could ever, thereafter, let it go.
everything it needed to know.
Wall, wall, reed wall, reed wall is generally the first line of the Babylonian versions of the Flood Story. In fact, the first non-Biblical translation of the myth in the 1870's rocked the Victorian age and was the opening salvo in the modern-day battle to contend that the Old Testament is not a history book, but one of spiritual metaphors. Since then, further research has proven that the Mesopotamian Flood myth far predates the creation of Genesis and firmly establishes that the story, which is so central to that entire region's psychology and conscious, is most probably based on some real cataclysmic event of the long distant past.
A leading contender for that event in the creation of the Bosphorus seaway. It is speculated that the creation of this amazingly narrow, thread-like sea channel that cuts through modern-day Istanbul and connects the Mediterranean to the Black Sea, is the cause. Formed in 5,600 BC (agriculture had by then created villages and towns, but had not yet flared into cities and city-states) it is suggested that the Black Sea was then a fresh water lake which had much shrunk in size due to the lack of melt water from the glaciers which had long since retreated north. However, on the other side of the land bridge, the levels of the Mediterranean had grown much higher, again owing to the ending of the Ice Age. These dual-pressures finally and terribly exploded into the creation of the Bosphorus, which would have discharged into the Black Sea three times the flow of Niagara Falls for over three hundred years before levels equaled. The resulting constant growth of the Black Sea, and the pressure of a steadily advancing shore line could have, it is suggested, created the Flood myth.
A few notes: "shanna" (pronounced SHAW-naw) is the Babylonian word for "by twos" and is specifically used in the oldest version of the tale known. "Ridván" (pronounced RIZ-von) is the Arabic word for "paradise" and is used in the Bahá'í Faith in several contexts; in the poem it refers to both the Covenant and a state of spiritual bliss.
In the end, regardless of the story's origin, the power of the Flood myth to teach the importance of obedience and trust in God, as well as a symbol of the eternal Covenant of God is undiminished.
Thank you for reading The Holy Mariner. I humbly appreciate your visiting the Book of Pain, and as always, I look forward to your comments.
The photograph of Lake Tahoe was taken from the Heavenly ski hill, observation deck and shows the Coriolis effect created by the wind swirling in the valley bowl in which the lake rests. For more photography, please visit the Book of Bokeh.
flickering like a taper in the night.
next to gutter—finally it gave out with a puff.
tearing out what little heart we had left.
Surely the Book of God is sufficient unto us!
was that second volley of seven hundred and fifty rounds.
This poem is about the Martyrdom of the Báb, the Prophet-Herald of the Bahá'í Faith, an event which took place in Tabriz, Irán on July 9, 1850. But it is also about a geo-political reality that affects us today, the splitting of Islám into two branches, Sunní and Shí'ah, and how these two historical events are intertwined.
Both stories are complex, but I will try to keep the explanation short. I should state at the outset that, like Christians are not Jews, Bahá'ís are not Muslims. Let me explain: Christianity is its own independent religion, as is Judaism—yet the Founder of Christianity was born a Jew and Christians believe in, and accept, the Divinity of the Jewish Prophets; as a Bahá'í I believe in, and accept the Divinity of the Prophet Muhammad, and Bahá'u'lláh, the Founder of the Bahá'í Faith was born a Muslim. But I am not a Muslim. The Bahá'í Faith is, like Judaism, Christianity, Islám, Buddhism and Hinduism, an independent, world religion.
The linkage of the Martyrdom of the Báb to the split of Islám into it's two main branches is more complex. To understand that, you have to understand how Islám was divided at all.
At root was the question of succession to the Prophet Muhammad, the Founder of Islám. Sunnís believe that the succession was properly followed through the election of a series of Caliphs, starting with Abu-Bakr, a wise, elderly man, a long time personal friend of the Prophet and an an early convert to Islám. Such a process of succession would have been typical in any major clan decision in Arabia at that time. Hence its quick acceptance by the majority of Muslims of the day.
The second Caliph (this is important when it comes to the explanation of the Shí'ah branch of Islám) was 'Umar Ibn al-Khattab, a fiery, driven person who was also an early convert to Islám.
Shí'ahs, on the other hand, contend that Muhammad had publicly designated His son-in-law, Alí, as His chosen successor at a sermon given in the last year of His life at the pool of Khum. Moreover they believe that shortly before His passing, Muhammad asked for writing materials to be brought, so that He could dictate His last wishes with regard to succession, but that 'Umar interdicted that command, saying that the Prophet was delirious from His illness and that, "The Book of God [referring to Islám's Holy Book, the Qur'án] sufficeth us." This act, Shí'ahs contend, scuttled hope for a unified Islám, caused the separation that still effects us today and ensured that 'Umar himself would one day secure the leadership of Islám, especially since Abu-Bakr, the first obvious choice, was an elderly man.
Today, the Sunní branch occupies the western portion of Islám, up to the northern two thirds of Iráq. The Shí'ah portion occupies the remaining one third portion of Iráq and continues on into the east, through Irán and into Afghanistan. Pakistan and into the Pacific, however, reverses this trend and is mostly Sunní. The division point between the two branches explains the current inter-Islám warfare that goes on in the south of Iráq and, therefore, much of the current political turmoil in that country.
'Abdu'l-Bahá, son of the Founder of the Bahá'í Faith, and Himself the Leader of the Bahá'í Faith after His Father's passing, states that the musket bullets used by the regiment to kill the Báb were made from the statement made by 'Umar as Muhammad lay dying. He means, by this, I think, that the statement, "The Book of God sufficeth us," (or the Book of God is sufficient unto us as it is cast in the poem) is corruptive in that it put 'Umar's personal will over the Will of God. Moreover, the method used—to dignify and justify such an act with reference to the Book of God—is particularly wrong as it coats 'Umar's ambition with a false sense of purity and holiness. In so doing, and in this context and at this extreme measure, it is a betrayal and attack on the ancient and enduring Covenant by which God directs man. The consequences of that one act, in its introduction of disunity, still resonate within Islám and the world today.
In the end, what more heinous act can be committed by man than to willingly reject God's Messenger to this world? And what more terrible way to do that than to coat the act as one performed out of piety and faith?
If you have made it this far, I sincerely thank you for reading To the test with its overlong explanation. I sincerely hope you have enjoyed it and I humbly appreciate your visiting the Book of Pain. As always, I look forward to your comments.


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Taitu Betul ( c. 1851 – 11 de febrero de 1918) (nombre de bautismo Wälättä Mikael) fue una noble etíope, emperatriz del Imperio etíope (1889–1913) y la tercera esposa del Emperador Menelek II de Etiopía. En 1887, junto a su marido Menelik II, entonces rey de la provincia de Shewa fundaron la ciudad de Addis Ababa, actual capital de Etiopía. Está considerada una de las referentes de la historia de las mujeres en África pioneras en la lucha contra el colonialismo.

Descendiente de una antigua familia noble en el norte de Etiopía, recibió una educación ortodoxa tradicional. También estudió materias poco frecuentes en el marco de estudio de las mujeres, no solo en África, en el periodo en el que vivió como relaciones exteriores. Después de varios matrimonios, Betul se casó en abril de 1883 con el rey de Choa Sahle Myriam, que necesitaba apoyo en el norte del país. Reforzado, Sahle Myriam se convirtió en rey de los reyes de Etiopía en 1889 con el nombre de Menelik II y Taytu Betul  se convirtió en una de las mujeres más influyentes de su tiempo.

Buena diplomática y vibrante nacionalista, Taytu Betul se opuso a las estrategias coloniales italianas en su país. En 1890 escribió al embajador de Italia: «quisierais hacer pasar a Etiopía por vuestro protectora, pero nunca será así»

La Emperatriz rechazó cualquier negociación que pudiera conducir a la pérdida de territorios etíopes. Por el contrario, su esposo buscó primero el consenso, antes de seguir el consejo de su esposa. Taytu Betul estuvo presente en 1896 durante la batalla de Adoua, donde los italianos fueron aplastados y organizó sobre el terreno el abastecimiento de las tropas. Su poder en la corte junto a su esposo crecía constantemente, aunque oficialmente no tenía responsabilidades especiales.

Poco apreciada por los rivales de Menelik y por parte del pueblo, fue apartada tras la muerte de su marido. Sigue siendo una figura destacada en la historia de Etiopía.

Biografía
Taitu Betul nació hacia el año 1851. Era la tercera de cuatro hijos en una familia aristocrática etíope, relacionada con la dinastía salomónica. Su padre era Ras Betul Haile Maryam  y su tío Wube Haile Maryam que era el gobernante de la zona norte de Etiopía en la década de 1840, y rival del emperador Teodoro II. Su familia paterna estaba en el poder en la provincia de Semien, proclamándose descendientes del emperador Susenyos I. Su padre era nieto de Ras Gugsa, miembro de la poderosa familia reinante de Yejju (Yejju), que era de origen oromo y se había convertido al cristianismo, y que había gobernado como regentes de los Emperadores en Gondar durante la Zemene Mesafint (Era de los Príncipes). Taitu tenía la reputación de estar especialmente orgullosa de su linaje en Yejju, Semien y Begemder. Después de cuatro matrimonios fracasados, Taitu Betul contrajo matrimonio con el rey Menelik II de la provincia de Shewa,  más tarde emperador  Menelik II de Etiopía.

Se reconoce que Taitu ejerció un poder político considerable como esposa de Menelik, tanto antes como después de su coronación como emperador en 1889. Encabezó la facción más conservadora en la corte que se resistía a los cambios propuestos por los que querían desarrollar Etiopía siguiendo líneas occidentales y llevar la modernidad al país. Profundamente suspicaz con las intenciones europeas hacia Etiopía, jugó un papel clave en el conflicto del Tratado de Wuchale con Italia, en el que la versión italiana, establecía Etiopía como un protectorado italiano, mientras que la versión amárica no. La emperatriz sostuvo una línea dura contra los italianos, y cuando las conversaciones se rompieron e Italia invadió el imperio de su colonia de Eritrea, ella marchó al norte con el emperador y el ejército imperial, comandando una fuerza de artillería en la histórica Batalla de Adua que terminó en una humillante derrota para Italia en marzo de 1896. Esta victoria fue la más significativa de cualquier ejército africano en combate contra el colonialismo europeo.

Menelik, que a menudo prevaricó y pospuso decisiones que pudieran resultar controvertidas con la respuesta "Sí, mañana" (Ishi, nega), encontró útil tener a su esposa en una posición lo suficientemente poderosa que decía rotundamente no (Imbi) a las personas y a las cuestiones que el personalmente no quería ofender ni rechazar. Como resultado, la emperatriz Taytu se hizo más impopular, mientras que Menelik seguía siendo muy querido en la corte.

El 27 de octubre de 1909, Menelik sufrió un grave ataque, que lo dejó incapacitado y el ejercicio de gobierno de hecho fue asumido por Taitu. El joven Iyasu V fue nombrado heredero y Ras Tessema Nadew fue nombrado regente. En 1910, mediante un golpe de Estado liderado por elementos de la aristocracia y de la Guardia Imperial excluyeron y limitaron decisivamente la influencia de la Emperatriz, quedando sus cometidos limitados al cuiadado de su marido, con lo que Taitu se desvaneció de la escena política. Taitu y Menelik no tuvieron hijos. Menelik murió en 1913 y fue sucedido por Iyasu V, su nieto de una hija procedente de un enlace anterior. Taitu fue desterrada al antiguo palacio de Entoto, junto a la iglesia de Santa María que había fundado años atrás, y donde su esposo había sido coronado emperador.

También se le atribuye un papel en la trama que relevó al emperador Iyasu V del trono en 1916, siendo sustituido por la emperatriz Zauditu, que era hija de Menelik II de otro matrimonio anterior, y que siempre estuvo cercana a la emperatriz Taitu y la invitó de nuevo a vivir con ella. Aunque Taytu declinó, volvió a asesorar a los gobernantes "de una manera modesta", según Chris Prouty.

Referencias

 Chris Prouty. Empress Taytu and Menilek II: Ethiopia 1883-1910. Trenton: The Red Sea Press, 1986. ISBN 0-932415-11-3

Enlaces externos

Gobernantes de Etiopía
Dinastía Salomónica
Mujeres de Etiopía del siglo XIX
Mujeres de Etiopía del siglo XX

redpajama_set_name: RedPajamaWikipedia


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Goalkeeper prepares for life after the game
Posted: Jul 18, 2019
Maximilian Loria arrived at Albion College thinking he would prepare for a career in accounting.
A marketing class in the recently completed spring semester may have changed his outlook, and he is using a summer internship at DTE Energy to help narrow his focus while making connections that will assist in his professional development.
Loria started in a marketing related job taking inventory of branded wearables assigned to 150 crew members working in the field. It is a busy work site with trucks coming in and out but traffic isn't anything new for the two-year starting goalkeeper for the Briton men's soccer team.
During an early July check in, Loria reported he updates the status of the projects performed by fieldworkers in gas operations each day. He has also been tasked with creating the standard work instruction, a document with step-by-step instructions of Loria's work that will be given to assist in the orientation of employees that follow him.
He admitted to having a good idea of how to use Excel, and the work is introducing him to different computer software.
"I expected an intense environment, but everyone has been helpful and nice," Loria said. "People are going out of their way to help me and they are making sure the internship is something I can build on as opposed to picking up the lunch."
Self described as timid and shy, Loria said one of his goals during the internship is learning to master the art of direct communication.
"I'm not comfortable, but I'm getting better at it," Loria said. "I have had a difficult time telling guys what to do without them taking it personally."
An international studies minor, Loria will continue his personal development next spring by traveling to Italy for a semester abroad.
For the latest information on the Albion men's soccer program, follow @AlbionMSoccer on Twitter and Albion_MSoccer on Instagram. General athletic news can also be found @gobrits on Twitter, AlbionAthletics on Instagram and Albion College Athletics on Facebook.
Joe and Julie Serra have given a $5 million leadership gift to launch a fundraising initiative to make two dreams a reality at Albion College. The first is a newly expanded fitness and student activity facility at the site of the current Dow Recreation and Wellness Center. The second is a new or renovated competition facility for the volleyball, men's basketball and women's basketball teams that currently call Kresge Gymnasium home.
The College is continuing to raise funds in support of both projects. To learn more, call 517/629-0446 or email advancement@albion.edu

redpajama_set_name: RedPajamaCommonCrawl


text:
Lawyering up: Can AI make legal more human?
For most people, dealing with the law and legal processes is stressful. Can Artificial Intelligence help change this?
Why AI fails in the wild
Dealing with AI's energy problem
Expectation vs. reality: AI narratives in the media
Gender bias in AI: building fairer algorithms
Searching for the Uncanny Valley
The 14 languages that you'll need to support this decade
English has been ruling the internet for long but the data show it's losing ground fast. Learn which languages you should be supporting in the new decade.
Driving the innovation engine as you scale
Prepare for take off: innovating with AI in the travel industry
Eastbound enterprise: adapting to the Chinese market
Scaling businesses: how I learned to embrace the growing pains
Move earlier. Do everything sooner: Workable's CEO on building a business abroad
To be customer centric, be employee centric first
Basic values like empathy should start at home and irradiate outwards into all customer-facing interactions. Learn how People Ops can help improve customer service by improving employee experience.
Should you always be honest with your customers?
How localization increases sales worldwide
Customer Experience Trends for 2020: same same, but different
Empathy: the final frontier in customer service
The most famous, and controversial, Christmas poem
It's the most famous Christmas poem of all time, but the truth about its real author remains unclear. Is it Clement Clarke Moore or Henry Livingston Jr.?
The restorative power of talking to strangers
The scandalous origins of gossip
Do you speak internet? How internet slang is changing language
Can the Voynich Manuscript even be translated?
The most famous communication disaster in the world
It's alive! Bringing innovation back with Night Lab
Night Lab is one of our oldest traditions and drivers of innovation. Now that it's back, where will it take us?
How People Ops can help shape company culture
Older, wiser, and better funded: inside Unbabel's Series C
Unbabel Talks: Tech insights from Lisbon to the world
The innovation business
Language November 13, 2018
Life imitating art: the quest for a universal translator
Rafaela Cortez , Editorial Manager
Looking for a universal translator? Read more about a vision of seamless translation that has captivated novelists and tech experts alike.
Despite technology's stubbornness in not giving us hoverboards, time travelling DeLoreans or pizza hydrators, there has been a lot that real life has borrowed from science fiction.
In the 19th century, visionary author Jules Verne described global networks, newscasts and videoconferences; sent us to the ocean's depths in submarines (1870); and launched us to the moon in projectile lunar modules (1865).
H.G. Wells devised a Heat-Ray much like our contemporary lasers, in The War of Worlds (1898); audio books and email, in Men Like Gods (1923); and atomic bombs (1914), in The World Set Free. The first credit cards appeared in a 1888 socialist utopian novel by Edward Bellamy.
Supercomputers have also been around for a while. In the iconic 2001: A Space Odyssey, based upon a 1950 short story by Arthur C. Clark, HAL 9000 is a sentient computer capable of speech recognition, natural language processing, automated reasoning, and, eventually, murder: "I'm sorry Dave, I'm afraid I can't do that." And we've marvelled as Professor X augments his telepathic ability, using Cerebro (1964) to detect mutant brain waves across the world.
The more we look for, the more we find. Although Mary Shelley's Frankenstein is considered the first true novel to consolidate the genre, lack of consensus on what science fiction really is makes it hard to define how long it has been around. Some trace it back to an allegoric 1616 novel by Johann Valentin Andreae called The Chemical Wedding — an alchemic quest that begins with an invitation to a royal wedding (however, as some authors such as Adam Roberts pointed out, it's quite a stretch to regard alchemy as science).
Others chalk it up to the utopian New Atlantis, an unfinished novel by Francis Bacon published in 1627, or Utopia, published in 1516, by Thomas More, who coined the term. We can even go beyond and look at the ironically titled A True Story. In this second-century A.D. satire by Lucian of Samosata, characters get lost on exotic islands (for instance, an insular wedge of cheese); travel to the moon only to find themselves in the midst of a war between the moon folk and the king of the Sun; get trapped inside a giant whale; and meet mythical creatures, the legendary Homer and Herodotus. Or, as I like to call it, an above-average Friday.
Regardless of what it is, its origins are deeply rooted in mythological storytelling, speculation about the world's invisible engines, fear of the unknown, and distinct visions of the future.
Waiter, there's a fish in my ear
There is one particular dream in modern science fiction that has been told over and over again. It was first mentioned in the 1945 novellete First Contact, and since then we've seen it in countless science fiction works, such as a device in Star Trek, a telepathic field in Doctor Who's Tardis, and as a mind-boggling fish in Hitchhiker's Guide to the Galaxy.
We could only be talking about the "universal translator," a contraption that removes the language barrier from extraterrestrial communication by instantly translating (or less commonly interpreting) any language — which is a remarkable feat considering Earth alone has around seven thousand of them.
It's easy to see why the universal translator is so wildly popular. In a connected world, language is arguably the last communication barrier. It's what keeps us from tapping into all of mankind's knowledge — from achieving universal understanding.
The sci-fi formulation I'm most partial to is Douglas Adam's universal translator, even though it's probably the most outlandish of them all. As he eloquently puts it:
The Babel fish is small, yellow, leech-like, and probably the oddest thing in the Universe. It feeds on brainwave energy received not from its own carrier, but from those around it. It absorbs all unconscious mental frequencies from this brainwave energy to nourish itself with. It then excretes into the mind of its carrier a telepathic matrix formed by combining the conscious thought frequencies with nerve signals picked up from the speech centers of the brain which has supplied them.
The practical upshot of all this is that if you stick a Babel fish in your ear you can instantly understand anything said to you in any form of language. The speech patterns you actually hear decode the brainwave matrix which has been fed into your mind by your Babel fish.
There has been no shortage of news claiming one tech giant or another has invented a real-life universal translator. Google recently came out with Pixel Buds, powered by their Pixel smartphone, Google Translate, and Google Assistant; Microsoft Translator claims to instantly translate in-person conversations with the help of a smartphone; and an incredibly successful Indiegogo campaign to build a similar device got 3181% funded, with the first million being raised in 2 hours.
There's no question that there is a strong desire, if not a dire need, for this technology. But before you grab your credit card, you should manage your expectations. First of all, none of these devices take into consideration cultural context and idiosyncrasies, non-verbal signals, and other language nuances that machines are very much oblivious to but linguists are quick to catch.
And secondly, these devices are as limited as the machine translation and speech recognition that power them, and despite all the advances in the past decades, fundamental issues have not yet been solved.
The idea behind a device that analyzes sentences and spews translations into an earpiece is not complicated, but it still relies on language, and one must wonder if that's the most efficient way to communicate. Make no mistake, we owe everything we have to language. It facilitated the mass-cooperation that gave rise to the complex social structures that undergird the societies and institutions we have today.
In his best-seller Sapiens, Yuval Noah Harari speaks about the importance of these myths:
"This mysterious glue is made of stories, not genes. We cooperate effectively with strangers because we believe in things like gods, nations, money and human rights. Yet none of these things exists outside the stories that people invent and tell one another. There are no gods in the universe, no nations, no money and no human rights — except in the common imagination of human beings. You can never convince a chimpanzee to give you a banana by promising him that after he dies, he will get limitless bananas in chimpanzee Heaven. Only Sapiens can believe such stories. This is why we rule the world, and chimpanzees are locked up in zoos and research laboratories."
Wait But Why's Tim Urban agrees, claiming that language advanced our collective knowledge at an unprecedented rate. However, in his masterpiece of nearly 40,000 words about Neuralink (yet another brainchild of Elon Musk), he points out that, when we communicate, we're effectively using 50,000-year-old technology. The same species that replaces their smartphones for a new, shinier model on average every two years.
Language is neither a fast nor lossless form of communication. In the process of compressing concepts and cognition into speech, we lose context, intention, nuance, and all that other useful metadata that would give a much broader picture to the receiver.
The receiver then has to figure out what to do with the lossy data they were left with, and reconstitute it in a way that can represent the original content. But, more often than not, the loss is irrecuperable. We incorporate those partial data into our set of preconceptions and fields of experience, and a message gains a meaning that is often very different from the original.
No wonder we fight over meaningless nonsense all the time.
This is, mind you, a gross oversimplification. The relationship between cognition and language is much more complex than any algorithm for compression and has been the subject of discussion for millennia.
Behaviorists like Skinner believe language learning is a process of reinforcement in which we're rewarded by better communicating our needs (i.e., crying and fussing is not as effective as calmly asking, "Mother, dear, would you please fetch me some water?"), while authors such as Chomsky and Greenberg believe languages share a set of linguistic universals and we are born with innate "language acquisition devices" that develop without instruction.
Supporters of the controversial Whorfian theory believe that language affects or — most controversially — even determines the way we think, and therefore people from different countries perceive the world differently, while authors such as Gentner view language as a part of our cognitive tool kit, creating a semiotic system to make sense of the world around us and fostering "higher order cognition."
Chomsky, for instances, suggests that, evolutionarily speaking, language's main purpose is not even communication, but representing thought.
When asked by Wiktor Osiatynski about nonlinguistic forms of thinking, Chomsky says:
"The analysis of linguistic structures could help in understanding other intellectual structures.
Now, I don't think there is any scientific evidence about the question of whether we think only in language or not. But introspection indicates pretty clearly that we don't think in language necessarily. We also think in visual images, we think in terms of situations and events, and so on, and many times we can't even express in words what the content of our thinking is. And even if we are able to express it in words, it is a common experience to say something and then to recognize that it is not what we meant, that it is something else.
What does this mean? That there is a kind of nonlinguistic thought going on which we are trying to represent in language, and we know that sometimes we fail."
This phenomenon explains away at least half of my interactions before 10 a.m. But, what if we could create a device that translates nonlinguistic concepts and images, communicating them directly into someone else's brain?
The year of our lord, 2049
Unbabel's engineers like to think about a not-too-distant future in which we've just unveiled our new line of nanopills composed of an array of AI+human-powered nanobots that flow through the blood stream, into the cortex, and facilitate brain-to-brain interfacing.
We'll be able to communicate using a lossless, descentralized system that transmits emotions through hormonal and neurotransmitter analysis, translates concepts into visual inputs, directly into the recipient's brain.
Amplification implants will be readily available so we can communicate instantly with anyone, anywhere. We'll be able to transmit terabytes of information in fractions of seconds.
We'll just know.
A vast network of bilinguals across the world instantly decodes this information and provides cultural context through the neural network, which essentially reduces the cost of translation to 0, allowing SMEs, the backbone of our modern economy, to prosper and trigger a wave of economic growth responsible for job and income creation, innovation, local development, and sustainability in developed and developing countries alike.
With no language barriers and universal access to all of mankind's knowledge, scientific research and world-wide collaboration enter a golden age. Major efforts will be put into reverting the climate crisis, fossil fuels will be completely abandoned, and we'll start harnessing and mastering clean energies with the help of solar power satellites, making the transition into a Kardashev type I civilization.
We'll even be able to communicate with animals — and finally explain to our dogs how sorry we are that we've stepped on their tail.
Of course, security would be a major issue. As the technology gets widespread, hackers will be constantly trying to manipulate the nanobots and access people's sensorial inputs and outputs, and naturally, the stakes are much higher. They could fabricate new memories, modify thoughts, re-wire our core foundations, change everything that defines who we are, and why we do the things we do (stay tuned for even weirder episodes of Black Mirror).
To mitigate this, communications would have to be subjected to higher and higher levels of end-to-end encryption, powered by secure distribution of symmetric session keys that are securely generated using quantum-resistant public key cryptography.
Our pipeline would be dramatically different. It would look more like a brain's neural network, composed of decentralized nodes through which information travels. Humans would no longer be the final part of the process, providing feedback and context, every step of the way.
In the end, we don't really know what the future holds. We may all end up living in a bitcoin-fueled nightmare where governments crumble and the bitcoin-rich build citadels to protect themselves from the convulsing bitcoin-less masses.
When it comes to future prediction and trend assessment, Alan Kay said it best:
"The best way to predict the future is to invent it."
All I can say is: We're working on it.
Artificial Intelligence / Language / Translation
Translating without an original: a literary scandal as big as The Beatles
Adam Mahler
Why translating idioms is hard
Should language be more gender neutral?
Maria Almeida
Accent discrimination: let's call the whole thing off


RUSSIA'S twin-headed eagle faces easterly towards Asia as good as west towards Europe. This far-sighted savage is near-as-dammit a heraldic coat-of-arms of Vladimir Putin, who regenerated a aged majestic symbol. So since does a boss of a nation with half a immeasurable lands fibbing easterly of Singapore need to make so many of his "pivot to Asia", announced dual years ago? That many readers informed with a much-maligned Asia focus of Barack Obama will not have listened of Mr Putin's hints during a opening between tongue and substance. And nonetheless a prevalent perspective among pundits is that Russia is indeed behind in Asia.
Once a Soviet Union and China were a hair-trigger divided from fight along their prolonged border. Today many see a new vital joining or even an fondness in a creation between Russia and China, a world's second- and third-biggest troops powers. The dual states' media paint Mr Putin and Xi Jinping, China's president, as strongmen buddies. In 2014 they sealed a outrageous understanding to move Russian gas to China. Recently, Russian sales to China of modernized weapons resumed after being halted a decade ago since of record cloning.
In September, China and Russia conducted corner naval exercises in a South China Sea, where China has showy territorial claims. Russia is strictly dubious about those, yet a exercises gave support to China's position. In short, a pair's "strategic partnership" is receiving unchanging upgrades. This year Mr Putin described a love-in as "all-embracing".
Belatedly, Russia has realised that there is some-more to Asia process than China. It wants change elsewhere in a Indo-Pacific region. Ties with India have strengthened by municipal arch co-operation and weapons sales. Russian ships have returned to Cam Ranh Bay, a pier in Vietnam once used by a Soviets.
A initial for Russia, Mr Putin hosted a intemperate limit of a Asia-Pacific Economic Co-operation (APEC), a informal talkfest, in Vladivostok in 2012. Last year Russia launched a possess annual conference in a same Pacific port, a Eastern Economic Forum. In Dec comes a distinguished tactful gambit—a revisit to Japan during a invitation of a primary minister, Shinzo Abe, to plead not usually mercantile co-operation yet also a fortitude to a territorial corner over a 4 southernmost Kurile islands, that Japan calls a Northern Territories. Stalin grabbed a islands in a shutting days of a second universe war; 7 decades on, a corner precludes a signing of a assent covenant and has detained a upsurge of Japanese income and imagination to a neglected Russian Far East. Mr Abe, yet a nationalist, is not in a macho cover of a mostly bare-torsoed Mr Putin. Nevertheless, he hopes to get a islands behind in a exposed man-to-man event with a Russian boss in a prohibited open in his home prefecture.
Mr Putin might penchant a experience. He knows that Japan wants to lift Russia divided from China, that Japan views as a grave threat. And Mr Abe has personal reasons to secure a manoeuvre over a Northern Territories: unfamiliar process is an patrimonial avocation among Japan's patrimonial politicians, and a signing of a assent covenant was a lustful wish of his late father, Shintaro Abe, a long-serving unfamiliar minister. So Mr Putin will slot Mr Abe's financial inducements yet make a derisory offer over a islands—perhaps a lapse of a dual smallest, hardly inhabited ones.
Most of all, Mr Putin will grin during appearing to flay divided America's arch Asian fan from a joined front of exasperation that Mr Obama fabricated after Mr Putin's cast of Crimea and his advance of eastern Ukraine. Indeed, demeanour closely during a Russian pivot, and it has small to do with rendezvous in Asia for a possess ends. Russia's trade process in a segment boils down to offered weapons to anyone who will buy them (including many of a claimants in a South China Sea dispute, thereby fuelling an arms race). Russia's trade with Asia accounts for a trifling 1% of a region's total, and Asia's mercantile spectacle has perceptibly overwhelmed a 6.4m Russians in a decayed cities of Russia's Far East. Many seethe that sprucing adult Vladivostok for a APEC limit cost $20bn, some-more than a London Olympics and some-more than Russia will spend building a segment in a years to 2025.
Asia is roughly immaterial to a vital needed of a pivot, that is to accelerate Russia's station in a all-consuming fight with America and a West. The gas understanding with China occurred usually after Western sanctions singular Russian options in Europe. Russia resents a terms on that it was struck, and suspects that China will find to renegotiate if gas prices stay low.
Bobo Lo, a Russia specialist, describes a "virtual reality" of promotion that insists that Russia and China, both state-directed economies with concerns about American power, demeanour during a universe identically. But mutual dread runs deep. Russia has been conditioned by a story of enlargement into Asia to demeanour down on China as a obtuse power, so a stream standing as a source of line for China feels humiliating. Elsewhere, Russia wants to criticise a American-led universe sequence of that it has been a biggest loser. By contrast, says Mr Lo, China has been a arch customer of that order, carrying adopted slashing mercantile reforms to gain on it. It knows that a many vicious attribute is not with Russia yet with America.
What, then, if Russia's family with America were to change? They have positively been strained, over Crimea, Ukraine and Mr Putin's partial in a drop of Syria. But usually suspect that Mr Putin and Donald Trump, America's president-elect, pursue a truce that both group contend they want. Suppose America cuts Mr Putin tardy in Europe, a segment of his genuine aspirations, and even a Middle East. What would occur to his Asian pivot? Pacific Russians have a caustic take on Moscow's majestic eagle. Its prophesy might take in both West and East, yet "Stoit zadom k Azii"—it stands with a behind to Asia.


text:
Q: Python function which returns its own signature with parameters Marked as solved because:
The solved solution provides a good-enough solution to the problem, even though it doesn't quite solve the problem of dynamically generating the function name on-demand.
I want to generate a function which returns its own signature with parameters. Is this possible in Python? So, the function gets generated by the call itself, and returns the string which represents its own name and parameters.
Here is a simple example of what I am looking for:
class Object(object):
  #Impl here?
  pass

a = Object()
returned_string = a.foo(param1 = 1, param2 = "cheese")

print(returned_string)
#should print: a.foo(param1 = 1, param2 = "cheese")
#or     print:   foo(param1 = 1, param2 = "cheese")

Important, foo is an arbitrary name and should not be "hard-coded" but generated.
The code should allow for the following:
 print(a.doodle(param1 = 32)) #prints: doodle(param1 = 32)
 print(a.bar(param42 = "pi")) #prints: bar(param42 = "pi")

without defining further functions.
Thanks :)

A: I am assuming what you mean is that once you have created an object, the function is able to return its own input parameters for that object. You can of course modify it to look like a string but what you want to return is the input parameters that are the signature of that object and funciton foo
class Object():
    def foo(self, param1, param2):
        self.param1 = param1
        self.param2 = param2
        return self.__dict__

a = Object()
returned_string = a.foo(param1 = 1, param2 = "cheese")

print(returned_string)

{'param1': 1, 'param2': 'cheese'}

Returning it as a string -
import inspect

class Object():
    def foo(self, param1, param2):
        self.param1 = param1
        self.param2 = param2
        d = self.__dict__
        f = inspect.stack()[0][3]
        return f+'('+', '.join([' = '.join([str(j) for j in i]) for i in d.items()])+')'

a = Object()
returned_string = a.foo(param1 = 1, param2 = "cheese")

print(returned_string)

foo(param1 = 1, param2 = cheese)

A: You should be able to do what you want using **kwargs. As an example:
def my_args_are(**kwargs):
    return "my_args_are({})".format(
        ", ".join("{0} = {1!r}".format(arg, val)
            for arg, val in kwargs.items()))

It works:
>>> my_args_are(param1 = 1, param2 = "cheese")
"my_args_are(param1 = 1, param2 = 'cheese')"

If you don't want to hardcode the name you can use inspect:
import inspect

def my_args_are(**kwargs):
    fname = inspect.currentframe().f_code.co_name
    argstr = ", ".join("{0} = {1!r}".format(arg, val)
                       for arg, val in kwargs.items()))
    return "{}({})".format(fname, argstr)

A: So here's the function you want:
import inspect

class Object(object):

    def your_function(**options):
        return f"{inspect.stack()[0][3]}({', '.join([str(key) + ' = ' + str(options[key]) for key in options.keys()])})"

So if you do:
a = Object()
and
a.your_function(abc="abc", ert=3)
it will return:
your_function(abc = abc, ert = 3)

redpajama_set_name: RedPajamaStackExchange


text:
Back to Journals » Clinical, Cosmetic and Investigational Dermatology » Volume 10
Clinical Trial Report
Topical application of ST266 reduces UV-induced skin damage
Authors Guan L, Suggs A, Galan E, Lam M, Baron ED
Received 24 July 2017
Accepted for publication 22 September 2017
Published 10 November 2017 Volume 2017:10 Pages 459—471
DOI https://doi.org/10.2147/CCID.S147112
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Jeffrey Weinberg
Download Article [PDF]
Linna Guan,1 Amanda Suggs,1 Emily Galan,1 Minh Lam,1 Elma D Baron1,2
1Department of Dermatology, Case Western Reserve University, 2Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA
Abstract: Ultraviolet radiation (UVR) has a significant impact on human skin and is the major environmental factor for skin cancer formation. It is also believed that 80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory changes in the skin via the increase in oxidative stress, DNA damage vascular permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin inflammation and DNA damage, which manifest as sunburn (erythema). ST266 is the secretome of proprietary amnion-derived cells that have been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies. We hypothesized that ST266 has anti-inflammatory effects that can be used to reduce ultraviolet (UV) erythema and markers of inflammation. In this study, we examined the in vivo effects of ST266 on post UV-irradiated skin by measuring erythema, level of cyclobutane pyrimidine dimer (CPD), and expression level of xeroderma pigmentosum, complementation group A (XPA). We demonstrated that ST266 has the potential to reduce the acute effects of UV-induced skin damage when applied immediately after the initial exposure. In addition, ST266 is shown to reduce erythema, increase XPA DNA repair protein, and decrease damaged DNA.
Keywords: ST266, photoaging, erythema, CPD, XPA, UV-induced DNA damage
Ultraviolet (UV) radiation (UVR) is known to be a tumor initiator and a tumor promoter.1 On the skin, UVR can cause neoplasia, atrophy, pigmentary changes, and wrinkling.1 UVR is believed to be accountable for up to 80% of the signs of skin aging.2 Morphologically, photoaging comprises cutaneous alterations such as deep wrinkles, roughness, sallowness, mottled dyspigmentation, and telangiectasia along with benign and malignant neoplasms of the skin.3Although effects of long-term UV exposure vary between individuals and are difficult to predict, short-term effects of UVR can be seen almost immediately on the skin as sunburn.2 After initial exposure to UVR, the damage to the skin results in an inflammatory process characterized by erythema and DNA damage.4 Recovery from UV-induced erythema is a process that requires various cytokines and factors.5
ST266 is the secretome of proprietary amnion-derived cells that has been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies.6–8 As a cellular cytokine solution, ST266 is collected by harvesting the proteins released from amnion-derived multipotent progenitor cells.6 Cultured cells release various signaling factors that can support or affect the growth, differentiation, and protein production of other cells.6
In this study, we investigated the potential of ST266 in the treatment of UV-induced erythema, which is considered as a surrogate marker of DNA damage. To determine the efficacy of ST266, erythema was evaluated at multiple time points post UV irradiation with and without ST266 application. Xeroderma pigmentosum, complementation group A (XPA) expression and cyclobutane pyrimidine dimer (CPD) levels were also evaluated to determine the extent of DNA damage and repair. XPA expression was investigated due to its key role in nucleotide excision repair (NER). Alternatively, CPDs are DNA lesions caused by UVR and are important in evaluating the extent of UV damage.9,10
Volunteer selection
After review and approval by University Hospitals of Cleveland Institutional Review Board, this study was conducted in accordance with the guidelines for good clinical practice and the Declaration of Helsinki (NCT02389777). All subjects were recruited through the Skin Study Center at University Hospitals of Cleveland. In all, 10 totally healthy adults older than 18 years with Fitzpatrick skin type (FST) of I–III were enrolled after they provided written informed consent.11 Subjects would have been excluded for history of photodermatosis or photosensitivity disorders, tanning bed use in the last 4 weeks, current intake of photosensitizer drugs (such as doxycycline and thiazide diuretics), current intake of immunosuppressant drugs, or active cancer or cancer within the last 5 years.
Mean erythema dose (MED)
MED testing was performed similar to a previous study.12 First, an eight-holed template with eight 1 cm2 circles was placed on the left buttock skin. The skin was then exposed to increasing doses of simulated solar radiation (SSR). SSR is a full spectrum light source that is used to mimic natural sunlight. SSR was provided by a 1000 W xenon arc solar simulator model 6271 (Oriel Instruments, Stratford, CT, USA) that emits UV wavelengths from 290 to 400 nm, with a dichroic mirror and 81017bis filter (WG320/1.5 mm). Bentham DM-150 double monochromator spectroradiometer was used to measure the spectrum and integrated irradiance. An IL1700 radiometer (International Light, Newburyport, MA) equipped with a sensor for UVA (SED 033, UVA filter 19672) and UVB (SED 240, UVB filter 15541) positioned 10 inches (25.4 cm) from the light source was also used to measure irradiance routinely. The amount of time used for irradiation was dependent on the subject's FST (Table 1). This setup is as described in a previous literature.13
Table 1 Eight increasing doses of SSR were given to determine the MED
Notes: The initial dose of SSR depends on the subject's FST. For example, a subject with FST of III would have received eight doses corresponding with the times boxed in red.
Abbreviations: FST, Fitzpatrick skin type; MED, mean erythema dose; SSR, simulated solar radiation.
Visual grading of the erythema was performed after 24 h to determine the visual MED. Grade "0" was given to the area that showed no redness. "Trace" grade was given to an incomplete circle of pink skin. Grade "1" was given to a complete circle of pink skin. Grade "2" was given to a complete, dark pink to red circle of skin. Skin that showed erythema with the shortest exposure time to SSR was the visual MED. Erythema was further quantified in each skin area that was SSR exposed as well as a nonexposed area three times using the CR-300 chromameter from Konica Minolta (Tokyo, Japan). The difference between the median chromameter reading from the unexposed skin and the median of the SSR-exposed reading is delta a*. Following COLIPA recommendations, the minimum erythema dose or MED is defined as the lowest SSR dose that results in a delta a of 2.5 units. This was calculated via linear regression using the log of the SSR exposure times plotted against delta a* values.14 Rearranging the y=mx+b equation, x was solved for at y=2.5. MED can then be converted to mJ/cm2 by multiplying the MED in seconds by the UVB irradiance (i.e., dose=irradiance×time) in seconds.
ST266 treatment
After determining the MED, a template exposing five 1-inch (2.5 cm) squares of skin was applied to the right buttock. These sites were numbered 1–5. Sites 1, 2, 3, 4, and 5 were irradiated with two MEDs of SSR, while the rest of the body was draped. ST266 solution (Stemnion, Inc., Pittsburgh, PA, USA) was applied as follows. Site 1 did not receive any ST266 treatment at all. Sites 2 and 3 were treated by investigators with ST266 immediately after irradiation. In all, 8–12 h later or at bedtime, subjects treated Sites 2, 3, 4, and 5 with ST266 at home. ST266 application was also applied by the subjects on Sites 2, 3, 4, and 5 the next morning, ~24 h after SSR. Between 24 and 36 h after SSR, the subjects returned to the Skin Study Center for Minolta chromameter assessment of erythema at all test sites, as well as for high-resolution digital photography (Canfield, Fairfield, NJ, USA). These assessments were repeated at 48 h and 72 h post SSR. Each test site was compared against a nontest site area (a) to determine the difference between the erythema of the test site and the nontest site (delta a).
Tissue analysis
In all, 6 mm punch biopsies were obtained at Site 1 (control) and Site 2 (SSR + immediate ST266 Rx) 24 h post SSR. Nine total samples were analyzed due to inadequate tissue quality from one subject.
Tissue analysis was performed similar to a previous study.12 Immunohistochemistry (IHC) was performed using the fixed biopsies that were embedded in paraffin and cut into 5 μm sections. Deparaffinization and dehydration were then performed by heating the skin samples in a epitope retrieval buffer at 95–97°C for 20 min and then cooling them for 30 min. The samples were blocked using 5% normal goat serum in a dilution buffer (Jackson ImmunoResearch Laboratories, Inc., West Grove, PA, USA) and 0.5% saponin (Sigma-Aldrich Co., St Louis, MO, USA) in 1× phosphate-buffered saline (PBS). The samples were subsequently incubated for 1 h at room temperature with polyclonal anti-XPA antibody (Thermo Fisher Scientific, Waltham, MA, USA) or with polyclonal anti-CPD antibody (Cosmo Bio, Tokyo, Japan) in the dilution buffer. The samples were washed in PBS and then incubated with Alexa Fluor 488- or 594-conjugated goat anti-rabbit secondary antibody (Thermo Fisher Scientific) to detect primary antibody as well as Vectashield Mounting Medium for fluorescence with 4',6-diamidino-2-phenylindole (DAPI; Vector, Burlingame, CA, USA) to visualize the nucleus. Every experiment included isotype controls to exclude nonspecific antibody staining. Images in this experiment were captured using an UltraVIEW VoX spinning disk confocal system (PerkinElmer Inc., Waltham, MA, USA) mounted on a Leica DMI6000B microscope (Leica Microsystems, Wetzlar, Germany) equipped with an HC PLAN APO 20×/0.7 objective. Solid-state diode lasers emitting 488 nm or 561 nm and 405 nm excitation light with emission filters were used to capture confocal images of Alexa 488- or 594-conjuated anti-rabbit secondary antibody and DAPI-stained images. MetaMorph Premier Software (Molecular Devices LLC, Sunnyvale, CA, USA) was used quantitatively to analyze the captured images. To quantify fluorescent intensity of the XPA- and CPD-stained samples, the nucleus of the DAPI-stained image was first encircled. The encircled region was then analyzed for fluorescent expression level of each corresponding antibody. MetaMorph was used to measure and record average pixel intensities of these regions. Microsoft Excel was allowed for further analysis of the data. Erythema, XPA, and CPD data were analyzed using paired t-test. A difference of <0.05 was considered as significant.
Ten subjects were recruited. Six subjects were males and four females, with ages ranging from 20 to 54 years. Eight subjects were Caucasian and two subjects were Hispanic/Latino.
Erythema post SSR
Subjects were irradiated in areas demonstrated in Figure 1. Figure 1 shows three representative subjects 24 h post SSR exposure who each had a control site (irradiated but not treated with ST266), area treated with immediate ST266, and area treated with ST266 after 8–12 h delay. It can be seen that the erythema is diminished in those treated with immediate ST266 but increased with delayed ST266 application. Primary data for the difference between nonirradiated skin and irradiated skin (delta a*) and visual MED grading at 24 h, 48 h, and 72 h are listed in Table S1.
Figure 1 ST266-treated sites 24 h after SSR exposure on three representative subjects.
Notes: Control sites are displayed in the top left corner. Delta a values are displayed under each treated site. Delta a is the difference between the erythema of the test site and the nontest site. Black scale bar =2.54 cm.
Abbreviation: SSR, simulated solar radiation.
The summary for erythema ~24 h post SSR exposure for all the subjects, evaluated using delta a*, is shown in Figure 2. The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 24 h post SSR is 9.99, while the mean for all 10 areas with immediate ST266 treatment is 3.74 and the mean for all 10 areas with delayed ST266 treatment (8–12 h post SSR) is 13.51. Using a two-tailed paired t-test, there was a statistically significant difference between the mean of the areas treated immediately with ST266 and that not treated with ST266 (p=0.00079). There was also a statistically significant difference between the mean of the areas treated with delayed ST266 and that not treated with ST266 (p=0.031).
Figure 2 Summary for delta a* 24 h post SSR exposure for all of the subjects.
Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 24 h post SSR is 9.99, while the mean with immediate ST266 treatment is 3.74 and the mean with delayed ST266 treatment (8–12 h post SSR) is 13.51. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.00079) and between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.031).
The summary for delta a* 48 h post SSR exposure for all the subjects is shown in Figure 3. The mean delta a* for all 10 subjects' areas corresponding to ST266 treatment 48 h post SSR is 9.62, while the mean with immediate ST266 treatment is 3.56 and the mean with delayed ST266 treatment is 12.09. There was a statistically significant difference between the mean of the areas treated immediately with ST266 and that not treated with ST266 (p=0.0070). There is a trend between the mean of the areas treated with delayed ST266 and that not treated with ST266 (p=0.089) 48 h post SSR.
Figure 3 Summary for delta a* 48 h post SSR exposure for all the subjects.
Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 48 h post SSR is 9.62, while the mean with immediate ST266 treatment is 3.56 and the mean with delayed ST266 treatment is 12.09. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.0070) and a trend between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.089) 48 h post SSR.
The summary for delta a* 72 h post SSR exposure for all the subjects is shown in Figure 4. The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 72 h post SSR is 7.56, while the mean with immediate ST266 treatment is 2.97 and the mean with delayed ST266 treatment is 10.64. There was a statistically significant difference between the mean of the areas treated immediately with ST266 and that not treated with ST266 (p=0.010). There is marginal significance between the areas of the subjects treated with delayed ST266 and those not treated with ST266 (p=0.065) 72 h post SSR.
Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 72 h post SSR is 7.56, while the mean with immediate ST266 treatment is 2.97 and the mean with delayed ST266 treatment is 10.64. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.010) and a marginal significance between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.065) 72 h post SSR.
XPA
Biopsies from nine out of the 10 subjects were analyzed using anti-XPA antibodies. One subject had insufficient tissue sample for immunostaining. All biopsies were obtained 24 h post SSR in two areas: 1) without ST266 treatment and 2) immediate ST266 treatment. Figure 5 shows the summary of XPA expression level measured using the mean of pixel fluorescence intensity. Six out of the nine subjects demonstrated higher XPA expression levels with immediate ST266 treatment when compared with no ST266 treatment, while two out of the nine subjects showed lower XPA expression levels with immediate ST266 treatment. One patient demonstrated to have approximately the same XPA expression level with and without ST266 treatment. The mean pixel fluorescence intensity for XPA expression level without ST266 treatment is 4395 arbitrary unit (AU), while the mean XPA expression level with immediate ST266 treatment is 4824 AU. However, two-tailed paired t-test was inconclusive with p=0.55.
Figure 5 Summary of XPA expression level measured using immunofluorescence.
Notes: Six out of nine subjects showed higher XPA expression level with immediate ST266 treatment when compared with no ST266 treatment. Subjects 4 and 9 demonstrated the opposite with higher XPA expression levels after immediate ST266 treatment. Subject 1 demonstrated approximately the same XPA expression level with and without ST266 treatment. The mean fluorescence for XPA expression level without ST266 treatment is 4395 AU, while the mean XPA expression level with immediate ST266 treatment is 4824 AU. Two-tailed paired t-test was unable to demonstrate significance (p=0.55).
Abbreviations: AU, arbitrary unit; UV, ultraviolet; XPA, xeroderma pigmentosum, complementation group A.
Biopsies from eight out of 10 subjects were analyzed using anti-CPD antibodies. The other two subjects' biopsies did not yield sufficient tissue for immunostaining. Figure 6 shows the summary of CPD level measured using the mean of pixel fluorescence intensity. Six out of eight subjects showed lower CPD levels with immediate ST266 treatment when compared with no ST266 treatment 24 h post SSR. The same subjects that expressed lower XPA levels with ST266 treatment also expressed higher CPD levels. The mean pixel fluorescence intensity for CPD level without ST266 treatment is 4175 AU, while the mean CPD level with immediate ST266 treatment is 3209 AU. The difference in CPD levels between no ST266 treatment and immediate ST266 treatment is marginally significant when analyzed using two-tailed paired t-test (p=0.053). Interestingly, in all six samples that showed an increase in XPA protein levels in the skin following treatment with ST266, there were fewer CPDs remaining in the skin 24 h post SSR. In the two samples that demonstrated lower XPA protein levels, there were more CPDs remaining in the skin 24 h post SSR. There was no association of gender, age, ethnicity, FST, medical history, family history, or medication history between the two subjects who had the reversed CPD and XPA findings.
Figure 6 Summary of CPD level measured using immunofluorescence.
Notes: Six out of eight subjects showed lower CPD levels with immediate ST266 treatment when compared with no ST266 treatment 24 h post SSR. Subjects 4 and 9 demonstrated the opposite with higher CPD levels after immediate ST266 treatment. The mean fluorescence intensity for CPD level without ST266 treatment is 4175 AU, while the mean CPD level with immediate ST266 treatment is 3209 AU. The difference in CPD levels between no ST266 treatment and immediate ST266 treatment is marginally significant when analyzed using two-tailed paired t-test (p=0.053).
Abbreviations: AU, arbitrary unit; CPD, cyclobutane pyrimidine dimer; SSR, simulated solar radiation; UV, ultraviolet.
In the current study, immediate ST266 application was shown to reduce UV-induced erythema and also affect DNA damage and repair pathways. Decrease in DNA damage is likely mediated through the upregulation of DNA repair enzymes such as XPA as demonstrated in Figures 5 and 6 in this study. Although the exact composition of ST266 has not been determined, it has been reported to contain anti-inflammatory cytokines, which could contribute to the decrease in erythema with ST266 treatment when compared to that without ST266 treatment.6 Furthermore, ST266 has been shown to contain transforming growth factor-β (TGF-β).6 One of the major receptors that is downregulated after UV exposure is TGF-β type II receptor.15 TGF-β is a known mediator of procollagen biosynthesis, and dysregulation of TGF-β pathway is associated with decreased procollagen biosynthesis.16 Whether ST266 also mediates cellular repair via this pathway would be worthwhile to investigate in future studies.
On the other hand, delayed ST266 application of 8–12 h after UV exposure was shown to have the opposite effect. Subjects treated with delayed ST266 showed increase in erythema compared with those not treated with ST266. It is known that signaling factors induced by UV have both proinflammatory as well as anti-inflammatory effects. Some of these key molecules that play dual roles are prostaglandins.17 Although data are limited, it has been shown in animal models that synthesis of prostaglandin D and prostaglandin F declines during acute inflammation but rises again during the resolution of inflammation.17 Prostaglandin E2 (PGE2), another proinflammatory lipid mediator, has also been shown to have potent anti-inflammatory effects depending on context.17 The anti-inflammatory effect of prostaglandins at a later time point suggests that they may also play a role in the reduction of erythema post SSR. If ST266 contains cytokines that inhibit prostaglandins, application at an early stage can prove to be anti-inflammatory, preventing the prostaglandin activation of inflammation. However, if ST266 application was delayed, inhibition of prostaglandins may produce the opposite effect in preventing resolution of inflammation. Future studies regarding ST266 and prostaglandin expression can further elucidate the mechanism.
Whereas this study focused on short-term biologic outcomes of UV, prevention of harmful UV effects in the long run would be the goal. Chronic inflammation increases mRNAs of various matrix metalloproteinases (MMPs), elastases, and other proteases, which eventually leads to loss of skin tone and resilience, increased roughness and dryness, irregular pigmentation, and deep wrinkles.18,19 Skin chronically exposed to UVR become photoaged through promotion of MMP expression, reduction of procollagen synthesis, and connective tissue damage.20 Bearing in mind the results in our preliminary study and suggested composition of ST266, we believe that ST266 is a potential tool to investigate not only the prevention of UV-induced erythema but also chronic photoaging. To elucidate some of these properties, further evaluation of changes in molecular markers and using protocols that simulate repeated or long-term UV exposure is necessary.
This study received funding from Stemnion, Inc.
Support for author, Linna Guan, was given by the American Federation for Aging Research (AFAR) through the Medical Student Training In Aging Research (MSTAR) Program.
In addition, this study has been supported in part by the National Institutes of Health (grant 5P30AR039750) via the Skin Diseases Research Center (SDRC) and the Ohio Department of Development, Center for Innovative Immunosuppressive Therapeutics (grant TECH 09023).
The authors thank Dr Scott J Howell for his assistance in image analysis.
The contents of this paper have previously been presented at the following conferences:
Guan LL, Suggs A, Galan E, Lam M, Baron E. Topical application of ST266 reduces UV-induced skin damage. Poster presentation: American Geriatric Society 2016 Annual Scientific Meeting; May 19–21, 2016; Long Beach, CA, USA.
Galan E, Guan L, Suggs A, Ahsanuddin S, Lam M, Baron ED. Topical application of ST266 reduces UV-induced skin damage. Oral presentation: Society for Investigative Dermatology 2016 Annual Meeting; May 11–14, 2016; Scottsdale, AZ, USA.
Authors EDB and ML contributed to the design of the study. Authors AS, EG, and EDB conducted the clinical portion of the study. LG and ML performed the basic science portion of the study and analysis of the data. LG, AS, EG, ML, and EDB helped to interpret results. LG drafted the manuscript with help from AS, EG, ML, and EBD. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
The authors report no conflicts of interest in this work.
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Lastowiecka-Moras E, Bugajska J, Młynarczyk B. Occupational exposure to natural UV radiation and premature skin ageing. Int J Occup Saf Ergon. 2014;20(4):639–645.
Gilchrest BA. A review of skin aging and its medical therapy. Br J Dermatol. 1996;135:867–875.
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Steed DL, Trumpower C, Duffy D, et al. Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty. 2008;8:e18.
Payne WG, Wachtel TL, Smith CA, Uberti MG, Ko F, Robson MC. Effect of amnion-derived cellular cytokine solution on healing of experimental partial-thickness burns. World J Surg. 2010;34(7):1663–1668.
Uberti MG, Pierpont YN, Ko F, et al. Amnion-derived cellular cytokine solution (ACCS) promotes migration of keratinocytes and fibroblasts. Ann Plast Surg. 2010;64(5):632–635.
Matsuda T, Saijo M, Kuraoka I, et al. DNA repair protein XPA binds replication protein A (RPA). J Biol Chem. 1995;270(8):4152–4157.
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Table S1 Summary of raw data for delta a* and visual MED graded at 24 h, 48 h, and 72 h
Note: Skin that could not be evaluated due to biopsies was noted with "Biopsy".
Abbreviations: ACCS, amnion-derived cellular cytokine solution; MED, mean erythema dose; SSR, simulated solar radiation.
© 2017 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.


text:
Bradley Carnell's dream job is to build a team from scratch for new US club
10 January 2022 - 17:26 By MARK GLEESON
Bradley Carnell will be building a soccer team in the US - St Louis City - from scratch before it joins Major League Soccer next year.
Image: Bradley Carnell
Former Bidvest Wits, Kaizer Chiefs and SuperSport United defender Bradley Carnell has landed the newest job in US soccer — he's been handed a blank canvas to build a brand new team.
But the former Orlando Pirates assistant coach will not actually get to sit in a dugout in a competitive match for more than a year. The former Bafana Bafana full-back will next year take charge of St Louis City, who will be joining Major League Soccer.
He has been appointed with a year to spare, effectively to scout and hire players and build a new team that will ready to go in just over 12 months. Major League Soccer has been steadily expanding over the years, allowing new teams to buy their way into the league, at up to $100m.
Last year Austin, Texas, became the latest market to have a side in the league, with the actor Matthew McConaughey among the owner-investors, and Charlotte FC will making their bow next month, when the new MLS season gets under way.
St Louis are then next up for the 2023 campaign.
MLS started in 1993 with 10 teams but is now up to 28 as soccer grows in the North American market.
St Louis City is the first female-majority owned team in MLS and hired the German Lutz Pfannenstiel as their sporting director. He in turn has recruited Carnell as the first head coach.
Pfannenstiel was working at the German club Hoffenheim when they bought Knowledge Musona from Kaizer Chiefs and knows Carnell well from his time in the Bundesliga.
Carnell left Pirates to join the Red Bull organisation and their New York franchise in 2017.
He was assistant coach but in 2020 acted as caretaker coach when Chris Armas was fired.
Armas is now the assistant to Ralf Rangnick at Manchester United, a job Carnell was linked with last month.
Carnell, who turns 45 this month, told his new club's website: "I am looking forward to establishing a team that reflects St Louis — one that's diverse, hardworking and community-led.
"I am thrilled to help create the future of the sport in an incredible soccer city."


text:
Tory MP Craig Whittaker claims 'BAME' communities not taking coronavirus pandemic seriously
PoliticsHome.com, 31 July 2020 by John Johnston
English people taking part in VE Day celebrations during Lockdown, May 2020
Tory MP Craig Whittaker has claimed 'Muslim and BAME' communities are not taking the coronavirus pandemic seriously following the announcement of new local lockdowns across England.
The Conservative MP, whose Calder Valley constituency is included in the latest local lockdown, has accused Muslim communities living in his area of failing to follow social distancing guidelines.
New restrictions were imposed late last night banning separate households from meeting indoors in Greater Manchester, East Lancashire and parts of West Yorkshire.
Health Secretary Matt Hancock said the move was in response to a spike in infections driven by a "lack of social distancing".
People gathering in Soho at the end of Lockdown, July 2020
But speaking to LBC, Mr Whittaker said: "What I have seen in my constituency is we have areas in our community and sections of our community that are not taking the pandemic seriously.
Asked if he was referring to the Muslim community, he replied: "Of course".
"If you look at the areas where we've seen rises and cases, the vast majority – not by any stretch of the imagination all areas – but it is the BAME communities that are not taking this seriously enough."
English people celebrating VE Day, May 2020
He added: "I've been challenging our local leaders for… three weeks, asking what we are doing to target these areas to let people know that this is a very serious problem.
"Until people take it seriously, we're not going to get rid of this pandemic.
"We have areas of high multiple occupancy who are in the same boat… and it doesn't specifically have to be in the Asian community, but that is the largest proportion.
"Look at the areas. You've got Bradford, Calderdale, Kirklees. Bradford, in particular, and Kirklees have two of the largest populations in West Yorkshire."
Pressed on whether he was talking about immigrant communities in those areas, he responded: "Yeah, well, immigrant and Asian population".
His comments come after Matt Hancock insisted the new restrictions had not been put in place to curtail gatherings during the Muslim festival of Eid.
English people on Brighton beach during lockdown, 2020
Speaking to the BBC's Today programme, he said: "No, and my heart goes out to the Muslim communities in these areas because I know how important the Eid celebrations are.
"I'm very grateful to the local Muslim leaders, the imams in fact, across the country who've been working so hard to find a way to have Covid-secure celebrations.
"For instance celebrating Eid in parks where there's more space available and of course outdoors is safer than indoors."
Editor's Note: STILL WE RISE added the four photographs illustrating this article – they do not form part of the original article published by Politics Home
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