand constant water exposure, and they work the same way as car wraps. Offices who need their company logos or brand decorated on the walls can commission a vinyl wrap company to create a wall mural for them. The graphics to be installed could range from a set of words like company slogans and policies to one with pictures of the company and their clients. Depending on your preferences, the design could run from serious to whimsical. As you can put pictures and words on vinyl wraps, both land and water vehicles can be used as an advertising tool because wherever they go, onlookers will be exposed to whatever design is on them.
0.998071	Why should a testing application use a custom terminal emulator compared to simulating the users' interactions or using a telnet emulator such as Putty? Cycle’s custom terminal emulator allows for much more robust and dynamic testing of terminal emulators by reducing the level of effort required creating the test scripts. Cycle allows users to interact with the terminal emulator in ways that would not be possible when using Putty, such as determining if text is located on the screen or where the cursor is located, copying text from the emulator for use in Feature Files, and running many terminal emulators from the same Cycle instance.
0.998488	The company had struggled financially from the beginning. But, under the leadership of the new president, the small business was thriving. The company was out of the red and into the black. The wages and benefits of all the employees had increased significantly. Everyone was excited about the future potential. As a result of the success, a decision regarding the direction of the company came to the forefront. Did the company expand to a new and uncharted market or continue to grow and build an even stronger financial foundation? Because of the recent volatility of the local economy, the president believed building a stronger foundation at least for the present was the best option. In contrast, one of the managers thought expanding the company in a new, exciting direction was the best direction. Instead of talking directly to the president in the group discussions, the manger made the decision to talk despairingly to the other managers about the leadership of the president. Triangles occur in relationships when person A has a conflict with person B and chooses to talk with person C rather than person B. What often motivates person A to talk to person C is the attempt by person A to manage his or her own emotional comfort. Person A’s conflict is with person B, not with person C. So it is much more emotionally comfortable for person A to speak with person C. As mentioned, person A’s conflict is with person B. Speaking with person C does not help toward resolving person A’s conflict with person B. The focus of person A going to person C is typically on viewing person B as being the problem. Consequently, person A does not really have to look at their contribution to the conflict. Focusing on the other person as the problem can be a way of distracting oneself from the discomfort of seeing his or her own contribution to the conflict. Since comfort is the primary motivation in triangles, person A involving person C focusing on person B, person A has accomplished the goal of managing his or her comfort level. It is too easy for person A when speaking to person C about person B to put themselves in a good light and person B in a negative light. This is usually a distortion. Though individuals may respond differently to conflict, each person generally has a part. When putting person B in a negative light person A is asking person C to accept the notion that person A is the better person than person B. Person A is asking person C to side with him or her against person B. This is destructive to relationships. Person A’s request to talk with person C about person B puts person C in a very awkward position. When person A comes to person C and complains about person B, this creates an implicit threat that if person C doesn’t agree with person A, person A could go speak with person D about person C. Typically, when person A goes to person C, person A presents a compelling case to person C about person B. So much so, that it may be difficult to disagree with or go against. Even if person C may know different they may not want to experience the discomfort of their own conflict with person A. One of the common reasons for person A to talk with person C is to solicit support and validation for their own behavior or perspective. By establishing an alliance with person C against person B, person A has created a gulf between all parties involved and has destroyed trust within the group or organization. Again, person A will likely not learn much about their contribution from the conflict with person B. In addition, by going to person C about their conflict with person B, person A has created additional conflict for himself or herself with person C. The motivation for person A to speak with person C instead of person B is usually personal comfort instead of personal growth. Personal grow usually is the result of some discomfort. When person A speaks with person C about person B, it creates a culture of fear and mistrust. It could be helpful if person A was genuinely asking person C for insight into his or her own behavior or perspective. Before you initiate a triangle or are being asked to participate in one, stop and think about what you really want for yourself and your relationships. The choices you make in response to conflict in your relationships matter and always have consequences. Triangles create division among community. They create a culture of distrust and fear. They are ways individuals hide from there own fears and fail to take responsibility for what they are responding to inside themselves. In contrast, if you go directly to the person you have a conflict with there is a chance for both of you to grow in your understanding of yourselves and each other. There is potential that you may have more in common than you realize. © 2018 Larry S Barber \| All rights reserved.
0.951095	Hyrule is first seen in The Legend of Zelda as the magical kingdom that serves as the setting for the adventures of a young boy named Link in his quest to save Hyrule's young princess, Zelda, from the clutches of the evil sorcerer Ganon. In this game, Hyrule is described as a beautiful kingdom with deep forests and tall mountains bordering a vast ocean to its southern and eastern borders. As Link explores the kingdom, he visits all the different parts of it, including the Lost Woods to the west-southwest, the Graveyard in the shadow of Death Mountain to the northwest, the coastline to the southeastern and eastern borders of the kingdom and even the strange forests in the southeastern region of the country. In this original incarnation of Hyrule, the land is shown to have many forests and lakes in addition to the mountainous terrain of Death Mountain. This would mark the gaming world's first experience in the land of Hyrule and began several long traditions that would continue to be featured in later incarnations of the kingdom and would be vastly expanded upon and improved by the game developers. Hyrule Historia claims that this land is not exactly Hyrule, but a place called Lesser Hyrule, which could very well be the remains of the once-great kingdom. The expanded Hyrule overworld featured in The Adventure of Link. The second appearance of Hyrule was in The Adventure of Link; as the game progresses it is revealed that the overworld featured in The Legend of Zelda is only a small sector of The Adventure of Link's grand landscape, dwarfing it in size. Because this title features three major continents separated by large straits of water, and seven unique towns and settlements, this incarnation of Hyrule is one entirely unique to The Adventure of Link. The original Hyrule overworld, featured in The Legend of Zelda is still explorable, but it is a tiny landmass south of Death Mountain. Hyrule borders a vast ocean; the landscape is much more varied with swamps, mountains, a graveyard, deserts and islands, in comparison to The Legend of Zelda. The hero also visits several towns that would later provide the namesakes of some very important characters in Ocarina of Time. This game would also mark the first use of dungeons and palaces as a plot device in Hyrule, a formula that would come to be used time and again in future games. In this game, Link traverses Hyrule to restore six magical crystals to their proper places within six other individual palaces in order to break the seal on the Great Palace and awaken Zelda with the completed Triforce. A Link to the Past marked the first appearances of such major landmarks as Lake Hylia, Zora's Waterfall, Hyrule Castle, and Kakariko Village. The mirror of Hyrule, the Dark World, was also made explorable and marks the only time that the Sacred Realm could be explored in any form. The Dark World appeared to be what Hyrule would be like if it were ruled by Ganon. The two worlds were closely linked, and what happened in one would even affect its twin in the other. This version of Hyrule began many of the more recurring elements of the kingdom, such as Hyrule Castle being the home of the Royal Family and the Lost Woods being the home of the Master Sword. This template of Hyrule would also be heavily replicated in future games as well. Ocarina of Time marks the first time the kingdom of Hyrule was represented in three dimensions. Familiar locations like Death Mountain and Lake Hylia returned, along with new locations such as Gerudo Valley, Lon Lon Ranch, and the Kokiri Forest. The geography of the land was rearranged, making Hyrule Field a central hub area between most of the major locations. Four Swords features yet another incarnation of Hyrule that contrasts with previous versions of the kingdom. Several locations appear in the game that have not yet appeared in any other, such as the Sea of Trees, the Chambers of Insight, and Talus Cave. Death Mountain makes a reappearance as one of the few recurring places that appears in this version of Hyrule. There is also a region above the clouds, where Vaati's Palace resides floating high above the land. The Wind Waker features a new incarnation of Hyrule, though it is sealed away beneath the Great Sea. This is the direct result of the Great Flood that occured as a product of the Goddesses in a timeline of events that occured before The Wind Waker; the survivors of the flood built a new country on the surface, where the highest mountains of Hyrule became islands. In terms of differences with other incarnations, Hyrule Castle now rests on an island in the middle of a large lake, fueled by a large river. On Hyrule's horizon, large, tall mountains exist; these help explain the existence of islands on the surface of the Great Sea. Ganon's Tower is located beyond a grand canyon leading into one of the kingdom-surrounding mountain ranges, not far from Hyrule Castle. Hyrule still retains a state of regality, despite its desertion and isolation on the seabed. The version of Hyrule featured in Four Swords Adventures shares many landmarks with the version of Hyrule featured in A Link to the Past. The Eastern Palace, Desert Palace, and what is suspected to be the Tower of Hera (the Tower of Flames) are in the same locations, as is Kakariko Village. Hyrule Castle also rests in a similar location to its A Link to the Past counterpart, at the very center of the kingdom, although this incarnation of the castle more strongly resembles the one featured in The Wind Waker. However, some locations have shifted as well. Lake Hylia is now in the northeast, and locations not featured in A Link to the Past are present, such as the Village of the Blue Maiden and Lon Lon Ranch. The southern part of the map is frozen due to Vaati's evil magic. The Dark World is again present, both as the northwestern portion of Hyrule and the base of Ganon's power, and as an actual mirror universe. Most of the Hyrulean races that were introduced in Ocarina of Time return in this game. The Gorons live on Death Mountain, the Deku Scrubs live in the Lost Woods, and the Gerudo live in the Desert of Doubt. A new race, the Zuna, are also introduced. The Zuna are a tribe of green-skinned desert nomads who are descended from the ancient Pyramid builders. Another major difference in this incarnation of Hyrule when compared to others is that a large ocean borders the entire continent upon which Hyrule rests. The geography of Hyrule presented in The Minish Cap introduces new locations such as the wild marshlands of Castor Wilds, the rocky Mount Crenel, and the eerie Royal Valley, while such common landmarks as Death Mountain and Kakariko Village are absent. Hyrule Field is divided into sectors, and locations such as Lon Lon Ranch and Hyrule Town (a different incarnation of Hyrule Castle Town) serve as major populated areas. Another recurring locale is the classic home of the Royal Family, Hyrule Castle, which sits to Hyrule Field's northern borders and plays a pivotal role in the progression of the game. Many areas can only be explored while Link is small, such as Melari's Mines or the Minish Village in the Minish Woods. A large part of the map is also covered in clouds and is known as the Cloud Tops. This is the home of the Wind Tribe and the location of the Palace of Winds. There is some continuity with locations from the rest of the Four Swords trilogy, as this game likely shows the palace before Vaati began using it as his residence, in addition to the Tower of Winds, which is revealed to have begun as the home of the Wind Tribe in this game. The Hyrule appearing in Twilight Princess is much larger than in previous games. The government is centralized in Castle Town, and Kakariko Village again appears at the base of Death Mountain. A sign at the entrance to the Hidden Village identifies it as "Old Kakariko," indicating that the Kakariko Village appearing in Twilight Princess may perhaps be the same one seen in Ocarina of Time. Hyrule Field is larger and again divided into sectors like it was in The Minish Cap. The kingdom appears to have a more developed system of roads, with fortified bridges like the Bridge of Eldin and the Great Bridge of Hylia guarding the roads. New locations such as Snowpeak and Ordon Village also appear for the first time. The Temple of Time reappears in this game, but has shifted locations. It is no longer in the main Castle Town as it was in Ocarina of Time, but its ruins are instead in the Sacred Grove, alongside the ruins of what appears to have been a city. This draws parallels with the Master Sword's location in A Link to the Past. This game also introduces the concept of Hyrule being divided into a province system, composed of Desert, Ordona, Peak, Faron, Eldin, and Lanayru provinces. Spirit Tracks is unique in that it features a distinct new land named after Hyrule. New Hyrule, as the land is named, features a unique and complex railroad system that was born out of the war with the Demon King Malladus. Its most notable features are the titular Spirit Tracks that span four directions all across the land and the Tower of Spirits at the center of the kingdom. These special tracks, the tower, and the four temples connected to the tower by the tracks, serve as the means as a lock, by which Malladus is kept bound in his prison deep beneath Hyrule. The re-established land of Hyrule features five realms: Forest, Snow, Ocean, Fire, and Sand. Each realm is different in climate, landforms, inhabitants, and culture. The Forest Realm is located in the southwest corner of "New Hyrule" and is a heavily forested area, but also features vast plains on its eastern side. The realm is home to most of the kingdom's Hylian population, who reside in the various settlements scattered around the Forest Realm. The capital of Hyrule, Castle Town, lies in the northern extreme of the realm. Other settlements include the lumberjack town of Whittleton, Aboda Village, the Trading Post, which is the home of the Linebeck Trading Company; Rabbitland Rescue, and the Forest Sanctuary. The Forest Temple, located deep within the realm's forests, provides power to the Spirit Tracks, and through the tracks the Tower of Spirits. The Snow Realm is located in the northwest corner of the kingdom and is covered with a blanket of snow which provides a suitable habitat for the conifer forests in the realm. The Anoukis, a race that migrated to the re-established land of Hyrule from their homeland of the Isle of Frost are also found in the realm, living in the Anouki Village. The realm also holds a number of stations including the Snow Sanctuary, Bridge Worker's Home, Wellspring Station, the Snowdrift Station, and the Slippery Station. At the northern end of the realm past a vast icy plain, where the Snow Temple is found. This temple possesses the same function as the Forest Temple. The Ocean Realm is located in the southeast part of Hyrule and is a vast large ocean, dotted with small islands and flourishing with sea life. A group of Hylians who make their living off of fish live in the small coastal village by the name of Papuchia Village. However, the citizens of the realm have been having trouble with the local gang of pirates residing at the Pirate Hideout. Other stations found in the realm include the Ocean Sanctuary and the Lost at Sea Station. Found deep within the depths of the ocean is the Ocean Temple, which powers the tracks leading to the Tower of Spirits. The Fire Realm is located in the northeastern corner of the kingdom, and comprises a large number of volcanoes, lava lakes, rocky mountains, and underground tunnels. The Gorons reside throughout the realm living in the Goron Village/Fire Sanctuary, Dark Ore Mine, and the Goron Target Range. At the top of the large Mountain of Fire in the center of the Fire Realm is the Fire Temple. This temple is source of the Force Gem that powers the realm's Spirit Tracks leading to the Tower of Spirits, but it also the source of the evil causing the violent volcanic eruptions troubling the inhabitants of the realm. The Sand Realm is located in the eastern part of Hyrule, between the Ocean and Fire Realms. It is a desolate, arid region with few inhabitants other than Malgyorgs. Its only stations are the Sand Sanctuary and the Sand Temple, a fortress built to guard the sacred Bow of Light. It is home to the Three Trials, a test of the worth of anyone who wishes to possess this powerful holy weapon. In Skyward Sword, Hyrule is known as the Surface for much of the game, and was also named Grooseland by Groose. Many enemies roam the land, as the armies of Demise. Link descends to Hyrule from Skyloft with the help of the Goddess Sword, and continues to travel back and forth between his homeland and the land below using Bird Statues. The surface is divided into three provinces, with names corresponding to their Twilight Princess counterparts. The woodlands in the Faron Province is the home of the Kikwi race and contains the Sealed Grounds, the Skyview Temple, and Lake Floria, home of the Water Dragon. Eldin Province is the northernmost province, inhabited by the Mogmas and home to the Earth Temple and Fire Sanctuary. Death Mountain does not appear by name in the game; its role is played by Eldin Volcano, which is generally believed to be the same location. Lanayru Province is a desert region in the far west, containing the Temple of Time, Lanayru Mining Facility, and the Sandship. This province was once a verdant green area surrounded by the sea, rich in minerals mined by the Ancient Robots. Hyrule in A Link Between Worlds closely resembles its appearance in A Link to the Past, with nearly all major features in the same locations as their counterparts in A Link to the Past and most areas having similar layouts. The main exceptions are dungeon entrances, with the House of Gales added to Lake Hylia where no such structure exists in A Link to the Past, certain smaller buildings, such as those in Kakariko Village, and caves, which have little in common with those of A Link to the Past. In this case Hyrule is connected by fissures to a parallel world known as Lorule. Lorule also resembles the Dark World of A Link to the Past, although not quite as closely, with certain major landmarks in different positions and chasms in the place of some of the Dark World's bodies of water. According to Encyclopedia, The Legend of Zelda takes place in a fraction of the land seen in A Link Between Worlds. 10,000 years prior to the events in Breath of the Wild, the defeat of Calamity Ganon heralded a lengthy age of peace and prosperity for Hyrule. This peace came to an abrupt end 100 years prior to Breath of the Wild when Calamity Ganon returned as an entity of Malice. The kingdom of Hyrule fell as Calamity Ganon seized control of the Divine Beasts and Guardians designed to protect the kingdom, leaving it covered in ruin. The former heart of Hylian civilization, Central Hyrule, suffered greatly from the Calamity's destruction. The Region, along with Hyrule Castle, became inhabited by Guardians and various monsters. The civilizations of Hyrule survived and continue to live in their settlements, with the Hylians in Hateno Village and Lurelin Village, the Sheikah in Kakariko Village, the Zora in Zora's Domain, the Gerudo in Gerudo Town, the Gorons in Goron City and the Rito in Rito Village. While the Sheikah survived the Calamity, they steeply declined from an era of technological prosperity. Long ago, they built the Sheikah Towers, the Ancient Shrines as well as the Divine Beasts and Guardians, all of which attest to their advanced level of science and technology. While the elder Impa still lives in Kakariko Village, the other surviving Sheikah elders, Purah and Robbie, relocated to the Hateno Ancient Tech Lab and Akkala Ancient Tech Lab respectively. They did this so that they would not be wiped out in one strike should Calamity Ganon attack again, allowing at least one of them to survive and speak to Link after he awakes from the Shrine of Resurrection. As a constant reminder of Calamity Ganon's enduring reach, periodic events known as Blood Moons occur, casting the night sky a crimson red and reviving all of Ganon's minions who fell. Hyrule only plays a minor role in the opening and closing of Majora's Mask, where a new section of the Lost Woods is revealed in the opening of the game. Link is searching the woods for "a friend with whom he parted ways" after the Child Timeline ending of Ocarina of Time. The Lost Woods are home to a portal leading to a parallel world to Hyrule called Termina. Link stumbles upon this portal when he chases the Skull Kid through it after a chance encounter in the Lost Woods. The young Hero of Time also returns to Hyrule through this same portal at the end of the game after he succeeds in saving Termina from the demon Majora and frees the Skull Kid from Majora's grasp. During the ending cinematic, a crude drawing of Link and the Skull Kid is seen in the Lost Woods. Hyrule in Oracle of Ages and Oracle of Seasons also plays only a minor role in the overarching storyline. The kingdom appears to be at peace, because Ganon was vanquished sometime in the past and the complete Triforce is safe in Hyrule Castle. When Link touches the Triforce, he receives a mark on his hand that signifies that he is the chosen hero of Hyrule. As the two games open, Link is shown riding a horse along a coastline (revealing that this version of Hyrule also has an ocean that borders it), and Hyrule Castle is shown from a distance when Link stops to take in the view and hears the Triforce's call from within the castle. These brief scenes are the only times gamers see Hyrule in the two games, and only one room is shown within Hyrule Castle, the room where the Triforce is kept. It is also revealed that, unlike in Termina, Hyrule is known to members of the two new lands visited by Link within the games. Nayru reveals that she knows that Link and Impa are messengers of Hyrule and Din is able to identify the Triforce mark on the back of Link's hand. This indicates that both Holodrum and Labrynna are different countries in the same universe as Hyrule, and not parallel dimensions like Termina. ↑ "Even something as simple as the aiming, which is handled not necessarily with a pointer but by moving your hand around, just like you would aim an item in real life, will make it that much easier for you to feel like you're in that world of Hyrule and experiencing the adventure that Link is, because you're so connected to what's going on." — joystiq's Interview with Shigeru Miyamoto, joystiq.com. ↑ "Aonuma says that the scene which concludes the trailer, in which Link leaps off a cliff into a sea of clouds, is an important story point. Instead of being raised in a village on the ground, he's been brought up in a town called Skyloft, which is a floating island. He's lived his life in the clouds, and has only recently "discovered" the land below, which he finds has been overrun with evil forces. You spend the game going back and forth between these two regions: Skyloft, and the ground below." — , kotaku.com. This page was last edited on 8 April 2019, at 05:13.
0.920289	Hibernating Garter Snakes: a must or an option..? The Mexican Black-bellied Garter Snake is a very unusual garter snake. In visual appearance it is strikingly different from the average garter snake. This species has a narrow pointy head, smooth and shiny scales and is short and stout built. It occurs only in Mexico and 4 subspecies have been described: Thamnophis melanogaster melanogaster, Thamnophis melanogaster canescens, Thamnophis melanogaster chihuahuaensis and Thamnophis melanogaster linearis. The subspecies are difficult to distinguish from each other, especially if the origin of the specimens is not exactly known. Just like the subspecies of Thamnophis eques (with which it coexists at many locations in central Mexico) this species is rarely encountered in private collections and Thamnophis melanogaster canescens is probably the only subspecies being kept in captive maintenance in Europe. The Mexican Black-bellied Garter Snake is a rather short species of garter snake. Maximum length mentioned in literature (Rossman, Siegel & Ford, 1996) is 86,4 cm. Most adult specimens are not much longer then 50-60 cm and 70 cm is even for a female a considerable size. Especially the females are relatively stout bodied. The dorsal color pattern is highly variable and many specimens are definitely more beautiful then the limited amount of pictures one can find in literature. The dorsal and lateral stripes may be present (al be it often vague) or absent. They also can be unspotted or heavily spotted. The belly of this snake can also vary from yellowish, greenish, black to striking bright red. In case the belly is not entirely black (only in the melanistic specimens) there is a black line in the centre of each belly scale. In T.m.canescens this black line may be small or absent, in other subspecies it can be relatively wide and solid. Gregory et al. (1983) reports a population inhabiting lake Cuitzeo which is extremely polymorphic: dorsum may be gray, green, brown, red, orange, pink or yellow, spotted or unspotted and striped or unstriped. En all of these possibilities occurs in varying combinations. Red specimens are definitely not exclusive for lake Cuitzeo. I have witnessed red individuals also in lake Chapala (Bol, 2010) and in lake Cajititlan. In lake Chapala I also found extremely beautiful melanistic snakes (Bol, 2010) which are almost 100 % black, much more so then the well-known melanistic common Garter Snakes (Thamnophis sirtalis). I have not seen any literature mentioning melanistic specimens. Mexican Black-bellied Gartersnakes do very well in captivity. Due to its moderate size it is recommended to keep them in a terrarium with a minimum size (for one adult couple) of 70 x 50 x 50 cm. They do well in a dry and well ventilated cage with just a water bowl for swimming and drinking. The water bowl should be big enough for them to submerge in. Local temperatures in the terrarium should rise to 30 – 35 °C. In a terrarium the adult snakes can often be seen basking in the cooler winter and spring months, but if the terrarium gets relatively warm the snakes like to hide underneath rocks etc. They can be very shy. Often one has to sneak into the room in order to observe the snakes. When they get older they show themselves a lot basking on a branch under the lamp and most specimens loose all of their shyness. Their eyesight is well developed and they can hunt on sight both above and underneath the water very well. Often they are very fast and their movements very precise during feeding. They feed on dead and live fish without problems. A hibernation will not be absolutely necessary although it is expected that they will have a resting period in nature when they are less active. A cool period in the terrarium of 2 – 3 months will probably be sufficient to keep the snakes in good health and to stimulate breeding. Up to now I hardly give the snakes a hibernation. But the snakes are clearly less active in the coldest winter months; they bask less and often refuse to eat for several months. So do not worry when this happens. During the winter months night temperatures in my snake room (and in the terrariums) drop at night to 8 – 12 °C. I keep most of my adult snakes in a completely dry terrarium with a water bowl. This species is also very suitable for a so-called “aqua-terrarium” with a lots of water and only a small (completely dry!) land part which is heated by a powerful lamp to 30 – 35 °C. In such a habitat terrarium the highly aquatic snakes will show more of their natural behavior. And they will be more visible. Currently I keep a group of subadults in such a aqua-terrarium and they do very well in this set up. The young are usually born in my terrariums in May, June or July. Thamnophis melanogaster canescens can be found from 1158 – 2545 meter above sea level. It is not known whether they hibernate in the wild. I have observed this species all through the month of November actively basking and feeding at several locations within Mexico. Habitat of Thamnophis melanogaster canescens: lake Cajititlan, Jalisco, Mexico. I have found them in the large lakes (Chapala, Cuitzeo, Magdalena, Cajititlan, Zacapu) where they occur with Thamnophis eques but also in canals and small creeks. Always very close to or in the water. They seem to remain active as long as day temperature rises above the 19 – 20 ºC (which usually occurs throughout the year in Jalisco and Michoacán). My recent article about Thamnophis eques scotti (Bol & Bruchmann, 2012) that can be found online in english on this website can serve as a standard recommendation (care sheet) for this species. Actually I keep this species often combined with Thamnophis eques (see the text about the different subspecies of T.eques). In the wild both species occur sympatric at many locations (personal observation). So the combination of these 2 species are just like they occur in the wild. The two species are so different as far as color, shape and size are concerned which makes it interesting to keep them together. My breeding groups consists of (offspring of) 9 unrelated wildcaught specimens originating from the lakes of Cuitzeo, Chapala and Cajititlan. So I have snakes available from unrelated parents, without much chance of inbreeding. I am breeding this subspecies since 2007. Due to the big variation in dorsal color and pattern this species is highly suitable to breed on color or pattern. Currently programs are set up for red, melanistic and grey-green spotted morphs. Bol, S., 2010. Exciting observations on two sympatric garter snakes in “la Laguna de Chapala”, Mexico. ( Part 1 of 2). The garter snake 15 (1): 16-27. Bol, S., 2010. Exciting observations on two sympatric garter snakes in “la Laguna de Chapala”, Mexico. ( Part 2 of 2). The garter snake 15 (2): 10-19. Bol, S. & H. Bruchmann, 2012. Scott’s Mexican Garter Snake (Thamnophis eques scotti; Conant, 2003) in the wild and in captivity. ( Part 1 of 2). The garter snake 17 (3): 15-25. Bol, S. & H. Bruchmann, 2012. Scott’s Mexican Garter Snake (Thamnophis eques scotti; Conant, 2003) in the wild and in captivity. ( Part 2 of 2). The garter snake 17 (24-31): 16-27. Rossman, D.A., N.B. Ford & R.A. Siegel, 1996. The Garter Snakes. Evolution and ecology. University of Oklahoma Press, Norman. My name is Steven Bol and on this website I would like to share with you my passion for North American Gartersnakes and Watersnakes.
0.999985	How to do your swim workout in the right way? Swimming is the most technical discipline in triathlon. Humans are not born to be good swimmers, because we have no flow line in the water and we can not breath under water.
0.981392	Sir Stelios Haji-Ioannou complained to the Press Complaints Commission that an article headlined "Stelios backs down as £71m jets in", published in The Daily Telegraph on 24 September 2011, made irrelevant and discriminatory reference to his race in breach of Clause 12 (Discrimination) of the Editors' Code of Practice. The article commented on the complainant's abandonment of plans to call an Extraordinary General Meeting of the easyJet company following an announcement by the company's management that a dividend would be paid to its shareholders, who included the complainant. It followed on from another item (under the same byline) that criticised the slow response by world leaders to Eurozone financial problems, and began by noting: "at least we've had one Greek bail-out this week...". It also referred to the complainant as "Greek-born", and its final sentence concluded that "the worry for easyJet... is that Stelios concludes his approach actually works - and, like Greece itself, is quickly back for more. Though why would he do that - he doesn't need the money, does he?" The complainant said the article had referred to his Greek Cypriot origins in order to undermine his credibility on financial matters. In his view, the analogy proposed between the Greek government's relationship with its foreign creditors and his relationship with easyJet rested only on his race, as the two situations were otherwise entirely different: the article had implied wrongly that, like the government of Greece, he had squandered money he did not deserve and now needed bailing out by his lenders. The right of shareholders of a company to demand dividends could not, the complainant said, be legitimately compared to requests for credit by non-creditworthy borrowers. He also objected to the final question posed by the columnist, which he considered left the inaccurate implication that - notwithstanding the claim that he was "richer, probably, than Greece" - he did in fact need "bailing out". The newspaper said that the analogy had been a light-hearted journalistic conceit in a comment piece. The word "Greek" was not pejorative per se, and its use in this context had not related to any "racial" attributes. The reference to a "bail-out" was intended to mean that the complainant had bailed out of the EGM. It could also suggest in a "wry" way that the complainant had been bailed out. It noted that the Commission had previously ruled that descriptions of a person's public persona included by way of background were not "irrelevant" under the terms of Clause 12 (i). The fact of the complainant's Greek Cypriot birth was widely in the public domain, and the article had contained nothing that could reasonably be construed as an attack on the complainant on the grounds of his race. Nonetheless, the newspaper offered to publish a clarification noting that it had not intended to suggest that the complainant required financial assistance or was financially inept by virtue of his Greek origin along with an apology if any contrary impression was given. The complainant strongly objected to the prominence given to his background as a Greek Cypriot in an article that criticised him. It was a matter of regret that this had upset and offended the complainant, but the role of the Commission was to decide whether it had also breached the requirements of Clause 12 in this area: "The press must avoid prejudicial or pejorative reference to an individual's race..." and "Details of an individual's race... must be avoided unless genuinely relevant to the story." The Commission has previously found (in Haji-Ioannou v Financial Times) that the complainant's Greek Cypriot origin is a part of his public persona, and that brief references to it are not "irrelevant" under the terms of Clause 12. On this occasion, rather than making brief allusions, the article under complaint had employed an extended metaphor, playing on this aspect of the complainant's background, comparing his actions with those of the Greek government in a manner that both parties described as "farcical". The Commission acknowledged the complainant's position that the connection between the Greek government's troubles and negotiations over a dividend to shareholders in easyJet was, in reality, tenuous. The connection had been made via the pun on the phrase "bail-out", and the Commission could understand the complainant's frustration that the two stories were being combined merely due to his connection to Cyprus. However, given that the complainant himself had made public reference to his Greek Cypriot background, the Commission considered that to prohibit the use of such a rhetorical device in the context of a fanciful commentary on recent financial news would be disproportionate. The PCC should be slow, in its view, to interfere in satirical comment, even if it is judged to be misguided by some, especially when no overtly prejudicial or pejorative terms were used in the article. In the Commission's view, the columnist had been entitled to make use of this ironic conceit as a means of commenting on parallels that he perceived in the two situations. This did not raise a breach of Clause 12 (ii) of the Code. The complainant considered that the article had implied - in a prejudicial manner - that he was financially imprudent by connecting him to the Greek government. The Commission disagreed. References to the complainant were clearly based on his actions in calling off the EGM, and the article made explicit reference to the fact that he was "hugely wealthy" (in contrast to the Greek government). While the analogy might be unwelcome - and the Commission welcomed the newspaper's offer of a clarification and apology to the complainant, in light of the distress the article had evidently caused - the Commission could not agree that it had constituted a prejudicial or pejorative reference to the complainant's race under the terms of Clause 12 (i). The complaint was not upheld.
0.962041	When does it make sense to choose an abstract class over an interface? Q: In Java, under what circumstances would you use abstract classes instead of interfaces? When you declare a method as abstract, can other nonabstract methods access it? In general, could you explain what abstract classes are and when you might use them? A: Yes, other nonabstract methods can access a method that you declare as abstract. But first, let's look at when to use normal class definitions and when to use interfaces. Then I'll tackle abstract classes. Some say you should define all classes in terms of interfaces, but I think recommendation seems a bit extreme. I use interfaces when I see that something in my design will change frequently. For example, the Strategy pattern lets you swap new algorithms and processes into your program without altering the objects that use them. A media player might know how to play CDs, MP3s, and wav files. Of course, you don't want to hardcode those playback algorithms into the player; that will make it difficult to add a new format like AVI. Furthermore, your code will be littered with useless case statements. And to add insult to injury, you will need to update those case statements each time you add a new algorithm. All in all, this is not a very object-oriented way to program. With the Strategy pattern, you can simply encapsulate the algorithm behind an object. If you do that, you can provide new media plug-ins at any time. Let's call the plug-in class MediaStrategy. That object would have one method: playStream(Stream s). So to add a new algorithm, we simply extend our algorithm class. Now, when the program encounters the new media type, it simply delegates the playing of the stream to our media strategy. Of course, you'll need some plumbing to properly instantiate the algorithm strategies you will need. This is an excellent place to use an interface. We've used the Strategy pattern, which clearly indicates a place in the design that will change. Thus, you should define the strategy as an interface. You should generally favor interfaces over inheritance when you want an object to have a certain type; in this case, MediaStrategy. Relying on inheritance for type identity is dangerous; it locks you into a particular inheritance hierarchy. Java doesn't allow multiple inheritance, so you can't extend something that gives you a useful implementation or more type identity. Choosing interfaces and abstract classes is not an either/or proposition. If you need to change your design, make it an interface. However, you may have abstract classes that provide some default behavior. Abstract classes are excellent candidates inside of application frameworks. Abstract classes let you define some behaviors; they force your subclasses to provide others. For example, if you have an application framework, an abstract class may provide default services such as event and message handling. Those services allow your application to plug in to your application framework. However, there is some application-specific functionality that only your application can perform. Such functionality might include startup and shutdown tasks, which are often application-dependent. So instead of trying to define that behavior itself, the abstract base class can declare abstract shutdown and startup methods. The base class knows that it needs those methods, but an abstract class lets your class admit that it doesn't know how to perform those actions; it only knows that it must initiate the actions. When it is time to start up, the abstract class can call the startup method. When the base class calls this method, Java calls the method defined by the child class. Many developers forget that a class that defines an abstract method can call that method as well. Abstract classes are an excellent way to create planned inheritance hierarchies. They're also a good choice for nonleaf classes in class hierarchies.
0.953995	I wrote this short story over ten years ago, and every once in a while I take it out, dust it off, revise a bit, and stow it away. I think it’s time to share it here. Autumn sighed, the rustle of dead leaves in a chill breeze. He stirred, his black eyes narrowing on Winter seated to his right. Minuscule snowflakes fell from her lashes as she blinked in return. She graced him with a slight nod, accompanied by the tinkling sound of icicles falling to the frozen ground. Autumn’s gaze skimmed over Spring with a blush, looking to Summer next. The man sitting to Autumn’s left also nodded, adding a nondescript gesture of one golden hand that stirred a sudden warm draft. Reluctantly, Autumn turned his gaze to the woman across the table. A garland of small blossoms twined through her red-gold hair, and dew clung to her flushed skin. Her eyes were the green of new leaves, wide and merry. It stirred something in him that he attempted to ignore. Oblivious, Spring nodded as well. The fragrance of honeysuckle and roses filled the air. It was time. As one they stood, and each moved to the left to take a new seat. It was Autumn’s turn in the large, ornate chair at the head of the table. He settled in with the dry scent of summer gone cold. A feast appeared on the crystal table. This was Autumn’s harvest bounty and his gift to the others. They ate heartily, for Winter was next and she gave no gifts. It seemed both an eternity and the blink of an eye, but the change in the air was unmistakable. It was Winter’s turn. She motioned impatiently to the others, giving them a cursory glance before standing to take the chair. The frozen fabric of her gown cracked and groaned as she moved, like the surface of an ice-covered pond. She stood tall and proud, for Winter answered to no one. Her gaze was the deep, dark color of a glacier’s heart. Those icy eyes turned jealously toward Spring, but only for a heartbeat. She was nothing if not observant, and she had seen the way Autumn stared at the lady of late. It did not bode well. The four could never deviate from the pattern, never leave their positions. The crystal table was to remain between them until the end of time, a barrier that maintained the order and the balance. So it had been since the very beginning. And Winter should know, for she had been the first. Her icy claws had etched the decree into the table’s crystal surface. She made the law, and it would not be broken. Spring fidgeted. She’d waited too long again, and she knew it. Winter did not give up her seat easily, and Spring was too timid to force her. They may have remained that way for eons, if impatient Summer hadn’t let out an audible sigh that smelled like sunlight and saltwater. Winter narrowed her eyes at him, but it was too late. Emboldened, Spring stood and took the chair. She did not meet Winter’s bottomless cobalt gaze, but her skin flushed warmly when she looked across the table at Autumn. His eyes stared at her and into her. They burned like dying embers and made her heart hammer in her chest. As she settled in to her seat, the room grew warmer and the table before them changed. The icy surface cleared, frost melting away as thin tendrils of ivy twined around the table legs. Fragrant blossoms opened, and the crisp smell of green growing things filled the air. The four breathed in the aroma of life as the Earth awoke from its cold slumber. This was the gift of Spring. Summer yawned, bored yet again. One golden hand tapped a mindless staccato beat on the table. The scent of flowers had grown cloying, as usual. Autumn shifted in his chair. Even selfish Summer could feel it. The careful balance that had been maintained for millennia teetered on a precipice. Change hung heavy in the air, though none said a word. When his time came, Summer grinned and swaggered to the head chair. He looked from Autumn to Spring and back again. The signs were unmistakable. Autumn’s dark eyes were hungry, while Spring’s rosy glow was warmer than ever. And yet, always they must remain opposites, by Winter’s decree. Summer once again read the words engraved on the tabletop as he took the seat. The precepts stated that the table would always remain in the center, each of them on one side until the end of time. That table was the crux, the axis upon which they all spun. It was the sun, and they were merely planets in orbit. Those words–carved by the cruel hand of Winter herself–were law, the stricture that bound them in this eternal dance. Summer’s mouth quirked, and it was the only warning any of them would receive. He stared defiantly into the imperious eyes of Winter as he lifted both arms high and brought them down upon the surface of the crystal table with every ounce of his strength. There was a moment of peace, a stillness completely absent of sound or movement. Then there was a sound oddly like a sigh, and Summer’s gift fell to the floor in shattered, sparkling pieces.
0.95348	Atopy and autoimmune thyroid diseases: melatonin can be useful? Recently, there has been growing interest in the relationship between allergic and autoimmune diseases. Allergy and autoimmunity can be considered two potential outcomes of dysregulated immunity and analysis of literature data shows a strong positive association between a history of Th2-mediated allergic disorders and Th1-mediated autoimmune disorders. Autoimmune thyroid diseases are the most common of all autoimmune pathological conditions. Currently, the mechanisms explaining an association among atopy, autoimmunity, and thyroid diseases are not fully understood. There are data in literature pointing to the relationship between melatonin and thyroid activity. Several studies have suggested a paracrine role for this molecule in the regulation of thyroid activity, documenting that administration, as an antioxidant, in thyroid tissues under conditions of increased oxidative stress, could be helpful to reduce the oxidative processes involved in autoimmune thyroid diseases. Although thyroid autoimmunity has been regularly associated with atopic conditions in children, the possible protective role of melatonin has not yet been investigated. This review summarizes what is known regarding the connection between atopy and autoimmune thyroid diseases, and analyses the probable beneficial action of melatonin. Hypersensitivity reactions of the immune system have been categorized into atopic and autoimmune reactions, depending on whether the antigen triggering the reaction is endogenous or exogenous, types of cellular and humoral components involved, and clinical symptoms . Atopy is an individual or familial tendency to produce IgE antibodies in response to low doses of allergens and to develop typical symptoms such as atopic dermatitis, allergic rhinitis, and asthma [2, 3]. Atopic diseases have increased in frequency in recent decades and now affect approximately 20 % of the population worldwide . The risk of developing atopic diseases is complex and is strongly influenced by both genetic and environmental factors [5, 6]. Atopy and autoimmunity are two potential outcomes of dysregulated immunity . The incidence of autoimmune diseases has increased in recent decades. Although these conditions have a multifactorial pathogenesis, one generally accepted model is that immune dysregulation, secondary to an infectious process or excessive exposure to an inciting or cross-reactive antigen, promotes a T helper (Th) 1 response leading to progressive inflammation and autoimmunity. Reciprocal counter-regulation of Th1 and Th2 cells predicts that Th1-type autoimmune disease and Th2-mediated allergic disease would occur in mutually exclusive populations of patients . However, data literature are controversial regarding true associations between atopy and autoimmune disease [9–12]. Recent observations have identified additional lymphocyte subsets, such as Th17 cells , soluble factors such as IL-9 and regulatory T cells (T reg) as a common link between atopy and autoimmunity. It has been reported that infantile atopy increases a predisposition to autoimmune disorders, suggesting that these two entities might have immune pathways, common to both pathological conditions, justifying partially the increased prevalence and/or the co-presence of atopic and autoimmune diseases [13, 14]. Conversely, Skaaby et al. did not find statistically significant associations between atopic predisposition and autoimmune disorders, although they could not exclude moderate effects of atopy on autoimmune disease. The thyroid gland is the most common organ affected by autoimmune disease. Autoimmune phenomena, especially thyroid autoimmunity, have often been associated with other autoimmune diseases, such as chronic urticaria in adults and children . Although thyroid autoimmunity has regularly been associated with atopy in children, the possible protective role of antioxidants, such as melatonin, has not yet been fully investigated, although its role has been documented in other atopic conditions, such as dermatitis and asthma [17, 18]. Melatonin plays key roles in several important physiological functions, including neuroimmunological actions and immunomodulatory effects in allergic diseases, although its potential use in atopic patients has rarely been considered . Experimental data suggested that melatonin inhibits development of atopic eczema, a condition accompanied by infiltration and activation of mast cells with release vasoactive and proinflammatory mediators, and reduces serum total IgE and IL-4. Furthermore, emerging evidence suggest that melatonin represents a potent antioxidant and protective substance in skin photobiology [20, 21]. It has been reported that melatonin also protects keratinocytes against ultraviolet (UV) radiation B-induced oxidative stress and DNA damage and that endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin, would represent one of the most potent anti-oxidative defense systems against the UV-induced damage to the skin . Melatonin, therefore, has been hypothesized as a potential therapeutic option also in atopic dermatitis (AD), protecting skin integrity and helping to maintain a functional epidermal barrier [23, 24]. Moreover, it has been documented that melatonin, regulating smooth muscle tone and influencing the immune response in allergic asthma, could be implicated in regulating bronchial hyper-responsiveness [25, 26]. Furthermore, melatonin may, however, act as a pro-inflammatory agent in asthma leading to bronchial constriction [17, 25]. There are some data in literature pointing to the relationship between melatonin and thyroid activity and its involvement in the hypothalamic-pituitary-thyroid axis . This review summarizes what is known regarding the connection between atopy and autoimmune thyroid diseases and analyses the possible protective role of melatonin. It has been proposed that innate immunity has a role in allergic inflammation, and epithelial cells, dendritic cells, natural killer lymphocytes, and mast cells might play a regulatory role in allergy. It has also been suggested that there is some form of cooperation between Th2 mediated allergy, and Th1 mediated inflammation responses . The adaptive cellular immune response has been characterized broadly as being polarized in two directions . Type 1 responses, directed by Th1 CD4+ T cells and identified by the signature cytokine interferon (IFN)-g, are considered as protective against infections by intracellular pathogens , and have been incriminated in the pathogenesis of autoimmune diseases, such as thyroid disease. Many other autoimmune diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, insulin-dependent diabetes mellitus and multiple sclerosis are associated with a Th1 phenotype . Autoimmune thyroid disease (ATD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Autoimmune thyroid diseases are characterized by infiltration of the thyroid by T and B cells which are reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function . ATD presents a hereditary component, as reported in several studies that show a definite genetic propensity for thyroid autoimmunity to run in families . The childhood prevalence of chronic autoimmune thyroiditis peaks in early to mid-puberty . By contrast, type 2 responses, directed by Th2 CD4+ T cells and identified by the signature cytokines interleukin (IL) -4, IL-5 and IL-13, are considered to play a pathogenic role in allergic diseases . Reciprocal counter-regulation of Th1 and Th2 cells predicts that Th1-type autoimmune diseases and Th2-mediated allergic diseases would occur in mutually exclusive populations of patients. However, recent observations have challenged the validity of the long-standing Th1/Th2 paradigm , and a far more complex story explaining the immunological basis of cellular immune-mediated host defence and the pathogenesis of autoimmune and allergic diseases is emerging. The new paradigm identifies additional lymphocyte subsets, such as Th17 T cells, Treg and novel soluble factors. These provide a new prism through which to examine the intersection of autoimmune and allergic disease (Fig. 1) . Mittermann et al. demonstrated that a considerable percentage of patients suffering from atopic dermatitis had enhanced IgE autoantibody levels against a broad variety of human proteins expressed in a variety of cell and tissue types. Furthermore, they showed that the levels of IgE autoantibodies were associated with severity of disease . Several studies reported a higher incidence of ATD in subjects affected by allergic diseases. Pedullá et al. showed an increased prevalence of thyroid autoimmunity in children with AD, underlining a significant relationship between the expression of AD and thyroid autoimmunity in a pediatric population . Furthermore, Pedullá et al. demonstrated that the frequency of thyroid autoimmunity was significantly higher among children with IgE-mediated AD than non-IgE-mediated AD, suggesting atopy and thyroid autoimmunity as potential outcomes of dysregulated immunity . Hidaka et al. suggested that eosinophils and their activation play an important role in inflammatory processes in allergic diseases. Th2 cytokines stimulate eosinophils and it has recently been found that the peripheral eosinophil count was increased in thyrotoxic patients with Graves’ disease . Moreover, the same authors demonstrated that an allergic condition is closely related to Graves’ disease and that a Th2-type immune response is crucial in the pathogenesis of Graves’ disease . Whereas oxidative reactions occur in all tissues and organs, the thyroid gland is an organ in which oxidative processes are widely signalized and are indispensable for physiological functions of the organism . Hydrogen peroxide acts as an electron acceptor at each step of thyroid hormone biosynthesis and is essential for thyroperoxidase (TPO) activity, the key enzyme in this process. In addition, antioxidative enzyme activity [superoxide dismutase (SOD), glutathione (GSH) peroxidase (GSH-Px) and catalase (CAT)] has been well documented in the thyroid . The use of various exogenous antioxidants in thyroid tissues has been shown to be beneficial in experimental (in vitro or in vivo) studies [43, 44]. Unfortunately, the applicability of different antioxidants has not yet been clearly confirmed in clinical studies and still no effective antioxidative medication is available for widespread use . Moreover, melatonin, an ubiquitous antioxidant molecule with pleiotropic action in many tissues, has protective effects against oxidative stress [46, 47], the thyroid included . There are data in literature pointing to the relationship between melatonin and thyroid activity. Several studies have suggested a paracrine role for this molecule in the regulation of thyroid activity. The antioxidant role of melatonin in the thyroid gland was first reported by Kvetnoy . It has been demonstrated that melatonin is, at rat thyroid level, synthesized by C cells -the minor neuroendocrine thyroid cell population- and, that melatonin receptors (MT)1 are present in follicular cells , suggesting a role for thyroid melatonin. Recently, another study has shown that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control, supporting the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. In particular, Garcia-Marin et al. analyzed both the effect of melatonin on the expression of the thyroid tissue-specific genes PAX8 and TTF1 and examined TSH regulation of key enzymes for melatonin biosynthesis, such as aralkylamine N-acetyltransferase (AANAT) and acetyl serotonin methyltransferase (ASMT). They showed both the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells and that AANAT and ASMT are regulated by thyroid-stimulating hormone. Furthermore, it has been demonstrated that thyroid C-cells synthesized melatonin under thyroid-stimulating hormone control, supporting the possible paracrine role for C-cell-synthesised melatonin within the thyroid . Additionally, Karbownik M. et al. commented the evidence that melatonin, acting as an antioxidant agent, influences thyroid growth, counteracting significant oxidative damage that occurs in the course of thyroid diseases, and the stimulatory effects of thyroid hormones . The same research group , in an experimental study, estimated melatonin effects on basal and iron-induced lipid peroxidation related to Fenton reaction in homogenates of the porcine thyroid gland, showing that the degree of lipid peroxidation was decreased, in a concentration-dependent manner, by melatonin, and supporting the protective role of this indolamine in preventing pathological processes, such as thyroid cancer, related to oxidative injury. Data in literature has shown melatonin action on the thyroid gland itself, such as the inhibitory effect of melatonin on cell proliferation and thyroid hormone synthesis [51, 52] or the protective effect of melatonin against oxidative damage in the thyroid gland [53, 54]. It has been well reported that the administration of chronic melatonin is efficient in protecting against the damaging effects of different prooxidants and that under basal conditions it does not change the level of oxidative damage to macromolecules . In addition, it has been evaluated that the effects of Caffeic acid phenethyl ester (CAPE) on Fenton reaction-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in porcine thyroid and the liver are similar to those caused by melatonin. Whereas CAPE decreased basal LPO in a concentration-dependent manner in both tissues, melatonin did not change the basal LPO level. When antioxidants were used together with Fenton reaction substrates, they prevented – in a concentration-dependent manner and to a similar extent – experimentally- induced LPO in both tissue effects of melatonin . Regulatory T cells are important components of the homeostasis of the immune system, as impaired regulatory T cell activity can cause autoimmune diseases and atopy . Atopy and autoimmunity are manifestations of immune system dysfunction and are referred to as distinct immunological reactions with common pathogenic mechanisms . The mechanism whereby ATD is associated with allergic diseases is poorly understood. Several researchers have observed serum histamine releasing activity in a subgroup of adult patients with chronic urticaria, which was attributable to an IgG autoantibody directed against the alpha chain of the high affinity IgE receptor of the mast cells or, less commonly, against IgE itself [59, 60]. It is important to identify infants at risk for developing lifelong chronic atopic and autoimmune diseases and utilize the critical window of opportunity early in life for therapeutic intervention that targets Th1- or Th2-specific responses revealing atopy or autoimmunity respectively. During the last decade, wide evidence has contributed to confirm the antioxidant and protective role played by melatonin in the normal, as well as in the prooxidant-agent insulted, thyroid-gland [43, 48, 63]. Finally, it has been documented that the administration of melatonin, as an antioxidant, in thyroid tissue under condition of increased oxidative stress, could be helpful to reduce oxidative processes involved in autoimmune thyroid diseases [27, 42, 48]. Melatonin is a molecule with an excellent biosafety profile, widely used for decades in some countries, and no serious side effects or treatment-related complications with short or long-term melatonin therapy in children and adults have been reported . In addition, further studies are necessary to elucidate the underlying mechanisms and the common pathways involved in atopy and thyroid autoimmune diseases. Therefore, melatonin could be hypothesized as a potentially useful agent in the treatment of ATD, but further studies are necessary to clarify the immunological-hormonal effects of this indolamine. The authors have no conflicts of interest disclosing what could be perceived as prejudicing the impartiality of the research reported. The authors declare that they have no sources of funding. All clinical data and supporting materials concerning the manuscript are available in case of Editorial request. GD Study conception and design of the manuscript. LM Writing up of first draft of the paper. SM-LC Helped draft the manuscript. CC Substantial contributions to the acquisition of data for the work. PI-SA Substantial contributions to the analysis of data for the work. TA Critical revision of the article for important intellectual content. All authors read and approved the final manuscript.
0.941913	There are many narratives in the Hebrew Bible/Old Testament and the New Testament, which demand a willing suspension of disbelief on the part of a twenty-first century person. Educated persons would admit that certain narratives reflect physical impossibilities, and hence they clash with the way things usually work in the world. For example, in the cycle of stories about the acts of Elisha in Second Kings (chapters 2-13) one finds, among other stories of the same sort, the story of an iron axe head that floated after falling into the Jordan River (6:1-7). Elisha, described as "the man of God," reputedly caused the axe head to rise to the surface by tossing a stick into the water. The claim in the narrative that the axe head floated violates the buoyancy principle of Archimedes of Syracuse (third century BCE) that states: an object will float if it is equal to or less than the amount of water it displaces (that is why aircraft carriers float). The weight of an iron axe head is not equal to or less than the weight of the water it displaces and hence it will not float. And common sense tells us that a stick tossed into the water would have no influence on what is essentially a law of physics.1 In order to think that the narrative describes something that actually happened, readers must suspend disbelief. Another narrative requiring a suspension of disbelief is the tradition of Joshua causing the sun to stand still in the sky to allow the Israelites to slay all their enemies, the Amorites, at Gibeon (Josh 10:6-14). And the sun stood still, and the moon stayed, until the nation took vengeance on their enemies. Is this not written in the Book of Jashar? The sun stayed in the midst of heaven, and did not hasten to go down for about a whole day. There has been no day like it before or since (Josh 10:13-14, RSV). The belief that the sun rises in the east, moves across the sky, and sets in the west, is an ancient superstition, shared by the biblical writers.2 This belief was proven incorrect only in the sixteenth century CE.3 Until that time it was believed that the sun and the planets circled the earth, which held a position in the center of the solar system. In other words they believed that the earth did not move, but today it is common knowledge that the earth moves in an elliptical movement around the sun. Narratives like these, which require a suspension of disbelief by most of us, are nevertheless accepted as a normal part of reality by the deeply pious; they have a high degree of confidence in the Bible and simply dismiss the idea that the event could not have happened by asserting: the Bible says it; I believe it; that settles it—as if the story about how we came by the Bible5 has no impact on the relative value of its ideas. Others offer a slightly more sophisticated theory to explain away some of the problems: God is in control of the universe; therefore God can do whatever God chooses in the universe. This latter statement disregards how the universe is thought to work in secular society; those who live by this statement are simply changing "reality" to correspond to their religious faith. A third way of handling problems in biblical narratives requiring a suspension of disbelief rejects the "laws" of physics by arguing the universe is not a closed system but rather an open system. Hence in the view of those who believe in miracles physical "laws" are only general rules that are sometimes suspended leaving open the possibility that miracles can occur. Was Archimedes wrong and Jesus really did walk on the water? 2For example, Gen 15:12; Exod 17:12; Jdg 14:18; 2 Chron 18:34; Matt 5:45; Mark 16:2; Eph 4:26. 3George Abell, Exploration of the Universe, 34-53. 4Compare similar stories about Elijah and Elisha in 1 Kgs 17: 8-16 (the jar of meal and the cruse of oil) and 2 Kgs 4:1-7 (the jar of oil). Each story contrasts limited amounts at the beginning and the abundant residue at the end exceeding that with which the story began. 5The Bible is a product of modern biblical scholarship. See the two brief descriptions of the science of textual criticism, which is basic to all critical approaches to the Bible: Fuller, "Text Criticism, OT," NIDB, 531-34; Holmes, "Text Criticism, NT" NIDB, 529-31. One way to look at the "suspending disbelief" passages is to consider that they represent a mimetic (imitation) writing dynamic. Dennis McDonald in his Mythologizing Jesus (2015) suggests that the authors of the gospels are finding a way to make Jesus competitive with the gods of Greco-Roman mythology, depicting him as not only breaking the laws of nature but doing so, contrary to the gods, with compassion. In Jesus' feeding of the 5000 and 4000, for example, he sees a mimetic representation in Mark of the feast of Nestor (Odyssey 3:1-67) and the feast of Menelaus (Odyssey 4:1-7)[pgs. 27-32]. He does this for 24 stories/situations found in the gospels, some more persuasive than others. For McDonald, mimesis has the following components: likelihood of accessibility to the previous text, can mimesis be found in the work of other ancient authors, how dense is the mimetic activity (# of parallels), is the order similar in both texts, is a distinctive trait common to both sources, how did the author attempt to emulate/rival his predecessor, and, practically, what parallels appear in the writings of the early (1000 CE)Byzantine poets. It would seem to me, that if mimesis is a viable category, then it's a small step from accepting a resurrection after death to performing miracles that rival the Greco-Roman gods before death. Dennis' book (The Homeric Epics and the Gospel of Mark) is a brilliant study of mimesis in Graeco-Roman antiquity. His argument is that Mark has in part given a mimetic rendering of stories in the Illiad and the Odyssey by Homer. I reviewed the book in an SBL seminar. My major criticism (which Dennis rejected) was that there was no way to disprove his thesis and declared myself a "wanna be" believer. But let's say Dennis was right. What do we do with these stories then? If Mark imitated Homer in certain stories does that get the evangelist off the hook by suggesting that s/he really didn't believe that Jesus did those things? Mark was just trying to improve Jesus' appeal to a Graeco-Roman audience so he could compete with their Gods. Could we then say that Mark was deceiving the public by his subterfuge and that it would be wrong for that reason to believe him. I would be more prone to think that Mark was imitating OT wonder stories. If it was not for Dennis' book, is there any other evidence that Mark had read Homer? I think that mimesis is a viable category but the essence of a good imitator is that you never know that s/he is imitating. And we are still stuck with the clash between such stories and the "laws" of physics. One could reason that Mark did not think of the mimesis as "deceiving the public," whether it be using Homer or OT wonder stories. He perhaps thought of the matter as a literary expression of the truth that Jesus power was consistent in life and death: if Jesus could break the law of death by God's raising him up from the dead to the benefit of others, he was certainly capable of breaking these other natural laws for the benefit of others. Mark perhaps thinks of this as a tool of persuasion in the Christian mission. In other words, now that the risen Jesus is here and in charge, it's perfectly ok to let him influence the earthly Jesus story. For those of us who live our lives in a shared conventional view of reality, Mark's view of what is real is idiosyncratic, calling upon us to confess what we know to not be so. In a conventional view of reality when an axe head falls into a river we don't look for a Man of God to recover it; we use a rake to search for it. I doubt that anyone really believed it possible ordinarily for an axe head to float. Normally, they "knew better." Stories of Moses had him in control of the water, as did stories of Moses, Joshua, Elijah, Jesus and their control of water, as Elisha could even heal h20. They had the "spirit" of their god in the midst of an area that relied on water. Makes for great propaganda, since those who heard or read of it realized that, though improbable, it was a sign of the power of God, not a physics lesson. The same is true for the other "signs" of a god toward those who had "good favor." I would not have said "improbable" as you do (line 6 from the top); I would have said "impossible." These kinds of events that we are discussing are exceptions to the way things happen in a contemporary conventional (i.e., ordinary) view of reality (one that everyone regardless of religious faith can affirm). Apparently enough people in OT times were credulous of such things happening so that the propaganda of the biblical writers worked, as well as Mark's propaganda working, to judge by the eventual conversion of the ancient world to Christianity. Today we still have people pushing the idea of living by exceptions to an ordinary view of reality where when axe heads sink in a body of water we take off shoes and socks and wade out to find it. Improbable in their world. I'm sure some believed it was possible. After some more reflection on the matter I'm thinking that where to "draw the line of disbelief" or "the line of distrust," if you will,can be adifficult matter. Let's take the dynamic of "trust" which can be found multiple times in Mark's gospel. Beginning with chapter 1, trust is pictured as central to matters such as healing and danger: The leper says, If you want to you can make me clean, four trusting people bring a paralytic before Jesus, disciples in the lake storm were admonished because of their lack of trust, the synagogue official was told to just have trust regarding his ill daughter, a bleeding woman was told that her trust had cured her, in a second lake episode the disciples were assured that there was no need to be afraid, a distraught father is told that all things are possible forone who trusts, Jesus' followers are described as little ones who trust Jesus, a blind man is told that his trust has cured him, we hear that trust can move mountains and that trust ensures the answering of prayer requests, a widow is commended for her trust in giving her entire livelihood to the temple. Where is the straight rigid rational line that can be drawn between trust and outcome in these life-pictures in the same manner as one can be drawn between an axe head and water buoyancy? That line is not there. In the following scenario, should I have suspended trust because I didn't have a scientific vision of the trust line? Several years ago I had multiple bypass heart surgery. Within five minutes of meeting the surgeon I knew that he trusted himself and cared for me, and that I trusted him to do the job. I further trusted the statisticians that vouched for a 98% success rate for the planned procedure. This would be similar to the ancients meeting Jesus, experiencing his trust in himself and care for them, and trusting the testimony of others in his past successes. Of course, the statisticians and here-say fall into unimportance if the procedure is needed no matter what. I have no idea how much the positive outcome of my surgery should be attributed to trust, but I'm sure that some of the positive outcome was due to the trust of many, including myself. The laws governing my trust, it would seem, are not any less important to me than those which control an axe head in water or how far a few loaves and fishes can be stretched for a meal. May I gather that the surgery and your rehab were successful and that must have been a great relief. I am not sure what you are suggesting that I should trust from the examples of trust you offer from Mark. Are you suggesting I should trust Jesus or Mark or the Bible or ??? in the matter of floating axe heads? The example from your life (surgery) reflects an instance of your trust that brought happy results. The surgeon appeared to you to be self confident (that is he trusted himself to perform the surgery successfully) and you developed from his self-confidence and professionalism an instant trust in him and his abilities to do the surgery--not to mention your were assured a 98% success rate. If, however, the surgeon had a patch over one eye and only one hand and did not present himself well, it is a better than even chance you would have consulted another surgeon. From my perspective axe heads are like heart surgeons with an eye patch and one hand. It is a better than even chance they will not float no matter how much I trust they will. I think all I'm trying to do is call attention to the reality that scriptural insights have their own value apart from the rules which determine whether or not axe heads float. Perhaps, if you chose to trust Jesus, or Mark, or the Bible, it would not be for the same reasons or dynamic that you trust an axe head not to float. Aha! Point taken. And you are correct in my view. Discerning readers know to ignore the crass violations of our common view of reality. But alas not all are discerning readers. That is to say not all suspend disbelief when reading of the floating axe heads and are taken in reading the story literally. There are other values offered to readers of the Bible, if one knows how to read it, as you point out. Charlie, I like how you put the word "laws" of physics in quotation marks. "In the west we inherit the idea of law as something being passed down by God, and it has even passed down into science where we discuss 'laws of nature.' You don't get the idea of law until you move to a culture where order is based on the idea of obedience. Code law is a tyrannical method of law by imposition. Common law is evolved by discussion of particular cases rather than referring all the time to abstract principles put down in words. PS: The 84 year old grandfather was the one who loved that poet I told you about, Robert Service... He also loved Omar Kayam and the Rubyiat. Thanks for weighing in with your well-thought out comment. Your observation by Alan Watts I concur with. But I cannot answer your questions at the end. There are just too many variables to be able to predict the future even when you have scientific data at your finger tips. I found your Jan. 17 discussion about the Bible and the "Laws of Physics" demonstrate an effective understanding of some of basic principles in which our universe operates. I felt a need to call attention to the apparent lack of understanding of these same Laws of Physics by both Elizabeth (Jan.25) and her quoted philosopher, Alan Watts. Both mistake the complexity & variability of our natural world as evidence the fixed Laws of Physics in which our natural world operates are unpredictable and irregular. An example of this is to consider the difficulty of the relatively easy prediction of the path of the iron axe head having been thrown in the water as to the extreme difficulty in predicting what the weather might be in the near future. Both events operate within the same fixed Laws of Physics but operate under tremendously different environments. Further, it appears Elizabeth mistakenly interpreted the varying life length of family members some of who smoked cigarettes and some that did not as being evidence of this interpretation of irregularity or unpredictability of the Laws of Physics. Again the variability is in the different human bodies rather than the Laws of Physics. No two human bodies are identical nor exist in identical environments. I hope this increases the understanding of the fixed nature of the Laws of Physics. Gene and Charlie, if you don't mind I do have a carry-over question from the previous blog with regard to cults. What exactly constitutes a "cult" in your estimation? Do you have a definition? If not, that's ok. I do agree with Jim that the variability is in the human body rather than the "laws" of physics... I also see the variability involved in predicting weather patterns in the near and distant future as well, which is why I am skeptical of these wild and fantastical doomsday scenarios put out by so-called "climate change" experts. In many ways what is described as being a cult lies in the eye of the beholder. The basic definition is "a system of beliefs and rituals." It is also described as "a religion regarded as unorthodox or spurious." It is also defined as "a small circle of persons united by devotion or allegiance to an artistic or intellectual movement or figure." These are of course objective descriptions. For me personally, Charlie's dictionary definitions are far too benign. As I said in so many words in a previous post, I think that a cult consists of followers so needy that they are brainwashed into a certain extremely narrow understanding of reality by a severely personality disordered leader who demands total allegiance and perhaps even suicide. This makes them a danger to humanity. When I was younger the group in Waco, Texas, and the Jim Jones followers would fit this definition. I was struck by the fact that with the exception of a few things your description of cult in the second sentence might well fit many of our accepted larger Christian religious institutions. For example: "needy followers"; "brainwashed"; "narrow understanding of reality"; "personality disordered teacher who demands allegiance." The exceptions are cast in pejorative words like "extremely"; "severely";"total";"perhaps even suicide" (which would not fit the Branch Davidians, I don't think). I am not really sure what you have in mind when you say "brainwashed." In what way is that different from "instruction" like Sunday school and catechism? My impression is that people who enter what is thought of as a cult enter it willingly. Those who are forcibly taken from a cult for "rehabilitation" into the general society, however, I understand are subjected to rigorous methods to dispel the teachings of the "cult." Is that kind of thing what you mean by "brainwashed"? I do tend to identify more with Gene's characterization of cults than Charlies... I have attended churches in my earlier years that felt like a cult to me, but I didn't know why. And it did feel like "brainwashing," so I do know what Gene meant by that. When Charlie asked what is the difference between brainwashing and receiving instruction from Sunday school and catechism- I would say it is this: I think it is a form of brainwashing to instruct your Sunday school students to believe that the power of their prayers can literally "make an axe head float." If they just pray hard enough and believe enough and have enough faith. To me, that is brainwashing and it feels cultish in my view. However, we as parishioners were free to come and go, and were not in any way forced to join their inner circle. I have to admit to being somewhat perplexed about why this subject matter seems to have become so complicated. The key to the cult is the leader - followers are expected to accept his/her directives without question and to remove themselves from affiliation with the institutions and associations of the mainstream culture. This doesn't mean that people don't enter the cult willingly. I'm not sure why you suggest that "many of our accepted larger Christian religious institutions" would be defined primarily by folks who are "needy, brainwashed, narrow in understanding of reality, with personality disordered leaders." What institutions might be described that way? Brainwashing is distinguished from other forms of learning by not allowing for dissent within oneself or the acceptance of different perspectives in others. The only appropriate response is cultural isolation and passing along the leader's perspective to offspring. In describing a group as "a cult," you appear, it seems to me, to think cults are a different sort of thing from other religious groups. On the other hand, I think that the differences between cults and churches is a matter of degree. A cult is a religious group with a strong leader who has views that don't agree with other religious groups. It is "out of the mainstream" (probably because of its small size and what the mainstream churches think of as odd teaching). Nevertheless it does exactly the same kinds of things that mainstream churches do: instructs its members, has worship services and Bible studies, has a definite belief system (some parts of which are shared by the mainstream churches!). The leader expects that his/her views will be followed by the members of the group, as any pastor, or priest would expect. The cultic group does not like to lose members, as is the situation with mainstream churches. Mainstream churches do not tolerate disagreement on certain main points of theological teaching. People who get too far outside the theological teaching of the group can be "churched" (that is kicked out, shunned, or forbidden from participating in what the church may conceive as mediating the grace of God--in Baptist and catholic churches it would be denial of participation in the Lord's supper or the Eucharist). As to what churches do these kind of things pick one from the phonebook. If I may offer one more reply. You hit the nail on the head with a great clarification: you're right, I do think that cults are a different sort of thing from other religious groups, and it's not a matter of a continuum. In the 70's I was a pastor in the United Methodist church. My experience was that most of the members never even opened the Book of Discipline and most of the attendees intermarried with members of other denominations and faiths who were even further removed from whatever United Methodism is. I even married a Jew and Christian in the church after the families agreed that the name of Jesus would not be used in the service. I was an active member in the local ministeriums, both UM and ecumenical. I never felt like I wasn't an integral part of the group. I've known Baptist pastors and RC priests and it never occurred to me to use cult in relation to their beliefs or activities. They were not personality disordered leaders micromanaging the lives of their followers and removing them from mainstream culture. One can find statements such as the following coming from the General Conference of the UM Church: "Especially critical for Christians...has been the struggle to recognize the horror of the Holocaust as the catastrophic culmination of a long history of anti-Jewish attitudes and actions in which Christians, and sometimes the church itself, have been deeply implicated." (Quoted in LeDonne and Behrendt, Sacred Dissonance, 2017, 120). This is not the kind of self-insight pronouncement made by cult leaders. Perhaps others have denominational experiences to share! I play a very limited to a non-existent role in the church (Southern Baptist)where we have been members for 38 years, although we were never stalwarts of the church. I was gone too often for that. Currently my bible study group tolerates my views which in class I usually limit to questions on the biblical text we are studying or by asking questions of those who put views on the table with which I might disagree and occasionally I can contribute with a comment about what is currently going on in the field of biblical studies. I am not there to convince them of anything. In fact I learn something new every Sunday that I participate. Gene, rather than micromanaging the lives and beliefs of your congregation... Was the focus of your ministry more about community service and outreach? It sounds like as a minister you were not bothered by dissent or disagreement. That's very rare. Thank you for the kind words. Methodism does have a strong community service and outreach component, and I participated in interracial programs, ecumenical programs, and a 24-hour counseling service hotline, but I would say that my primary interest was to stimulate life changing insight through a challenging presentation of the scriptures at Sunday morning worship. It was very hard for me to decide if Jesus did or said this or that, being twenty years before the Jesus Seminar published their scholars' voting results. Up to that point all we had was the competing opinions of individual great minds! What do I think about dissent and disagreement - it's healthy when the proponents respect and value each other. Yes it certainly is healthy when the proponents respect and value each other- I couldn't agree more. If I had attended a church like yours, Gene, I would probably have had a much better experience. The most uplifting teachers are those who help you develop your own unique perspective about spiritual teachings- rather than imposing their own perspective upon the student. It definitely sounds like you were among the former and not the latter!
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0.92835	The ongoing mobilization of mammalian transposable elements (TEs) contributes to natural genetic variation. To survey the epigenetic control and expression of reporter genes inserted by L1 retrotransposition in diverse cellular and genomic contexts, we engineered highly sensitive, real-time L1 retrotransposon reporter constructs. Here we describe different patterns of expression and epigenetic controls of newly inserted sequences retrotransposed by L1 in various somatic cells and tissues including cultured human cancer cells, mouse embryonic stem cells, and tissues of pseudofounder transgenic mice and their progeny. In cancer cell lines, the newly inserted sequences typically underwent rapid transcriptional gene silencing, but they lacked cytosine methylation even after many cell divisions. L1 reporter expression was reversible and oscillated frequently. Silenced or variegated reporter expression was strongly and uniformly reactivated by treatment with inhibitors of histone deacetylation, revealing the mechanism for their silencing. By contrast, de novo integrants retrotransposed by L1 in pluripotent mouse embryonic stem (ES) cells underwent rapid silencing by dense cytosine methylation. Similarly, de novo cytosine methylation also was identified at new integrants when studied in several distinct somatic tissues of adult founder mice. Pre-existing L1 elements in cultured human cancer cells were stably silenced by dense cytosine methylation, whereas their transcription modestly increased when cytosine methylation was experimentally reduced in cells lacking DNA methyltransferases DNMT1 and DNMT3b. As a control, reporter genes mobilized by piggyBac (PB), a DNA transposon, revealed relatively stable and robust expression without apparent silencing in both cultured cancer cells and ES cells. We hypothesize that the de novo methylation marks at newly inserted sequences retrotransposed by L1 in early pre-implantation development are maintained or re-established in adult somatic tissues. By contrast, histone deacetylation reversibly silences L1 reporter insertions that had mobilized at later timepoints in somatic development and differentiation, e.g., in cancer cell lines. We conclude that the cellular contexts of L1 retrotransposition can determine expression or silencing of newly integrated sequences. We propose a model whereby reporter expression from somatic TE insertions reflects the timing, molecular mechanism, epigenetic controls and the genomic, cellular and developmental contexts of their integration. Approximately half of the human and mouse genomes is comprised of various classes of transposable elements (TEs). These TE insertions have mobilized by distinct mechanisms and accumulated over evolutionary time [1–4]. Until recently, such mobilization was thought to occur almost exclusively in germline cells or early in embryogenesis . However, recent studies established that L1 retrotransposons, along with other classes of mobile genetic elements, also can move actively in somatic cells, i.e., in mouse, rat and human neural progenitor cells, in the developing brain, and in certain human cancers [6–11]. This ongoing movement of endogenous TEs including L1 retrotransposons can result in diverse genetic consequences. These include insertional and deletional (indel) gains and losses of genomic fragments, exon shuffling, insertional mutagenesis of genes, probably chromosomal translocations and inversions, and expression of retrotransposon-initiated fusion transcripts (RIFTs), among others [12–22]. Much of our existing knowledge about TE-related genetic disruption was derived from specific examples of de novo insertions causing diseases in mouse and man [23–25]. By contrast, the epigenetic marks established at newly mobilized TEs have not been well characterized. Cytosine methylation is a key epigenetic regulatory mark localized predominantly within extant L1 retrotransposons and other TEs in mammalian genomes. It has been strongly associated with their transcriptional silencing and regulation, and may affect expression of adjacent genes [26, 27]. Cytosine methylation can be inherited either through mitotic or meiotic cell divisions, and in general are stably maintained. In normal somatic cells, L1 retrotransposons are heavily methylated at CpG dinucleotides, but in most cancers they become hypomethylated, potentially resulting in increased transcription and mobilization [9, 28–30]. A recent study of host epigenetic responses to L1 retrotransposition in various somatic cells including embryonal carcinoma (EC) cells showed that newly integrated L1 reporters were silenced by de novo transcriptional gene silencing (TGS) . The epigenetic modifications at newly inserted L1 retrotransposons included histone deacetylation, but not de novo cytosine methylation. By contrast, more strongly repressive epigenetic marks including cytosine methylation have been identified at recently inserted L1 elements that were transmitted via meiotic cell division through the mouse germ line in a transgenic mouse model . Similarly, reporter genes that were transduced by retrovirus mobilization or integrated randomly as a transgene typically were methylated rapidly after integration in mammalian cells [33, 34]. Such silencing has been associated with the source and sequence content of the reporter genes themselves. In classic examples of variable epigenetic silencing at mammalian TEs, changes in epigenetic marks (e.g., methylcytosine density) at pre-existing, integrated endogenous retroviruses (ERVs) have resulted in highly variable expression of nearby genes, resulting in variable phenotypes in genetically identical siblings. Variable but heritable phenotypes in the classic pseudo-agouti mouse model illustrate this impact of epigenetic regulation of an existing TE on neighboring gene expression [35–37]. The term “variegation” describes this epigenetically mediated variability in phenotypes. Typically such phenotypic variation is due to the relatively unstable inheritance of epigenetic controls at a so-called “metastable epiallele”, from a cell to its daughter cells . A related and profoundly important question asks how widespread and functionally significant are the heritable impacts of TEs on gene expression and regulation . To investigate how different cellular contexts and mechanisms of transposition may impact reporter expression and epigenetic silencing of newly mobilized TE insertions, we developed new and highly sensitive real-time reporters. We compared the reporter expression and silencing of newly integrated L1 insertions vs. of new piggyBac (PB) insertions. We corroborated recently reported results about cytosine methylation established at new L1 integrants transmitted through the mouse germ line . We observed variable reporter expression and epigenetic controls established at newly integrated L1 elements that mobilized in different genomic, cellular and developmental contexts. To define the genetic consequences of de novo L1 retrotransposition, several research groups have engineered L1 donor constructs to track mobilization [19, 40–42]. In each of these retrotransposition assays, the L1 donor was marked in its 3′ untranslated region (UTR) by a reporter gene disrupted by an artificial intron (AI). Identification of the spliced reporter gene in host genomic DNA indicated that the newly integrated element had undergone expression and splicing as an RNA intermediate, confirming that it was a bona fide product of L1 retrotransposition . To assess expression of L1 reporters that are newly mobilized by retrotransposition, we constructed novel, real-time reporter assays. Their expression levels would not be influenced by positive or negative selective pressures imposed on the cells. We first chose TEM1, encoding a beta-lactamase, to generate an exquisitely sensitive reporter assay in living cells. Its expression levels can be quantified over a very large dynamic range extending over four orders of magnitude (Additional file 1: Figure S1: ). This greatly exceeds sensitivity of other real-time reporters used in L1 retrotransposition assays. We also chose green fluorescent protein (GFP) as a second, convenient but less sensitive reporter for particular assays. Mimicking the design of other retrotransposition reporter constructs, we introduced the AI into donor cassettes to disrupt the TEM1 or GFP open reading frames (ORFs), respectively. The AI would be spliced from L1 RNA transcripts at the time of retrotransposition, so a newly integrated reporter cDNA would lack the AI and therefore could be expressed as the intact gene . We marked the full-length, retrotransposition competent, human L1.3 retrotransposon with a novel TEM1-AI reporter cassette. The resulting construct was subcloned into a stably maintained, episomal vector, i.e., pCEP4, resulting in pDES46 (Fig. 1a). Cultured human cancer cells, i.e., HCT116 and HeLa, were transfected. To assure stable maintenance of the donor plasmid episome, transfected cells were selected for Hygromycin resistance. In parallel we introduced a transient plasmid expressing GFP alone, to measure transfection efficiency. To measure beta-lactamase expression levels as a surrogate for active retrotransposition, we incubated transfected cells with CCF2-AM fluorescent substrate. Two enzymatic activities are required in this real-time assay. First, constitutive cellular esterases cleave the –AM esters, resulting in trapping of the charged CCF substrate in the cytoplasm (Additional file 1: Figure S1A). Next, the reporter beta-lactamase cleave the beta-lactam ring in CCF, disrupting fluorescence resonance energy transfer (FRET) and changing the fluorescence emission wavelength from green to blue. After incubation with CCF2-AM, cells were examined by fluorescence microscopy . Uncleaved CCF2 inside the cells would fluoresce green, implying low or absent beta-lactamase expression. In turn, this indicated either no retrotransposition, integration of only truncated TEM1 reporter gene, or silencing of the newly integrated reporter gene (Additional file 1: Figure S1). The presence of blue fluorescence indicated high levels of beta-lactamase expression and therefore robust L1 retrotransposition without silencing of the newly integrated reporter gene (Fig. 1b; Additional file 1: Figure S1). We confirmed that L1 retrotransposition was the mechanism of reporter mobilization and integration in the transfected cells. We used PCR to amplify the integrated TEM1 reporter gene across the spliced (excised) AI junction [13, 40], using primers DES657 and DES658 (Additional file 1: Table S1). To determine the detailed structures of several diverse integrants, we employed a PCR-based assay (Additional file 1: Figure S2 and Table S2) . First, we restricted genomic DNA using common 4 bp-cutting restriction endonucleases. Appropriate adaptors were ligated onto compatible overhangs, and PCR primers annealing to the L1 and the adaptor respectively were used [22, 44]. Insertion-host genomic junctions were recovered as PCR products and were assessed by Sanger sequencing, resulting in the recovery of 9 independent integrant sites. Although several integrants were not long enough to include any L1 sequence or even full-length reporter genes per se, they nevertheless were bona fide L1 retrotransposition events (Additional file 1: Figure S2 and Additional file 1: Table S2), as their structures included target site duplications (TSDs), a poly(A) tail, and occasional 5′ inversions [13, 45, 46]. At an L1 integrant on chromosome 2, an intact, spliced TEM1 gene had been inserted (Additional file 1: Figure S2). Its spliced structure and its TSDs confirmed that it had been retrotransposed. After selection on Hygromycin for 10 d, bulk populations of transfected cells were screened for beta-lactamase expression by treating them with CCF2-AM (Fig. 1b). Fluorescence microscopy revealed that the beta-lactamase expression was “variegated”. Some individual cells fluoresced bright blue, indicating robust expression of beta-lactamase as the reporter for the occurrence of at least one retrotransposition event. Other immediately adjacent cells in the same colony appeared green, indicating that the integrated reporter gene was not expressed and therefore was potentially silenced. Many other cells displayed various intermediate shades of blue and green, implying partial silencing or less-than-maximal expression of the TEM1 reporter (Fig. 1b). To quantify TEM1 reporter expression in individual cells incubated with CCF2-AM, we used flow cytometry . Wide-ranging fluorescence emissions ranging from green to blue were visualized using fluorescence microscopy for individual cells in the bulk population of transfected cells (Figs. 1b and c), and quantified using flow cytometry. Blue/green ratios were calculated as a surrogate score for beta-lactamase activity . These ratios ranged from <10 to well over 150, thereby demonstrating a large dynamic range over which beta-lactamase was differentially expressed in individual cells (Fig. 1c; Additional file 1: Figure S1). To standardize the blue and green signals in flow cytometry, all-green and all-blue cell populations also were assayed in each experiment (Additional file 1: Figure S3). To test heritability of reporter expression or silencing through multiple rounds of mitotic cell division, we isolated individual cells from these mixed populations by limiting dilution, and then grew up subcloned progeny cells. The resulting cellular clones were stained with CCF2-AM and then visualized by fluorescence microscopy (Fig. 1d). Resulting subcloned daughter cells recurrently stained various shades of blue and green, documenting continued variability in reporter expression. Occasional colonies contained mostly blue cells, indicating high levels of reporter expression amongst most of the cloned daughter cells. However, even in such predominantly blue subclones, occasional green cells arose, indicating the stochastic and dynamic establishment of reporter silencing. Upon a second round of cell subcloning by sequential limiting dilution, again we observed mitotically heritable patterns of reporter expression, revealing mostly stable (blue) or variable (mixed) expression of L1 reporter integrants. This result again suggested that while the states of reporter expression or silencing were mostly heritable, they also could oscillate (Fig. 1d). This variability in expression implied that the newly inserted L1 reporters are epigenetically regulated. To assess whether the variable L1 reporter expression could be attributed to variable numbers and locations of newly integrated L1 reporters, we used Southern blotting to investigate eight related cell lines that had been subcloned from the same initial population of HeLa transfectants (Fig. 2). These clones and their subclones displayed different levels of L1 reporter expression, i.e., either mostly high (staining blue), or variegated (mixed, oscillating) cells including many that were green (i.e., low beta-lactamase expressing). A radiolabeled probe specific for the β-lactamase reporter was used to detect the reporter gene copies in the clones. Almost all subclones shared 7 or more bands of various molecular weights, including a dominant one similar in size to the donor pDES46 episome. Occasional single bands also were detected in a few of the individual clones (Fig. 2), without apparent correlation with expression levels, suggesting gains or losses of additional retrotransposition events. Although the reporter expression levels diverged markedly between these cell clones, the pattern of TEM1 bands was mostly similar amongst the cell clones and subclones. This suggested that the variable reporter expression was likely due to epigenetic variation between the clones, since their genetic variation appeared to be limited. In previous studies of human L1 retrotransposition in cultured cancer cells, expression of the integrated Neo R reporter was enforced by positive selection [13, 40]. Selection with the drug G418 imposed a requirement for strong expression of the Neo resistance gene, since cells lacking it would be killed. Thus we reasoned that epigenetic marks observed at newly retrotransposed Neo R reporters could have been in favor of active, euchromatic marks. In addition to finding many truncated de novo L1 insertions, we previously mapped two full-length L1 insertions, on chrs. 2 and 14 of transfected HCT116 cells . These newly inserted sequences that were retrotransposed by L1 each included 5′ transduction of adjacent 5′ CMV promoter fragments. Their identification provided us with a unique opportunity to study de novo cytosine methylation, established both at the inserted reporter and several kilobases upstream in the 5′ transduced sequences and in the proximal L1 5′ UTR. We measured DNA methylation using conventional bisulfite conversion followed by PCR amplification and sequencing. We found virtually no DNA methylation at the 5′ UTR of both insertions, as only 2.9 and 0.4% of all CpG dinucleotides at those locations were methylated, respectively (Fig. 3). In addition, as expected, the spliced reporter integrants at the 3′ ends of these full-length L1 integrants also were almost entirely unmethylated; only 0.4% of all their CpG dinucleotides were methylated (Fig. 3). To confirm that the host cells still harbored effective maintenance methyltransferase activity, we measured cytosine methylation within the proximal portion of 5′ UTRs of pre-existing genomic L1Hs elements. They were densely methylated (~64% on average, Additional file 1: Figure S4), confirming that methylated CpG dinucleotides (meCpG) are maintained in the cultured cancer cells. The bisulfite sequencing assay may underestimate unmethylated cytosine content at CpG dinucleotides, as many cytosines undergo spontaneous deamination over time [48, 49], resulting in TpG dinucleotides. Such pre-existing mutations are indistinguishable from unmethylated CpG dinucleotides upon treatment with bisulfite. In mutant double knockout (DKO) HCT116 cells, which lack both the maintenance DNA methyltransferase gene DNMT1 and the de novo methyltransferase DNMT3b , cytosine methylation at pre-existing L1 elements was markedly reduced. Only ~6.5% of all CpG dinucleotides remained methylated in DKO cells (Additional file 1: Figure S4), reflecting a ~90% reduction in L1 methylation. Because cytosine methylation is a strong and stable mediator of transcriptional gene silencing (TGS) , we compared L1 transcript levels in DKO cells vs. their parental (wildtype) controls. We conducted expression profiling by performing long-read serial analysis of gene expression (LongSAGE) . We corroborated the results using several other transcript profiling methods (manuscript in preparation). Transcription of pre-existing genomic L1 templates (measured at their 3′ ends) was only minimally detectable in HCT116 cells (Additional file 1: Table S3), as expected . By contrast, L1 transcript levels were increased modestly (approximately 3-fold) in the DKO cells (Additional file 1: Table S3), consistent with derepression of the TGS regulating their expression. We conducted bisulfite sequencing to examine cytosine methylation levels at several independently retrotransposed, spliced TEM1 reporter integrants. After their retrotransposition, inserted L1 reporter sequences were retained in the host cell genomes in the absence of imposed positive selection. As was the case with L1-Neo R integrants (Fig. 3), both the integrated L1 reporter TEM1 (including 18 CpG dinucleotides in an amplicon spanning the splice site in an artificial intron), and an L1 integrant including a portion of the SV40 promoter and TEM1 reporter (including 20 CpGs) were almost completely unmethylated (Additional file 1: Figure S5). Therefore de novo cytosine methylation played no role in silencing or variegated expression of the TEM1 reporter in these cultured cancer cells (Fig. 1). These results corroborated what we observed after positive selection on Neo R (also driven by the SV40 promoter as described in and ), suggesting that regardless of imposed selection, only minimal methylation is established at new L1 integrants. Several of the newly integrated sequences retrotransposed by L1 that were recovered from HeLa cells had inserted into repetitive elements pre-existing in the host genome (Additional file 1: Table S2). Nevertheless, bisulfite sequencing analysis of new reporter insertions in bulk showed that most were unmethylated (data not shown). This result suggests that the epigenetic controls established at de novo L1 insertions do not reflect spreading of the repressive marks already maintained at neighboring, extant repetitive elements. The heritability and the variability in L1 reporter expression in cultured cancer cells suggested that new L1 insertions are epigenetically silenced. To evaluate the possibility that histone tail lysine acetylation could be involved in L1 reporter silencing, we investigated several subcloned cell lines harboring reporter integrants whose expression was variegated or mostly repressed. We treated the cells with various histone deacetylase (HDAC) inhibitors including 100 nM trichostatin A (TsA), 10 mM sodium butyrate, 1 μM scriptaid, 1 nM apicin, and 5 mM nicotinamide (Fig. 4 and Additional file 1: Figure S6). Each of these agents was added in standard growth medium to the cultured cells. Upon incubation for 24 h, expression of the silenced reporter gene was reactivated in virtually all cells. Treated cells showed consistently high levels of TEM1 reporter expression, as demonstrated by their uniform blue fluorescence upon staining with CCF2-AM (Fig. 4 and Additional file 1: Figure S6). Thus a broad range of HDAC inhibitors from different mechanistic categories was active in de-repressing the silenced reporters. Upon withdrawal of the HDAC inhibitor TsA from derepressed cells by washout of the drug, silencing of the TEM1 reporter was gradually re-established over 1 – 3 days (Additional file 1: Figure S7). This resetting of L1 reporter silencing demonstrated that it can be dynamically re-established and is reversible. In addition, the state of reporter expression generally appears to be heritable (Fig. 1d). Thus we conclude that the establishment and maintenance of L1 retrotransposon silencing in cultured human cancer cells is consistent with a de novo epigenetic mechanism involving dynamic changes in histone lysine deacetylation, but not cytosine methylation. To study epigenetic controls at de novo L1 integrants in other cellular and developmental contexts, we induced new mobilization of a highly active synthetic L1 retrotransposon in mouse ES cells. The Bruce4 parental ES cell line was transfected with linearized pJH435, resulting in an inducible, codon-optimized synthetic mouse L1 (smL1, ORFeus) donor present in the genome of the resulting Truck_305 cells . We activated L1 retrotransposition by infecting the Truck_305 cells with an adenovirus expressing Cre recombinase, to remove the floxed beta-geo gene from their donor construct. This resulted in the juxtaposition of ORFeus ORF1 and ORF2 directly downstream of the CAG promoter, thereby activating smL! transcription and potentially their mobilization . After exposing the Truck_305 mES cells to Cre, individual colonies were picked without regard to GFPuv expression, to derive subclonal populations potentially harboring new smL1 insertions. Genomic DNA was isolated from several of these mES cell clones. We did not routinely screen for GFPuv expression using excitation light in the UV range, because a high fluorescence background was observed in cultured cells. In addition, the UV light required to excite GFPuv would be expected to damage the cells when examined, so they could not be cultured further. Instead, linear amplification mediated-PCR (LAM-PCR) was performed to recover any new L1 ORFeus integrants, regardless of their expression of GFPuv. They were sequenced and mapped, and custom bisulfite sequencing primers were designed. Genomic DNA was modified with sodium bisulfite, and then PCR amplification was performed using primers internal to the reporter, or alternatively to target individual integrants. Amplicons were cloned and sequenced. The results showed heavy methylation of the retrotransposed reporter gene, assayed either in bulk or from individual L1 integrants (Fig. 5). To evaluate silencing of a second, independent reporter gene, we also transfected pJL5, a donor plasmid encoding L1 ORFeus marked by TEM1-AI in its 3′ UTR, into mES cells (not shown). Minimal expression of integrated L1 reporters was observed, consistent with dense de novo cytosine methylation resulting in strong silencing. An alternative explanation for low beta-lactamase expression was that L1 ORFeus did not retrotranspose efficiently in mES cells. However, this same donor element mobilized very actively in various cultured cancer cell lines [19, 55]. Upon limiting dilution, we observed rare mES subclones that exhibited stable, robust reporter expression, suggesting derepressed newly retrotransposed reporter insertions. However, their DNA methylation was not investigated further. To study the epigenetic modifications established at new L1 integrants in vivo, we obtained several tissues from a transgenic mouse model, in which L1 ORFeus had retrotransposed initially in “pseudofounder” animals. Pseudofounder mice were defined as those mice in the first generation that harbored new, spliced L1 insertions but lacked the unspliced donor element. Their progeny also harbored some of the same, newly retrotransposed L1 ORFeus insertions as were present in the initial pseudofounders themselves, showing that these genomic L1 insertions could be transmitted through the germ line. The new L1 insertions likely had retrotransposed from the donor episome, immediately after its injection as a transgene and before its loss due to cell division during early embryogenesis . We measured de novo cytosine methylation established at the newly mobilized L1 ORFeus integrants in the pseudofounders, as well as at some of the same integrants transmitted to offspring [55, 56]. Genomic DNAs isolated from various somatic tissues from members of three pedigrees were treated with sodium bisulfite and sequenced (Fig. 6). The results showed that almost all of the CpGs in independent de novo L1 integrants were methylated in two independent pseudofounder mice, F235 and F234 (Fig. 6), in a variety of somatic tissues including the tail and various internal organs. We also used locus-specific primers to conduct bisulfite sequencing PCR at particular genomic targets (Fig. 6). Tail DNA samples from N2 generation mouse B386 and its progeny B864 and B867 (N3 generation) were used for this more focused study. As was the case with the bulk assays, almost all CpG dinucleotides at the specific genomic target sites were methylated (Fig. 6d). Dense cytosine methylation also was observed in other somatic tissues and at independent L1 insertions in mouse B389 and its offspring, as well as in other mice (Fig. 6; data not shown). Taken together, these results demonstrated that: a) new L1 insertions occurring early in embryogenesis underwent dense, de novo methylation during development; b) methylation was maintained through differentiation into a range of tissues in the developing organism; and c) methylation at such new L1 insertions was maintained and/or re-established upon their transmission through the germline. To compare reporter integrants mobilized by different mechanisms into distinct genomic targets, the same reporter genes, including TEM1 and green fluorescent protein (GFP), were engineered to be mobilized as cargo by PB DNA transposons. A large majority of HeLa cells harboring newly transposed integrants displayed stable, robust expression of the reporters when mobilized by PB (Fig. 7). We observed a bimodal distribution of reporter expression, i.e., with individual cells displaying either robust expression or no expression (Fig. 7) and minimal or no variegation. As a negative control, we transfected the reporter gene plasmid alone, without PB transposase. In resulting transfected cells, no integration events were detected, the transient donor plasmid harboring the unintegrated reporter gene was gradually lost, and no reporter gene expression was observed after several days in culture. In cells that had been transfected with PB transposase and the reporter donor, and then subcloned by limiting dilution, we occasionally observed a small fraction of the cells expressing stably diminished levels of the reporter protein. In additional control experiments, we also launched PB transposons carrying comparable reporter genes in mES cells. As was observed in cancer cell lines, expression levels of integrated PB reporters in mES cells remained at high levels even after many days of culture (Fig. 7). No variegation or decreases in reporter expression were detected. Therefore, they underwent no or only minimal epigenetic silencing. Flow cytometry experiments confirmed a biomodal distribution of reporter expression in mES cells with PB transposition, indicating a lack of variegation and silencing of PB insertions (not shown), distinct from that observed after L1 retrotransposition. Endogenous retrotransposons comprise a substantial portion of the mouse and human genomes. Several distinct TE families have modified the mammalian genome profoundly over evolutionary time [57, 58]. The genetic and genomic changes caused by endogenous mobilization of human or mouse L1 retrotransposons have been well studied. By contrast, the epigenetic regulation of de novo L1 integrants has not been evaluated fully in the wide-ranging biological contexts in which retrotransposition can occur [39, 59]. Here we investigated the expression and epigenetic silencing of newly integrated L1 reporters in cultured human cancer cells, mouse ES cells, and in several tissues of pseudofounder transgenic mice and their progeny. The results revealed distinctive patterns of L1 reporter expression and associated epigenetic marks, which are associated with the genomic, cellular and developmental contexts of mobilization. Newly retrotransposed and integrated L1 reporters in cultured human cancer cells frequently were silenced. This silencing was heritable, as daughter cells tended to display levels of reporter expression that were similar to their parents after mitotic cell divisions (Fig. 1). However, L1 reporter expression also was variegated and oscillated dynamically, as it occasionally ranged from almost completely silenced to high levels of expression over just a single or a few cell divisions (Fig. 1). Despite virtually identical patterns of L1 insertoins at a genetic level, cell clones displayed marked differences in phenotypes, suggesting epigenetic regulation of reporter expression (Fig. 2). New L1 reporter integrants remained almost completely unmethylated, even after many cell divisions, regardless of their expression levels (Fig. 3). L1 reporters were silenced rapidly by histone tail deacetylation, as shown by strong, uniform reactivation of reporter expression upon treatment with any of several diverse HDAC inhibitors (Fig. 4, Additional file 1: Figure S6). Histone deacetylation-mediated L1 silencing was re-established within 2–3 days in most cells upon removal of those inhibitors (Additional file 1: Figure S7). We speculate that this variegated expression of reporter sequences retrotransposed by L1 in cultured cancer cells may reflect the timing of their integration, i.e., at later stages of somatic development (Fig. 8), when cellular de novo methyltransferases are expressed at low levels . Retrotransposon silencing typically may be both incomplete and stochastic . Thus the observed variegation in new reporter expression may be explained by this stochastic nature of L1 silencing. Although variegation typically is mitotically stable, the inheritance of a heterochromatic state may rapidly switch from a repressed chromatin state to an open state . The variegated pattern of cells expressing high and low L1 reporter level observed here could be due to rapid changes in chromatin structure induced by L1 integration . An alternative explanation for variegation of L1 reporter expression in cultured cancer cells could be related to genome-wide hypomethylation observed in most human cancers. In contrast to the variegated, HDAC-mediated silencing of newly retrotransposed L1 integrants in cultured cancer cells, new L1 insertions in mouse ES cells were silenced by dense de novo CpG methylation (Figs. 5 and 8). Totipotent mouse embryonic stem (mES) cells can be viewed as a surrogate for the undifferentiated cells present in early embryos. Notably, abundant de novo methyltransferases are expressed in both ES cells and early postimplantation embryos . In addition, we observed that new L1 integrants, present in the differentiated somatic tissues of adult pseudofounder mice, also were stably silenced by dense cytosine methylation (Figs. 6 and 8). This dense cytosine methylation may represent faithful maintenance of the initial epigenetic marks established very early during embryogenesis when the insertions occurred (Fig. 8). Dense cytosine methylation in mES cells may mimic epigenetic controls established in early development in vivo (Figs. 5 and 6). One plausible explanation is that de novo DNA methyltransferases, which are highly expressed in early embryogenesis and in ES cells , could target the newly inserted L1 cDNA sequences, which initially would be unmethylated at time of integration. In developing embryos, these enzymes normally re-establish DNA methyation after a wave of hypomethylation erases most methylcytosine marks. A recent study of extant L1 expression in human ES cells suggested that predominantly those elements localized in expressed genes were expressed, while others located outside of such genes were not . However, this differential expression of L1 elements may reflect overlapping expression of flanking gene exons which would include intronic L1s, rather than the specific expression of intronic L1s per se. In addition, the activation of endogenous L1 expression, upon reprogramming somatic cells into induced pluripotent stem (iPS) cells, also implied that epigenetic derepression of silenced elements can occur . By contrast, another group reported that silencing of TEs is stable during reprogramming of somatic cells to iPS cells . We conclude that the distinct types of reporter expression and epigenetic regulation of new L1 insertions observed in mES cells or somatic tissues in vivo, in comparison with those in cultured somatic cells, could be related to the different cellular contexts or stages of differentiation in which L1 mobilization occurred initially (Fig. 8). We inferred that the observed epigenetic marks at de novo L1 integrants could reflect the developmental timing at which they integrated (Fig. 8), by defining the epigenetic marks established and then maintained at new integrants. Notably, we measured reporter expression and epigenetic silencing long after the time of retrotransposition per se, i.e., after many cell divisions. This limitation was due to current technical constraints, since initially the L1 donor elements had retrotransposed in individual cells that are experimentally inaccessible except by single cell cloning and sequencing, or upon embryonic development and tissue differentiation. The resulting, distinct forms of silencing at newly integrated L1 reporters observed in various contexts may have important implications for the expression of the L1s themselves, for the regulation of other genes neighboring the new insertions, and for chromosomal architecture. We conclude that de novo L1 retrotransposition can contribute to significant variability in epigenetic marks established in cellular genomes. In contrast to our observations about a lack of de novo methylation at newly inserted L1 seuqences, previous experiments have demonstrated that newly inserted foreign DNA can undergo de novo methylation in cultured somatic cells [67, 68]. Therefore, as a control, we used PB DNA transposons to mobilize the same reporter genes, both in cultured cancer cells and in mES cells (Fig. 7). Although our L1 or PB reporters are comparable to transgenic insertions of foreign DNA in various cellular contexts, there are several fundamental differences. For example, the target site preferences of L1 retrotransposition vs. PB transposition vs. random integrants of transgenesis are all distinct. While multiple copies of a transgene frequently can recombine at a single genomic locus , individual copies of L1 reporter genes typically integrate at interspersed genomic sites. We observed two key differences in silencing of de novo L1 reporter integrants vs. PB integrants. First, we observed minimal or no variegation of PB reporter expression; instead, their expression appeared to be mostly “all or none”. Second, the percentage of cells in which PB reporter integrants were silenced was much lower than that with variegated or silenced L1 integrants. These results also are consistent with a lack of PB integrant silencing observed in vivo [70, 71]. We speculate that these differences between L1 vs. PB reporter expression or silencing may reflect different genomic target site preferences of their mobilization. The differences also could be related to differences in the mechanisms of transposition by these elements. Thus, in comparison with the target sites of new L1 integrants, which are enriched slightly in intergenic genomic regions or are distributed randomly , more than half of PB integrant sites are enriched inside expressed genes . Alternatively, the PB-mobilized insertions would include PB inverted terminal repeats which could serve as insulators. However, a recent study showed that incorporation of bona fide insulator sequences flanking the transgenic PB reporter genes increased their expression . This suggests that the PB sequences themselves may possess only minimal insulator activity. In a recent study of epigenetic silencing of new L1 insertions in human embryonic carcinoma (EC) cells, histone deacetylation was identified as the silencing mechanism . We note important similarities and differences between that study’s results and our data. We confirmed that histone deacetylation occurs at new L1 insertions, but only in cultured cancer cells and not in mES cells. We found that new L1 insertions were densely methylated in mES cells (Fig. 5), whereas new insertions in hEC cells were not silenced by cytosine methylation . The discrepancy could be attributed to differences in the host cells’ species of origin; different epigenetic mechanisms operating in hEC vs. mES cells; distinct structures or sequences of the mobilized elements themselves; or various extents to which the cells had differentiated in vitro. Notably, ES and EC cells represent very different stages of differentiation , despite similar levels of expression of “stem cell-like” markers such as OCT4. ES cells are derived from the inner cell mass of developing embryos, while EC cells are derived from germ cell tumors. Compared with ES cells, the EC cell line PA-1 represents a later stage of embryogenesis. Mouse EC cells have been shown to express full length RNA and ORF1p from pre-existing L1 elements . However, a possible relationship between de-repressed chromatin in mES cells or hEC cells and the establishment of de novo epigenetic controls established at new L1 insertions is still unclear. We also studied silencing of newly mobilized L1 insertions in vivo, both in differentiated tissues of pseudofounder mice and in their offspring. By contrast, the prior study did not include an analysis of silencing of new integrants in vivo . In addition, the mobile genetic elements used as controls in the two studies to compare with L1 mobilization were very different. In the prior study, HIV-like retroviruses mobilized the transgenic reporter genes , whereas we used PB, a DNA transposon, to compare with L1 reporter silencing. These control vectors differ in their mechanisms of integration, genomic target sites, and the frequency of insertions generated per host genome. Each of these factors could play significant roles in shaping the downstream epigenetic silencing marks established at the new insertions. We acknowledge potential limitations in our study. First, to investigate the state of expression and epigenetic regulation of newly inserted sequences that were mobilized by TEs, we artificially marked the L1 and PB donor elements using engineered, heterologous reporters including several different strong promoters and terminators. In comparison with native, unmarked elements, these reporter genes incorporated into donor TEs potentially could interfere with their mobilization. Moreover, upon integration they could trigger antisense transcripts or otherwise artificially trigger or disrupt silencing by mimicking actively transcribed, protein-coding gene. A recent study noted that differences in promoters, reporter sequences or integration sites could influence reporter expression and thereby affect the study conclusions . Second, we did not investigate L1 insertions that had newly integrated in germ line tissues. Extensive research has been conducted on the epigenetic control of pre-existing TEs in germ tissues during embryonic development. They appear to undergo a wave of demethylation followed by two distinct waves of de novo cytosine methylation [32, 79]. PIWI-interacting small RNAs (piRNAs), whose transcription is frequently initiated from TEs in germ tissues, mediate their regulation and silencing. Recent evidence also indicates that DNA methylation in hES cells is induced by PIWI/piRNA-mediated silencing. Small RNAs also may play important roles in guiding establishment of de novo methylation in somatic tissues . We currently are studying roles of possible small RNAs, e.g., including those generated from antisense transcripts , in targeting de novo methylation. Third, new insertions were not identified immediately after their integration in single cells. This approach has become technically possible recently, so we could identify and characterize new insertions in individual cells or very small subclonal populations within a few cell divisions of integration. Their minimal allelic fractions would require use of ultra-deep sequencing, making further analysis technically difficult but feasible for the first time. Fourth, we did not perform chromatin immunoprecipitation (ChIP) experiments to assess enrichment of particular histone modfiications at the new L1 integrants, although we measured cytosine methylation in detail. However, in a recent paper describing L1 reporter silencing by histone deacetylation in hEC cells, confirmatory ChIP data were strongly consistent with our HDAC drug inhibition studies (Fig. 4, Additional file 1: Figure S6). The donor TE constructs used here did not include a means to terminate conditionally their capacity for ongoing retrotransposition. Future designs will incorporate this feature, to avoid the potential for ongoing genetic variability, e.g., after subcloning individual cells. In some cases, rather than assay for reporter expression, we monitored retrotransposition by using PCR-based assays to identify genomic insertions of newly transposed reporter genes. As was the case with reporter expression assays used here, we did not select positively or negatively on cells harboring such inserted sequences to preferentially include expressed reporters or exclude silenced reporters. And finally, although in vivo mouse models harboring control PB donor elements have been developed, whereby we could compare their silencing during development and in diverse tissues, such strains were unavailable to us. However, published studies have indicated that PB insertions typically are not silenced even when selection is not imposed [70, 80]. In summary, we showed here that the expression and silencing of newly integrated sequences mobilized by L1 retrotransposition appear to be associated with the cellular, developmental and genomic contexts of their integration. We hypothesize that the distinct epigenetic marks set up at new TE insertions that integrated in different cellular or developmental contexts may have various downstream consequences. For example, recent evidence suggests that most new somatic L1 insertions mobilized during human cancer development can mediate only minimal, if any, impacts on neighboring gene expression, unless they cause direct insertional mutagenesis of coding exons [11, 25]. By contrast, new insertions occurring early in development could more significantly disrupt the expression of neighboring genes, in part because their allelic fraction would be higher. In addition, the epigenetic silencing including cytosine methylation that is established at them would be expected to be more repressive and stable (Fig. 8). Thus we speculate that somatic TE that integrated early in development would exert stronger disruptive effects on neighboring genes, because more repressive epigenetic controls including methylcytosine marks would be established at them. These findings can be compared with those of Doerfler et al., who characterized de novo methylation established at foreign DNA introduced into mammalian cell genomes . We propose that these findings may have important practical implications for evaluation and understanding of new TE insertions in various biological contexts. For example, they may facilitate a novel experimental assay of transposition timing, i.e., to identify when the elements mobilized in vivo. Thus we would expect to find dense cytosine methylation strongly repressing newly integrated, polymorphic L1 insertions that were mobilized early in development or passed through the germ line (Fig. 8). Such integrants might be present at a high allele fraction (e.g., 50%, in heterozygosity). By contrast, a somatic L1 polymorphism occurring later in development or differentiation would be expected to be mosaic, so it would be present at a much lower allelic fraction in one tissue and not another, such as in a tumor but not in matched normal tissues. This type of new insertion would be silenced more dynamically and reversibly by histone deacetylation. These epigenetic characteristics would suggest that its mobilization occurred in differentiated somatic cells. Analysis of newly inserted genomic sequences retrotransposed by L1 in various somatic cells and tissues revealed distinct patterns of expression and epigenetic regulation. In cancer cell lines, the newly retrotransposed integrants typically underwent rapid transcriptional gene silencing, but they lacked cytosine methylation, and their reporter expression was reversible and oscillated frequently. Silenced or variegated reporter expression was strongly and uniformly reactivated by treatment with inhibitors of histone deacetylation. By contrast, newly inserted sequences retrotransposed by L1 in mouse embryonic stem (ES) cells underwent rapid silencing by dense cytosine methylation. Similarly, de novo cytosine methylation at new integrants also was observed in several distinct somatic tissues of adult pseudofounder mice. We conclude that the host cellular and developmental contexts of retrotransposition are significant determinants of reporter expression and epigenetic silencing at newly integrated sequences mobilized by L1 retrotransposition. We have proposed a model whereby reporter expression of somatic TE integrants reflects the timing, molecular mechanism, epigenetic controls and the genomic, cellular and developmental contexts of their mobilization. To construct an L1 donor launched from an episomal plasmid, i.e., pDES46 (Fig. 1), where human L1 was marked by the TEM1-AI beta-lactamase/artificial intron (AI) reporter cassette inserted into its 3′ UTR, we first deleted the BamHI site in ORF2 of human L1.3 as present in pJM101/L1.3 (kindly provided by Dr. John V. Moran, Univ. Michigan) using site-directed mutagenesis. The L1.3/NeoR-AI promoter cassette was then moved into pBSII-KS using NotI and BamHI. We then introduced double-stranded oligonucleotides (containing Bst1107I -HSVTKpolyA-MluI) to replace the NeoR-AI and promoter fragments from pJM101/L1.3. BseRI sites were introduced to flank both TEM1 (sequences obtained from the vector pBLAK-b which were then codon optimized) and beta-globin AI, using fusion PCR. Both of these constructs were cut out using BseRI and ligated together seamlessly. The resulting L1.3/TEM1-AI construct was then excised from pBSII-KS using NotI and BamHI and ligated into pCEP4 (Invitrogen), yielding pDES46. As previously described, a conditionally activated mouse synthetic L1 donor, i.e., pJH435 (Fig. 5), was constructed by introducing a loxP-stop-loxP cassette between a strong composite promoter and the ORFeus L1 donor . This construct consisted of a composite CMV immediate early enhancer and modified chicken beta-actin promoter; a floxed beta-geo/stop cassette comprised of a hybrid beta-galactosidase/neomycin phosphotransferase fusion gene and triple tandem copies of the SV40 late polyadenylation signal; L1 ORFeus ORF1 and ORF2 ; a GFP-based retrotransposition indicator cassette with its own promoter and polyadenylation signal; and beta-globin polyadenylation signal. The constitutively active mouse synthetic L1 donor, i.e., pJL5, was prepared by cloning the TEM1-AI reporter cassette into the 3′ UTR of L1 ORFeus. Similar to pDES46, pJL5 also was cloned in the episomal plasmid pCEP4 backbone. HCT116 (human colorectal carcinoma) cells, kindly provided by Drs. Ina Rhee, Christoph Lengauer and Bert Vogelstein (Johns Hopkins University), were cultured in McCoy’s 5A modified medium (Gibco, Life Technologies) supplemented with 10% heat inactivated fetal bovine serum (FBS) and 1% penicillin-streptomycin (P/S), at 37 °C and 5% CO2 in a humidified chamber. HeLa.JVM (a subclone of human cervical carcinoma) cells, provided by Dr. John V. Moran (University of Michigan), were cultured in Dulbecco’s Modified Eagle Medium (DMEM) with the same supplements as HCT116 cells. E14Tg2a.4 mouse embryonic stem (ES) cells, derived from 129P2 ES cells, were provided by Dr. Allan Bradley (Sanger Institute) and the BayGenomics resource. They were cultured without feeder cells in Glasgow’s Modified Eagle’s Medium (Sigma Aldrich) supplemented with 10% ES cell-qualified FBS, 1% non-essential amino acids, 1% L-glutamine, 1% sodium pyruvate, 0.1 mM 2-mercaptoethanol (2ME) and ESGRO (Millipore) at 1000U/mL in a 7% CO2 atmosphere. Fugene 6 (Roche Applied Science, USA) was used to transfect the cultured cancer cell lines. Cells were transfected with pDES46 and were selected on Hygromycin (Invitrogen) at 0.3 mg/ml for 2 weeks. Resulting HygroR cells were cloned by limiting dilution into 96-well plates and screened for single colonies. Colonies were assayed for TEM1p beta-lactamase expression using the CCF2-AM assay . Certain colonies were picked for further downstream analysis. Mouse ES cells including Bruce4 cells (provided by Dr. Colin Stewart, NCI; ), and the resulting Truck_305 cells containing a mouse synthetic L1 ORFeus donor transgene (purchased from Ozgene ), were grown in high-glucose DMEM, supplemented with 15% ES-cell-qualified FBS, 1% L-glutamine, 1% non-essential amino acids, 0.1 mM 2ME, 50 U/ml of P/S and ESGRO in 10% CO2. For feeder cells, Neo2-expressing mouse embryonic fibroblasts (MEFs) were cultured in DMEM supplemented with 10% FBS and 1% P/S, in 5% CO2, arrested using Mitomycin C or gamma irradiation, and seeded in dishes. The mES cells were added 2–3 days after feeder cell seeding. To activate L1 retrotransposition in these cells, an adenoviral vector encoding Cre recombinase was introduced to excise the lacZ LSL cassette. Briefly, one million Truck_305 cells were incubated for 30 min with the adenoviral Cre vector (Viral Technology Laboratory, NCI Frederick) in a 7% CO2 incubator, at various multiplicities of infection (MOIs) ranging from 10 to 200 per cell, and then plated into a well of a 6-well dish that was pre-seeded with mouse feeder (PMEF) cells. Cells were evaluated for cell death by light microscopy after 18 h incubation. Based on the extent of cell death and colony morphology, MOIs 25 and 50 were found to be optimal. Cell clones exposed to these MOIs were expanded. After at least 12 d in culture, with periodic changes of culture medium, cells were stained with crystal violet and X-gal, to visualize the colonies and assay for presence of the lacZ LSL cassette. ES cell clones that did not stain blue with X-gal, which indicated activated smL1 expression and potential retrotransposition, were propagated. To quantify beta-lactamase activity and protein expression, cells were stained with CCF2-AM substrate (Life Technologies) by replacing culture medium with 1 mL loading solution (2 μL of a 1 mM CCF2-AM solution, 16 μl of Solution B, 10 μl of 250 mM Probenicid (Sigma) and 972 μl Hanks’ Balanced Salt Solution, HBSS) per 9.6 cm2 well. Cells were incubated in the dark at room temperature for one hr with gentle shaking, washed with HBSS, and visualized using an Axiovert 200 M inverted fluorescence microscope (Zeiss) equipped with blue/aqua and beta-lactamase ratio filter sets (Chroma Technology Corp.) and either an ORCA-ER high resolution digital camera (Hamamatsu Photonics) using Openlab software (version 4.0.2, Improvision), or a Zeiss camera using AxioVision software. Flow cytometric analysis was performed using a BD LSR II flow cytometer with a 405 nm violet laser, 440/40 nm (blue) and 530/30 nm (green) filters, and FACSDiva software (BD Biosciences). Ratios of blue to green intensities were collected as a linear parameter. Each flow cytometry session included positive and negative controls to normalize outputs. Transgenic founder and pseudofounder mice were generated by pronuclear injection of linearized, marked smL1 donor cassette into fertilized eggs as described previously . The unspliced L1 donor construct as well as spliced new genomic L1 insertions were identified by PCR amplification of the reporter gene, into and/or across the AI, respectively. Pseudofounder mice were defined by the presence of new spliced L1 insertions and the absence of the unspliced donor element. Their progeny were generated by backcrossing the founder and pseudofounder mice with wildtype mice. Certain de novo L1 integrants were transmitted in heterozygosity. To extract genomic DNA, we added 600 μL lysis buffer with 420 μg/mL of proteinase K to cells growing in a 48 well plate. Lysis buffer consisted of 50 mM Tris-Cl, pH 8.0, 100 mM EDTA, 100 mM NaCl and 1% SDS. Next, 200 uL saturated NaCl was added, followed by an equal volume of isopropanol. After centrifugation, DNA pellets were washed with 70% ethanol, dried and resuspended in TE buffer. Southern blotting was performed to identify lengths and amounts of genomic fragments harboring new TE insertions. Genomic DNA was electrophoresced, blotted, and probed for the TEM1 reporter using standard methods. For recovery of TE integrants in cultured cancer cells using inverse PCR (iPCR), genomic DNA isolated from clonal populations of cells was digested with a restriction enzyme (RE) such as XbaI, EcoRI or HindIII. Upon heat inactivation of the RE, digested products were diluted to 1 ng/μL in a total of 500 μL, and incubated with T4 DNA ligase overnight at 16 °C for intra-molecular ligation. After ethanol precipitation, DNA was resuspended and used in iPCR reactions using primers DES682 and DES209 which annealed to the 3′ end of the retrotransposed cassette. PCR reactions consisted of 40 cycles at 94 °C for 30 s, 55 °C for 30 s and 72 °C for 2 m 20 s. Each of the several bands observed by gel electropheresis after PCR were cloned into pCR2.1 using TOPO cloning kit (Invitrogen) and transformed into bacteria. Colony PCR using M13 forward and reverse primers was used to identify bacterial colonies containing cloned insert. PCR products were cleaned up and sequenced. To map de novo insertion sites, Sanger sequence reads were aligned against the reference human genome (hg19) using Blat. To map new L1 integrants in mES cells using linear amplification-mediated (LAM-) PCR, we chose three ES cell clones (i.e., 1B6, 1C6 and 2B2) in which the spliced (i.e., retrotransposed) reporter gene had been identified by PCR assays. LAM-PCR reactions were set up with 50 ng gDNA from each ES cell clone, 2 nM dNTPs, 5 nM 5′-biotinylated primers DES3171 or DES3174, 1 uL of Advantage 2 enzyme in 1× buffer (Clontech), for 50 cycles (20 s at 95C, 45 s at 60C, and 90 s at 68C). Streptavidin-coated magnetic beads (200 mcg) were washed twice in 100 μL of binding buffer (1 M NaCl, 5 mM Tris, pH 7.5, 0.5 mM EDTA) using a magnetic separation stand, resuspended in 50 μL of 2× binding buffer, and mixed with the linear PCR reaction. The suspension was incubated for 60 min at RT under constant agitation, and then washed three times in 200 μL of wash buffer (10 mM NaCl, 5 mM Tris pH7.5, 0.5 mM EDTA and 0.01% Triton X-100). For second-strand synthesis, the matrix-bound DNA was resuspended in 20 μL of a reaction mixture containing 500 nM dNTPs, 100 ng/μL random hexamers, 5 U Klenow enzyme (New England Biolabs) and 1× NEB Buffer 2, and incubated at 37C for 60 min. After washing first with wash buffer and then twice in 1× reaction buffer, dsDNA was restricted using HaeIII or Sau3AI (NEB) at 37C for 2 hr, washed again in wash buffer followed by twice in 1× ligation buffer, and ligated with either HaeIII adapter (DES3177 and DES3178) or Sau3AI adapter (DES3177 and DES3179) using T4 DNA ligase at 16C overnight. To elute products, beads were resuspended in 5 μL of 0.1 N NaOH and incubated at RT for 10 min. The eluate was separated from the matrix using the magnetic stand, and was neutralized by adding 5 μL of Tris-Cl, pH 7.0. To perform nested PCR, 1 μL of the eluate or from a 1/100 dilution from the first round of PCR was added as template in a second (nested) PCR reaction in 50 μL. Primers for the adapter (DES3181) and nested adapter (DES3182) were paired with DES3172 and nested primer DES3173 (HaeIII), or DES3175 and nested primer (Sau3AI), respectively, in the donor plasmid. Products were cloned into the Topo-TA pCR2.1 backbone (Invitrogen). To map integration junctions, Sanger sequencing was performed. Bisulfite sequencing was performed using either the EZ DNA Methylation kit (Zymo Research) or the Qiagen Epitect kit, following the manufacturers’ instructions, respectively. Alternatively, we prepared fresh sodium hydroxide, sodium bisulfite and hydroquinone solutions to denature and treat DNA samples, which were then purified using Microcon-30 centrifugal spin columns (Amicon, Millipore) . The culture medium for cells growing at 50–70% confluence was replaced by medium containing one of HDAC inhibitors including TsA, scriptaid, apicidin, butyrate and nicotinamide (Sigma Chemical Co.) at the specified concentrations. After treatment for a specific time (12–24 h), the cells stained using the CCF2-AM assay and observed using a fluorescence microscope. We thank Drs. Colin Stewart (previously at NCI-Frederick), John V. Moran (Univ. Michigan), Jeffrey S. Han (Tulane Univ.), Ina Rhee, Christoph Lengauer and Bert Vogelstein (Johns Hopkins Univ.), Allan Bradley (Sanger Institute) for providing cell lines and reagents; Anthony S. Baker (Ohio State University) for expert help in preparing figures; Jennifer Malloy and Jonathan Cherry (Zeiss) for assistance in setting up filters in fluorescence microscopy; Kathleen Noer (NCI-Frederick) for assistance with flow cytometry experiments; and members of the Symer laboratory for helpful discussions. Funding for this study was provided by 1Z01BC010628, Intramural Research Program, National Cancer Institute, National Institutes of Health (D.E.S.); and by the Ohio State University Comprehensive Cancer Center (D.E.S.). Previously unpublished plasmid constructs will be provided to academic researchers upon request. MK, JL, SEF, KEH, JCS, TLS, PKT, WA and DES generated reagents and/or experimental data; MK and DES analyzed data and helped to draft and edit the manuscript; MK, JL, WA, JDB and DES participated in various stages of the design of the study; DES conceived of the study; and DES supervised experiments, analyzed data, and wrote and edited the final manuscript. All authors read and approved the final manuscript. The use of mice was approved by an Institutional Animal Care and Use Committee (Drs. Wenfeng An and Jef Boeke, Johns Hopkins University).
0.944522	What are the pros and cons of a juvenile probation officer career? Get real job duties, career prospects and salary information to see if becoming a juvenile probation officer is right for you. Juvenile probation officers supervise and monitor young people who have been convicted of a criminal offense and subsequently released on parole. Pros and cons to becoming a juvenile probation officer can be learned by reading below. When someone commits a crime, he or she might be placed on probation. This is true for juvenile offenders too. While on probation, the offender must avoid breaking any more laws and committing any other crimes. Other criteria also have to be met. These criteria can vary from offender to offender. If an offender doesn't follow these rules, the offender might be sent to prison. As a juvenile probation officer, you'll work with offenders of an age to be considered legal minors. After evaluating them, you can figure out the best treatment plan and use the resources necessary to rehabilitate them back into society. You'll stay in regular contact with the offenders you're assigned and regularly perform searches of their premises if necessary. You'll also file reports on the offender's progress. The U.S. Bureau of Labor Statistics (BLS) expected a -1% decline in employment from 2012-2022 for probation officers. When compared to other occupations, this growth is slower than average. This decline is being attributed to limits on state and local government funding over the decade. However, despite the decline in employment, job opportunities are expected to be plentiful due to lessened competition for this occupation. In May 2014, the BLS reported that probation officers earned about $25 an hour. This resulted in a salary of about $53,000 on average annually. This career saw earnings of around $83,000 for the top ten percentile of wage estimates. Illinois, New Jersey, Connecticut, New York and California were the states that paid the highest on average for juvenile probation officers. Juvenile probation officers ideally have a bachelor's degree in a field such as psychology, social work or criminal justice. Some employers are willing to hire individuals who have work experience in those fields in place of formal postsecondary education. Other fields that juvenile probation officers come from include counseling, corrections, parole, criminal investigations and substance abuse treatment. After being hired, you'll go through a training program from the federal or state government. This program is followed by a certification test. From there, you'll work as a probationary officer for a year and then be hired on full time. Some agencies require juvenile probation officers to be 21 years old or older, pass a drug test and possess a current driver's license. The appropriate amount of education and work experience is a big factor for employers hiring juvenile probation officers. Other qualities employers seek for this occupation includes good communication skills and the ability to handle stress well. Juvenile probation officers often work with troubled individuals, so you have to be able to be comfortable around them and clearly communicate with them on what needs to be done. You can also bring the concerns of your assignment back to your employer and ensure that the needs of the juvenile are met. You can learn additional qualities employers wanted in juvenile probation officers by reading some information below that was taken from November 2012 job postings. An opening in Ohio called for a juvenile probation officer who has taken classes in criminology, social work and criminal justice. A juvenile probation officer job in Texas required applicants with a bachelor's degree in criminal justice, social science or behavioral science. In Nebraska, an employer preferred juvenile probation officer applicants with a master's degree and who could speak Spanish as well as English. A training program with the Montana Law Enforcement Academy must be completed by applicants for a juvenile probation officer job in Montana. Earning a graduate degree is a significant way to stand out from other juvenile probation officers. Although it isn't required for most positions, some employers look for juvenile probation officers with a master's degree. This is especially true when it comes to supervisory positions. Prior work experience in social work, criminal justice, law enforcement and psychology is valuable as well to stand out from applicants with less experience. Critical thinking and decision making skills can help set you apart from other juvenile probation officers. You have to be able to come up with immediate ideas when a crisis arises and be able to resolve any issues in an appropriate and effective manner. If you want to help people better themselves without working with criminal offenders, consider being a social worker. In this occupation, you'll work with people who need help with emotional, mental and behavioral issues. You can predominantly focus on children and families if that is your interest. This could involve helping with issues such as child abuse, divorce or unemployment. Child, family and school social workers earned about $44,000 on average annually according to the BLS in May 2011. From 2010-2020, the BLS projected a 25% growth in employment for social workers. If you would rather work with offenders in jail instead of offenders out of jail, look into becoming a correctional officer. These professionals oversee prisoners who are serving time in jail or awaiting trial. The overall goal of a correctional officer is to keep a safe environment for the prisoners while trying to help rehabilitate them. The BLS expected a five percent employment growth for correctional officers from 2010-2020. Correctional officers had average yearly salaries of roughly $43,000 in May 2011.
0.936397	In a democratic one-party system, the party may fear losing power if they do not listen to the views of the public. Most of the present structure, however, dates to the. The France-based watchdog group Reporters Without Borders ranked China 176 out of 180 countries in its 2016 worldwide. Environmental issues The traffic in In recent decades, China has suffered from. Chinese mathematicians were the first to use. The Chinese government has responded to foreign criticism by arguing that the right to subsistence and economic development is a prerequisite to other types of human rights, and that the notion of human rights should take into account a country's present level of. So how is this possible in a one party system? Since Xi has come to power, experts have noted an apparent easing of tough rhetoric against, and even a promotion of, traditional beliefs in China. In 2012, the structure looked like this. In practice, however, monitoring and crackdowns often target peaceful activities that are protected under international law, say human rights watchdogs. The incumbent premier is , who is also a senior member of the , China's de facto top decision-making body. The demonstrations were eventually by force in early 2014. Within the framework of this ideology, religion was treated as a 'contorted' world-view and people believed that religion would necessarily disappear at the end, along with the development of human society. After the in 1945, Taiwan, including the , was returned to Chinese control. The type of government found in China is that which combinesdemocratic ideals, federalism, socialism, and authoritarian … ism. China maintains healthy and highly diversified trade links with the European Union. China's coastline along the Pacific Ocean is 14,500 kilometers 9,000 mi long and is bounded by the , , and seas. Urbanization Map of the ten in China 2010 China has urbanized significantly in recent decades. In 2012, Bloomberg and the New York Times both on the private wealth of then Party Secretary Xi Jinping and Premier Wen Jiabao. State Councillors : Liu Yandong, Liang Guanglie, Ma Kai, Meng Jianzhu, Dai Bingguo. The party prohibits its nearly ninety million party members from holding religious beliefs, and it has demanded the expulsion of party members who belong to religious organizations. He enacted Qin's reforms throughout China, notably the forced standardization of , , road widths i. Portuguese China is thought to derive from Chīn , which may be traced further back to. Bo, once the charismatic Party Secretary of Chongqing in southwestern China, is now in prison. And the country went from its shattered state to the China we know today. Politics: What are the disadvantages and advantages of one party rule? For much of the country's dynastic era, opportunities for social advancement could be provided by high performance in the prestigious , which have their origins in the. Rulers may be succeeded or rotated peacefully within established systems of governance. Archived from on 11 May 2010. Terminal 3 of is the 2nd-largest airport terminal in the world. No one could deny that its leaders, from Mao to Deng, from Jiang to Hu and to Xi next year, differ as widely in political outlooks and policy priorities as those who move in and out of power under any other political systems. However, in recent years, China's rapid economic growth has contributed to severe consumer inflation, leading to increased government regulation. An upcoming study in the linguistics journal Language found that 27 Philadelphia stenographers, presented with recordings of Black English grammatical patterns, made transcription errors on average in two out of every five sentences, and could accurately paraphrase only one in three sentences. Urban air pollution is a severe health issue in the country; the estimated in 2013 that 16 of the world's 20 most-polluted cities are located in China. The state recognizes five religions: Buddhism, Catholicism, Daoism, Islam, and Protestantism. Dynastic rule ended in 1912 with the , when a replaced the. The People's Republic of China is a single-party republic. Cockell had once forgotten about a dried petri dish of Chroococcidiopsis for 10 years,. China is additionally involved in multilateral disputes over the ownership of several small islands in the East and South China Seas, such as the and the. As China is a de facto , the holds ultimate power and authority over state and government serving as the. Chinese officials stated that spending on the military will rise to U. Policy is implemented more quickly and efficiently. Access to foreign media remains heavily restricted. Examples of one-party nation-states are , , and. The Qing dynasty also began experiencing in which tens of millions of people died, especially in the , the failed that ravaged southern China in the 1850s and 1860s and the 1862—77 in the northwest. But, in practice, these provisions have remained dead letter. In , governments regularly get voted in and out, but no elections have produced even the minimal corrections required to address their monumental distress. Then successfully docked with Tiangong-2 on 19 October 2016. In 2011 China's highways had reached a total length of 85,000 km 53,000 mi , making it the. The national average broadband connection speed is 9. However, they fell quickly when their conscription for public works and a in provoked widespread unrest. In 2014, the internal freshwater resources per capita of China reduced to 2,062m 3, and it was below 500m 3 in the , while 5,920m 3 in the world. In 2012, China's official was 0. High level of heavy metal exposure can also cause permanent intellectual and developmental disabilities, including reading and learning disabilities, behavioral problems, hearing loss, attention problems, and disruption in the development of visual and motor function. Citizens, Democracy, and Markets Around the : Congruence Theory and Political Culture. It is an example of Taoist temple that hosts various chapels dedicated to popular gods. In the winter, northern winds coming from high-latitude areas are cold and dry; in summer, southern winds from coastal areas at lower latitudes are warm and moist. New York: Columbia University Press. Economic reforms beginning in the 1980s that aimed at improving efficiency and work motivation sought to smash the iron rice bowl and link employment and income more directly to individual effort.
0.999815	John Scott Atkinson was 6 years old when Vietnam War: The last United States combat soldiers leave South Vietnam. The Vietnam War, also known as the Second Indochina War, and in Vietnam as the Resistance War Against America or simply the American War, was a conflict that occurred in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vietnam and the government of South Vietnam. The North Vietnamese army was supported by the Soviet Union, China, and other communist allies; the South Vietnamese army was supported by the United States, South Korea, Australia, Thailand and other anti-communist allies. The war is considered a Cold War-era proxy war by some US perspectives. The majority of Americans believe the war was unjustified. The war would last roughly 19 years and would also form the Laotian Civil War as well as the Cambodian Civil War, which also saw all three countries become communist states in 1975. Vietnam War: The last United States combat soldiers leave South Vietnam. The Vietnam War, also known as the Second Indochina War, and in Vietnam as the Resistance War Against America or simply the American War, was a conflict that occurred in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vietnam and the government of South Vietnam. The North Vietnamese army was supported by the Soviet Union, China, and other communist allies; the South Vietnamese army was supported by the United States, South Korea, Australia, Thailand and other anti-communist allies. The war is considered a Cold War-era proxy war by some US perspectives. The majority of Americans believe the war was unjustified. The war would last roughly 19 years and would also form the Laotian Civil War as well as the Cambodian Civil War, which also saw all three countries become communist states in 1975. John Scott Atkinson was 8 years old when India's first satellite Aryabhata launched in orbit from Kapustin Yar, Russia. India, also called the Republic of India, is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. It is bounded by the Indian Ocean on the south, the Arabian Sea on the southwest, and the Bay of Bengal on the southeast. It shares land borders with Pakistan to the west; China, Nepal, and Bhutan to the northeast; and Bangladesh and Myanmar to the east. In the Indian Ocean, India is in the vicinity of Sri Lanka and the Maldives. India's Andaman and Nicobar Islands share a maritime border with Thailand and Indonesia. India's first satellite Aryabhata launched in orbit from Kapustin Yar, Russia. India, also called the Republic of India, is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. It is bounded by the Indian Ocean on the south, the Arabian Sea on the southwest, and the Bay of Bengal on the southeast. It shares land borders with Pakistan to the west; China, Nepal, and Bhutan to the northeast; and Bangladesh and Myanmar to the east. In the Indian Ocean, India is in the vicinity of Sri Lanka and the Maldives. India's Andaman and Nicobar Islands share a maritime border with Thailand and Indonesia. John Scott Atkinson was 10 years old when Star Wars is released in theaters. Star Wars is a 1977 American epic space opera film written and directed by George Lucas. It is the first film in the original Star Wars trilogy and the beginning of the Star Wars franchise. Starring Mark Hamill, Harrison Ford, Carrie Fisher, Peter Cushing, Alec Guinness, David Prowse, James Earl Jones, Anthony Daniels, Kenny Baker, and Peter Mayhew, the film focuses on the Rebel Alliance, led by Princess Leia (Fisher), and its attempt to destroy the Galactic Empire's space station, the Death Star. Star Wars is released in theaters. Star Wars is a 1977 American epic space opera film written and directed by George Lucas. It is the first film in the original Star Wars trilogy and the beginning of the Star Wars franchise. Starring Mark Hamill, Harrison Ford, Carrie Fisher, Peter Cushing, Alec Guinness, David Prowse, James Earl Jones, Anthony Daniels, Kenny Baker, and Peter Mayhew, the film focuses on the Rebel Alliance, led by Princess Leia (Fisher), and its attempt to destroy the Galactic Empire's space station, the Death Star. John Scott Atkinson was 18 years old when Space Shuttle program: STS-51-L mission: Space Shuttle Challenger disintegrates after liftoff, killing all seven astronauts on board. The Space Shuttle program was the fourth human spaceflight program carried out by the National Aeronautics and Space Administration (NASA), which accomplished routine transportation for Earth-to-orbit crew and cargo from 1981 to 2011. Its official name, Space Transportation System (STS), was taken from a 1969 plan for a system of reusable spacecraft of which it was the only item funded for development. Space Shuttle program: STS-51-L mission: Space Shuttle Challenger disintegrates after liftoff, killing all seven astronauts on board. The Space Shuttle program was the fourth human spaceflight program carried out by the National Aeronautics and Space Administration (NASA), which accomplished routine transportation for Earth-to-orbit crew and cargo from 1981 to 2011. Its official name, Space Transportation System (STS), was taken from a 1969 plan for a system of reusable spacecraft of which it was the only item funded for development. John Scott Atkinson was 22 years old when Nelson Mandela is released from Victor Verster Prison outside Cape Town, South Africa after 27 years as a political prisoner. Nelson Rolihlahla Mandela was a South African anti-apartheid revolutionary, political leader, and philanthropist who served as President of South Africa from 1994 to 1999. He was the country's first black head of state and the first elected in a fully representative democratic election. His government focused on dismantling the legacy of apartheid by tackling institutionalised racism and fostering racial reconciliation. Ideologically an African nationalist and socialist, he served as President of the African National Congress (ANC) party from 1991 to 1997. Nelson Mandela is released from Victor Verster Prison outside Cape Town, South Africa after 27 years as a political prisoner. Nelson Rolihlahla Mandela was a South African anti-apartheid revolutionary, political leader, and philanthropist who served as President of South Africa from 1994 to 1999. He was the country's first black head of state and the first elected in a fully representative democratic election. His government focused on dismantling the legacy of apartheid by tackling institutionalised racism and fostering racial reconciliation. Ideologically an African nationalist and socialist, he served as President of the African National Congress (ANC) party from 1991 to 1997. John Scott Atkinson was 32 years old when Columbine High School massacre: Eric Harris and Dylan Klebold killed 13 people and injured 24 others before committing suicide at Columbine High School in Columbine, Colorado. The Columbine High School massacre was a school shooting that occurred on April 20, 1999, at Columbine High School in Columbine, an unincorporated area of Jefferson County, Colorado, United States, in the Denver metropolitan area. In addition to the shootings, the complex and highly planned attack involved a fire bomb to divert firefighters, propane tanks converted to bombs placed in the cafeteria, 99 explosive devices, and car bombs. The perpetrators, senior students Eric Harris and Dylan Klebold, murdered 12 students and one teacher. They injured 21 additional people, and three more were injured while attempting to escape the school. The pair subsequently committed suicide. Columbine High School massacre: Eric Harris and Dylan Klebold killed 13 people and injured 24 others before committing suicide at Columbine High School in Columbine, Colorado. The Columbine High School massacre was a school shooting that occurred on April 20, 1999, at Columbine High School in Columbine, an unincorporated area of Jefferson County, Colorado, United States, in the Denver metropolitan area. In addition to the shootings, the complex and highly planned attack involved a fire bomb to divert firefighters, propane tanks converted to bombs placed in the cafeteria, 99 explosive devices, and car bombs. The perpetrators, senior students Eric Harris and Dylan Klebold, murdered 12 students and one teacher. They injured 21 additional people, and three more were injured while attempting to escape the school. The pair subsequently committed suicide. John Scott Atkinson was 34 years old when The September 11 attacks, a series of coordinated suicide attacks killing 2,996 people using four aircraft hijacked by 19 members of al-Qaeda. Two aircraft crash into the World Trade Center in New York City, a third crashes into The Pentagon in Arlington County, Virginia, and a fourth into a field near Shanksville, Pennsylvania. The September 11 attacks were a series of four coordinated terrorist attacks by the Islamic terrorist group al-Qaeda against the United States on the morning of Tuesday, September 11, 2001. The attacks killed 2,996 people, injured over 6,000 others, and caused at least $10 billion in infrastructure and property damage. Additional people died of 9/11-related cancer and respiratory diseases in the months and years following the attacks. The September 11 attacks, a series of coordinated suicide attacks killing 2,996 people using four aircraft hijacked by 19 members of al-Qaeda. Two aircraft crash into the World Trade Center in New York City, a third crashes into The Pentagon in Arlington County, Virginia, and a fourth into a field near Shanksville, Pennsylvania. The September 11 attacks were a series of four coordinated terrorist attacks by the Islamic terrorist group al-Qaeda against the United States on the morning of Tuesday, September 11, 2001. The attacks killed 2,996 people, injured over 6,000 others, and caused at least $10 billion in infrastructure and property damage. Additional people died of 9/11-related cancer and respiratory diseases in the months and years following the attacks. John Scott Atkinson was 36 years old when Invasion of Iraq: In the early hours of the morning, the United States and three other countries (the UK, Australia and Poland) begin military operations in Iraq. The 2003 invasion of Iraq was the first stage of the Iraq War. The invasion phase began on 20 March 2003 and lasted just over one month, including 21 days of major combat operations, in which a combined force of troops from the United States, the United Kingdom, Australia and Poland invaded Iraq. This early stage of the war formally ended on 1 May 2003 when U.S. President George W. Bush declared the "end of major combat operations", after which the Coalition Provisional Authority (CPA) was established as the first of several successive transitional governments leading up to the first Iraqi parliamentary election in January 2005. U.S. military forces later remained in Iraq until the withdrawal in 2011. Invasion of Iraq: In the early hours of the morning, the United States and three other countries (the UK, Australia and Poland) begin military operations in Iraq. The 2003 invasion of Iraq was the first stage of the Iraq War. The invasion phase began on 20 March 2003 and lasted just over one month, including 21 days of major combat operations, in which a combined force of troops from the United States, the United Kingdom, Australia and Poland invaded Iraq. This early stage of the war formally ended on 1 May 2003 when U.S. President George W. Bush declared the "end of major combat operations", after which the Coalition Provisional Authority (CPA) was established as the first of several successive transitional governments leading up to the first Iraqi parliamentary election in January 2005. U.S. military forces later remained in Iraq until the withdrawal in 2011.
0.999867	T lymphocytes (=T cells) defend our body against infections with microbes. They require activation by antigen-presenting cells, in particular dendritic cells (DCs). These DCs collect antigens in various tissues, migrate to draining lymph nodes, and activate the T cells there. The mechanism of cross-presentation enables DCs to activate CD8+ T cells (Kurts et al, Nat Rev Immunol, 2010), which are crucial for the immune defense against viruses, intracellular bacteriae and tumors, and in vaccination (Figure 1). We have previously shown that DCs can also destroy harmful CD8+ T cells, and thereby prevent them from damaging our own body. This form of peripheral immune tolerance is known as cross-tolerance. If it fails, autoimmune diseases result, such as type I diabetes mellitus or multiple sclerosis (Figure 2). Other forms of peripheral immune tolerance include the induction of regulatory T cells, which can suppress harmful T cells. We are interested in suppression of harmful B cells, and prevention of autoantibody formation, which play important roles in various autoimmune diseases such as glomerulonephritis or rheumatoid arthritis (Figure 2). Our third topic of interest is the role of dendritic cells and other myeloid cells in local immune responses regulation non-lymphoid tissues, with a special emphasis on the urogenital tract (Kurts et al, Nat Rev Immunol, 2013). We wish to understand the immune mechanisms underlying diseases such as glomerulonephritis, and cystitis/pyelonephritis: Furthermore, we study DCs in the eye, the intestine and the heart. The cell biology of cross presentation is one of the greatest enigmata in this field. For a long time, it was thought that antigen “crosses” from late endosomes into the MHC class I presentation pathway. We have shown that antigen needs to be taken up by distinct receptors, such as the mannose receptor, into a indistinct endosomal compartment for cross-presentation (Burgdorf et al, Science 2007). Loading of MHC I molecules with antigenic peptides occurs in this compartment, and this process is regulated by TLR/MyD88-signaling, which translocated the molecular machinery from the endoplasmic reticulum to the endosomes (Burgdorf et al, Nat Immunol, 2008). These findings showed that TLR signaling not only controls signal 2 of T-cell activation (costimulation), but also signal 1 (Antigen presentation). Furthermore, we identified the elusive organelle for cross presentation of soluble antigen. Cross presentation requires direct interaction of several immune cells, i.e specific CD8+ and CD4+ Th cells, CTL). CD4+ Th cells need to provide a second opinion as to whether an antigen presented by the DC warrants CD8+ T cell activation (= classical cross priming). We have shown that also NKT cells can provide this second opinion (= alternative cross priming). Furthermore, while Th cells induced production of CCR5-binding chemokines, NKT cells caused DCs to produce CCR4-binding chemokines. Both chemokines synergistically enhance the efficiency of cross presentation (Semmling et al, Nat Immunol, 2010). Based on our findings, it has been proposed to term these chemokines „Signal 0“, in extension of the classical “Signal 1&2” hypothesis by Bretscher und Cohn. Signal 0 chemokines allow CD8+ T cells to more efficiently locate those DCs that present relevant antigen. We currently study the underlying mechanisms and whether other chemokine receptors are involved in immune cell migration during cross-priming. Regulatory T cells (Treg) are well known to control autoreactive T cells. Less is known about their role in regulating harmful B cells. We have shown in vivo that Tregs prevent the production of auto-antibodies against self antigens in the pancreas or the kidney by inducing B cell apoptosis. To this end, Tregs express PDL-1 and physically interact with the PD-1+ B cells (Gotot et al, PNAS 2012). These findings showed that Tregs directly suppress the rather than indirectly by curbing help through follicular helper T cell. Normally, PD-1 signaling in these cells stimulates B-cell responses through CD40 signaling. However, in the case of autoantigens, Tregs are present and their suppressive effect on B prevails. These findings also explained why PD1 deficiency in mice and men led to autoantibody formation. We are currently employing these findings for the treatment of autoantibody-mediated diseases. We have generated novel tools to study kidney diseases and DCs (Tittel et al, Nat Methods 2012). We showed that kidney DCs are the first cells that sense invading bacteria in pyelonephritis and respond by producing chemokines and cytokines, which recruit immune effector cells for rapid innate immune defense (Tittel et al, JASN 2011). In the bladder we identified a novel immune regulatory function of certain macrophages that use the cytokine TNF to regulate the immune response of neutrophilic granulocytes in bacterial infection (Schiwon et al, Cell, 2014). We were among the first to describe DCs in the kidney (Krüger et al, JASN 2004). We demonstrated that DCs promote glomerulonephritis progression by presenting glomerular antigen to Th cells (Heymann et al, J Clin Invest 2009; Hochheiser et al, JASN 2011). These findings clarified why tubulointerstitial infiltrates are tightly associated with nephritis progression, and identified kidney DCs as a therapeutic target. Our recent work identified the fractalkine receptor CX3CR1, a widely used marker for mononuclear phagocytes with unknown function, as kidney-specific chemokine receptor (Hochheiser et al, J Clin Invest, 2013). These findings identified a selective therapeutic target in glomerulonephritis. Finally, we study the role of inflammasomes in kidney fibrosis, the common end-stage of many kidney diseases that leads to irreversible loss of kidney function and the need to undergo dialysis. We discovered that post-operative ileus (POI) is an immune-mediated disease induced by pathological interaction between intestinal muscle cells and immune cells. POI is the most prevalent complication after intestinal surgery and results in serious medical complications and billions of cost to the health system. We discovered that intestinal DCs sense the surgical trauma and stimulate resident Th1 memory cells. These recirculate through the body and settle in all gut segments. There, they produce IFNg that stimulates resident macrophages to produce nitric oxide, which directly paralyses intestinal muscle cells, causing ileus (Engel et al, Nat Medicine 2010).
0.999996	Is there anything more fun than a costume party? All the moments that involve the party - from the organization to the big day - are great fun. A costume party can be planned for birthday celebrations (especially those that mark a significant time in life, such as 15 years, 18 years and 30 years), school (for graduations or year-end balls), business or end-of-the-year reunion) or just to gather friends without a specific reason. The fact is that in all these occasions it fits a celebration to the fantasy. This is perhaps the most interesting and fun topic of the party: defining the theme. You can let your imagination fly high and think from the most common and recurring themes such as the 60s, or go to something more specific like a movie - Harry Potter is a good example - or TV series. Other common themes are Halloween, the June party and the carnival. These parties, besides being an opportunity to take fantasy out of the closet, are still a way to enjoy the holidays and calendar dates. You can also think of topics like cinema, music, sports, literature, fairy tales and historical periods such as prehistory or medieval times. Looking for inspirations in ancient civilizations may also be interesting, in which case the suggestions are the Egyptians, the Persians or who knows even the Latin American Indians. But you can also choose to leave the theme of the party free and allow your guests to define the theme of their own fantasies. The important thing is to decide whether the party will be thematic or not as soon as possible, since it is this small and significant detail that will guide the whole organization of the party to fantasy. And a tip: never send the invitation without setting the theme. The guests are lost and will feel the unpreparedness of the organization. After setting the theme, choose the location. This is also a very important stage for the success of the costume party. Some themes combine especially with open places and in the midst of nature, such as a medieval-themed party. Already others like a 60's costume party look better if held in an enclosed space. Determine the location of the party according to the theme and how much you are willing to spend to complete it. If the money is short the tip is to do it at home or ask for that legal farm of your friend loaned. Set theme and location it's time to start sending party invitations. The date and time of the party by then should already be set. Distribute the invitations 30 days before the party, enough time for the guests to plan and look for the costumes. And by the way, make it clear in the invitation that to enter the party is essential the use of fantasy according to the theme. Enjoy and make the themed invitation, so your guests already have that taste of what is to come and you can surprise them. Fantasy party, as a rule, has to be colored. This guarantees the air of relaxation and joy typical of this type of event. Colors can be combined together in a harmonious and fun palette, or use them freely, like a true rainbow. Balloons, streamers and masks are a great way to make the fancy party decor inexpensive and affordable. Another way to cheapen the cost of decorating is to invest in paper flowers and candles. The DIY concept - Do It Yourself - or the famous "Do It Yourself" can also be incorporated into the fancy party decoration. Recyclable materials like pet bottles, glass and cans give that extra touch in the decor. The fantasy party is by itself relaxed and casual. For this reason, treats that can be eaten by hand without the need for dishes and cutlery fit perfectly into this type of party. To leave them in the mood of the party, invest in shapes and colors that refer to the chosen theme. As for drinks, do not miss the traditional juices, soft drinks, water and beer. But to make a charm at the party, serve some drinks - alcoholic and non-alcoholic - very colorful. Another tip is to serve punches. How fancy am I going? When thinking fantasy is creative and do not be afraid to dare. You can buy one ready, have it done at a seamstress or do it on your own. Also innovate in the use of different materials to create futuristic fantasies and well original. But be careful not to make the fantasy uncomfortable. Remember that you will have a whole night ahead to dance, talk and have fun and the last thing you will want is a fantasy of tightening or limiting your movements. A fantasy party to stay in history needs proper lighting and a selection of songs to make everyone dance. You can choose to hire a DJ or a band depending on your budget. But it is also possible to control the sound on its own, so you have a play list able to hold the animation throughout the party. Picture 1 - Want a fancy and luxurious fancy party? So take inspiration from this table. Picture 2 - Feathers and feathers: from the invitation to the menu. Picture 3 - For a cheap fantasy party decoration invest in balloons, streamers and paper embellishments. Picture 4 - All attention to the bar. Picture 5 - A stall of lights and colors to surprise your guests. Picture 6 - Chocolate at will. Image 7 - A fantasy party inspired by the discomusic times. Image 8 - Light and shine on the dance floor. Picture 9 - How about an instant photo machine for your guests to eternalize the party? Picture 10 - The gold is the base color of this party to the fantasy, complemented by the black and red. Image 11 - Flowered Skulls! Picture 12 - A photo machine on each table. Picture 13 - Moulin Rouge! The musical turned movie is the theme of this party. Picture 14 - Even the cake comes dressed for the party. Image 15 - Crepe paper strips give a sensational effect to the party. Picture 17 - And if all your favorite movies become a party theme, have you thought about that possibility? Image 18 - Playing cards may suggest various themes for a costume party, including Las Vegas or Alice in Wonderland. Image 19 - Here, vinyl records saw sousplat. Image 20 - In this party, the masks accompany the dishes. Image 21 - Paper flags and flowers to color the party. Image 22 - Day of the dead celebrated outdoors. Picture 23 - What to do with toy springs? Fantasy party decoration of course! Picture 24 - Masks are the symbol of the fancy parties. Picture 25 - Can it be more playful than a fantasy party? Children who say so. Image 26 - The elegance of the black and gold lent to the decoration of the costume party. Image 27 - Tunes holding the cutlery. Image 28 - Serpentine on all sides. Picture 29 - Chairs with tulle skirt. Picture 30 - A colorful fantasy party in the middle of nature: the yellowish lighting guarantees the cozy atmosphere for the celebration. Picture 31 - The costume party can have a rustic footprint too. Image 32 - A menu right at the entrance to the party. Picture 33 - Night of games! Image 34 - The candlelight. Picture 36 - Pillows to accommodate the guests. Image 37 - A neat corner for the bar of the costume party. Picture 38 - And what about a luminous sign to decorate the party? Picture 39 - A table decorated in a relaxed and very irreverent way. Image 40 - A glass that looks more like a disco ball? It can only be his fantasy! Image 41 - Ladies and gentlemen, the theme of the party is "The Circus". Image 42 - Fantasy party with funeral touch. Picture 43 - Eat, drink and dance! Have you seen any similar titles in the movies? Image 44 - Fantasy party decorated with field flowers and delicate fabrics. Image 45 - Balloons, confetti and blinks. Picture 46 - For an elegant party go of black, white and silver. Image 47 - Paper masks. Image 48 - The theme is rainbow. Picture 49 - Here comes the woman bird. Picture 50 - And the child ice cream cone! Picture 51 - The dream of the wedding realized in the celebration to the fantasy. Picture 52 - Masks and feathers: have these accessories in hand to distribute to those guests who have forgotten the fantasy; You bet, there's always one! Image 53 - Drinks and lights to "light up" the party. Image 54 - Shiny curtain and paper folds. Image 55 - A scenario within the costume party. Picture 56 - Light and soft shades contrasted by dark velvety green: a decoration and both for the costume party. Image 57 - Look what paper stars can do for the party decoration. Image 58 - From the outside you can already have an idea of what is inside the party. Image 59 - A little macabre for a costume party? Image 60 - A well-decorated bar enhances the fancy party.
0.998129	Could I clean Phalaenopsis orchid leaves with moisture cloth? Yes you could clean Phalaenopsis orchid leaves with a moist cloth. That should work very well. You should not use any cleaning materials to do so. And of course be gentle with the leave not to hurt or bruise it. As an aside, some professional orchid growers will wipe orchid leaves with milk and a soft cloth. This will help polish the leaves and can help with mineral stains.
0.999712	Recognise the types of business organisations. Be able to compare and contrast the different types of business organisations. Explain why businesses change their organisational structure over time. 1. How would you recognise the different types of Business Organisations? There are six ownership structures that a business may use: sole trader, partnership, private limited companies (LTD and DAC), public limited companies, co-operatives and state-owned enterprises. Expanding businesses may alter their organisation structure by engaging in alliances and/or franchising its business model. Business Organisations may also be classified by their main location(s) of operations: indigenous and transnational firms. 2. Compare a Co-operative and a Private Limited Company as forms of business ownership using the headings: Finance; Control; Liability. Finance: One of the main attractions of the private limited company structure is the ability to raise capital by selling shares up to a maximum of 149 shareholders. Profits are distributed to shareholders in the form of dividends. Co-operatives in Ireland may find it difficult to access funding. Because each member has an equal say, there is less incentive for members to contribute more capital to the co-operative. Members receive a share of the profits in proportion to their turnover with the co-operative (producer co-operative) or as a percentage of the savings (credit union). Control: A private limited company is controlled by the shareholders based on the rule “one share one vote”. The shareholders elect a board of directors who are responsible for the running of the company. The board of directors elect a Managing Director (MD) or a Chief Executive Officer (CEO) who is responsible for managing the company on a day-to-day basis. The original shareholders can maintain control of the company as long as they continue to hold 51% of the ordinary share capital. Co-operatives have a democratic structure, where each member has one vote, “one member one vote”, with majority decision making. Members have an equal say in the running of the co-op regardless of the number of shares held. An elected management committee are responsible for the running of the co-operative. Liability: The shareholders of a private limited company have limited liability. This means that the shareholders are not personally liable and can only lose the amount of their original investment if the business fails. Just like private limited companies, the members of co-operatives have the protection of limited liability. This means their liability is limited to the amount invested in the co-operative. 3. Contract Business Alliances and Franchising as different types of business organisations. Business Alliance is an agreement between two or more businesses to pool resources and expertise to work together over a specified period of time or to complete a specified project, while all parties maintain their separate identities. Usually alliances result in cost reductions and/or improved services for the customer. Marketing alliances with businesses on the home and foreign markets are quite common, e.g. one enterprise may agree to sell or distribute another enterprise’s products or services. Pricing alliances are used to share the other enterprise’s customers using discounts. Example: Aer Lingus is a member of the Oneworld Alliance. Franchising involves the granting of a licence (permission) by a franchisor (franchise creator) to the franchisee entitling the franchisee to sell the product or service but under its name. The franchisor would have a well-established name in the marketplace and an established reputation. Entrepreneurs (franchisee) can set up their own businesses and be their own boss enjoying reduced risk because of the pre-designed format of the enterprise. Examples: McDonald’s, Starbucks. 4. Discuss reasons why a business enterprise would change its organisation structure over time. Finance: If more capital is needed for the development of the business, then a move from being a co-operative or a private limited company to being a public limited company might be necessary. Marketing: The expansion of markets may be better served by joining a business alliance with another enterprise, either abroad or in Ireland, e.g. for the distribution of the firm’s goods. Opportunity: A new business opportunity, the opportunity to diversify into another line of business or enhance the existing businesses products may offer itself in the form of a franchise agreement. Privatisation/Nationalisation: The state may wish to free itself of business that can be owned and managed successfully by the private sector. It could therefore change its state owned enterprise into a public limited company to enable the sale to take place effectively and offer the opportunity to the public to invest and become the new owners. During the recent recession the government gave billions of euro to financial institutions to help them survive in return for shares, this resulted in the nationalising (state ownership) of a number of public limited companies. Expansion/Economies of Scale: The business enterprise may wish to grow larger. With size comes the burden of extra specialisation where one individual simply cannot do all things and more people and expertise are needed, e.g. specialists in finance, marketing, production. The move from a sole trader to a private limited company may be suitable for this purpose. 5. Describe the steps involved in the formation of a Private Limited Company (both an LTD and DAC). The procedures for establishing a private limited company are set out in the Companies Acts 2014. There are two types of private limited company, a company limited by shares (LTD) and a designed activity company limited by shares (DAC). Step 1: Certain legal documents must be prepared. Form A1: This gives details of the company name, its registered office, details of secretary and director(s), their consent to acting as such, the subscribers and details of their shares. Constitution: Every company must have a constitution which is printed and signed by each subscriber. The constitution of a company sets out the basic legal limits under which the company operates, such as activity, capacity, finance and internal rules. The constitution of the company must state the company’s name; the type of company to be registered (LTD, DAC); the liability of members; details of where the company proposes to conduct its business and the company’s Registered Office. The constitution of an LTD. comprises a single document (Articles of Association, without an objects clause), whereas a DAC must also have a Memorandum of Association. The Articles of Association: This document sets out the internal rules and regulations of the company. It describes, for example, the voting procedures for meetings and it sets down the quorum necessary for a valid meeting. The standard internal rules of a company are now set out in the Companies Act 2014 which eliminates the need to have extensive articles in the constitution. The Memorandum of Association: This document sets out the relationship between the company and the general public. It includes the name of the company with DAC after it, indicating limited liability and the objectives of the company. It includes the signatures of the people who formed the company and the authorised share capital clause. Step 2: These two documents are then sent to the Registrar of Companies at the Companies Registration Office with the appropriate fee. Step 3: The Registrar will not register a constitution unless he or she is satisfied that all the requirements in relation to the form of the constitution under the Companies Act have been complied with. If the Registrar is satisfied that all is in order, he or she will then certify in writing that the company is incorporated and issue a certificate of incorporation. The certificate of incorporation is conclusive evidence that the Company is registered under the Companies Act 2014. This in effect is the business birth certificate or licence to begin trading as a private limited company. The business is now incorporated and a separate legal identity in the eyes of the law, meaning that it can sue or be sued in its own name. Franchising continues to be an important contributor to the Irish Economy. In 2018, the Irish Franchise Association reported that the Franchising sector in Ireland is worth an estimated 2.5 billion euro and employs approximately 43,000 people in full-time jobs. (A) Analyse the reasons why a business start-up might choose the franchise model of business organisation. (B) Outline the advantages for an existing business of choosing franchising as a method of business expansion. Less risk of business failure: Franchising provides a person who wishes to open a business with the opportunity of replicating a proven, well established business model (tried and tested formula). The franchisee (person setting up the business) pays the franchisor (existing business) for the right to use the franchisors trade name and business system, therefore, they benefit from brand recognition giving access to an existing customer base which results in guaranteed sales. Reduce Costs: Centralised or group purchasing power can result in cost saving, for example costs of a nationwide marketing campaign can be shared between all franchisees. The new franchisee can benefit from economies of scale generated by the franchisor. Bulk discounts, gained by the franchisor as a result of bulk purchasing are passed onto individual franchisees, allowing them to charge lower prices and generate larger profits. Training and on-going support is provided in the start-up and development of the business by the franchisor. Managerial training is provided by the franchisor, the franchisees have access to the experience and systems of the franchisor. New product development is undertaken by the franchisor, business start-up advice and staff training programmes will help the new franchisees in their businesses. Banks are more likely to lend money. Failure rates for franchises are far lower than the failure rates for new independent businesses and for that reason banks are more willing to lend money. It is a form of expansion which requires low capital investment by the franchisor, as the capital used to expand the business comes from franchisees. Buildings, equipment and all other resources needed for the new business are supplied by the franchisee. In fact, the franchisor is paid an initial franchise fee plus royalties based on a percentage of turnover (sales). Franchising permits a more rapid expansion. By using the franchisees’ capital, the franchisor is able to establish a large number of outlets in a short period of time. Rapid expansion can be achieved without incurring the overheads and costs associated with opening company-owned restaurants. An owner will be more attentive than a manager. By franchising the business, the franchisor places the expansion of his/her business in the hands of people who are motivated to make it work and are therefore more likely to succeed. The franchisor can be assured that the person operating its restaurant will be “attending to business” as much as they would. Economies of scale There is strength in numbers. The successful franchisor can command deals with various suppliers and can control supplies to various franchisees. The cost savings can increase the franchisor’s profits. Q1 Explain the term “transnational company” and give one example. Q3 Distinguish between a ‘Strategic Alliance’ and a ‘Franchise’ as methods of business expansion. Q4 Complete the table of the features of the two types of private limited company. Q5 Outline two differences between a sole trader and a partnership. Q6 Column 1 is a list of Business Organisations. Column 2 is a list of possible explanations of these terms. 1. Public Limited Company (PLC) A. Has unlimited liability. 2. Franchise B. Is owned by between two and twenty people generally and is common in the accountancy and legal professions. 3. Co-operative C. Owned, financed and controlled by the Government. 4. Sole Trader D. A licence granted by a business to another to sell its products or services in return for a fee. 5. State-owned enterprise E. Shares are quoted/traded on the Stock Exchange. F. Democratically controlled and jointly owned by its members. Q7 In the box below name two examples of each type of business organisation. Q8 Outline two reasons why a sole trader may change its organisation structure to a private limited company.
0.993566	Provide a program that is developmentally appropriate, where children are encouraged to learn according to their individual needs and interests. Provide many experiences, materials, opportunities, and time for children to develop socially, emotionally, intellectually, and physically. Provide a safe and nurturing environment where children explore, experiment, manipulate, and use their natural curiosity to solve problems and learn about the world around them. Provide experiences and activities that foster a child’s self-esteem, self-trust, and positive feelings toward learning. Provide a learning experience that meets the needs of both the children and their parents. Provide opportunities for children to develop independence, and a desire to be self-motivated, responsible learners.
0.999902	For anyone starting a new marine aquarium the first question is what are good beginner fish. Fortunately, there are a lot of marine fish that are relatively easy to keep when several guidelines are followed. First the fish selected should be healthy and feeding when they are added to the tank. Second they should be acclimated slowly and carefully, preferably by first adding them to a quarantine tank before they are added to the display tank. Lastly, they should be matched in terms of size and temperament with the other fish with which they are going to be housed. Good beginner fish are often thought to be those that can tolerate poor water conditions or wide variations in a tank’s conditions, which are often the hallmark of a new tank. There are fish that fall into this category, but over the long term they are usually too aggressive to be kept in the confines of a small tank with other fish. It is far better to set up a tank properly using the latest and best methodology and then adding fish of similar dispositions. As mentioned above one of the critical aspects of putting a group of fish together is to choose fish of similar size and temperaments. Fish can be grouped into three general categories: docile, aggressive and predatory and they should be kept with fish of similar dispositions. These can then also be expanded further to include size. When selecting fish to start in a tank they should be matched for both size and disposition. It is not however a hard and fast rule, as it is possible to mix fish with one type of disposition with those from another if care is taken. The size consideration is just as critical in that if a large or even moderately sized fish from the predatory group is mixed with a small fish from the docile or even the aggressive group, the smaller fish will usually end up as food. Some of the fish in the docile group would include small sized clownfish, firefish, gobies, cardinalfish, assessors, marine betas, flasher wrasses and blennies. Aggressive fish would include angelfish, tangs, rabbitfish, hawkfish, hogfish, most wrasses and dottybacks. Predators would include groupers, lionfish, triggerfish, snappers, and moray eels. There are exceptions within every group usually based on size such as the orchid dottyback (Pseudochromis fridmani) would probably fall in the docile group due to its small size, while the Tomato or Maroon Clownfish would probably be considered in the aggressive group. So these groupings should be more of a guideline rather than the only way to do things. Also there are variations within the species itself. There have been reports of blennies that have attacked and killed anything put in their tanks as well as angelfish that have harassed and killed groupers. Damselfishes (Pomacentridae) These are generally considered the best beginner’s fish as they are hardy, inexpensive and colorful. Unfortunately they are highly territorial and very aggressive. In small or medium tanks they will claim the entire tank as their own and harass any fish that enter their domain. For these reasons they may not be the best choice for small beginner’s tanks, although they do quite well in larger tanks when they are housed with other aggressive fish. Exceptions to this are the Yellowtail blue damsel and the Green chromis both of which can be considered on the docile end of the scale and can be housed in schools. Anemonefish (Amphiprion) The clownfish and especially the percula clown are the fish that get more people interested in the hobby than any other. They are best kept alone or in known male-female pairs. They can be kept with or without an anemone and they should housed only one pair to a tank. Most are docile to moderately aggressive, with the exceptions being the larger types, which can be very aggressive especially if an anemone is present. Prone to Brooklynella infections and parasitic worms they should be quarantined before being placed in a display tank. Gobies (Gobiidae) The gobies are a very diverse group with the largest number of species of any fish group. They inhabit virtually every niche of the reef from the spines of a sea urchin to the tentacles of some jellyfish. They are a small bottom-oriented group that displays little aggression except toward other similar looking relatives. They require adequate hiding places and good water quality. Blennies (Blennidae) Blennies usually sit on aquarium décor and can be aggressive to other small bottom dwelling fish. Most feed by grazing algae from the rocks and stay fairly small. Only one should be kept in a tank, as they can be aggressive towards other blennies. Firefish These small elongated fish are good for a passive community. They are extremely hardy, colorful and eat most small meaty foods. They are prone to jumping from the tank, so their tank should be covered. They also have a tendency to fight with members of their own species and with other gobies and firefish if inadequate hiding places and cover are not provided. Dwarf Angelfish (Centropyge) The dwarf angelfish are generally small colorful individuals that do well when housed singly in a tank. They can also be kept as pairs if they can be sexed or obtained as pairs but they may fight to the death if two males are housed together. They should be fed a diet high in plant material and they do better if some algae is present in their tank. Cardinalfish (Apogonidae) Moe than 170 species, many of which are nocturnal. They are extremely hardy and non-aggressive although they will swallow anything that fits in their mouth. They need caves and other hiding places in order to thrive. Should be fed small plankton like foods. Angelfish (Pomacanthidae) The angelfish group includes some of the most stunning of all marine fish. Unfortunately most of the species are suitable only for the more experienced fishkeeper. Do best when acquired small and allowed to acclimate to their new surroundings gradually. Need a diet high in plant material to which some sponge is added for some species. Most of the species require larger tanks as they grow large and can become quite aggressive. Marine Bettas and Assessors (Plesiopsidae) Both species are extremely disease resistant and not aggressive. Good choices for the passive aquaria although the betta may eat crustaceans including cleaner shrimp. They are extremely cryptic so hiding places are essential for their well-being. Marine Bettas also consume bristleworms so they also offer this benefit. Dottybacks (Pseudochromidae) Hardy and often very colorful these elongate fish can also be very aggressive. One specimen per tank unless it’s very large and plenty of hiding places can be provided. They are prone to color loss unless a varied high quality diet is provided. Commercial propagation of many of these species is now being achieved with their being some diminution of the aggressive qualities a result. Wrasses (Labridae) This is a very diverse family (over 600 species) with the large members being very aggressive. The larger fish will eat their smaller tankmates so care should be taken when choosing tankmates. For passive community tanks flasher (Paracheilinus) and fairy (Cirrhilabrus) wrasses make good tankmates as long as their need for almost constant feeding with plankton is met. Surgeonfish (Acanthuridae) These flatly compressed fish contain some of the most frequently kept fish. They require large tanks with lots of swimming space and can be aggressive to other members of their species if their tank is not large enough. They require lots of plant material in their diet and are prone to lateral line disease if their dietary requirements are not met. The also have a very thin mucous coat on their body so they are prone to ick and other parasitic infections after shipping so they should be quarantined before being placed in their final home. Rabbitfish (Siganidae) Similar in shape to the surgeonfish these fish have poisonous hollow dorsal spines, which they use for protection. They can deliver a painful sting if they are touched. They require lots of swimming space and are herbivores like the surgeonfish. They can be housed in groups or schools in large tanks. Lionfish (Scorpaenidae) These fish are predatory, but are rarely aggressive to each other. The dorsal spines are venomous and while their stings are rarely fatal they can be quite painful and require medical attention. They should be fed only once or twice per week with chunks of white fleshed fish once they have been weaned from live food. Otherwise they have a tendency to develop fatty livers and die. Groupers (Serenade) Most are very hardy and some species are aggressive to large tankmates. They will eat or attempt to eat fish that are up to ¾ of their length so care should be taken when selecting tankmates. They are not overly active and spend much of their time sitting in a cave or hiding place so this should be taken into consideration when selecting tankmates. They also grow quite rapidly from the small individuals that are usually available so they can rapidly outgrow most tanks. Triggerfish (Balistidae) These fish are popular due to their striking colors, interesting behaviors and their resilience to poor water quality and disease. Their dispositions vary from combative to compliant. They are in general one of the more aggressive and territorial fish so they should almost always be the last fish introduced into a tank. They will eat almost anything and will do so with vigor so they should not be housed with any passive non-aggressive feeders.
0.988516	(Natural News) The more fried potatoes you eat, the higher your chances of death. That was the conclusion researchers came to at the end of their study, which has been published in The American Journal of Clinical Nutrition. According to the researchers, people who ate fried potato products, like french fries, tater tots, and hash browns, more than twice a week significantly increased their mortality risk. For their study, the researchers carefully tracked the eating habits of 4,440 people, between the ages of 45 to 79 years old, over an eight-year period. During the course of the study, a total of 236 participants died. The researchers turned to the food frequency questionnaires the participants answered, and from there they found that the majority of these participants frequently consumed fried potatoes. Conversely, the researchers noted that potatoes prepared via other means (such as by steaming or roasting) were not associated with a greater risk of death. Additionally, fried potatoes by themselves were not stated to cause death. What makes fried potatoes dangerous? Potatoes are relatively nutritious vegetables: They’re packed with fiber, potassium, magnesium, and even some antioxidants; they’re also devoid of fats, sodium, and cholesterol. This changes with the cooking and consumption methods, however. Frying and the quality of cooking oil used can greatly alter the nutritional value of potatoes. Hydrogenated vegetable oils like corn and canola oil have polyunsaturated fats that degrade when constantly heated and reheated. These damaged fats are strongly linked to promoting inflammation within the body that becomes the starting point of a plethora of health problems. For foods like french fries, the hydrogenated oils are just the beginning: French fries themselves contain high glycemic carbohydrates that surge insulin into the bloodstream and bring in unhealthy fats. Moreover, the trans fats in french fries can increase the prevalence of heart diseases, as can the high amounts of sodium chloride. Acrylamide is a more recent discovery but it adds to the dangers of fried potatoes. This substance forms in starchy foods that have been exposed to high-temperature cooking; specifically, when carbohydrates and the amino acid asparagine are cooked together. Acrylamide is considered both a carcinogenic and genotoxic substance, meaning that it has the potential to cause cancer and damage the genetic material of our cells. Unfortunately, acrylamide is plentiful in potatoes since these vegetables are full of asparagine and carbohydrates. Use avocado oil or coconut oil for frying. These oils have no hydrogenated fats or trans fats, and they remain stable at high temperatures. If you must add salt to your fried potatoes, opt for healthier varieties like Himalayan crystal salt. This particular kind of salt offers beneficial minerals you won’t find in regular table salt. Roasting and baking are cooking methods that don’t require a lot of oil, making them the superior cooking methods over frying. If you can avoid the frying pan, do so and utilize your oven instead. Visit FoodSupply.news for other stories about what foods are good for you and which foods can harm you.
0.99994	Calculate aerodynamic forces and moments for a flight dynamics model. You can supply aerodynamic coefficients in body, stability, or wind axes, or you can import aerodynamic coefficients from the U.S. Air Force Digital Data Compendium (DATCOM). You can also specify whether forces and moments are calculated in body or wind axes.
0.728663	Each group should choose a recorder who will read aloud the assigned section and record the group's responses to the questions outlined below. 1. Have someone in the group read the poem aloud. As the poem is being read, note both the narrative of the poem and the language used to describe the woman getting dressed. What is the relationship between the speaker and the woman? 2. Look at the words (adjectives, verbs, nouns) of the poem. What words stand out? How do these words relate to each other? What image of the woman do these words suggest? 3. To whom is the poem addressed? What is the speaker's attitude towards the woman? How does the title contribute to the poem? How do the poem's form (such as the break between stanzas) and (perhaps more importantly) the speaker's rhetorical strategy shape our view of the woman? 4. Given your responses to the previous questions, how would you characterize the poem's tone? Choose 3-5 words or phrases which best illustrate your answer to present your reading to the class. 1. Have someone in the group read the poem aloud. As the poem is being read, note both the narrative of the poem and the language used to describe the London morning scene. What scenes are presented? Are there any similarities between the scenes? Differences? 2. Look at the words (adjectives, verbs, nouns) of the poem. (Note: "Betty" was an all-purpose name for a maid; "Moll" was a lewd or promiscuous woman of a low social class, a harlot). What words stand out? How do these words relate to each other? What image (sight, sound, smell) or view of London do these words suggest? 3. To whom is the poem addressed? What is the speaker's attitude towards the morning scene? How does the poem's form (rhyme scheme, sentence grammar) contribute to the shape of its narrative? 1. Have someone in the group read the poem aloud. As the poem is being read, note both the narrative of the poem and the language used to describe the morning scene. What scenes are presented? 2. Look at the words (adjectives, verbs, nouns) of the poem. What words stand out? How do these words relate to each other? What is the relationship between the "he" and the clock? What image (sight, sound, smell) or view of the morning scene do these words suggest? 3. To whom is the poem addressed? What is the speaker's attitude towards the morning scene? How does the title contribute to the poem? How does the poem's form -- particularly its phrasing and sentence structure -- shape our view of the morning scene? Return to Phil Nel's syllabus for English 112W, section 5 (M-W-F).
0.996289	With iSkysoft Data Recovery, now anybody can recover data themselves, painlessly. Safe, complete data recovery is just a few clicks away: Scan, Preview and Recover. Using the latest powerful scanning algorithms, it can scan any Mac-based hard drive or external hard drive without destroying any data, and lets you recover data in no time at all. 4 recovery modes cover virtually all data loss scenarios, such as accidental deletion, formatting, improper operation etc. • Wizard Mode Recovery - simply answer 2 easy questions and the rest of the recovery will be finished by the program. • Lost Data Recovery - Retrieve lost data emptied from your Trash bin or deleted by Command + Delete. • Partition Recovery - Recover data from lost, deleted, resized and corrupted partitions. • Resume Recovery - Save your scan results to perform data recovery later. • Recover almost any file, including but not limited to documents, photos, video, music, email, and archive files. • Recover from any internal and external hard drive, SD card, USB flash drive, digital camera, memory cards, iPod, media player and other portable devices. • Fully compatible with 10.8 (Mountain Lion), 10.7, 10.6 and 10.5. • Recover data from HFS+, HFSX, FAT16, FAT32, exFAT, and NTFS files systems. How do you know whether each recoverable file is exactly what you want? iSkysoft Data Recovery lets you preview lost files before they are recovered, help you recover data at your pace and quickly find the files you need. • View photos in thumbnail or cover flow view and easily check image quality before recovery. • Preview video and audio files to check whether or not they're what you are searching for. • Open documents, email and archive files to see they're intact and the ones you need. • Only scan files of the selected file type to save time. • Find your files in seconds with file filters and folder trees. • Easily distinguish valid and invalid files before data recovery. • Recover lost files complete with original file names and file folders.
0.999997	This game simulates pool on your computer with full 3-D environment and perfect 3Dd sound. It features easy and addictive game play,supports 3-Ball,8-Ball,9-Ball,15-Ball,Straight,Rotation,BlackJack and Bonus games. 3D Live Pool can be played by either one or two players. The following section describes the details. selected group, then pocket the eight, to win the game. On every shot if a player pockets the eight, he loses the game. 1.You pocket the cue ball or your opponent's balls. 2.When you shoot, the cue ball fails to hit any ball in your group first. 3.When you shoot, you neither pocket a ball nor make any ball hit a cushion. Note: At least four balls must hit cushions on the first stroke otherwise balls will be re-racked and game will restart. Bonus Pool is very addictive though it's a single player game.You should not miss it if you want to be a pool shark. Nine balls are racked in a diamond shape, your task is to pocket them all in 20 shots. With one ball pocketed, you score 100, but if you fail to do so, you lose 100 instead. You can get bonus points according to how you pocket the balls. is the ball sequence you pocketed. The balls in one bracket were pocketed successively. So, In bracket (4,7,9),there are two 'successive pots',and in (6,2),you have one. For each 'successive pot', you'll get 500 bonus points. So you totally have 3 'successive pots' in your pocketed sequence, then you'll get 500 X 3=1500 bonus points. Now look at the pocketed sequence again, you'll find 4 follows 3,6 follows 5, 7 follows 6 and 8 follows 7,they are called 'sequential pots', for each 'sequential pot', you'll get 500 bonus points too. So, you'll get 500 X 4=2000 bonus points. The total bonus points you'll get is 1500+2000=3500. Another example, if your pocketed sequence is (1,2,3,4,5,6,7,8,9), It means you have 8 'successive pots' and 8 'sequential pots', then you'll get 500 X 8 + 500 X 8 = 8000 bonus! But it's extremely hard to get. If you fail to pocket all balls in 20 shots or you pocket the cue ball, you lose the game. Nine lowest numbered balls are racked in a diamond shape, the one is at the apex and the nine is in the center. Any ball that drops on the break is legal if the one is hit first.On every shot the player must hit the lowest-numbered ball first, failure to do so is a foul. Players who pocket the cue ball, commit a foul. The player who pockets the nine ball legally wins the game. Note: The balls may be pocketed in any order, and in particular the 9-ball may be pocketed at any time. The rule is only that the lowest-numbered ball must be the first one hit, so if you can knock the 1-ball into the 9-ball in such a way that the 9-ball goes into a pocket, you can win a frame very quickly. Fifteen balls are racked in a triangle and all the object balls are placed randomly. On every shot, you must pocket a ball, otherwise you commit a foul. If the cue ball goes in, it is a foul. If you miss or the cue ball goes in, you lose your turn. The player who pockets the most balls wins the game. Fifteen balls are racked in a triangle, the one is at the apex and the two and three are in the other two angles. On every shot the player must hit the lowest numbered ball first. Failure to do so is a foul. Players who pocket the cue ball, commit a foul. Any pocketed ball is spotted on original point when a foul is committed. The player who pockets the most balls wins the game. Ten lowest-numbered balls are racked in a triangle shape, the one is at the apex and the ten is in the center. Any ball that drops on the break is legal if the one is hit first. On every shot the player must hit the lowest-numbered ball first, fail to do so is a foul. Players pocket the cue ball, commit a foul. Player who pockets the ten ball legally wins. Fifteen balls are racked in a triangle and all the object balls are placed randomly. On every shot, you must pocket a ball. If the cue ball goes in, it is a foul. Any pocketed ball is spotted when a foul is committed. The player who pockets more than 61 points(each ball has a point value equal to its number) wins the game. Fifteen balls are racked in a triangle and all the object balls are placed randomly. On every shot, you must pocket a ball. If the cue ball goes in, it is a foul. Any pocketed ball is spotted when a foul is committed. The player who pockets 21 points(each ball has a point value equal to its number) wins the game. If total points more than 21, total point reset to 0. Press 'Ctrl' key and move mouse backward and forward to strike the cue ball with the cue stick. If you want to look at a ball closely, hit TAB key to show the mouse cursor, then move the cursor onto the ball.
0.936432	Ask any marketer what the starting point and backbone to a successful digital marketing strategy is and chances are they'll tell you that it's content. Content is the spark that ignites an effective marketing strategy and what keeps it going strong throughout, but not just any content will do. What you use for your digital marketing should be quality content that draws in readers and helps drive traffic to exactly where you need it to be. If you can build a solid foundation with great content, the rest can be built upon that. So, how do you go about creating content that's not only good, but also catches people's attention and makes them want to learn more? During my time in the marketing industry I've learned countless strategies, read endless tips and heard so many secrets centered around creating great content for digital marketing. I eventually found that, no matter what I was reading or hearing, the basic message was the same. There are guidelines your content should follow, certain aspects that make it appealing to a reader. From this realization came my three rules of content: Informative, Interesting and Relevant. No matter what niche the content is for or where it will be posted, these three characteristics are a must for quality content. Informative: The content should provide valuable and useful information to the reader. It should teach them at least one or two things or answer at least one question they have. This can be adjusted depending on where the content will be published (such as a blog, website, add or social media) and what the main purpose of the content is. The information can range from general information like you might find in a blog post, to strategic information like you might find on a website or in an ad. For example: If the main purpose of the content is to showcase the products and services a company offers, the information provided should teach the reader what these products and services do and why they're beneficial. If the purpose of a piece of content is to drive traffic to a certain website, the information provided should tell the reader why they need to go this website and what visiting the website will do for them. Interesting: While information is a key factor in great content, information alone won't do the trick. You have to keep in mind that real people are reading this content, so it has to be interesting; the content needs to catch and keep their attention from the title to the last period. Things like facts, statistics, metaphors, analogies and funny anecdotes are all great ways to keep people interested in what they're reading. Another good rule of thumb is to not be too technical, keeping a conversational tone and using words and phrases that are easily understood is your best bet when it comes to keeping your readers reading. Nobody wants to read blog posts full of technical jargon or boring drawl. Ask yourself this question: If I stumbled across this piece of content online, would I be interested enough to read it in it's entirety? If the answer is no, try and figure out why that is and how you can change that. Relevant: The final rule for creating great content is also one of the most important. Relevance applies to a few different things: The content must be relevant to the niche, business, or company that it's being written about. In addition to this, it must also be relevant to the audience it's being written for. Knowing your target audience is important, but ensuring the content you're writing is relevant to that audience is even more important. Writing properly relevant content comes from doing research: Knowing enough about the subject of your content and who it is being written for to make it relevant to both. This is another thing that is going to keep your readers interested and wanting to read more. Following these three rules will help you create quality content that will be effective in any area of digital marketing. Anytime you complete a piece of content, ask yourself: Does the content follow these three rules? If the answer is no, it's essential that you read through what you've written and figure out why. Without these three elements your content will have a hard time accomplishing what you need it to. Things like driving traffic and attracting readers will come easier when your content is informative, interesting, and relevant.
0.962983	A girl in a restaurant asked me "Are you single?". I happily replied "Yes". She took away the extra chair in front of me.
0.997708	Generate more capital and revenuesIt techniques has higher conversion rates and provide profitable benefits for you and your business in terms of better and higher revenues. It also helps to reach door to door and farther-reaching markets both locally and abroad. It enables you to carry out campaign to their products and services. It gives platform to small and medium enterprises the chance to compete against large enterprise. It helps to deal with multiple customers even worldwide, without having physical stores or branches in these locations. We helps to automate and grow your business with digital techniques like search engine optimization (SEO), search engine marketing (SEM), content marketing, influencer marketing, content automation, campaign marketing, data-driven marketing and e-commerce marketing, social media marketing, social media optimization, e-mail direct marketing. Associating and furnishing your clients with appropriate engagement focuses can give you an understanding of what your focused-on gatherings of people need. This imperative data will direct you towards making the correct arrangement of next moves, give your clients a far and away superior experience, grow great associations with them – picking up their devotion and assume that you will require when your business starts to develop.
0.999947	"One word which summarizes my creative process is 'daring'. I am not afraid to be wrong." How were you originally motivated to become an immunologist? a) Vaccination (teatanus, whooping cough, diptheria, small pox, polio) had essentially eradicated various diseases, while treatments of diseases were making little headway. I wanted to be associated with a "prevention" approach rather than a "treatment" approach to medicine. b) At this time, immunologists were in a few departments, but it was clear to me that soon these physicians would branch into all areas of medicine. I loved medicine and I wanted to keep my options open, so I chose immunology, knowing I could practice in medicine, pediatrics, pathology, microbiology, biochemestry, or many other areas. Therefore, I chose the field of immunology because I wanted to focus on the preventative side of medicine Ð addressing problems before an illness stuck. Immunology also exposed me to numerous disciplines within the medical field. One word which summarizes my creative process is "daring." I am not afraid to be wrong. Most successful scientists differ from people in other walks of life because in our profession, we are often wrong. In science, the definition of the "creative process" is thinking of an idea, testing it, and finding that your hypothesis is wrong most of the time. Trial and error is a daily part of science. However, if one equates being wrong to failing, his or her science will be dull and mundane; one must be daring enough to explore a new path, but confident enough to be wrong. We often learn as much from our mistakes as from our successes. I pride myself in having been wrong often, but right enough of the time to make my life very exciting and fulfilling. What ideas do you have for a future colony on Mars? My ideas about a future Mars colony can be divided into two categories: Preparations and Experiments. The scientific community would gain useful and valuable information from both the groundwork prior to a Mars colony as well as the actual experiments performed on the planet. 1. Prior to colonizing on Mars, the plan should establish an artificial environment, similar to the Biosphere 2 experiment in Arizona. What kind of controlled environments would be required to grow plants and recycle water? Can one mimic Earth's atmosphere and humidity? 5. Consider issues of fertility testing and in-vitro fertilization. 6. Discuss and determine most important medications, hospital equipment, and health personnel needed for the mission and specify the ideal number and ages of colonists to send to Mars. 7. There is a T cell suppression (or at least a decrease in peripheral blood T cells) with weightlessness. The months or years required to get to Mars could leave travelers immunosuppressed and susceptible to endogenous infections. This consideration must be addressed and precautions taken before embarking on a Mars colonization effort. 8. Harold Muchmore, the recently decreased member of the Infectious Diseases Section, studied colonists in Antarctica. Interestingly, these people developed upper respiratory infections that swept through the colony on a periodic basis throughout the winter. Apparently, some viruses are carried by the colonists reactivate and become infectious again in a carrier. They are then spread through contact. While our friends on Mars are likely to be spared the yearly bout of influenza, they are almost certain to develop infections with other viruses which will make their stay there similar to our experience here on Earth. Experiments: What can we learn from Mars? 1. There is much less sunlight on Mars, so sunburn will be much more difficult and the frequency of melanoma should be lower. However, the lack of an ozone layer could actually raise the rate. Determining whether immune suppression is important in melanoma is one undertaking which could be learned from Mars. Fortunately, a spacesuit can easily protect the user against UV radiation. 2. Mars' gravity must be different from ours: how will this affect maintaining muscle tone or even internal organ functions of the human colonists? 3. What are the implications of introducing E. coli and other organisms carried by the colonists in Mars? Will they take root but develop in different ways? 4. The allergens on Mars should be interesting. Dust organics and inorganics might have chemical compositions not found on Earth and be new antigens for our immune systems. Colonists might need an antihistamine and nasal steroids. If there ever was life on Mars, then it is very likely that allergens never seen on Earth would be prevalent and poised to cause problems. 5. If there is life on Mars, are there pathogens for which we have no natural immunity? Previously unencountered pathogens had a major impact during colonization of the world; the colonists introduced germs that decimated most native peoples, and occasionally the reverse occurred. Are we prepared to address unknown pathogens? Are we capable of using known methods to combat unknown germs?
0.999992	Malaria is present worldwide but particularly high risk in tropical and subtropical countries. According to the recent World Malaria Report, released in November 2017, there were 216 million cases of malaria in 2016, up from 211 million cases in 2015. All travelers should check the risk of malaria before traveling to a particular destination. Prevention is based on avoiding mosquito bites. Travelers should take practical steps to avoid mosquito bites such as weather clothing to cover body, using mosquito repellents and mosquito nets. Antimalarial drugs can also be used to prevent malaria when used with all other preventative measures. Malaria symptoms include fever, shivering, sweating, muscle aches, headache, and vomiting. Symptoms are similar to flu-like and can be accompanied by other symptoms. The most serious form of malaria can be life-threatening so if in doubt, seek medical advice quickly. There are a number of antimalarial drugs available in the UK for those traveling to high-risk areas. Depending on where you are traveling to and other factors such as your activities, accommodations, and length of stay, will determine if you require antimalarial drugs. Book a consultation to assess your risk of malaria before traveling.
0.999997	Let’s say an average office building is 30 floors and there are 200 employees per floor. That means a total of 200 x 30 = 6,000 employees work there. Assuming that 10% are out of office at anytime and the number of visitors are negligible, we can say total number of employees in the building is 6,000 x 0.90 = 5,400. Given people in the office usually arrive to work within a short window of time, I’d like to design the elevator in a way that employees don’t wait for longer than 30 seconds. Let’s assume that the 5,400 people arrive uniformly within 60 minutes in the morning. Let’s say that the elevators are designed in a way that in the building are going to stop at a max of 5 floors, the speed of the elevator is 3 meters per second, each floor is 3 meters long, and it takes an elevator 15 seconds to open, unload some people in each floor and close and it takes elevator 60 second to get filled in ground floor. Let’s also assume the stops are disrtibuted unifromly. In other words, distance between the stops is 30 / 5 = 6 floors or 6 x 3 = 18 meters. 5 stops x (18 meter / 3 meter per second) + 5 x 15 seconds + 30 seconds + (30 floors x 3 meters / 3 meters per second) = 30 + 75 + 30 + 30 = 165 seconds or around 3 minutes. In other words, one elevator can do 60 minutes / 3 minutes = 20 rides in an hour in the peak time. Let’s say each ride can consist of 20 people. This means that one elevator can help move 20 x 20 = 400 within one hour in the morning. Given total number of employees in the building is 5,400, we would need 5,400 / 400 = 13 elevators to move everyone to their floor in the morning in a way that no one has to wait for longer than 30 seconds. I like the approach @Nimesh, but I didn’t quite understand how the 30 seconds wait time came into play in your solution. Here’s mine. Please let me know what you think. To answer this, we need to figure out the rate at which we can move people (supply) and how many people to move (demand). We also need to consider: elevator capacity, acceptable wait time, and peak times. 1500*2/3 = 1000 people per hour after adjusting for not everyone coming to work in peak time. We want to use peak time as our basis for the demand because if we can handle the load in peak time, we can be sure we can handle the load during off peak. To figure out the supply, we need to calculate how quickly one elevator can return. this is approximately 2 minutes. So it takes 2 minutes for an elevator to be re-used. In that time, how many people will be waiting? 1000 people/60 min = aprx 17 people per minute, so 34 people every two minutes. If we want 30 seconds as the max wait time, then we need to move 9 people per 30 second increment (17 people per minute /2). If each elevator can carry 10 people, then in 2 minutes we’d need 4 elevators because there are 4 30-second intervals in 2 minutes. If we want to have wait time be 1 minute max, then we’d need to carry 17 people every minute. If the elevator can only take 10 people, we’d need two sets. In 2 minutes, there’s 2 1-minute intervals, so that requires 4 elevators. If the elevator can take 20 people and acceptable wait time is 1 minute, then we’d only need 2 elevators! So the levers are elevator capacity and acceptable wait time. A sanity check is in my building there’s 4 elevators. It’s 15 floors. I don’t think I’ve ever waited for longer than 1 minute. So it is reasonable estimate.
0.905508	Today marks a momentous occasion - today is the first day of 2018! Here's hoping your celebratory activities were in equal parts memorable and enjoyable. Other than the new year arriving today, today is special for another reason - the launch of the Parris tool for machine learning training automation. TL;DR: this makes the training of algorithms easier on you. But, pertaining to the title of the post, the Parris automated ML training tool is out today in its first iteration on Github. It's an open source project for which I'm hoping others find use in, and within which to find opportunities to contribute. Parris is a tool for automating the training of machine learning algorithms. If you're the kind of person that works on ML algorithms and spends too much time setting up a server to run it on, having to log into it to monitor its progress, etc., then you will find this tool helpful. No need to SSH into instances to get your training jobs done! stops the EC2 instance when it has finished. The primary purpose of this tool is to reduce the amount of repetitive setup it takes for you to train your machine learning algorithms, and in doing so save some cost by utilizing your server's compute hours more effectively (server starts the training jobh as soon as it's launched, and stops when you've configured it to stop). Consult the Getting Started guide! It's very detailed and walks you through a full setup, all the way to launching a machine learning training job and terminating it. Be warned that you'll find it easiest if you have an AWS account already set up. This tool is missing something. Can I contribute to this? Absolutely! Feel free to open an Issue to track the missing item while I and/or others work on it, or open a new Pull Request if you've already coded your addition. Hoping to hear that this tool has helped you!
0.999998	I want my daughter to grow up bilingual. How do I encourage language development in two languages at the same time? Globally speaking, growing up in a multilingual environment is really quite normal, though it is perhaps less common, and certainly less encouraged, in the United States. Monolingual parents, teachers, and other adults occasionally worry that exposing young children to more than one language will "confuse" them and/or cause a delay in their language development. There is in fact no evidence linking a bilingual environment to increased risk of language delays or disorders. Children regularly exposed to multiple languages do often tend to begin saying their first words later than their monolingual peers, but not by much. When they begin to talk, they might pick one language to use at first, but they'll generally demonstrate understanding of both. For young children developing language for the first time, the motivation is built in; they want to communicate with you! As for the exposure, that's what you provide. There are a number of ways parents can provide sufficient exposure to two languages for the children to learn both. Probably the most common is the "one language per parent" model; for example, Mom speaks Spanish and Dad speaks English. My experience with children raised with this model is that the child will start out speaking the language that the parents speak to each other, which is often the dominant language of the community where they live. A couple I know in Germany (American dad, German mom) have been using this approach with their toddler son, who speaks only German but understands his dad just fine when he speaks English. He's heard his dad speaking German with his mom and others in the community, so he knows Dad will understand him when he uses German. On the other hand, he knows a lot of people in his community don't understand English, so he's figured out that the most efficient way to begin is with the language that everyone knows (at least everyone in his world). Smart kid, huh? He'll add English later, assuming his dad keeps providing the exposure. Another approach is "one language per setting," where the parents use one language at home and another when they're out and about. I don't actually know anyone who's done this, so I'm not sure how well it works. My feeling is that it would be harder to provide adequate exposure to the "out and about" language, but that depends on the family's habits and practices. This may be a more viable option for children being raised by a single, bilingual parent. I've also heard of other approaches that don't seem to work so well, such as switching back and forth "as the spirit leads," or speaking one language on Monday, Wednesday, and Friday and the other on Tuesday, Thursday, and weekends. My opinion about these is that they do not adequately provide the children with an opportunity to compartmentalize their languages. Most bilingual people (children and adults alike) tend to favor one language or another according to the context they're in (work versus play, for example). Children are well-adapted to spotting patterns, and an "as the spirit leads" approach does not provide a pattern to spot; going according to the days of the week probably won't work well for infants and toddlers, since the concept of a seven-day week is something that generally develops later. If your family is monolingual, it is harder to create a multilingual environment in the early years. Hiring a bilingual babysitter who is willing to use a second language with the child can be an option if you have the means, but many don't. In that case, starting in preschool or elementary school may be possible. The older a child gets, the more difficult it is to learn a foreign language, but elementary school is still early enough for a child to develop native or near-native fluency of a foreign language. Some communities have language immersion schools for the purpose of fostering bilingualism, but in the United States these are mostly limited to large urban areas and competition for admission is pretty stiff. Unfortunately, the prevailing practice here is to wait until high school to begin even giving children the option to learn a foreign language. Getting back to your question, the way to encourage your daughter's language development in two languages at the same time is, quite simply, the same way as you would with one language - by creating a language-rich environment. Talk to her a lot, use a wide variety of vocabulary, and provide a healthy and varied diet of communication activities. Just do it with two languages rather than one. By raising your daughter bilingual, you are providing her with a tremendous asset and blessing. She'll thank you when she's an adult - in two languages!
0.99902	Much of automotive design took cues from the latest technological advances and cultural trends. The "fin" was no exception. The origin of fins began with the 1948 Cadillac when designer, Harley Earl, drew inspiration from the twin tailed P38 Lightning aircraft. Designs started off small and transformed into the tall piercing fin with taillights. Some looked like jet flames and others had more curves to look like the after burners of space rockets. The 1959 Cadillac had two thruster "flames" on each fin. The 1957-1959 Desoto had three. The incorporation of the tail light into the fin design was pushed to new heights and beauty. The 1960 Chrysler New Yorker and 300 were stunning examples of fin design. General Motors and Chrysler embraced the boldness of the fin. They engaged in a game of one-up-manship to see who could produce the highest, flashiest fins. Ford took a more restrained approach and produced beauties such as the 1957 Thunderbird with its subdued and elegant fin. Later, Ford enlarged the after burner taillights in the shape of turbine engines to ensure the impact and flash of the design. While fins were sometimes hyped as functionally dysfunctional and only used for looks, they indeed had a function. They were a symbol of prosperity and a fine design tool which sold cars. According to Harley Earl, tailfins gave customers an "extra receipt for their money in the form of a visible prestige marking." Some of the most iconic fins almost did not exist. General Motors had already perceived the fin to be outdated by the late 1950s. They were already planning to shelve the fin design. What GM had planned for car design could be seen in the 1958 Chevrolet with fins becoming more horizontal and curvaceous. General Motors went even more radical with the 1959 "Bat Wing" Chevy and the outstanding Buick Electra. A young designer named Chuck Jordan happened to drive to the Chrysler Factory and saw rows of the big-finned "Forward Look" Plymouths. Jordan and other younger designers warned the senior design staff that General Motors was going to be out-designed and also out-sold. General Motors tabled the planned designs and developed the larger fins, especially on the flagship make, Cadillac. The stellar 1959 Cadillac fin was the result. Fins were seen in every make and model. Station wagons had fins. The modified pickups Chevrolet El Camino and the Ford Ranchero proudly displayed fins. Some makes, such as the stunning Dodge Lancer, had staggered or double fins as did the intriguing Dodge Polara and the 1958 Packard. Plymouth had several outstanding fin designs. Even European cars such as the Mercedes Benz sprouted fins. The smaller auto manufacturers had notable fin designs. Studebaker, under the influence of Raymond Loewy, produced the outstanding Hawk series in 1957. Kaiser Frasier showed fins on the Henry J. The 1958 Nash Rambler had compact yet striking fins. Hudson had muted fins in 1957, its last year of production. As the Post War era moved on through the 1960s, the fin transformed into horizontal style cues. Fins became lower, wider, more incorporated into the body of the vehicle. The muscle car era produced one last notable aerodynamically functional fin, (which was now called a "wing") and it could be found on the speed demon Super Bird and the Daytona. These were some of the fasted production cars made up until that time. Perhaps the fin has not entirely died. "Spoilers" remain a popular design detail even on modern automobiles. While the glory days of the fin are past, the models produced during this era remain a testament to the joyous optimism and stylistic mastery of the times. Finned vehicles remain highly collectible and elicit sheer delight with owners and viewers alike. Earl's directive in design was "Go all the way and then back off." The radical designs of the fin etched an indelible mark on the legacy of car design.
0.941046	What's the best way to embed a calendar into my website? I'd like to create something that allows people to add events to the calendar but cannot seem to find one that works. You are describing an interactive calendar which would require that it be hosted somewhere else and brought onto your Yola website. Yola doesn't have accessibility for people to access the site through the published site, only through the website builder. There are a number of providers that supply interactive calendars but most are not free subscriptions. Another option is to use something like Google Apps calendar and allow users access to your calendar for updates and so on.
0.999678	In this delightful 3 minute video, Verizon, the $187 billion telecom giant whose former associate general counsel, Ajit Pai, is now in charge of the Federal Communications Commission, begs you to believe that it's totally in favor of the free and open internet. "The FCC is not talking about killing the net neutrality rules," claims Verizon general counsel Craig Silliman in an "interview" recently posted on Verizon's official YouTube page. "And in fact, not we nor any other ISP are asking them to kill the open internet rules. All they're doing is looking to put the open internet rules in an enforceable way on a different legal footing." I'm not quite sure how to square these claims with Verizon's actual behavior. After all, the telecom has a long and glorious history of taking the FCC to court to protest anything even remotely resembling what we now call net neutrality, or the principle that all data should be treated equally. In practice this means that your ISP, whether it's Comcast, T-Mobile, or, yes, even Verizon, doesn't have the right to control what websites you visit, nor the right to speed up, say, its own streaming video service at the expense of ruining your Netflix binge-a-thon with endless buuuffeerring. Silliman then blames "advocacy groups" for "stirring people up with outrageous claims," implying, effectively, "Nothing to see here, move along." Which is weird, given that an advocacy group of his own, USTelecom, which is a lobbyist whose membership ranks also includes the likes of AT&T and Frontier, makes a scary-sounding argument of its own when it claims that net neutrality will have a "devastating impact on internet freedom." I don't quite understand how regulating ISPs to ensure that they don't mess with your internet somehow takes away internet freedom, but here we are. Here's what's going on: ISPs like Verizon are scared to death of the net neutrality regulations that are currently on the books because they're exactly that: codified rules that are plain and clear and easily enforced. The regulatory burden of strong net neutrality is so onerous, they claim, that they wouldn't be able to continue to invest in the kind of internet infrastructure that has made America the envy of… exactly no one. The tl;dr? Verizon is upset it has to actually abide by the rules of the road. Sad.
0.995232	Where did Sigmund Freud get the term id? Sigmund Freud’s original term for the unconscious mind was not id but es, the indefinite pronoun it in German. Freud borrowed that term from a physician, Georg Groddick, who in turn had borrowed it from his teacher Ernst Schweninger. As Freud’s ideas became popular in English-speaking countries, translators felt that simply calling the unconscious it was too vague and unscientific. They replaced it with its Latin translation, id.
0.999994	How does dynamic program generation work? The secret to Viv is the system actually writes its own code. In contrast to any other similar system, it is a profound and monumental giant leap forward. The structure of the Voice First world is held together by Intelligent Agents. Intelligent Agents use AI (Artificial Intelligence) and ML (Machine Learning) to decode volition and intent from an analyzed phrase or sentence. The AI in most current generation systems like Siri, Echo and Cortana focuses on speaker independent word recognition and to some extent the intent of predefined words or phrases that have a hard coded connection to a domain expertise. Viv uses a patented exponential self learning system as opposed to the linear programed systems currently used by systems like Siri, Echo and Cortana. What this means is that the technology in use by Viv is orders of magnitude more powerful because Viv's operational software requires just a few lines of seed code to establish the domain , ontology and taxonomy to operate on a word or phrase. In the old paradigm each task or skill in Siri, Echo and Cortana needed to be hard coded by the developer and siloed in to itself, with little connection to the entire custom lexicon of domains custom programmed. This means that these systems are limited to how fast and how large they can scale. Ultimately each silo can contact though related ontologies and taxonomies but it is highly inefficient. At some point the lexicon of words and phrases will become a very large task to maintain and update. Viv solves this rather large problem with simplicity for both the system and the developer. Specimen of the developer console identifying domain intent programing. Viv's team calls this new paradigm the "Dynamically evolving cognitive architecture system". There is limited public information on the system and I can not address any private information I may have access to. However the patent, "Dynamically evolving cognitive architecture system based on third-party developers" published on December 24th, 2014 offers an incredible insight on the future. A dynamically evolving cognitive architecture system based on third-party developers is described. A system forms an intent based on a user input, and creates a plan based on the intent. The plan includes a first action object that transforms a first concept object associated with the intent into a second concept object and also includes a second action object that transforms the second concept object into a third concept object associated with a goal of the intent. The first action object and the second action object are selected from multiple action objects. The system executes the plan, and outputs a value associated with the third concept object. Some consumers and enterprises may desire functionality that is the result of combinations of services available on the World Wide Web or “in the cloud.” Some applications on mobile devices and/or web sites offer combinations of third-party services to end users so that an end user's needs may be met by a combination of many services, thereby providing a unified experience that offers ease of use and highly variable functionality. Most of these software services are built with a specific purpose in mind. For example, an enterprise's product manager studies a target audience, formulates a set of use cases, and then works with a software engineering group to code logic and implement a service for the specified use cases. The enterprise pushes the resulting code package to a server where it remains unchanged until the next software release, serving up the designed functionality to its end user population. This Viv patent is a landmark advance for Intelligent Agents and the resulting Voice First devices and uses case that will be developed on the platform. The process for adding new domain experience is a simple process in the developer app. To define a new intent, the domain is established by programing a horizontal flow chart that helps to define ontology and taxonomy with in the entire system. The results are lines of code that will forever be dynamically changing and connecting as more domains of intent are established. Viv literally programs itself. This is process is related to self modifying code that has been around since the 1960s from assembly language to Cobol. However the process that Viv uses is radically more advanced. "(Siri-Alexa) I want to pick up a Pizza on the way to my girl friend's house and I would like to find a perfect wine to pick up along the way. Also would like to bring her flowers." Currently Siri and Alexa could not understand the intent of this paragraph, nor could it easy connect to the six domains and many ontologies to produce a useful result. Viv could learn this in a few minutes and constantly connect with new intent domains by expanding the ontological references each domain represents. You will set privacy fences around any information that Viv learns and you will be able to choose to allow the system to share this data with any intent domain. Of course security and privacy will always be an issue with Intelligent Agents and Viv is working on a new model that will quickly define what is logically private and potentially shareable with permissions. Specimen of the current domain cloud. Note the appearance of Payments and Money. Specimen flow chart from "Dynamically evolving cognitive architecture system based on third-party developers" patent. FIG. 1 illustrates a block diagram of an example plan 100 created by a dynamically evolving cognitive architecture system based on third-party developers, in which action objects are represented by rectangles and concept objects are represented by ovals, under an embodiment. User input 102 indicates that a user inputs “I want to buy a good bottle wine that goes well with chicken parmesan” to the system. The system forms the intent of the user as seeking a wine recommendation based on a concept object 104 for a menu item, chicken parmesan. Since no single service provider offers such a use case, the system creates a plan based on the user's intent by selecting multiple action objects that may be executed sequentially to provide such a specific recommendation service. Action object 106 transforms the concept object 104 for a specific menu item, such as chicken parmesan, into a concept object 108 list of ingredients, such as chicken, cheese, and tomato sauce. Action object 110 transforms the list of ingredients concept object 108 into a concept object 112 for a food category, such as chicken-based pasta dishes. Action object 114 transforms the food category concept object 112 into a concept object 116 for a wine recommendation, such as a specific red wine, which the system outputs as a recommendation for pairing with chicken parmesan. Even though the system has not been intentionally designed to create wine recommendations based on the name of a menu item, the system is able to intelligently synthesize a way of creating such a recommendation based on the system's concept objects and action objects. Although FIG. 1 illustrates an example of a system creating a single plan with a linear sequence that includes three action objects and four concept objects, the system creates multiple plans each of which may include any combination of linear sequences, splits, joins, and iterative sorting loops, and any number of action objects and concept objects. Descriptions below of FIGS. 4, 5, and 6 offer examples of multiple non-linear plans with splits, joins, and other numbers of action objects and concept objects. Just in this simple sentence "I want to buy a good bottle wine that goes well with chicken parmesan" there are dozens of intent domains that would be connected. Viv's can build a result dynamically even if this question has never been asked before. Viv operates on the intent domains from the extracted words in the sentence and in real time constructs an answer. Viv Labs will be opening the system up to developers and I am predicting a land rush similar to when Apple opened up the App store for the iPhone. Content application program interface providers desire branding, to sell advertising, and/or to sell access to restricted content. Data providers and data curators want recognition, payment for all content, and/or payment for enhanced or premium content. Transaction providers desire branding and transactions via selling of some good or service. Advertisers desire traffic from qualified end users. A single person or organization may play more than one of these roles. The shift from push mechanisms of the current adversing paradigm to the pull mechanisms of Voice Commerce will define the rise of Voice Payments. Currently even the most technically defined payments companies are not in the position to adapt to the new paradigms. This type of system may sound very familiar to most of us, this is very close to the manner that humans learn. We assemble domains and form ontologies that connect intent. On December 24th, 2014 when I first viewed the "Dynamically evolving cognitive architecture system based on third-party developers" patent from Six Five Labs, "goose bumps" ran through my entire body, for in that moment I saw what I have been studying since 1989 in my Voice manifesto. I spoke to this in some detail recently here on Quora . In this Quora Knowledge Prize posting I detail how Voice First systems will completely change advertising, commerce and payments. I got into more details in the industry publication Tech.pinions . Viv is the first system to pull together the right elements of speech recognition, speech synthesis, AI, ML, self modifying programs, commerce and payments in such a way that I assert in 10 years 50% of computer interactions will be via Voice primarily on Voice First devices. The Viv we see today (May 9th, 2016) is one small step in this direction, but a giant leap for the future of computers. Brian Roemmele's answer to Is Amazon Echo (and/or Siri and other voice assistants) actually useful, or is it just a novelty? Are usage and retention of these products growing?
0.950242	Key qualities for a successful manager today. :red_flag: Make blue sky (Very few people are comfortable with the idea that they will be doing exactly what they are doing today. Great managers anticipate people's dissatisfaction. :red_flag: Put themselves about (Most managers now accept the need to find out not merely what their team is thinking, but what the rest of the world, including their customers, is saying. :red_flag: Exploit strengths, not weaknesses; in themselves and in their people (Weak managers feel threatened by other people's strengths. Great managers have no truck with this destructive thinking. They see strengths, in themselves as well in other people. :red_flag: Make themselves redundant (learn new skills and acquire use information from the outside world, and time immediately pass them on. So managers are perpetually on the look-out the higher-level activities to occupy their own time while constantly passing on tasks that they have already mastered. Which style do you think gets the best out of people? :red_flag: positive action on an individual basis. If colleagues are working in a, a team, and one or two colleagues need to be criticised, criticise those people in private, on an individual basis. :red_flag: a sense of justice. Treat people fairly, but ac difficult decisions have to be made, staff are more likely to accept those decisions if they feel they've been treated fairly, and with a sense of justice. :red_flag: involvement and availability. Take an interest in your staff, maintain an open flow of communication, the so-called management by walking about. The key feature of this is not to give the impression to staff that you don't trust them, that you're supervising their work, but you're taking an interest in their work. :red_flag: consideration, respect and trust. Most people respond according to the way they're treated. So if you treat people with politeness and dignity, the chances are, the majority of staff will respond in a similar manner. :red_flag: Recognition and credit - people can be praised to success. Let people know you acknowledge good work. Management styles, their advantages and downsides. The main difference between leaders and managers is that leaders have people follow them while managers have people who work for them. A successful business owner needs to be both a strong leader and manager to get their team on board to follow them towards their vision of success. :red_flag: Leaders create a vision, managers create goals. :red_flag: Leaders are unique, managers copy. :red_flag: Leaders take risks, managers control risk. :red_flag: Leaders grow personally, managers rely on existing, proven skills. :red_flag: Leaders build relationships, managers build systems and processes. :red_flag: Leaders create fans, managers have employees. Which leadership skills do you consider the most important?
0.999758	Do you want to use a timer to turn on/off TV at certain time? You can do this with TV on/off timer setting. ※ To use this function, current time should be set. If current time is set to “user setting”, you need to reset the current time when TV power is turned off. - Input : Select the input mode you want to watch when TV is turned on. - Channel : Set channel you want to watch when TV is turned on. ※ While it is set as HDMI, Component, and External Input, TV turns on automatically, but if the peripheral (eg. Set-top box) is off, it will display “No signal” after 15minutes of display, TV will automatically be turned off. ※ “No signal” appears when the power of external devices (set-top box) is turned off, and the external devices are connected to TV for timer on. When “no signal” message lasts for more than 15 min., TV is turned off automatically. - Hour, minute : Set hour and minute. ※ If you use a set-top box, TV is turned off at preset off time, set-top box power is not turned off at the same time.
0.99948	What does writing an essay about death entail? ❶Popular Questions My family is a small family with three people. Moreover, there are contrary opinions to judge the issue of the death penalty. In my opinion, the existence of the death penalty is necessary. It is very expensive to hold someone in prison for life. Every year the government has to pay much money on the prisoner of life imprisonment. On the other hand, if a murder is provided by all common people, it is unfair for all common people to raise the murder who is a killer. We work hard in the world, why do we have to pay our salary to a murder? Nothing the murder done, but the crime does. It seems too ridiculous to raise a murder who makes a big mistake for a life. Second, the death penalty can frighten and hinder committing crime. To prevent people not to take other people easily, they should know they would die if they kill somebody. Another reporter shows that the Korea has abolished the death penalty for seven years, but the crime rate has been increase. The existence of death penalty warns people not to commit serious crimes easily, and prevent the crime rate increase. I agree that life is a valuable present which God gives us. So the life is very important for us. A murder may take more over one life. Who can give the chance for the victim to live? The power of executing the death penalty is a warning to tell people not to murder others. Enforcing death penalty is a way to confess the relatives of dead people. And I have not seen any research that would substantiate that point. Evidences from around the world have also shown that this punishment has no deterrent effect on crime. Amnesty International stated that, in in the USA, the average murder rate for states that used the death penalty was 5. In in Canada, 27 years after the country abolished the death penalty the murder rate had fallen by 44 per cent since , when capital punishment was still enforced. Far from decreasing the crime rates and making the country safer, the punishment has been shown to have a hardening effect on society. Capital punishment is unfair regarding of a wrong done to innocents. Why deprive ourselves of any chance to redeem such errors? Making judgments about other and decide whether they should live or die is unjust for anyone. Courts of Justice are known to make numbers of errors, which means it is unreasonable to allow defendants with the least doubt of guilt to be sentences to death. One cause of the death of innocents is because of the false information given by witnesses. Timothy Hennis, for example, a US Army Sergeant who was convicted of murder and sentenced to death in because the wrong information given by one witness which had mistaken Hennis for someone who looked like him. Capital punishment causes discrimination towards black people. Baldus, a law professor in University of Iowa found that black defendants were 1,7 times more likely to receive the death penalty than white defendants and that murderers of white victims were 4,3 times more likely to be sentenced to death than those who killed blacks. He argued that his death sentence was tainted by racial bias. Nationwide, blacks and whites are victims of homicide in roughly equal numbers, yet 80 percent of those executed had murdered white people New York Times, The odds of receiving a death sentence are nearly four times higher if the defendant is black than if he or she is white. In conclusion, there are many reasons why death penalty has to be abolished. For some nations, it was a broader understanding of human rights. For example, Spain abandoned death penalty in , stating that the death penalty has no place in the general penal system of advanced, civilized societies. Similarly, Switzerland abolished the death penalty because it constituted a flagrant violation of the right to life and dignity. Justice Chaskalson of the South African Constitutional Court stated that, "the rights to life and dignity are the most important of all human rights… and this must be demonstrated by the State in everything that it does, including the way it punishes criminals. The death penalty is a major issue that brings up a lot of arguments in our society. The most important question concerning the death penalty is whether it should be abolished or not. Keywords: death penalty should be abolished essay. The death penalty is the act of punishing someone to death for an offense. Questions have been arisen to whether death penalty should be abolished in countries around the world. The pro's and con's of death penalty. The Death Penalty Should be Abolished Essay Sample According to the Death Penalty Information Center (DPIC), there have been executions in the United States since These executions have been performed through electrocution, gas chamber, hanging, firing squad, and the most common lethal injection, which over people have been executed by this method. Why the Death Penalty Should Be Abolished Why should the death penalty be abolished? The death penalty should be abolished because of many reasons. Many people believe the saying, 'an eye for an eye'. But when will people realize that just because someone may have killed a loved one that the best thing for that person is to die also.
0.999866	Instead of making contributions to potentially many different superannuation funds on a regular basis, employers can elect to use a clearing house to manage the distribution of their SG contributions and any voluntary contributions such as salary sacrifice. A clearing house service involves the employer providing one super contribution to the clearing house provider, which then distributes contributions for each employee in line with choice of fund requirements as notified by the employer. This could include distributing contributions to an employee's chosen fund or the employer's default super fund. The small business superannuation clearing house was introduced on 1 July 2010 and can be used by any small business employer with less than 20 employees with an aggregated turnover below $2 million. Instead of paying for the use of another clearing house, eligible small business owners can use this facility as a free clearing house to satisfy their SG obligations including managing employee choice of fund. When are contributions to a clearing house 'made'? Employer contributions made to clearing houses do not count towards meeting an employer's SG obligation until they are received by the complying super fund (chosen or default). However, an exception applies for small business employers using the small business superannuation clearing house, who have their contributions count for SG purposes when they are received by the small business clearing house. for employer tax-deduction purposes, a contribution has not been 'made' until it is received by a complying super fund or RSA, even if the small business superannuation clearing house is used. for contribution cap purposes, an employer contribution will count at the time it has been received by the complying super fund or RSA and has been allocated to the member's account.
0.998934	What are we having for dinner? Garbage! This is a fun meal to prepare for a large number of people. You can add your favorite vegetables and seasonings and generally personalize this to suit yourself. Purchase a new galvanized garbage can. Wash it well and scald it. The first time you use it, it may leak a little bit. Prepare about 24 ears of roasting corn by removing the outer husks and removing the silk. Leave a few of the inner husks on. Stand the corn up in the bottom of the garbage can. You want to make a firm base of the roasting corn, so use more or less as needed. Wash red potatoes, but do not peel. Peel onions, and cut into quarters. Prepare several heads of cabbage by cutting each head into sixths. Prepare carrots by washing and cutting in half. Note: You can use any vegetables - it's your choice. Place all the vegetables on top of the corn. Salt and pepper as desired as you go. Top all the vegetables with smoked sausage, Italian sausage, Polish sausage, hot dogs, or whatever you desire. Pour a large pot of boiling water over the top. Cover the garbage can and set it on the prepared grill. Cook for about 2 hours. If using a charcoal grill, watch the fire and add more coals occasionally.
0.995536	What are the cheapest places for digital nomads? Find out 2019's top 12 destinations, and all the reasons why you'll love spending time in each of them! I recently quit my day job to travel full time and chase my dream of being a freelance writer. There’s a lot of talk lately about more and more people choosing to take up the digital nomad lifestyle. It seems like everyone is hopping on this train (sometimes literally), and the number of people who consider themselves digital nomads is expected to continue growing. So what exactly is a digital nomad? A digital nomad is a person who works remotely via the internet, affording them the freedom to travel full-time and work from anywhere with a WiFi connection. Although it may appear nothing but glamorous, being a digital nomad takes dedication, effort, and resilience. Choosing to be a nomadic entrepreneur means mastering the balance of work and play, and although location-independence is ultimately a pretty sweet setup, not all locations are created equally for digital nomads. There are many factors that a digital nomad should consider before choosing their next location, including cost of living, WiFi availability, crime rates, and how difficult it is to secure a visa. For this list, I began with 50 places that are popular among digital nomads. I then eliminated any places with particularly high violent crime rates or particularly low WiFi reliability. Once that was done, I calculated the “nomad cost” of each city. The nomad cost is the cost per month for a digital nomad to stay in a hotel or private room with private bath in a hostel and eat out three times a day. Actual costs may be a bit lower, depending on how far out of the city-center you’re willing to stay, whether you’re able to prepare your own meals, and whether you choose to branch out to include private vacation rentals and short-term apartment rentals, but these “nomad costs” should give you a good idea of cost of living. There are other factors to consider, such as weather, availability of diet-specific foods, proximity to tourist attractions, and public transportation options, but these are all personal preferences and this list should give you a good starting point for deciding which place is best for you. These are some of 2019's best, most cost-efficient places in the cheapest countries for digital nomads. Visa information is accurate for citizens of the US, UK, Canada, and Australia, unless otherwise noted. Nomad costs are listed in US dollars. Ko Lanta is one of Thailand’s most beautiful islands, known for its pristine beaches, rainforests, and world-renowned diving and snorkeling. Compared to Chiang Mai, which tops many lists of best places for digital nomads, Ko Lanta offers a quieter, more authentic Thai experience with much less pollution, two common complaints of digital nomads in Chiang Mai. Ko Lanta also boasts an incredibly low nomad cost of just $360! Thailand offers a double-entry tourist visa, with each entry valid for 60 days. Each entry can be extended to 90 days, granting a total of 180 days. Add in the delicious Thai food and I’m completely sold on Ko Lanta! Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Thailand! The digital nomad cost for Ubud is a low $452. There is a very healthy digital nomad community which offers co-working spaces and networking opportunities, not to mention the chance to meet new friends who understand the lifestyle. The area is known for friendly locals, beautiful scenery, and a great vegetarian scene. US, UK, and Canadian citizens can secure a 30 day tourist visa upon arrival, which can be extended an additional 30 days once. For longer visits, you’ll need to apply before you arrive. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Indonesia! In comparison to other Vietnamese hot spots for digital nomads, such as Hanoi and Ho Chi Minh City, Da Lat has the lowest crime rate and nomad cost. Da Lat also sets itself apart from many other Vietnamese locations because of its temperate — as opposed to tropical — climate. The city is sometimes called “The City of Eternal Spring” and the beautiful weather lends itself to tons of natural beauty. Yet another distinctive characteristic of Da Lat is the architecture. French settlers once inhabited the area, leaving behind a European feel, the reason behind Da Lat’s other nickname, “Little Paris”. The nomad cost for Da Lat is just $600. Vietnam’s visa requirements seem to change fairly often, but currently tourist visas are available for 30-90 day visits. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Vietnam! Siem Reap appears to be an up-and-coming hotspot for digital nomads for two reasons: the easy visa process (30 days upon arrival with the ability to extend an additional 30 days) and the low nomad cost of $690. Siem Reap has co-working spaces and cafes with acceptably fast WiFi connections and nearby are the famous temples of Angkor Wat. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Cambodia! Serbia is often overlooked by digital nomads, but those who have spent time working in Belgrade seem to have had very good experiences, noting the friendly people and reliable internet. And, with a nomad cost of $750, Belgrade is the cheapest city in Europe on the list. Best of all? No visa is required for US, UK, and Australian citizens for visits up to 90 days. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Serbia! Colombia has a long reputation for being high in crime, but Medellin’s crime rate has been decreasing for a while now and most of the crime that does exist in Colombia is highly unlikely to affect digital nomads. The WiFi is good, there are many co-working spaces if you prefer to do your work there, and the food is great! Visas are valid for 180 days and easy to procure, and the nomad cost is just $823. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Colombia! Tirana is one of the cheapest places for digital nomads in Europe, with a nomad cost of only $820. Tirana has personality, featuring colorful buildings, street art, and statues scattered around the city. Albania as a whole is known for delicious, fresh food. Greece, Macedonia, Kosovo, and Montenegro are all neighboring countries, meaning if you do get tired of exploring the hidden beaches and old-fashioned villages, you can take a quick trip out of the country. Another huge perk for American citizens is the ability to stay in Albania for up to one year with no visa. Citizens of Australia and the UK are allowed 90 days with no visa, and Canadians are given 30 days. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Albania! The biggest upside to Georgia as a whole is the fact that citizens of the US, UK, Canada, Australia, and New Zealand are not required to have a visa for stays less than one year, making it the most generous country on our list in terms of letting people hang out for a while. In Tbilisi people are friendly, crime is super low, wine is abundant, free WiFi is easy to find, and the culture is rich. With a low nomad cost of $870, I can’t think of a reason NOT to spend time in Tbilisi. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Georgia! Many digital nomads pass up Sri Lanka because of spotty WiFi, but I’ll let you in on a little secret. Sri Lanka has some of the cheapest prepaid data in the world and prepaid SIM cards are easy to find. Colombo’s nomad cost is $1,059. The biggest upside to Sri Lanka is in its landscape, wildlife, tranquility, and relatively high number of English speakers. Digital nomads do not need a visa for stays up to 90 days in Sri Lanka. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Sri Lanka! Digital nomads in Kaohsiung can enjoy a cheaper cost of living, better weather, and a more relaxed atmosphere than their counterparts in Taipei. You can get your culture fix at one of Kaohsiung’s carnival-like night markets, sip some of the best tea in the world, and try out the exciting culinary flavors that the Taiwanese are famous for. Oh, and did I mention that statistically, Kaohsiung is the safest place on our list? The nomad cost in Kaohsiung is $1,150 but I’ve read several accounts of digital nomads finding significantly cheaper accommodations through short-term apartment leases. There’s no visa required for stays up to 90 days for citizens of the US, UK, Australia and Canada. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Taiwan! Timisoara has been called one of Europe’s most underrated cities because of its beautiful architecture, interesting history, and vibrant atmosphere. It’s also one of the three safest spots on our list. You won’t need a visa for stays up to 90 days, and the nomad cost for Timisoara is $1,159. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Romania! There’s over 2,400 years of history in Sofia, but the city is current with the times in terms of infrastructure and readily available high-speed internet. Digital nomads in Sofia will also enjoy the friendly locals, the beautiful mountains and lakes, and the possibility of skiing! Nomad cost in Sofia is $1,200, and you can visit Bulgaria for up to 90 days with no visa. Make sure to check out Worldpackers' awesome work exchange and volunteer programs in Bulgaria! Well, I think I just planned out my next two years of travel! I hope this list has been helpful! For more information on nomad cost and all the best spots and cheapest countries for digital nomads, check out NomadList! What are your favorite spots as a digital nomad? Do you think I left out any of the best spots? Tell me in a comment below. I hope you’re all as excited about the adventures still to come in 2019 as I am!
0.961458	Newspapers have a distinguished history in Florida, dating back to the East Florida Gazette (1783), which was the first newspaper published in Florida. During the early 1800s, the Seminole Wars began and were comprised of conflict between various Native America populations, the black population and the white population. In 1821, Florida was relinquished by Spain and became a United States territory. During this time, The Floridian was published in Pensacola and the Florida Gazette in St. Augustine. Although there were less than 40,000 people living in Florida in 1830, James Owen Knauss claimed that there were forty-four published newspapers at the time. His book Territorial Florida Journalism is considered to be one of the only sources of information on Florida newspapers of this time. On March 3, 1845 Florida became the 27th state admitted to the Union. The population in Florida this year had risen to approximately 66,000. In the time leading up to the Civil War, the number and influence of Florida newspapers had significantly increased. Many of the papers were strongly influenced by political views. Some of these include the Florida Whig (Marianna),The Whig Banner (Palatka), The Southern Confederacy (Jacksonville), The True Southerner (Tampa), and the Florida Union(Jacksonville). There were only twenty-six weekly newspapers during this time, all of which played a large role in broadcasting news regarding daily issues such as slavery and support for secession and war. The Tallahassee Floridian and Journal was an early supporter of secession, even urging citizens to form militias. During this time the St. Augustine Examiner and the Key of the Gulf were a few of the newspapers seized by the Union. In 1873, the Gainesville New Era began publication as the first African-American owned newspaper in Florida. After the Civil War, Florida newspapers went on to wield heavy influence on the political and social development of Reconstruction. A total of forty-two newspapers were published in Florida at this time. The period of Reconstruction had a significant impact on the state, leading to an economic boom that resulted in increases of building, expansion, and tourism. Newspapers were covering war, epidemics, the land boom, the automobile industry, and natural disasters. In 1905, there were approximately 600,000 people living in Florida and 173 published newspapers, including nineteen daily papers. Post-World War I, the number of dailies grew to fifty-three, though that number dropped to forty-six by 1927 due to the collapse of the land boom. As Florida evolved into a more urban state, newspaper circulation drastically increased in large urban areas such as Jacksonville, Miami, and Tampa and coverage began to shift from local to national news. Newspapers in large urban areas also began featuring international news. Florida newspapers have become extremely diverse, largely in part due to population movements into the south part of the state. There are currently close to two million Hispanics residing in Florida and approximately 280 Spanish-language newspapers listed in the United States Newspaper Program database. There are also fifty-two African American newspapers currently identified in Florida. Newspapers played a crucial role in Puerto Rico's history in the time between 1836 and 1922. Colonial authorities, the elite, political actors, labor activists, women, etc. were the primary users of newspapers during this time, using newspapers to promote their activities. The relationship between Puerto Rico and the United States was also brought to light in many of the newspapers of this time. In the early 19th century, the printing press arrived in Puerto Rico. The first Puerto Rican newspaper, La Gaceta de Puerto Rico, was published in 1807. It included insular and European views while reflecting the views of the Spanish government and eventually became a means of official communication. In 1821 Puerto Rico's first daily, Diario Liberal y de Variedadesde Puerto Rico, began printing with focus on the discussion of farmers rights to own land. The Spanish Crown regained power in 1834 and began to censor the press. After the Chamber of Commerce was established, the Boletin Mercantil de Puerto Rico was founded with its primary intentions being to promote commerce, industry, agriculture, and literacy production. Movements toward independence and the abolishment of slavery were condemned by both La Gaceta and the Boletin Mercantil. In 1866, Spain introduced a new printing law which considered it a crime to write against the King and the Royal Family, the Legislative Chambers, the Parliamentarians, and other ministers or government officials. This law was extended to Puerto Rico between 1869 and 1870. The censorship was lifted in 1870, leading to the beginning of forty-five newspapers in Puerto Rico between 1870 and 1874. The First Spanish Republic was established in 1873, paving the way for the foundation of conservative and liberal newspapers, such as Don Simplico, Don Candido, La Verdad, El Avisador del Comercio, El Semanario Puertorriqueno. With the Spanish American war ensuing, Governor Primo de Rivera's delivered a press conference in 1873 stressing the importance of the press, yet asked for moderation to avoid alarming the population or offending the U.S. government. The fall of the First Spanish Republic in 1874 gave way to a period of conservatism and repression. Despite Governor General Jose Laureano Sanza's intellectual repression, two of the most important liberal newspapers appeared in San Juan: El Buscapie and El Clamor del Pais. These were later censored and punished for criticizing the tyranny of Spanish governors, while other papers made their debuts in other cities. One of the most important newspapers founded was La Integridad Nacional, a publication of the party Incondicional Espanol. In 1887 liberals were severely persecuted, journalists and editors were imprisoned and condemned to death, which led to the disappearance of many newspapers. El Porvenir and El Escarpelo ceased production in 1889. The year 1890 marked a change for newspaper publications with the beginning of nineteen newspapers; twnety-five more followed suit in 1891 and in 1892 an additional twenty-seven were established. El Noticiero, successor to El Diario de Ponce, was founded by Ramon MarÃa. In 1893, Aguadilla published its first newspaper La Region. Voz del Pueblo, directed by Pedro Acevedo Rivera, replaced Aguadilla's El Criollo. The press in Puerto Rico underwent great transformation in the 1890s. Puerto Rican journalism gave way to critical news and information, journalists became more professional, and editors began to rely more on facts than opinion. Luis Munoz Rivera, founder of the Union Party, established La Democracia, one of the first Puerto Rican newspapers to take advantage of new technologies and became one of the most influential papers of the time. La Correspondencia de Puerto Rico was founded by businessman Ramon B. Lopez and published interesting news, swaying away from siding with any political group or ideology. During this time the labor movement was developing and Ensayo Obrero was the first newspaper associated with it. Prior to the Spanish American War, there was great discussion on the role of the US newspapers as instigators of the war, of the reaction of the European press, and of the Caribbean's economic dependency on US markets. During the Spanish American War, many correspondents of the US traveled to Cuba and Puerto Rico to cover events related to war. Reports of these journalists were published in papers such as the Equator-Democrat, the Herald, Harperâ's Weekly, Chicago Record and the Chicago Daily News. Puerto Rican journalists admired the idea of free speech found in US newspapers and the press carefully followed its development knowing that the war would change their fate. Prior to the transference of Puerto Rico's sovereignty to the US, the first English newspaper, The Porto Rico Mail, was published. After becoming a US territory, La Gaceta replaced Spain's coat of arms with the American eagle. Years following the war featured continued persecution of journalists. La Democracia was repressed by the government, leading to beginning of Diario de Puerto Rico also founded by Luis Munoz Rivera. Both papers supported the idea of autonomy for Puerto Rico and suffered censorship. In 1901, El Aguila de Puerto Rico was founded and promoted annexation and statehood. Union Obrera published in 1902 focused on the labor movement; La Correspondencia de Puerto Rico became political, while El Boletin adopted a journalistic approach. By the end of the early 1900s, English newspapers such as The Portorrican Student, The Horticultural News, and Porto Rico Progress began publication. El Diario de Puerto Rico, Puerto Rico Ilustrado, and El Mundo were three of the most important Puerto Rican newspapers during this time. El Diario de Puerto Rico was very influential and continues publication as El Nuevo DÃia. Puerto Rico Ilustrado significantly impacted literacy production at the time, and El Mundo became one of the most popular newspapers.
0.999912	This table lists the international rankings of South Sudan in all categories that are published in the CIA World Factbook, and those that we derived from them. Additional international rankings of South Sudan can be found in the main country ranks menu. Budget expenditures $2,259,000,000 143 FY 2013 est. Budget revenues $437,000,000 187 FY 2013 est. Budget surplus (+) or deficit (-) % of GDP -15.50 117 FY 2013 est. Distribution of family income - Gini index 46.0 33 2010 est. GDP - composition, by end use - exports of goods and services (%) 64.90 36 2011 est. GDP - composition, by end use - government consumption (%) 17.10 58 2011 est. GDP - composition, by end use - household consumption (%) > 34.90 153 2011 est. GDP - composition, by end use - imports of goods and services (%) -27.20 30 2011 est. GDP - composition, by end use - investment in fixed capital (%) 10.40 124 2011 est. GDP - official exchange rate $11,770,000,000 133 2013 est. GDP - per capita (PPP) $1,400 161 2013 est. GDP - purchasing power parity $14,710,000,000 144 2013 est. GDP - real growth rate (%) 24.70 1 2013 est. Inflation rate(consumer prices) (%) 1.70 75 2013 est. Population below poverty line (%) 50.60 15 2009 est. Taxes and other revenues 3.7 178 FY 2013 est. Carbon dioxide emissions from consumption of energy 2,016,000 148 2011 est. Crude Oil - exports 291,800 26 2010 est. Crude Oil - production 220,000 38 Second half of 2013 est. Crude Oil - proved reserves 3,750,000,000 28 1 Jan 2013 est. Electricity - consumption(kWh) 694,100,000 159 2010 est. Electricity - from fossil fuels 30.7 123 2010 est. Electricity - from hydroelectric plants 66.3 26 2010 est. Electricity - from other renewable sources 3.0 53 2010 est. Electricity - installed generating capacity 255,200 155 2010 est. Electricity � production (kWh) 881,300,000 150 2010 est. Natural gas - proved reserves (cu m) 63,710,000,000 61 1 Jan 2013 est. Age structure 0-14 years - female 2,593,241 67 2014 est. Age structure 0-14 years - male 2,699,556 65 2014 est. Age structure 0-14 years (%) 45.80 6 2014 est. Age structure 15-24 years - female 1,084,810 77 2014 est. Age structure 15-24 years - male 1,210,962 74 2014 est. Age structure 25-54 years - female 1,742,842 92 2014 est. Age structure 25-54 years - male 1,622,776 94 2014 est. Age structure 25-54 years(%) 29.10 133 2014 est. Age structure 55-64 years - female 166,664 127 2014 est. Age structure 55-64 years - male 198,106 107 2014 est. Age structure 55-64 years(%) 3.20 105 2014 est. Age structure 65 years and over - female 106,806 139 2014 est. Age structure 65 years and over - male 136,932 118 2014 est. Age structure 65 years and over (%) 2.10 121 2014 est. Birth Rate(births/1,000 population) 37.68 13 2014 est. Death Rate(deaths/1,000 population) 8.42 77 2014 est. Dependency ratios - elderly dependency ratio (%) 6.40 97 2014 est. Dependency ratios - potential support ratio 15.60 45 2014 est. Dependency ratios - total dependency ratio (%) 82.80 24 2014 est. Dependency ratios - youth dependency ratio (%) 76.40 23 2014 est. Drinking water source - UnImproved � rural 92.7 1 2012 est. Drinking water source - UnImproved - total 91.1 1 2012 est. Drinking water source - UnImproved - urban 84.3 1 2012 est. HIV/AIDS - adult prevalence rate (%) 2.70 23 2012 est. HIV/AIDS - deaths 12,900 22 2012 est. HIV/AIDS - people living with HIV/AIDS 153,800 33 2012 est. Infant mortality rate � female (deaths/1,000 live births) 63.15 16 2014 est. Infant mortality rate � male (deaths/1,000 live births) 72.92 16 2014 est. Infant mortality rate � total (deaths/1,000 live births) 68.16 16 2014 est. Median age � female (years) 17.00 154 2014 est. Median age � male (years) 16.60 156 2014 est. Median age � total (years) 16.80 151 2014 est. Net migration rate (migrant(s)/1,000 population) 11.94 13 2014 est. Population 11,562,695 75 Jul 2014 est. Population growth rate (%) 4.12 3 2014 est. Sanitation facility access - Rural Improved (% of population) 7.3 143 2012 est. Sanitation facility access - Total Improved (% of population) 8.9 148 2012 est. Sanitation facility access - Urban Improved (% of population) 15.7 138 2012 est. Total fertility rate (children born/woman) 5.43 9 2014 est. Urbanization - urban population (%) 18 174 2010-15 est. NOTE: The information regarding the international rankings of South Sudan on this page is derived from the CIA World Factbook 2015. No claims are made regarding the accuracy of international rankings of South Sudan contained here. All suggestions for corrections of any errors about international rankings of South Sudan should be addressed to the CIA.
0.855392	Eike Fuhrken Batista da Silva was born on the 3rd November 1956, in Governador Valadares, Minas Gerais, Brazil, and is a businessman probably best recognized for being the chairman of the Brazilian conglomerate EBX Group, which includes five companies – OGX, MPX, LLX, MMX, and OSX. His career in the business industry has been active since the 1980s. Have you ever wondered how rich Eike Batista is, as of late 2016? According to authoritative sources, it has been estimated that the total size of Eike’s net worth is equal to (minus) -$1 billion; in 2012, his net worth was over $30 billion, making him the 7th richest man in the world and the richest in Brazil, accumulated through his career in the business industry. However, his net worth is currently negative, as his company suffered a catastrophic collapse. He also released the book “The Heart Of The Matter” (2011), which helped increased his net worth. Eike Batista was raised with six siblings in Brazil by his father, Eliezer Batista da Silva, who was a businessman, Minister of Mines and Energy, and a former president of Companhia Vale do Rio Doce, and his mother, Jutta Fuhrken. While he was in his teens, the family moved to Europe, and lived in Geneva (Switzerland), Düsseldorf (German), and Brussels (Belgium). Upon matriculation in 1974, he enrolled at the Rhenish-Westphalian Technical University of Aachen in Germany to study metallurgy, while his parents returned to his hometown. While studying and living in Germany, Eike began to earn money by selling insurance policies from door to door, but returned to Brazil in the 1980s, and started working in gold and diamond trades. Little by little, his name became known as one of the best salesmen, and he soon earned enough to start a gold trading firm, AutramAurem, and after only a year and a half, Eike had earned $6 million. After that he started another, bigger company, EBX Group, and firstly implemented a mechanized alluvial gold mining plant in the Amazon, which added a considerable amount to his net worth. When he was 29 years old, Eike was appointed as the CEO of TVX Gold, the mining company being listed on the Canadian Stock exchange, giving him much needed knowledge about and access to global capital markets. His EBX Group saw the light of the day in 1984, and until 2013 his net worth only increased; through EBX Group, Eike started several more companies, including OGX (oil and gas), MMX (mining), LLX (logistics), OSX (offshore services and equipment), NRX Newrest, Gloria Place, MDX, PINK FLEET, with operations throughout Brazil and South America. However, recently the values of his companies have dropped enormously, particularly OGX, such that he is now trying to rebuild his businesses, and raise himself out of personal debt. When it comes to speak about his personal life, Eike Batista was married to model Luma de Oliveira from 1991 to 2004; they are the parents of two boys. His current residence is in Rio de Janeiro, Brazil. In his free time, he enjoys swimming, running, and he practices marine sports. He is active on his official Twitter account, on which he has a huge number of followers.
0.999543	Write a 700- to 1,050-word paper discussing the positive and negative implications of the Welfare Reform Act of 1996 on Medicaid. Respond to one or more of the following questions in your paper: Did the Welfare Reform Act cause existing Medicaid beneficiaries to lose necessary coverage? Do eligible Medicaid candidates sometimes remain un-enrolled even though they are needy as a result of the Welfare Reform Act? Is the Welfare Reform Act effective in reducing welfare fraud and increasing personal responsibility? Has the Welfare Reform Act been successful in meeting its intended goals? Include a minimum of two references from the Internet or University Library.
0.936853	The oldest Sinhalese Prakrit inscriptions found are from the third to second century BCE following the arrival of Buddhism in Sri Lanka, the oldest extant literary works date from the ninth century. The closest relative of Sinhala is the Maldivian language. Sinhala has two main varieties – written and spoken. It is a good example of the linguistic phenomenon known as diglossia. Sinhala (Siṃhāla) is a Sanskrit term; the corresponding Middle Indo-Aryan (Eḷu) word is Sīhala. The name is a derivation from siṃha, the Sanskrit word for "lion"Siṃhāla is attested as a Sanskrit name of the island of in the Bhagavata Purana. The name is sometimes glossed as "abode of lions", and attributed to a supposed former abundance of lions on the island. the loss of a vowel length distinction; long vowels in the modern language are due to loanwords (e.g. vibāgaya "exam" < Sanskrit vibhāga) and sandhi, either after elision of Intervocalic consonants (e.g. dānavā "to put" < damanavā) or in originally compound words. An example for a Western feature in Sinhala is the retention of initial /v/ which developed into /b/ in the Eastern languages (e.g. Sanskrit viṃśati "twenty", Sinhala visi-, Hindi bīs). An example of an Eastern feature is the ending -e for masculine nominative singular (instead of Western -o) in Sinhalese Prakrit. There are several cases of vocabulary doublets, e.g. the words mässā ("fly") and mäkkā ("flea"), which both correspond to Sanskrit makṣikā but stem from two regionally different Prakrit words macchiā and makkhikā (as in Pali). Sinhala diglossia can also be described in terms of informal and formal varieties. The variety used for formal purposes is closer to the written/literary variety, whereas the variety used for informal purposes is closer to the spoken variety. It is also used in some modern literature (e.g. Liyanage Amarakeerthi's Kurulu Hadawatha). The writing system for Sinhala is an abugida, where the consonants are written with letters while the vowels are indicated with diacritics (pilla) on those consonants, unlike English where both consonants and vowels are full letters, or Urdu where vowels need not be written at all. Also, when a diacritic is not used, an "inherent vowel", either /a/ or /ə/, is understood, depending on the position of the consonant within the word. For example, the letter ක k on its own indicates ka, either /ka/ or /kə/. The various vowels are written කා /kaː/, කැ /kæ/, කෑ /kæː/ (after the consonant), කි /ki/, කී /kiː/ (above the consonant), කු /ku/, කූ /kuː/ (below the consonant), කෙ /ke/, කේ /keː/ (before the consonant), කො /koː/, කෝ /koː/ (surrounding the consonant). There are also a few diacritics for consonants, such as /r/ in special circumstances, although the tendency nowadays is to spell words with the full letter ර /r/, plus either a preceding or following hal kirima. One word that is still spelt with an "r" diacritic is ශ්‍රී, as in ශ්‍රී ලංකාව (Sri Lankāwa). The "r" diacritic is the curved line under the first letter ("ශ": "ශ්‍ර"). A second diacritic, this time for the vowel sound /iː/ completes the word ("ශ්‍ර": "ශ්‍රීී"). For simple /k/ without a vowel, a vowel-cancelling diacritic (virama) called හල් නිරීම /hal kiriːmə/ is used: ක් /k/. Several of these diacritics occur in two forms, which depend on the shape of the consonant letter. Vowels also have independent letters but these are only used at the beginning of words where there is no preceding consonant to add a diacritic to. Sinhala has so-called prenasalized consonants, or 'half nasal' consonants. A short homorganic nasal occurs before a voiced stop, it is shorter than a sequence of nasal plus stop. The nasal is syllabified with the onset of the following syllable, which means that the moraic weight of the preceding syllable is left unchanged. For example, tam̆ba 'copper' contrasts with tamba 'boil'. Long /əː/ is restricted to English loans. /a/ and /ə/ are allophones in Sinhala and contrast with each other in stressed and unstressed syllables respectively. In writing, /a/ and /ə/ are both spelt without a vowel sign attached to the consonant letter, so the patterns of stress in the language must be used to determine the correct pronunciation. Most Sinhala syllables are of the form CV. The first syllable of each word is stressed, with the exception of the verb කරනවා /kərənəˈwaː/ ("to do") and all of its infected forms where the first syllable is unstressed. Syllables using long vowels are always stressed. The remainder of the syllables are unstressed if they use a short vowel, unless they are immediately followed by one of: a CCV syllable, final /j(i)/ (-යි), final /wu/ (-වු), or a final consonant without a following vowel. The sound /ha/ is always stressed in nouns, adjectives, and adverbs, and so is not pronounced /hə/ except in the word හතලිහ /ˈhat̪əlihə/ ("forty"), where the initial /ha/ is stressed and the final /hə/ is unstressed. Sinhala distinguishes several cases. Next to the cross-linguistically rather common nominative, accusative, genitive, dative and ablative, there are also less common cases like the instrumental. The exact number of these cases depends on the exact definition of cases one wishes to employ. For instance, the endings for the animate instrumental and locative cases, atiŋ and laᵑgə, are also independent words meaning "with the hand" and "near" respectively, which is why they are not regarded to be actual case endings by some scholars. Depending on how far an independent word has progressed on a grammaticalisation path, scholars will see it as a case marker or not. Sinhala distinguishes three conjugation classes. Spoken Sinhala does not mark person, number or gender on the verb (literary Sinhala does). In other words, there is no subject–verb agreement. An exception to this is formed by statements of quantity which usually stand behind what they define. Example: "the four flowers" translates to මල් හතර /mal hatərə/, literally "flowers four". On the other hand, it can be argued that the numeral is the head in this construction, and the flowers the modifier, so that a better English rendering would be "a floral foursome" As is common in left-branching languages, it has no prepositions, only postpositions (see Adposition). Example: "under the book" translates to පොත යට /potə jaʈə/, literally "book under". Sinhala has no copula: "I am rich" translates to මම පොහොසත් /mamə poːsat/, literally "I rich". There are two existential verbs, which are used for locative predications, but these verbs are not used for predications of class-membership or property-assignment, unlike English is. There are almost no conjunctions as English that or whether, but only non-finite clauses that are formed by the means of participles and verbal adjectives. Example: "The man who writes books" translates to පොත් ලියන මිනිසා /pot liənə miniha/, literally "books writing man". There is a four-way deictic system (which is rare): There are four demonstrative stems (see demonstrative pronouns) මේ /meː/ "here, close to the speaker", ඕ /oː/ "there, close to the person addressed", අර /arə/ "there, close to a third person, visible" and ඒ /eː/ "there, close to a third person, not visible". Sinhala is a pro-drop language: Arguments of a sentence can be omitted when they can be inferred from context. This is true for subject—as in Italian, for instance—but also objects and other parts of the sentence can be "dropped" in Sinhala if they can be inferred. In that sense, Sinhala can be called a "super pro-drop language", like Japanese. Example: The sentence කොහෙද ගියේ [koɦedə ɡie], literally "where went", can mean "where did I/you/he/she/we... go". ^ a b c d "Sinhala". Ethnologue. Retrieved 6 April 2017. ^ Hammarström, Harald; Forkel, Robert; Haspelmath, Martin, eds. (2017). "Sinhala". Glottolog 3.0. Jena, Germany: Max Planck Institute for the Science of Human History. ^ "Census of Population and Housing 2011". www.statistics.gov.lk. Retrieved 6 April 2017. ^ "Census of Population and Housing 2001" (PDF). Statistics.gov.lk. Retrieved 16 November 2013. ^ a b Jayarajan, Paul M. (1 January 1976). History of the Evolution of the Sinhala Alphabet. Colombo Apothecaries' Company, Limited. ^ a b "Introduction ~ හැඳින්වීම - Wikibooks, open books for an open world". en.wikibooks.org. Retrieved 6 April 2017. ^ Paolillo, John C. (1997). "Sinhala Diglossia: Discrete or Continuous Variation?". Language in Society. 26 (2): 269–296. ISSN 0047-4045. ^ Gair, James W. (1968). "Sinhalese Diglossia". Anthropological Linguistics. 10 (8): 1–15. ISSN 0003-5483. ^ Caldwell, Robert (1875). "A comparative grammar of the Dravidian or South-Indian Family of Languages". London: Trübner & Co.: 86. ^ "Chinese Account of Ceylon". The Asiatic Journal and Monthly Register for British and Foreign India, China, and Australia. 20: 30. 1836. ^ "WWW Virtual Library Sri Lanka : Sri Lanka: A Short History of Sinhala Language". Lankalibrary.com. Retrieved 16 November 2013. ^ "UNESCO Collection of Representative Works, Sinhalese Series". London: George Allen and Unwin Limited. 1970. ^ "Ancient Scripts: Sinhala". www.ancientscripts.com. Retrieved 7 April 2016. Look up सिंहल or Sinhala in Wiktionary, the free dictionary. Wikivoyage has a phrasebook for Sinhala.
0.986983	Web services are "self-contained, self-describing modular applications that can be published, located, and invoked across the Web". They are based on a set of independent open platform standards to reach a high level of acceptance. Web services framework is divided into three areas: communication protocol, service description, and service discovery and specifications are being developed for each one. More and more, users want to deal with complex applications controlled by an explicit process model. Most of specifications languages (WSFL, XLANG, BPEL4WS) propose a set of operators in order to describe the service in a modular way. The basic services are messages driven and the operators are related to the orchestration of activities. In the previous work, we have developed a generic agent capable to fully control the interaction process with a Web service given its specification. This paper presents an alternative approach, which overcomes a limitation of our preceding algorithms, and we briefly describe them. We develop dense time semantics for an XLANG specification. The semantic of a specification is a timed automaton.
0.984686	Market research is a key factor in maintaining competitiveness over competitors. Market research provides important information to identify and analyze the market need, market size and competition. Market-research techniques encompass both qualitative techniques such as focus groups, in-depth interviews, and ethnography, as well as quantitative techniques such as customer surveys, and analysis of secondary data. Market research began to be conceptualized and put into formal practice during the 1920s, as an offshoot of the advertising boom of the Golden Age of radio in the United States. Advertisers began to realize the significance of demographics revealed by sponsorship of different radio programs. Market research is a way of getting an overview of consumers' wants, needs and beliefs. It can also involve discovering how they act. The research can be used to determine how a product could be marketed. Peter Drucker believed market research to be the quintessence of marketing. There are two major types of market research. Primary Research sub-divided into Quantitative and Qualitative research and Secondary research. Through Market information one can know the prices of different commodities in the market, as well as the supply and demand situation. Market researchers have a wider role than previously recognized by helping their clients to understand social, technical, and even legal aspects of markets. Market segmentation is the division of the market or population into subgroups with similar motivations. It is widely used for segmenting on geographic differences, personality differences, demographic differences, technographic differences, use of product differences, psychographic differences and gender differences. For B2B segmentation firmographics is commonly used. SWOT is a written analysis of the Strengths, Weaknesses, Opportunities and Threats to a business entity. Not only should a SWOT be used in the creation stage of the company but could also be used throughout the life of the company. A SWOT may also be written up for the competition to understand how to develop the marketing and product mixes. It is important to test marketing material for films to see how an audience will receive it. There are several market research practices that may be used: (1) concept testing, which evaluates reactions to a film idea and is fairly rare; (2) positioning studios, which analyze a script for marketing opportunities; (3) focus groups, which probe viewers' opinions about a film in small groups prior to release; (4) test screenings, which involve the previewing of films prior to theatrical release; (5) tracking studies, which gauge (often by telephone polling) an audience's awareness of a film on a weekly basis prior to and during theatrical release; (6) advertising testing, which measures responses to marketing materials such as trailers and television advertisements; and finally (7) exit surveys, that measure audience reactions after seeing the film in the cinema. The availability of research by way of the Internet has influenced a vast number of consumers using this media; for gaining knowledge relating to virtually every type of available product and service. It has been added to by the growth factor of emerging global markets, such as China, Indonesia and Russia, which is significantly exceeding that of the established and more advanced B2C E-Commerce markets. Various statistics show that the increasing demands of consumers are reflected not only in the wide and varied range of general Internet researching applications, but in online shopping research penetration. This is stimulated by product-enhancing websites, graphics, and content designed to attract casual "surfing" shoppers, researching for their particular needs, competitive prices and quality. According to the Small Business Administration (SBA), a successful business is significantly contributed to by gaining knowledge about customers, competitors, and the associated industry. Market research creates not only this understanding, but is the process of data analysis regarding which products and services are in demand. The convenience and easy accessibility of the Internet has created a global B2C E-commerce research facility, for a vast online shopping network that has motivated retail markets in developed countries. In 2010, between $400 billion and $600 billion in revenue was generated by this medium also, it is anticipated that in 2015, this online market will generate revenue between $700 billion and $950 billion. The influence of market research, irrespective of what form it takes, is an extremely powerful incentive for any type of consumer and their providers! Beyond online web-based market research activities, the Internet has also influenced high-street modes of data collection by, for example, replacing the traditional paper clipboard with electronic 'Internet-ready' versions such as the Ferranti MRT, the first such device. The UK Market Research Society (MRS) reports research has shown that on average, the three social media platforms primarily used by Millennials are LinkedIn, Facebook and YouTube. Social Media applications, according to T-Systems, help generate the B2B E-commerce market and develop electronic business process efficiency. This application is a highly effective vehicle for market research, which combined with E-commerce, is now regarded as a separate, extremely profitable field of global business. While many B2B business models are being updated, the various advantages and benefits offered by Social Media platforms are being integrated within them. Business intelligence organization have compiled a comprehensive report related to global online retail sales, defining continued growth patterns and trends in the industry. Headed "Global B2C E-Commerce and Online Payment Market 2014" the report perceives a decrease in overall growth rates in North America and Western Europe, as the expected growth in the online market sales, is absorbed into the emerging markets. It is forecast that the Asia-Pacific region will see the fastest growth in the B2C E-Commerce market and replace North America as the B2C E-Commerce sales region leader, within a few years. This effectively, offers a significant, motivational platform for new Internet services, to promote user market research-friendly applications. The primary online sale providers in B2C E-Commerce, worldwide, includes the USA based Amazon.com Inc. which remains the E-Commerce revenues, global leader. The growth leaders in the world top ten are two online companies from China, both of which conducted Initial Public Offering (IPO) this year; Alibaba Group Holding Ltd. and JD Inc. Another company from the top ten is Cnova N.V., a recently formed E-Commerce subsidiary of the French Group Casino, with various store retailers developing and expanding their E-Commerce facilities worldwide. It is a further indication of how consumers are increasingly being attracted to the opportunities of online researching and expanding their awareness of what is available to them. Service providers; for example those related to finance, foreign market trade and investment promote a variety of information and research opportunities to online users. In addition, they provide comprehensive and competitive strategies with market research tools, designed to promote worldwide business opportunities for entrepreneurs and established providers. General access, to accurate and supported market research facilities, is a critical aspect of business development and success today. The Marketing Research Association was founded in 1957 and is recognized as one of the leading and prominent associations in the opinion and marketing research profession. It serves the purpose of providing insights and intelligence that helps businesses make decisions regarding the provision of products and services to consumers and industries. This organization knowledge of market conditions and competition is gained by researching relevant sectors, which provide advantages for entry into new and established industries. It enables effective strategies to be implemented; the assessment of global environments in the service sectors, as well as foreign market trade and investment barriers! Research, is utilized for promoting export opportunities and inward investment, helping determine how to execute competitive strategies, focus on objective policies and strengthen global opportunities. It is a medium that influences, administrates and enforces agreements, preferences, leveling trading environments and competitiveness in the international marketplace. The retail industry aspect of online market research, is being transformed worldwide by M-Commerce with its mobile audience, rapidly increasing as the volume and varieties of products purchased on the mobile medium, increases. Researches conducted in the markets of North America and Europe, revealed that the M-Commerce penetration on the total online retail trade, had attained 10%, or more. It was also shown that in emerging markets, smart-phone and tablet penetration is fast increasing and contributing significantly to online shopping growth. This page was last modified on 13 January 2016, at 08:59.
0.974335	Trends across the finance industry. What to know about the emerging trends affecting finance sectors. Part of being a successful CFO is staying up to date on industry news and the latest trends that may affect your organization. Businesses rely on C-suite level executives to lead change, communicate to the executive team, empower and train their own employees, and be aware of things that could help or hinder their business. Here are some emerging trends that CFOs should be aware of as they research trends in the financial marketplace. One area that CFOs should be aware of is the growing role of CFO responsibilities in certain organizations. Because CFOs are tasked with managing finances, many organizational, operational, and strategic responsibilities are falling to the CFO, with some organizations doing away with the role of COO entirely and folding their previous job duties into an expanded CFO role. Many CFOs are now tasked with more strategy-related to-dos, particularly pertaining to strategy around financial performance. While the bottom line continues to be the business of most CFOs, it’s important to think holistically and understand customer or client expectations and satisfaction as part of a way to drive more revenue. Technology continues to drive change in the financial services sector. Users expect faster transactions and more personalized services, and digital apps and software are rising to meet this need in the marketplace. AI, blockchain, and other revolutionary digital solutions are helping to create better, faster experiences for customers. Savvy financial officers should pay attention to the technology that continues to drive and grow the financial services industry. The trends of cloud accounting and automation continue to dominate accounting. Both of these technologies help to free up resources and with addiitonal resources – specifically money or manpower – accounting firms can redirect that to marketing and customer acquisition. In fact, some accounting operations are using automation to not only increase the efficiency and accuracy of certain parts of their business, but to also increase client outreach – through triggered emails (like around tax time) or emails that run as part of campaign to help educate customers with relevant information. Another accounting specific trend is that some businesses are choosing to outsource their own accounting services. While there are some advantages to having an on-site accounting team at your organization, it can be beneficial and strategic to outsource through an accounting firm or agency. It can offer businesses the ability to connect with accounting-only professionals, often at a lower cost than the salary of accounting employees. Financial trends – like these and others – continue to be vetted by finance experts, with many showing a lot of potential for growing a successful financial strategy or increasing business reach and impact. What are trends in finance that your business has noticed making an impact on the finance industry or your business industry? Do you feel that staying mindful of emerging trends in finance is important to keeping a business moving forward and financially viable? Do emerging trends strike you as something to consider as part of a long-term strategy or are they too new to consider as a serious part of business strategy?
0.996988	They know the best areas and slopes to ski on any given day. They know the the best place and/or ski lift to start and end the day. They know the best way to get there. You don't waste time trying to figure out where to ski, where you were, or where you have to go. Throughout the day, They know where you are and where to go, based on your skiing ability and preferences. The know which areas and slopes have the best conditions for your skiing preferences and ability, at that time, on that day. They know the best times and the best lifts to get around during the day. They can even check on conditions throughout the day. They know the best places for lunch and the best time to be there. They can provide pointers to help you ski better. They can pick the best places to meet up or go to, if someone might want to ski elsewhere or take a break during the day and meet up later. They can contact the hotel or taxi to make or change arrangements for your return to the hotel. They can provide local history, geography and all kinds of information that cannot be found anywhere else. If visibility is reduced due to weather conditions such as falling snow, all you have to do is follow the guide. If you have a problem, the guide is as there to help you, including getting assistance if necessary. Having a guide will not only reduce most, if not all the stress you might experience when visiting an large ski area with a large number of different places to ski, especially if you have not skied there previously. You are able to spend and enjoy far more time skiing slopes that are best suited for your skiing, than could possibly be done without the guide. Although it will add to the total cost of the trip, it is well worth it, because it will increase the value and amount of skiing you will be able to enjoy far more than the added cost. Last, but by far not the least: A local certified ski instructor/guide can take you "off piste" (off the marked & groomed runs), including untracked powder and/or difficult runs, because the guide knows the slopes and can match your skiing ability to the conditions.
0.964502	Show me a country which didn’t have slaves. America was not unique. Why don’t you make a picture of a black man being hung by the Mauritanian flag? America may have had slaves 200 years ago, but Mauritania has slaves today.
0.997099	When one decides to travel to Europe one should make sure that they know how the weather of the place since when the weather is warm It always means that one will be packing very light clothes to wear with them. When one is travelling one should always make sure that they get to know the style of the place you are headed to and with this one will be able to carry the most stylish clothes and look good. One should also make sure that they plan for their stops ahead and this way one will be knowing what to buy where, and with this one is able to save a lot of money with them. Having a good budget of what one will be using when they are travelling is very important and that way one is very sure that they will be able to get what they planned for. When one is travelling one should always make sure that they get to buy the tickets early enough and this way one will always get them at a cheaper price and also one is able to get the seat they want either in a train or the aero plane. The exchange rate is one of the things that one should always be checking around and with this one should make sure that they get the best rate for the country they are travelling to and this should also be done in advance. When its off season, this is the best time for one to travel and this way one is able to get the best out of it and also one is able to save money. Of the best times when one should always travel is during winter time, and this way one is able to save a lot of money with it and also have the best deals with him since this is a time when most people will be working. If you decide to stay in one spot for quite some time then one should make sure that they become a temporary local and one is able to enjoy a lot and also have some extras. When you become something of a local you will be able to learn more and also one should always make sure that they always avoid the tourist traps, this way one will not be spending a lot when they are there.
0.999873	By now, most everyone has read a myriad of of opinions, blogs, message boards and news stories on Mario Lemieux's statement regarding the aftermath of an ugly, incident-filled, mauling of his Pittsburgh Penguins at the hands of the New York Islanders. Garnering even more attention, has been the backlash by fans, players and media members concerning Lemieux's statement. If by some chance you missed it click here. The "unacceptable and embarrassing" actions that Lemieux was referring to no doubt included the Islanders’ Matt Martin sucker-punching an unaware Max Talbot, Islanders’ Michael Haley, lauching himself at Talbot and then Penguins goalie Brent Johnson; and no doubt Trevor Gillies elbowing of Penguins’ Eric Tangradi in the head, who continued to punch him while Tangadi lay prone on the ice, then shouted at and mocked him as Gilles was forced off the ice surface. Lemieux's comments were harsh to be sure, however, the backlash did not come from the NHL, at which his comments were directed, but from elsewhere. NHL Commissioner Gary Bettman, chose to take no action against Lemieux, and stated that the comments would not be discussed or debated publicly. Yet, that did not give Lemieux any reprieve from the likes of the Edmonton Journal, Don Cherry, Zenon Konopka, Jeremy Roenick or countless fans and bloggers. Most of Lemieux's critics thought his comments were ill-timed or overly dramatic, but the word that crept up over and over was "hypocritical". Paraphrasing: Cherry doesn't understand why Lemieux was OK with Brent Johnson knocking Rick DiPietro's lights out, and that Matt Cooke works for Lemieux and never criticizes him. You don't even have to watch the video to know that Don Cherry is a moron, so we won't waste our time enumerating every nonsensical comment, but some of his arguments were made elsewhere. Many outlets made references to Cooke, Goddard leaving the bench to fight Michael Haley, Johnson hurting DiPietro in a fight a few days prior, and how the Penguins lead the league in penalty minutes and fighting majors. Now, do you have to agree with Lemieux's statement? No. I'm not sure that I do. Can you accuse him of not having the best timing and being reactionary? However, the criticism that he received was not about these issues. Repeatedly, we read the same unscientific accusation that sought evidence to support a pre-conceived notion, not the other way around. First, the point that because the Penguins lead the NHL in fighting majors and Johnson's breaking the face of DiPietro, Lemieux has no grounds for argument. These are weak and ill-conceived concepts. Fighting is part of the game. It always has been and always will be. Most fights are for spark or retalition of liberties taken on another player within the confines of a game. Lemieux made no statement regarding fighting. What we are sure he didn't like, was much of the violence in this game was a premeditated foolish display in response to DiPietro's misfortune in a consensual skirmish. Regarding the other idea of Lemieux being a "hypocrite" as long as he employs Matt Cooke. This will assuredly be a topic of debate, but the facts win out over heart-felt opinion. Cooke's history and the incidents that occurred during the game in question are completely unrelated. Regardless of how you view Matt Cooke, you won't find tape of him attacking goaltenders, throwing shots at a player, hitting him while he is down, and then taunting him afterward. You won't find evidence of him sucker punching anyone, anywhere. Sure he makes questionable safety decisions. You can reasonably accuse Cooke of not respecting other players. Granted, his propensity for knee on knee collisions happen far too often to be excused, but they happen no more frequently than Alex Ovechkin's. His latest suspension was a result of an unnecessary hit on Fedor Tyutin, not a dirty one. Cooke has a record for questionable and dangerous decisions, but his rap sheet does not include a single incident that is in line with Gilles', Haley's or Martin's. Public opinion is just that, opinion. Many times evidence, facts or reality have little to nothing to do with the formation of these opinions/criticisms. The criticism of Mario Lemieux is no exception.
0.99982	Imagine being immortal, what would you pay to be Immortal? You can omit the first 'high'. Firstly, I will highlight the existence of immortality-granting SCPs and SCPs that are themselves immortals. The article seems to be a rather direct take on the 'immortality is bad' concept, especially the path that associates it wit great pain. It is too simplistic of a route, and does nothing interesting with the concept. The researcher's rant essentially becomes something that does not resonate strongly with users. For a concept well-played in fiction already, you need to play with the known concepts even more. Also, why would the researchers essentially use themselves to study the SCP? D-class exist largely to handle the more dangerous situations, after all.
0.999545	Every scene you play as an actor, no matter how old you are, will require a deep understanding from you. You need to understand who the character is, what the context of the scene and larger story is, and countless other aspects of the scene that will make your work on and with it shine. In our opinion, there are five steps you need to take to truly understand a scene. To help walk you through and illustrate them, let’s use the following scene scenario as a setup for the five steps that will help you work on your character and the scene: You are a 17-year-old whose mom has just returned from three months at a drug rehab facility. You’ve been living with your dad while she was getting help and even though she’s back home and clean, she is still struggling and not the fully-recovered mom you hoped to find. Step 1: Determine the given circumstances. The given circumstances are what you know from the text based on what the writer has told you with his or her words. Your mom has been in rehab detoxing from drugs. You have been living with your dad while she was away. Now that she is home, you’re getting used to what life is like with a recovering, struggling parent. Step 2: Find your deep wish. Also known as your objective, this is what your character needs to happen. In the above scene, your deep wish is to have your mother be the role model you always wanted and be a loving, protective, participating parent. You have been without this your whole life and have suffered greatly. Step 3: Identify the opponent or obstacle. Internal or external, this is something that gets in the way of you getting what you want. In life, we don’t always have an obstacle but in acting, there must be one to create the struggle. If it’s too easy to get what you want without a fight, there’s nothing interesting happening. The obstacle in this scene could be that your mom is in too much pain and not willing to get well right now. Now that you have your identified your deep need and discovered what’s in the way of achieving it, you’ll need to personalize the situation to make it true for you. Begin this process by looking at the character’s situation and asking what might be going on in your life that could lead to a similar problem or challenge to overcome. What you choose to work with can be imaginary/fictional, but the meaning must hold true. This the most vital part. Acting is doing. What are you going to do to get what you want? Perhaps you beg and plead with your mom to stop using drugs. Maybe you start parenting your mom in a role reversal to get your—and her—needs met. It’s in this doing, this action, that you become a compelling actor.
0.94274	The text of the bill below is as of Apr 9, 2008 (Introduced). To amend the Employee Retirement Income Security Act of 1974 and title 11, United State Code, to provide necessary reforms for employee pension benefit plans. This Act may be cited as the Employees’ Pension Security Act of 2008 . The assets of a pension plan which is a single-employer plan shall be held in trust by a joint board of trustees, which shall consist of two or more trustees representing on an equal basis the interests of the employer or employers maintaining the plan and the interests of the participants and their beneficiaries. Except as provided in clause (ii), in any case in which the plan is maintained pursuant to one or more collective bargaining agreements between one or more employee organizations and one or more employers, the trustees representing the interests of the participants and their beneficiaries pursuant to subparagraph (A) shall be designated by such employee organizations. Clause (i) shall not apply with respect to a plan described in such clause if the employee organization (or all employee organizations, if more than one) referred to in such clause file with the Secretary, in such form and manner as shall be prescribed in regulations of the Secretary, a written waiver of their rights under clause (i). In any case in which clause (i) does not apply with respect to a pension plan which is a single-employer plan because the plan is not described in clause (i) or because of a waiver filed pursuant to clause (ii), the trustee or trustees representing the interests of the participants and their beneficiaries shall consist of one or more participants under the plan elected to serve as such in accordance with this clause. The Secretary shall provide by regulation for a secret ballot of the participants under the plan for purposes of such election, and for certification of the results thereof to the participants (and any employee organization referred to in clause (ii)) and to the employer. in subparagraph (A) (as so redesignated), by striking ‘‘the plan’’ the first place it appears and inserting ‘‘in the case of a plan other than a pension plan which is a single-employer plan, the plan’’. The amendments made by this title shall apply with respect to plan years beginning after 180 days after the date of the enactment of this Act. The Secretary of Labor shall prescribe the initial regulations necessary to carry out the provisions of such amendments not later than 90 days after the date of the enactment of this Act. The plan sponsor and plan administrator of a pension plan described in paragraph (1) shall have a fiduciary duty to ensure that each participant and beneficiary under the plan, in connection with the investment by the participant or beneficiary of plan assets in the exercise of his or her control over assets in his account, is provided with all material investment information regarding investment of such assets to the extent that the provision of such information is generally required to be disclosed by the plan sponsor to investors in connection with such an investment under applicable securities laws. The provision by the plan sponsor or plan administrator of any misleading investment information shall be treated as a violation of this paragraph. The Secretary may assess a civil penalty against any person of up to $1,000 a day from the date of the person's failure or refusal to comply with the requirements of section 404(c)(6) until such failure or refusal is corrected. Section 502(a)(6) of such Act (29 U.S.C. 1132(a)(6)) is amended by striking (7), or (8) and inserting (7), (8), or (9) . The amendments made by this title shall apply with respect to investments made on or after the date of the enactment of this Act. Notwithstanding any other provision of this section, unless the corporation or the court, in the case of a distress termination pursuant to subparagraph (B)(ii), has determined that reasonable efforts to consider available alternatives to termination (including, but not limited to, alternatives described in section 4042(c)(4)) have been undertaken by such person (and, in the case of a plan maintained pursuant to a collective bargaining agreement, have been undertaken by the bargaining parties in good faith bargaining), the plan may not be terminated. A participant or beneficiary of the plan or an employee organization representing such participants or beneficiaries may bring an action in the appropriate court to challenge such determination by the corporation and seek equitable relief or must be afforded an opportunity to be heard by the appropriate court if a court is making such determination. in the sentence following the sentences inserted by paragraph (1), by striking the preceding sentence and inserting the first sentence of this paragraph, . Section 4042(c) of such Act (as amended by subsection (b)) is further amended by inserting after the fourth sentence the following new sentence: ‘‘If any party consisting of the plan sponsor, a plan participant, or (in the case of a plan maintained pursuant to a collective bargaining agreement) the employee organization representing plan participants for purposes of collective bargaining disagrees with any such determination by the corporation, such party may intervene in the proceeding to challenge the determinations of the corporation.’’. Section 4042(c) of such Act (as amended by the preceding provisions of this section) is further amended by adding after the seventh sentence the following: ‘‘The corporation and the plan administrator may proceed with such an agreement only if they have made reasonable efforts to consider available alternatives to termination (including, but not limited to, alternatives described in paragraph (4) of this subsection) and the plan participants and beneficiaries have been provided with at least 60 days notice before such agreement is given effect. During such 60-day period, a participant or beneficiary of the plan or an employee organization representing such participants or beneficiaries may bring an action in the appropriate court to seek appropriate equitable relief if such reasonable efforts have not been made.’’. Prior to making any determination referred to in the preceding provisions of this subsection, the corporation shall consult with the plan participants and (in the case of a plan maintained pursuant to a collective bargaining agreement) the employee organization representing plan participants for purposes of collective bargaining to determine whether there are any reasonable available alternatives to termination (including, but not limited to, alternatives described subparagraph (B). Financing or loans sought by any member of the plan sponsor’s controlled group, with or without assistance from the corporation, in order to obtain plan financing, including back-up guarantees to any such financing which the corporation is hereby authorized to provide for such purpose. New plan structures agreed to by the parties, such as transfer of plan liabilities to multiemployer plans, new benefit formulas for new hires or non-vested participants, or other plan restructuring alternatives agreed to by the parties. Reinsurance which the corporation is hereby authorized to obtain for the plan. An agreement by the parties authorizing alternative funding schedules, approved by the corporation, which would modify plan funding, subject to the minimum funding requirements for the plan under part 3 of subtitle B of title I. Purchase by the plan sponsor of an annuity contract to cover liabilities of the plan, which the corporation is hereby authorized to guarantee as necessary to secure such a contract. the right of participants and beneficiaries to challenge determinations under this section. Section 4042(a) of such Act (29 U.S.C. 1342(a)) is amended by adding at the end the following new sentence: ‘‘Prior to commencing proceedings under this section with respect to any plan, the corporation shall provide notice to plan participants and beneficiaries of the right to challenge determinations under this section, written in a manner likely to be understood by the participant or beneficiary.’’. The amendments made by this title shall apply with respect to any plans undergoing termination proceedings pursuant to section 4041 or 4042 of the Employee Retirement Income Security Act of 1974 which are pending on or after the date of the enactment of this Act. Subject to subparagraphs (A), (B), and (C), allowed unsecured claims for benefit liabilities to participants and beneficiaries under a single-employer plan (as defined in section 4001(a)(15) of the Employee Retirement Income Security Act of 1974) in connection with the termination of the plan, in excess of the benefits payable to the participants and beneficiaries by the Pension Benefit Guaranty Corporation under section 4022 of the Employee Retirement Income Security Act of 1974 in connection with such termination. Except as provided in subsection (b), section 401 and the amendment made by such section shall take effect on the date of the enactment of this Act. The amendment made by section 401 shall not apply with respect to cases commenced under title 11 of the United States Code before the date of the enactment of this Act.
0.966884	If a possum is under your shed and you sprinkle shake away around the shed, will it be to freightened to come out? Shake Away Small Animal granule is basically fox urine and bobcat urine in a granular form. The idea behind this is that it creates a "Predatory Scent" that scares away animals from certain areas. It almost always depends on the animals and if they are scared of the fox or bobcat "smell". I normally recommend to use this product as a preventive measure, and not as a corrective measure. All I can say is to try it and see. Also how about using a water hose and trying to spray it out? Be sure that after the possum is gone, you use a good hardware type mesh screen or something to keep it from going back under.
0.993768	Improve GPS accuracy by a building photo and a 2D map in urban environments. Example: GPS tells me a location, but with several meters inaccuracy. If I also have a photo and the map, I know only at certain positions could I see a building looks like that, then I can probably find out where am I more accurately. Step 1: Find vertical building edges in the photo, represent them in a tilt-invariant way: Tilt-Invariant Vertical Edge Position (TICEP) features. Step 2: We don't know (and we can't know for sure) which building the camera looks at. So for each building, compute Location-Orientation Hypotheses (LOHs) as if it is the building in the photo. Step 3: Remove unreasonable LOHs, then select the one nearest to the noisy GPS reading. And that's our final result! Note: not guaranteed to 100% find better position than GPS, but generally speaking achieves better accuracy. Example: The correct LOH (much more accurate than GPS as geometry doesn't lie!) can be selected as long as GPS falls into the red area (the refinable area).

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