A Christmas Carol. In Prose. Being a Ghost Story of Christmas known as A Christmas Carol, is a novella by Charles Dickens, first published in London by Chapman & Hall in 1843 and illustrated by John Leech. A Christmas Carol recounts the story of Ebenezer Scrooge, an elderly miser, visited by the ghost of his former business partner Jacob Marley and the spirits of Christmas Past and Yet to Come. After their visits, Scrooge is transformed into a gentler man. Dickens wrote A Christmas Carol during a period when the British were exploring and re-evaluating past Christmas traditions, including carols, newer customs such as Christmas trees, he was influenced by the experiences of his own youth and by the Christmas stories of other authors, including Washington Irving and Douglas Jerrold. Dickens had written three Christmas stories prior to the novella, was inspired following a visit to the Field Lane Ragged School, one of several establishments for London's street children; the treatment of the poor and the ability of a selfish man to redeem himself by transforming into a more sympathetic character are the key themes of the story.
There is discussion among academics as to whether this is a secular story, or if it is a Christian allegory. Published on 19 December, the first edition sold out by Christmas Eve. Most critics reviewed the novella favourably; the story was illicitly copied in January 1844. He went on to write four other Christmas stories in subsequent years. In 1849 he began public readings of the story, which proved so successful he undertook 127 further performances until 1870, the year of his death. A Christmas Carol has been translated into several languages. A Christmas Carol captured the zeitgeist of the mid-Victorian revival of the Christmas holiday. Dickens had acknowledged the influence of the modern Western observance of Christmas and inspired several aspects of Christmas, including family gatherings, seasonal food and drink, games and a festive generosity of spirit; the book is divided into five chapters, which Dickens titled "staves". A Christmas Carol opens on a bleak, cold Christmas Eve in London, seven years after the death of Ebenezer Scrooge's business partner, Jacob Marley.
Scrooge, an ageing miser, dislikes Christmas and refuses a dinner invitation from his nephew Fred—the son of Fan, Scrooge's dead sister. He turns away two men who seek a donation from him to provide food and heating for the poor and only grudgingly allows his overworked, underpaid clerk, Bob Cratchit, Christmas Day off with pay to conform to the social custom; that night Scrooge is visited at home by Marley's ghost, who wanders the Earth entwined by heavy chains and money boxes forged during a lifetime of greed and selfishness. Marley tells Scrooge that he has a single chance to avoid the same fate: he will be visited by three spirits and must listen or be cursed to carry much heavier chains of his own; the first spirit, the Ghost of Christmas Past, takes Scrooge to Christmas scenes of Scrooge's boyhood, reminding him of a time when he was more innocent. The scenes reveal Scrooge's lonely childhood at boarding school, his relationship with his beloved sister Fan, a Christmas party hosted by his first employer, Mr Fezziwig, who treated him like a son.
Scrooge's neglected fiancée Belle is shown ending their relationship, as she realises that he will never love her as much as he loves money. They visit a now-married Belle with her large, happy family on the Christmas Eve that Marley died. Scrooge, upset by hearing Belle's description of the man that he has become, demands that the ghost remove him from the house; the second spirit, the Ghost of Christmas Present, takes Scrooge to a joyous market with people buying the makings of Christmas dinner and to celebrations of Christmas in a miner's cottage and in a lighthouse. Scrooge and the ghost visit Fred's Christmas party. A major part of this stave is taken up with Bob Cratchit's family feast and introduces his youngest son, Tiny Tim, a happy boy, ill; the spirit informs Scrooge. Before disappearing, the spirit shows Scrooge two hideous, emaciated children named Ignorance and Want, he mocks Scrooge's concern for their welfare. The third spirit, the Ghost of Christmas Yet to Come, shows Scrooge a Christmas Day in the future.
The silent ghost reveals scenes involving the death of a disliked man whose funeral is attended by local businessmen only on condition that lunch is provided. His charwoman and the local undertaker steal his possessions to sell to a fence; when he asks the spirit to show a single person who feels emotion over his death, he is only given the pleasure of a poor couple who rejoice that his death gives them more time to put their finances in order. When Scrooge asks to see tenderness connected with any death, the ghost shows him Bob Cratchit and his family mourning the death of Tiny Tim; the ghost allows Scrooge to see a neglected grave, with a tombstone bearing Scrooge's name. Sobbing, Scrooge pledges to change his ways. Scrooge awakens on Christmas morning a changed man, he makes a large donation to the charity he rejected the previous day, anonymously sends a large turkey to the Cratchit home for Christmas dinner and spends the afternoon with Fred's family. The following day he gives Cratchit an increase in pay, begins to become a father figure to Tiny Tim.
From on Scrooge treats everyone with kindness, generosity a
Activated CDC42 kinase 1 known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene. TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor. ACK1 interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein -stimulated GTPase activity of Cdc42Hs; this binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and, directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. ACK1 or TNK2 has been shown to interact with AKT, Androgen receptor or AR, a tumor suppressor WWOX, FYN and Grb2. ACK1 interaction with its substrates resulted in their phosphorylation at specific tyrosine residues.
ACK1 has been shown to directly phosphorylate AKT at tyrosine 176, AR at Tyrosine 267 and 363, WWOX at tyrosine 287 residues, respectively. ACK1-AR signaling has been reported to regulate ATM levels, ACK1 is a survival kinase and shown to be associated with tumor cell survival, hormone-resistance and radiation resistance; the activation of ACK1 has been observed in prostate, pancreatic and ovarian cancer cells. ACK1 transgenic mice, expressing activated ACK1 in prostate gland has been reported. Ack1 has emerged as a new cancer target and multiple small molecule inhibitors have been reported. All of these inhibitors are in the pre-clinical stage. Mahajan, K. Malla, P. Lawrence, H. R. Chen, Z. Kumar-Sinha, C. Malik, R. … Mahajan, N. P.. ACK1/TNK2 Regulates Histone H4 Tyr88-phosphorylation and AR Gene Expression in Castration-Resistant Prostate Cancer. Cancer Cell, 31, 790-803.e8. Https://doi.org/10.1016/j.ccell.2017.05.003 TNK2 human gene location in the UCSC Genome Browser. TNK2 human gene details in the UCSC Genome Browser
Wuchuan, is a county of Inner Mongolia Autonomous Region, North China, it is under the administration of the prefecture-level city of Hohhot, the capital of Inner Mongolia. Wuchuan has an area of 4,885 km2 with a population of 171,000, it is connected to Hohhot by the Huwu Highway. Zhaohe Grasslands, a popular tourist site, is nearby. According to the earliest records, the name Wuchuan comes from the "Book of Zhou", dating from 398 AD, the "History of the North". Human activity can be traced back as far as 10,000 years; the archaeological site at Daqingshan village includes many artefacts from the Dayao Culture and proves that the area was suitable for human habitation at that time. Another Paleolithic site at Erdaowa Village has an estimated age of 10,000 years. Many stone tools were found there, including knives and axes, indicating that the occupants of the area were hunter-gatherers. A more recent site from 5000 BC was found at Jinergou. Better stone tools and pottery were unearthed; the tools were of types used for building and making clothes, proving that agriculture was well established at that time.
In the Three Sovereigns and Five Emperors period, about 2800BC, many tribes settled at Wuchuan. These included the Yunzhou, Shefang and Guifang; the Yellow Emperor's war against Yunzhou was recorded in the Records of the Grand Historian by Sima Qian. During the Shang and Zhou Dynasties, King Wu of Zhou fought against the Guifang tribe many times winning the battle after 3 years. Around 302BC, Wuchuan belonged to the State of one of the Warring States; the king of Zhao defeated Hulinloufan and built a wall near Daqing Mountain to stop the advance of the northern tribes. This event was recorded in the "Water Jingzhu"; the wall is now called the South Daqing Mountain Great Wall. Wuchuan plays a role in the history of the Qin Dynasty and the Han Dynasty the Battle of Changping of Zhao Kuo. During this time, Wuchuan was controlled by the Xiongnu, a nomadic people famous for their bronzes and animal carvings. A Xiongnu dagger together with some knife-shaped coins from the State of Yan were unearthed at Tuchenzi Village, indicating that cultural exchanges between the Xiongnu and the Han Chinese were extensive at that time.
A total of more than 20 ancient tombs of the Qin and Han period have been discovered in Wuchuan. Wuchuan was one of the capitals of the Southern and Northern Dynasties. A tomb was found at Tuchenliang village, containing ancient coins and many other bronze and iron artefacts. A Roman gold seal was unearthed at Touhao village and some Persian silver coins from the Sassanid Dynasty were discovered at Baidao Cheng village; this indicates that during the period of the Northern Wei and Tang dynasties, a northern silk road existed, stretching from Xi'an to Datong to Huhhot and crossing Daqing Mountain to Wuchuan reaching the Middle East and Rome. In 916, Wuchuan belonged to the state of Qidan. Archeological sites have been found from the Yuan and Jin states; some Song Dynasty coins were unearthed. In addition, eight ancient tombs and seven ruins of towns from that period were discovered around the area of Dongtucheng along the river Qiangpan