Penulis : Fuyuhara Patora
Ilustrator : Usatsuka Eiji
Penerjemah : Lumia
Editor : Lumia 
PDF : Lumia
http://uebu-novel.blogspot.co.id/

Question 1. Ghats at Varanasi is located in which state of India?
Answer: Uttar Pradesh.

Question 2. Where is Junagarh Fort in India?
Answer: Bikaner.

Question 3. What is the height of Lotus Temple?
Answer: 34 m.

Question 4. Prithviraj Chauhan was an Indian king from which dynasty?
Answer: Chahamana.

Question 5. UNESCO World Heritage Site 'Elephants Caves' is located at where?
Answer: Gharapuri in Mumbai.

Question 6. What is the capital of Sri Lanka?
Answer: Colombo.

Question 7. Saturn is the ____ planet from the Sun?
Answer: Sixth.

Question 8. Physicist 'Albert Einstein' was born on which date?
Answer: 14 March 1879 in Germany.

Question 9. Slogan 'tum mujhe khoon do main tumhe azadi dunga' given by whom?
Answer: Netaji Subhash Chandra Bose.

Question 10. World War I (WW1) ended on which date?
Answer: 11 November 1918.

Question 11. Indian writer 'Bankim Chandra Chattopadhyay' born on which date?
Answer: 27 June 1838.

Question 12. In which year the Rabindranath Tagore won the 'Nobel Prize in Literature'?
Answer: 1913.

Question 13. Which is the highest civilian award of the Republic of India?
Answer: The Bharat Ratna Award.

Question 14. Who was first captain of India national football team?
Answer: Gostha Pal.

Question 15. What is the capital of Japan?
Answer: Tokyo.

Question 16. Indian Railways Founded in which year?
Answer: 8 May 1845.

Question 17. Where is the Bhojtal Lake in India?
Answer: Bhopal, Madhya Pradesh.

Question 18. Bogibeel Bridge (in the Indian state of Assam) stand over which river?
Answer: Brahmaputra river.

Question 19. Goa is famous for what?
Answer: Beaches.

Question 20. WWW is stand for what?
Answer: World Wide Web.

Question 21. What is the biggest bone of the human body?
Answer: Femur.

Question 22. Who was the originator of the Bhakti movement in Punjab?
Answer: Guru Nanak.

Question 23. When is 'World Environment Day' celebrated?
Answer: June 5.

Question 24. Where is India's first underground nuclear explosion?
Answer: In Pokhran.

Question 25. Who is the Chief Advisor to the governor?
Answer: Chief Minister.

￼

Kishen

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All Rights ReservedView Non-AMP Version

Finally, the downloadable version of the first two Volumes is available on my p@treon.  To download it, you just have to be ANY TIER AT ALL.  Even a 1$ tier gives you the right to download the PDF version of the volume.  Also,  I won't be offended if you just pledge 1$ once just to download the book.  So go ahead!  Buy me a coffee.  :)
PinkCulture

A pervert father that tries to hold back his nature.. A bitchy devout wife that treats him like a servant. A father in law that collects most of his earnings. This is Carl’s life. Now Carl decides that it is time to put everything behind him and start anew, but an incredible discovery about his father in law makes him decide that it is time to teach him a lesson… of course in his own, pervert way... This is my first attempt at writing. Constructive criticism is always welcome. Also, I am not a native english speaker so do expect grammar errors to pop up.
-The tags clearly indicate that this novel is not something that everyone can stomach.  If you can't handle it, then don't read it.  leaving a review that only says "this is disgusting" just exposes your bigotism.

-All character and situations are pure producs of my imagination.  Any resemblance to actual people or events is completeley coincidental.  DON'T TRY TO REPRODUCE THE ACTS DEPICTED IN THIS BOOK IN REAL LIFE!  NO MATTER WHERE YOU LIVE, IT IS CRUEL AND ILLEGAL!!!

Source; https://www.marxists.org/archive/marx/works/download/pdf/Manifesto.pdf
 Manifesto of the Communist Party 
by Karl Marx and Frederick Engels February 1848 
Written: Late 1847; First Published: February 1848; Source: Marx/Engels Selected Works, Vol. One, Progress Publishers, Moscow, 1969, pp. 98-137; Translated: Samuel Moore in cooperation with Frederick Engels, 1888; Transcribed: by Zodiac and Brian Baggins; Proofed: and corrected against 1888 English Edition by Andy Blunden 2004; Copyleft: Marxists Internet Archive (marxists.org) 1987, 2000, 2010. Permission is granted to distribute this document under the terms of the Creative Commons Attribution-Share-Alike License. 
Table of Contents 
Editorial Introduction.............................................................2 
Preface to The 1872 German Edition.................................................4 
Preface to The 1882 Russian Edition.................................................5 
Preface to The 1883 German Edition.................................................6 
Preface to The 1888 English Edition..................................................7 
Preface to The 1890 German Edition...............................................10 
Preface to The 1892 Polish Edition..................................................12 
Preface to The 1893 Italian Edition..................................................13 
Manifesto of the Communist Party................................................14 
I. Bourgeois and Proletarians.....................................................14 
II. Proletarians and Communists...................................................22 
III. Socialist and Communist Literature..............................................28 
1. Reactionary Socialism....................................................28 
A. Feudal Socialism...................................................28 
B. Petty-Bourgeois Socialism.............................................29 
C. German or "True" Socialism..........................................29 
2. Conservative or Bourgeois Socialism........................................31 
3. Critical-Utopian Socialism and Communism...................................32 
IV. Position of the Communists in Relation to the Various Existing Opposition Parties.......34 
Letter from Engels to Marx, 24 November 1847......................................35 
Draft of a Communist Confession of Faith............................................36 
The Principles of Communism...................................................41 
Demands of the Communist Party in Germany.........................................55 
The Paris Commune. Address to the International Workingmen's Association, May 1871......58 
Endnotes......................................................................67

After properly telling my mother that I was going for a jog and may visit the mall, I went and to the bank to deposit my 200k on my cobwebbed filled account.

Double checking myself in the mirror, I really do seem to be going younger.

Well whatever. Its fifteen minutes after seven so dashed to the cemetery. I brought my old backpack with me this time.

---

After making sure nobody is around and out of range from the CCTV cameras, I stored the backpack in my inventory. I made stretches just like how Goku does it and began my morning run.

After a two hours it seems that running is not a chore for me anymore. I decided to extreme and ran from the cemetery to Baclaran. I used the Coastal Road highway to get there.

I ran and was chased by a couple of rabid dogs during the journey, don't own a dog and not take care of them assholes!

The dash for fifteen minutes made me produce sweat for the first time. I pulled out a clean towel out of the inventory, after making sure no one is around. Paranoia is a great help when you have super powers.

Its a good thing I don't have a noisy system that berates or forces me to do quests and stuff. Just a quiet life with an ability...just for me.

---

I went inside the church to get some rest.

Baclaran is famous for Baclaran Church where devotees of mother mary pray for almost anything. There's a tradition, if I remember correctly, that you need to complete Wednesday masses in order for you "wish/prayer" to be fulfilled.

I dunno if its once a month or after 2 weeks but testimonials are sometimes read before or after the mass. These letters are sometimes thanks because their wishes are fulfilled---whether they overcame diseases or got employed at an exclusive company, some relationships blossomed or a couple had a child.

Its always a nice feeling to hear some positives, so I stayed a bit and listened. You can light a candle so you prayer will---I dunno get an edge? Or something...the candles are not free and you need to make a donation.

Its a faith situation...if you're not a scumbag or have a sense of decency...I guess you can pay. Or yeah...if your poor I guess you can opt out of paying. But some have pride and at least one Piso...they will try to donate.

I'm wearing my backpack by the way and a couple of children are asking for alms. With a sleight of hand, I pretended to get something out of my bag. I ordered bucket meals from Jollibee and McDo and cloned the hell out of them. I gave each children a bucket meal.

Their questioning gazes as I pull buckets out of buckets from a small backpack, was quite hilarious.

"Its magic! This kuya knows a few magic tricks so don't worry all your pretty heads!"

I also gave some to poor elderly who are eyeing me from afar and reasoned that I'm doing a magic show on youtube or something and someone is taking a video somewhere.

I love the internet age!

---

After depositing 200k at a bank in Baclaran, I took a Jeepney towards Divisoria. The land of all things cheap and affordable.

I was planning to upgrade my current gaming potato setup, I could've just visited a mall in our town of Las Pinas City...but I did jog to Baclaran and I haven't visited Divisoria in a while, with money of course!

So yeah.

After changing coins again to paper money, I again have 200k in my inventory. I kept a close eye on my environment, I'm a paranoid guy and I distrust anyone even an elderly or a child.

This day and age anyone is desperate to try something.

Especially in Divisoria, no one visits the place without money with them.  I strapped my backpack in front of me so no robber can slash it and steal from it...even though its empty. I stored all my important documents and stuff in my inventory.

So my bag is actually empty right now...but again I'm paranoid.

---

Too bad haggling is not the norm anymore but back in the past, you can haggle prices on stuff here...but since its microchips and computers...prices are fixed.


I bought everything that needs to be upgraded: motherboards, processor, video card, audio card, wireless adapter, mechanical keyboard and mouse, both wireless and wired PC (personal computer) speakers, a new controller, a very powerful PSU (power supply unit), a 4k monitor, a T.V. and cable card, 64GB RAM card, 5 TB HDD and SSD and an air conditioner (split type) that is to be delivered later in the day.

Its already 3pm and mother texted me again on where the hell am I. I texted back that I did some shopping and lied that I was successful in selling something.

"Yeah I sold some stuff and I bought an aircon for my room. Kindly please sign it for me ma."

"Aircon" How the hell did you get money!? Did you rob a bank?"

"Yes. With tons of gold at my disposal, I will rule the world!!! Nyahahaha!!! But seriously ma, the aircon delivery will come by...please take care of it!"

"Yeah, yeah. I will deal with "the aircon delivery" *snicker"

*Toot toot

I don't need your snappy snicker ma!

Jeez.

I stored everything back in my inventory including the bag and took a ride back to Baclaran.

From there I ran again towards home.

---

I pretended to bought a bucket meal and as usual mother and father are eyeing me like a criminal. The aircon was delivered and installed not for free as I paid for it and mother as usual was eyeing me evilly as I turned it on. My room had never had an aircon so yeah, the cooling effect was a big difference.


My room only has one window and it doesn't circulate the air well. Having this monster was a blessing. I locked the door quickly and started on my upgrade work.

It just took me a couple of minutes to assemble and was now waiting for the cloning process of my old HDD (hard disk drive) to the new 5TB (terrabyte) one.

They did say idle hands is the devil's playground, I was wondering then does my infinite power only for making copies of items? I mean the word infinity if you take it literally, actually can be interpreted in many ways.

Like time.

I wish I have that remote thingy from that movie, not an exact copy but instead an actual ability or super power. I browsed the computer that was handling the cloning of my drive, and took a look at some of the functions and program.

The power of time. If I had that then I wouldn't need to clone coins and changing them into paper currency. I would bet on a lotto number...solo winner. In one fell swoop I would have instant money in my account.

How do I this...do I need to read up about time and "chrono elements" and shit?

*Sigh

I guess reading about it would just be wasting a bit of time but if I'm successful...I can retrieve the wasted time in the future.

Meh...might as well do it.

---

I spent hours reading books and PDF (portable document format) about time, including science fiction novels and stories. I even told mother to not disturb me because I'm doing something related to a business venture. That quieted her down a notch and I evaded a possible sermon scenario.

I really don't understand it.

*Sigh

I wish there was a program you know like in computers, that can collect all the knowledge I gathered and just...poof give it to me like a download or...

<Analyzing compiled data...>

<Decrypting...>

<Running scenarios...>

<Complete.>

<Download: Y/N?>

Um. Yes?

"AHHHHHH!!!!!!!"

Holy fucking shit! So this is what Edward Nygma felt when he downloaded brainwaves from those that bought his blender apparatus in that Batman movie.

Ugh.

After five agonizing minutes, I feel refreshed and enlightened. I hopped to the shower as I was drenched in sweat like literally buckets. I even borrowed our mop and mopped my floor.

---

I know about time now but its still not enough.

I tried using infinity power but the knowledge of mortals about something that is intangible and transcends dimensions is just not enough. I did get a new ability: computer.

Aside from Infinity, Video Game the word Computer is now under my profile. I can now literally download books into myself. Not just books but PDF files as well, straight off the monitor screen.

My easy money dream crashed and burn.

*Sigh

I guess the usual proven way of manually depositing money is the best way...for now.

I logged into my computer and created a gym membership account. Its a semi-prestigious gym and the minimum is 1k a month...basically a total of 14k upfront with a trainer.

I settled everything and I can start tomorrow.

I'm doing this. Never been to a gym before but I really need to exceed my body limit and having a trainer to teach me and push me maybe the thing I need.

---

The gym is in Alabang, I took a jeepney and got there before eight. The place is high tech according to the brochures, I had my backpack equipped and headed to my locker.

After changing to my new decent gym apparel that I bought, I asked for my trainer.

Its a girl.

A very young looking girl

*Sigh

I forgot to specify that I needed a male trainer...I guess no backsies. Let's just get this over with...


"Hello Mr. Drenal! My name is Lucy and I'm your trainer for 12 sessions during the course of you gym usage."

"Yes...uh hello."

"No need to be shy sir, we with that I mean "I" will make sure you will get your money's worth of our gym experience. Right this way please..."

Lucy suggested all kinds of routine and I managed to fulfill them all, according to her instructions. I memorized everything she taught, just in case she isn't here or something---wouldn't wanna be looking like a total noob.

I opted for an extreme workout, Lucy was reluctant at first but I said that she can decide if I can't take it anymore or if I'm struggling too much---then she can stop me then.

After a full three hour workout, I decided to stop and follow Lucy's instruction...

"Good workout sir! Hmm..."

She abruptly stopped midway in her sentence and suddenly started touching my body and arms.

"The workout seems to already showing signs of paying off...weird. Uhh...sorry if I offended you in anyway by invading your private space sir it...was just a momentary impulse...and...and..."

"Its okay! I guess it just means just how good you are if I'm already showing signs of improvement, am i right?"

"Uhh...yes! Yes!! Well will I be expecting you again sir?"

"I'll visit the day after tomorrow...I do need to pace myself right?"

"Yes! So let me show you the showers. Right this way please!"

I'm scared of public showers but I guess I can't help it.

---

Its eleven thirty.

Almost lunch. Although I have tons of food and snacks in my inventory...oh wait!

There's a park somewhere where BPO (business process outsourcing) employees use to hangout. I guess I can eat this shawarma there and I do have a small orange drink in my inventory too.

After eating five shawarmas and ten orange sodas later, I enjoyed the view until noon. It was getting hot and I decided to jog home. After finding a public toilet, I changed into my jog wear and started the journey home.


I think I will get there by four or five...maybe just before evening.

---

For six months, I have a routine: going to the gym three times a week, playing video games when not going to the gym, visiting Baclaran church and selling gold to different cities around Luzon.

You heard me.

I sell gold now and I'm keeping trillions of pure gold, its literally 9,999,999,999,999 in my gold currency bar on my inventory right now.

So this is what a millionaire feels like.

I upgraded our internet, using the online pay system and we are using T1 (tier) internet now...pricey but there's no helping it. I cannot feel the lag anymore. After years of training to handle lag, I and my computer have reached the pinnacle.

Also during these past six months, I contracted a few people and decided to build a house on the empty lot my parent owned. I talked to them about it and they agreed to let me build it---since they said that it was actually mine in the end. So we can move there temporarily as I was planning on upgrading our current old house...since its already thirty years.

Hopefully before the end of the year the house will be finished.

During these same six months, I discovered more uses for infinity. 

I can control temperature now. Unfortunately I cannot reduce the temperature past 1 degree. But increasing it? Limitless. I now make custom gold coins for myself. I sometimes do anime characters or some superhero logo.

Unfortunately by doing this the "gold coin" is considered an item, meaning it occupies a space on my game inventory.

I also unleashed my inner vigilante and criminal tendency by creating a computer worm using my "download" skill on computer program books and any PDF file---both legal and illegal, about hacking and software. 

The "money worm" as I call it, scans the digital highway for illegal accounts of any person on the planet. It then steals 1-2% of those illegal accounts and distributes it on ten of my Cayman offshore account, zigzagging across trillions of online accounts before doing so. 

God I love the internet...the dark web is the way to go.

So yeah I'm a billionaire now. I have digital money AND actual legal money. I spent my criminal money to give my parents an all expense paid tour of the whole Philippines. I told them once they completed it they we'll talk about the abroad tour.

My original account handled by mother still receives money but not like my separate account that earns millions. I can see that she still checks it from time to time so---yeah. Its a precaution against herself for knowing too much.

I'm currently alone and cannot leave the house because of my gym membership and overseeing the house construction on the other side of the street.

Also by watching the house construction...I discovered that I have unlocked a skill...building structures and customizing it according to my taste...

...the kind of things a middle aged guy thinks of using his powers on...use it for good? for justice? hell no!

Já faz muito tempo que essa maldição se inicia, e estou planejando acabar com isso de uma vez por todas. Eu já não sinto mais minha pele, e já não sinto mais dor, mesmo que eu queira. No início, era para ser apenas uma novela visual normal, com garotas bonitinhas e escolhas. Mas no fim, se tornou um verdadeiro inferno, com demônios e sofrimento.
Há alguns dias, um colega de trabalho meu me adicionou um link por e-mail e pediu para que eu instalasse aquele jogo chamado "Doki Doki" e alguma coisa que não me lembro mais. Em uma primeira vista, depois de pesquisar um pouco sobre o jogo (eu não iria instalar um link aleatório no meu computador), parecia divertido e tranquilo. Uma estética colorida e uma história melosa, que mostrava meninas de anime em um clube de literatura, onde encontrariam seu "primeiro amor". Mas eu me enganei. O que me aguardava era pior. Da primeira mensagem com o link, iniciamos um diálogo rápido.
(Resposta) "Obrigado! Vou instalar". (Resposta) "Ok, mas, você realmente vai jogar?" (Resposta) "Claro, foi você que me mandou o link. Pq?" (Resposta) "Nada não. Mas ... quer um conselho? Olha lá, ok?"
Eu não havia entendido o porquê do "aviso", mas optei por não perguntar o porquê daquilo, já que eu não queria alongar a conversa. Pensei que ele provavelmente estaria falando de possíveis cenas eróticas ou pesadas, ou seja, nada com que eu se preocupasse. Após agradecer e me despedir, eu instalei o jogo. Após alguns segundos, uma tela preta corrompeu a tela do meu computador e a minha sanidade. O aviso de conteúdo do início e o logo da "Team Salvato" não apareceram. O menu do jogo mostrava apenas uma tela vazia, sem as garotas, ea trilha sonora de abertura não estava tocando. Após escolher a opção de "Novo Jogo", uma caixa de texto apareceu:
"Por favor, escolha seu nome." . Um close extremamente grande da caixa de diálogo comprimiu a tela do meu computador, fazendo com que eu não conseguisse escrever meu nome. Tentava, mas não isolar. À aquela altura, o jogo já havia subitamente crashado. Uma estática forte apareceu na tela, seguida por outra tela preta.
Desanimado com aquilo, eu convenci a mim mesmo que algo não estava certo. Minimizei a janela do jogo e abri a Biblioteca de arquivos para ver se havia alguma coisa que eu pudesse consertar. Em torno de um minuto procurando, descobri que apanhados mais dois arquivos que incorporados alimentados com o jogo. Um era um bloco de notas e o outro, um arquivo em PDF.
Ao abrir o bloco de notas, descobri que havia um texto (enorme, por sinal) codificado inteiramente em binário, ou seja, eu não conseguiria entender bulhufas. O arquivo em PDF mostrava o que parecia ser um print de uma imagem do Google Maps, mostrando uma captura de imagem embaçada de uma pessoa deitada em um chão gramado, enquanto outra corria para fora da visão da câmera. As duas pareciam estar diante de uma espécie de prédio, parecido com uma escola, talvez. Não dei importância para nenhum dos arquivos e ignorei-los.
Desapontado, voltei á tela do jogo, e para a minha surpresa, uma linha de download estava exposta, dizendo: "dokidokidefeault.exe" recarregando ... , e o carregamento já estava em 96%. De repente, vários flashes de uma espécie de código morse e números aleatórios piscaram ao redor da tela, e então, a tela apagou mais uma vez. Ela piscou em vermelho, verde e por fim azul, várias e várias vezes. Meus olhos arderam, e eu tivo que pegar neles para poder passar. A luz daquelas núcleos que passavam era realmente extremamente intensa.
Logo, uma tela preta retornou e uma caixa de texto apareceu: "Continuar com a História?" , e dois botões de "sim" e "não" como referência. Por um impulso, muito confuso com tudo o que havia acontecido, eu decidi apertar em "não", mas quando notei, a opção "sim" clicou-se por si mesma. Eu apenas perguntava o que era aquilo.
O jogo finalmente começou. Eu estava em uma sala de aula vazia e escura, e a iluminação do cenárioconselhava à noite. Não tendo muita coisa para fazer, já que nenhum personagem apareceria tão cedo, origini para analisar o local. Eu logo avistei uma sombra que estava nitidamente para trás de uma das janelas da sala, ea silhueta dela era irreconhecível. A figura piscava e desaparecia em questões de frames. Uma caixa de texto apareceu, mas só mostrava números, letras e códigos aleatórios se estendendo. De repente, eu recebi um papel de uma cadeira da sala, na qual continha um poema. Em uma fonte bonitinha, estava escrito:
"O Homem" Um homem tão belo agora jazia ao vale da glaucoma Tal beleza não era vista pelos olhos secos dos mortais Tal beleza brilhava e cegava todos os montes do vale Porém, tal beleza se corrompeu. Esta luz vos corromperão também Mas agora, tal homenzinho chorava. Suas lágrimas escorriam como lâminas. Titio não pode saber. Papai chorou. Mamãe gritou. Agora, todos o deixarão. Afogou-se em seu reflexo nu. Alimentou-se, orgulhoso, de sua própria carne. Agora perece sobre seus braços próprios. Já não podes mais escapar.

ENCERRADO
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AC power plugs and sockets
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This article is about mains power connection devices used in domestic and light commercial environments. For other types, see Industrial and multiphase power plugs and sockets.
AC power plugs and sockets connect electric equipment to the alternating current (AC) power supply in buildings and at other sites. Electrical plugs and sockets differ from one another in voltage and current rating, shape, size, and connector type. Different standard systems of plugs and sockets are used around the world.

Plugs and sockets for portable appliances became available in the 1880s, to replace connections to light sockets with wall-mounted outlets. A proliferation of types developed for both convenience and protection from electrical injury. Today there are about 20 types in common use around the world, and many obsolete socket types are found in older buildings. Coordination of technical standards has allowed some types of plug to be used across large regions to facilitate trade in electrical appliances, and for the convenience of travellers and consumers of imported electrical goods.

Some multi-standard sockets allow use of several types of plug; improvised or unapproved adaptors between incompatible sockets and plugs may not provide the full safety and performance of an approved socket-plug combination.

Concepts and terminology	
History	
Application issues	
Types in present use	
Comparison of standard types	
Adaptors	
Unusual types	
Single phase electric stove plugs and sockets	
See also	
References	
External links	
Last edited 2 days ago by Northamerica1000
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(French)Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder 
(German) Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder 
Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder  

English) Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder  
(Chinese) Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunch

ing for thunder 

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(French)Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder 

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Bro every single time I take a bite of my crisps it thunders but I can barely hear it cos of my munching, could it be that I'm literally just mistaking my crunching for thunder 

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This article is about mains power connection devices used in domestic and light commercial environments. For other types, see Industrial and multiphase power plugs and sockets.
AC power plugs and sockets connect electric equipment to the alternating current (AC) power supply in buildings and at other sites. Electrical plugs and sockets differ from one another in voltage and current rating, shape, size, and connector type. Different standard systems of plugs and sockets are used around the world.

Plugs and sockets for portable appliances became available in the 1880s, to replace connections to light sockets with wall-mounted outlets. A proliferation of types developed for both convenience and protection from electrical injury. Today there are about 20 types in common use around the world, and many obsolete socket types are found in older buildings. Coordination of technical standards has allowed some types of plug to be used across large regions to facilitate trade in electrical appliances, and for the convenience of travellers and consumers of imported electrical goods.

Some multi-standard sockets allow use of several types of plug; improvised or unapproved adaptors between incompatible sockets and plugs may not provide the full safety and performance of an approved socket-plug combination.

Concepts and terminology	
History	
Application issues	
Types in present use	
Comparison of standard types	
Adaptors	
Unusual types	
Single phase electric stove plugs and sockets	
See also	
References	
External links	
Last edited 2 days ago by Northamerica1000
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In the infantile state of a new universe were many creatures in their starting phase, one of which was a juice pouch and straw that would challenge any vegetables from the cabbage patch to a round of fisticuffs, ultimately overcoming them and absorbing their power, thus, it became formidable and left behind an entire and complete heritage behind. This being was later known to be none other but...The Succ Sage.

The self named Genius Gang, a group of intellectuals with knowledge far beyond the norm of this infantile universe then began to rise and found this heritage, allowing them to begin their ascent to the higher realms.

The Scrummy Bummy Lore is an incomprehensive, shortened archive of the real events that the Genius Gang went through on their path.

Translator's Note: As the best translator in the world, it is easy to assume that my translation will be complely on point, however, the Scrummy Bummy Lore, being written in the language of the Gods, was far too complex for even a genius like I to translate fully, as I, just like you, am a mere mortal. Please do read this novel with an open mind, keeping in mind that not only are there multiple meanings that we do not understand, but also many that can eventually be understood through comprehensive thought. I myself feel as though I have matured as not just a person, but as an entity in this vast universe that we call our home after reading this novel.

In short, I must say that if the human race ever evolves to the point where we can incorporate the Scrummy Bummy Lore into our national curriculum as the most significant subject, I can die knowing that humanity shall live on to achieve great things.

Author's note.
This chapter has magic in it. Unfortunately, I can't use the font for magic on this site. Therefore I've set up a ******* where you can download a PDF of this chapter for free. If you wish to read this chapter with the magical text I suggest you go to https://www.*******.com/drblackbooksstoriesandpoems?fan_landing=true 
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


My heart leaped from my chest as the strange person turned the corner. His stature and physical features were that of a human child, but his eyes were that of a demon. Not one speck of white was shown, only red, the same deep red from the orb. Surely he was the one that the monsters feared. "Well, where's the orb you two?"

"" Master's voice echoed, but just before she could finish the spell, the child's hand tore through the person in front of me. That person slowly turned invisible while coughing up blood.

"Marcia!" Jonah's voice barely resonated. My ears rang as I caught Marcia in my hands. "Bastard!"

"Jonah! Get them out of here!" Master stepped between the child and me. My magic seeped out of me, and all I could think of was how I wished I was better at healing.

"Master! I'll fight with you!" Jonah ran over to Master's side, ready for a fight.

"YOU'LL DIE! He's not someone we can fight."

"" I chanted as I was pulled away. Jonah ran. Pain coursed through me as Marcia took a deep breath. Ah! She's still alive. I clutched my chest as I threw Marcia over my shoulder and ran away from that- that red-eyed beast.

We ran while warding off monsters — nothing on our minds but to survive. Finally, we made it to the safe house, and after sealing the door, Jonah and I fell to the ground, covered in wounds. Death surely awaits us.

"Wake up! Wake up, or you will surely die! Wake up, my child! Awaken your powers and rescue your friends."

"But that kid will find us."

"That man has gone. Now leave and find help. Don't die here. WAKE UP!"

My body heated up. I opened my eyes, Jonah was on the floor beside me, and Marcia was sitting in a corner rocking back and forth. Every move brought searing pain, blinding me. I forced myself to my feet. If that kid is really gone, then I need to get Jonah to a doctor.

I picked my brother up and threw him over my shoulder. He groaned in pain. I headed over to Marcia; she backed away from me for a second, almost like she didn't recognize me. Her wound disappeared after I poured my magic into her, but she didn't seem right. I held my hand out, and she reluctantly reached for it.

I ran down the mountain with Marcia in tow. The sun peeked over the horizon as dawn passed over the forest. That village gets closer and closer. As I rush towards it, I only wish to run in the opposite direction. The weight of Jonah on my shoulders presses me forward. The people most important to me keep me from fleeing. They saved me from that village once, so now I'll use that village to save them.

A young boy who is rejected by his village finds himself being taken into a loving home by two other orphaned children. Their caregiver "Master" raises them to learn how to be a Guardian and protect the world from monsters by using magic.

siRNA miRNA Vector CRISPR/Cas 9GenePharma custom siRNA oligo is purified by HPLC, 100% removed the unpaired single-stranded oligos contaminants from the products, the price is cheap, and the quality is high.


RNA interference (RNAi) is an ancient biological mechanism used to defend against external invasion. It theoretically can silence any disease-related genes in a sequence-specific manner, making small interfering RNA (siRNA) a promising therapeutic modality. After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO® (patisiran) and GIVLAARI™ (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-term pharmaceutical history of human beings, siRNA therapy currently has set up an extraordinary milestone, as it has already changed and will continue to change the treatment and management of human diseases. It can be administered quarterly, even twice-yearly, to achieve therapeutic effects, which is not the case for small molecules and antibodies. The drug development process was extremely hard, aiming to surmount complex obstacles, such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity, stability, specificity and potential off-target effects. In this review, the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed. All clinically explored and commercialized siRNA delivery platforms, including the GalNAc (N-acetylgalactosamine)–siRNA conjugate, and their fundamental design principles are thoroughly discussed. The latest progress in siRNA therapeutic development is also summarized. This review provides a comprehensive view and roadmap for general readers working in the field.

Introduction

Gene therapy is a promising therapeutic platform because it targets disease-causing genes in a sequence-specific manner, which enables more precise and personalized treatment of diverse life-threatening diseases.1 By introducing a certain nucleic acid modality to the desired tissue of the patient, gene expression can be downregulated, augmented or corrected. Small interfering RNA (siRNA), microRNA (miRNA) and inhibitory antisense oligonucleotides (ASOs) are representative molecules used to trigger gene inhibition, whereas plasmid DNA, messenger RNA (mRNA), small activating RNA (saRNA), splicing-modulatory ASOs and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) systems are usually employed to increase or correct target gene expression.2,3,4 Currently, many therapeutic programs have been explored to treat certain diseases.

RNA interference (RNAi) is a natural defense mechanism for the invasion of exogenous genes.5,6 RNAi modalities, e.g., siRNA and miRNA, can knockdown the expression of target genes in a sequence-specific way (Fig. 1) by mediating targeted mRNA degradation (for siRNA and miRNA) or mRNA translation repression (for miRNA). As a result of the slight differences between siRNA and miRNA, siRNA can typically trigger more efficient and specific gene silencing than miRNA, whereas one miRNA may compromise the expression of several different target genes simultaneously. Hence, siRNA and miRNA have different roles in pharmaceutical practice.

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Review Article

Open Access

Published: 19 June 2020

Therapeutic siRNA: state of the art

Bo Hu, 

Liping Zhong, 

[…]

Xing-Jie Liang 

Signal Transduction and Targeted Therapy volume 5, Article number: 101 (2020) Cite this article

11k Accesses

14 Citations

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Metricsdetails

ABSTRACT

RNA interference (RNAi) is an ancient biological mechanism used to defend against external invasion. It theoretically can silence any disease-related genes in a sequence-specific manner, making small interfering RNA (siRNA) a promising therapeutic modality. After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO® (patisiran) and GIVLAARI™ (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-term pharmaceutical history of human beings, siRNA therapy currently has set up an extraordinary milestone, as it has already changed and will continue to change the treatment and management of human diseases. It can be administered quarterly, even twice-yearly, to achieve therapeutic effects, which is not the case for small molecules and antibodies. The drug development process was extremely hard, aiming to surmount complex obstacles, such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity, stability, specificity and potential off-target effects. In this review, the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed. All clinically explored and commercialized siRNA delivery platforms, including the GalNAc (N-acetylgalactosamine)–siRNA conjugate, and their fundamental design principles are thoroughly discussed. The latest progress in siRNA therapeutic development is also summarized. This review provides a comprehensive view and roadmap for general readers working in the field.

Download PDF

Introduction

Gene therapy is a promising therapeutic platform because it targets disease-causing genes in a sequence-specific manner, which enables more precise and personalized treatment of diverse life-threatening diseases.1 By introducing a certain nucleic acid modality to the desired tissue of the patient, gene expression can be downregulated, augmented or corrected. Small interfering RNA (siRNA), microRNA (miRNA) and inhibitory antisense oligonucleotides (ASOs) are representative molecules used to trigger gene inhibition, whereas plasmid DNA, messenger RNA (mRNA), small activating RNA (saRNA), splicing-modulatory ASOs and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) systems are usually employed to increase or correct target gene expression.2,3,4 Currently, many therapeutic programs have been explored to treat certain diseases.

RNA interference (RNAi) is a natural defense mechanism for the invasion of exogenous genes.5,6 RNAi modalities, e.g., siRNA and miRNA, can knockdown the expression of target genes in a sequence-specific way (Fig. 1) by mediating targeted mRNA degradation (for siRNA and miRNA) or mRNA translation repression (for miRNA). As a result of the slight differences between siRNA and miRNA, siRNA can typically trigger more efficient and specific gene silencing than miRNA, whereas one miRNA may compromise the expression of several different target genes simultaneously. Hence, siRNA and miRNA have different roles in pharmaceutical practice.

Fig. 1

￼

Schematic illustrations of the working mechanisms of miRNA (a) and siRNA (b)

Full size image

Since the establishment of the RNAi concept in 1998, siRNA therapeutics have experienced many ups and downs. In 2001, Tuschl et al.7 successfully silenced the expression of a specific gene by introducing chemically synthesized siRNA into mammalian cells, leading to the emergence of a developmental upsurge. Although siRNA therapy once suffered due to the obstacles of its stability, specificity and delivery, advances in chemical modification and delivery brought the field to a robust and rapidly developing area of research again in recent years. After a 20-year journey, the United States Food and Drug Administration (FDA) and the European Commission (EC) approved ONPATTRO® (patisiran, ALN-TTR02) as the first commercial RNAi-based therapeutic for the treatment of hereditary amyloidogenic transthyretin (hATTR) amyloidosis with polyneuropathy in adults in 2018.2,8 Recently, the FDA-approved GIVLAARI™ (givosiran, ALN-AS1) for the treatment of adults with acute hepatic porphyria (AHP).9,10,11,12

siRNA has innate advantages over small molecular therapeutics and monoclonal antibody drugs because siRNA executes its function by complete Watson–Crick base pairing with mRNA, whereas small molecule and monoclonal antibody drugs need to recognize the complicated spatial conformation of certain proteins. As a result, there are many diseases that are not treatable by small molecule and monoclonal antibody drugs since a target molecule with high activity, affinity and specificity cannot be identified. In contrast, theoretically, any gene of interest can be targeted by siRNA since only the right nucleotide sequence along the targeting mRNA needs to be selected. This advantage confers the siRNA modality with a shorter research and development span and a wider therapeutic area than small molecule or antibody drugs, especially for those genes that are unfeasible for development with such strategies.

Although siRNA holds promising prospects in drug development, several intracellular and extracellular barriers limit its extensive clinical application. Naked and unmodified siRNA possesses some disadvantages, such as (1) unsatisfactory stability and poor pharmacokinetic behavior and (2) the possible induction of off-target effects. The phosphodiester bond of siRNA is vulnerable to RNases and phosphatases. Once it is systematically administered into circulation, endonucleases or exonucleases throughout the body will quickly degrade siRNA into fragments, thus preventing the accumulation of intact therapeutic siRNA in the intended tissue. In theory, siRNA only functions when its antisense strand is completely base-paired to the target mRNA. However, a few mismatches are tolerated by the RNA-induced silencing complex (RISC), which may lead to undesired silencing of those genes with a few nucleotide mismatches. In addition, the RISC-loaded sense strand of siRNA may also knockdown the expression of other irrelevant genes. Moreover, unformulated and unmodified siRNA may lead to the activation of Toll-like receptor 3 (TLR3) and adversely affect the blood and lymphatic systems.13 These discoveries have raised many concerns about the undesirable effects and pharmaceutical issues of siRNAs.

To maximize the treatment potency and reduce or avoid the side effects of siRNA, researchers have made great efforts to investigate various chemical modification geometries and to develop many different delivery systems. As a result, a series of modification patterns were proposed and evaluated preclinically and clinically with respect to their effects on activity, stability, specificity and biosafety. Delivery materials derived from lipids, lipid-like materials (lipidoids), polymers, peptides, exosomes, inorganic nanoparticles, etc., have been designed and investigated.2,8,14,15,16,17,18,19,20,21,22 As a result, several modification patterns and delivery platforms have been employed in clinical studies. Here, the detailed evolution and advances in the modification and delivery technologies of siRNA are comprehensively summarized and discussed. This review provides an overview and a handbook for reviewing siRNA therapeutic development.

siRNA modification

During the early stages of developing siRNA therapeutics, many agents were designed based on completely unmodified or slightly modified siRNA to arrive at appropriate tissue and then silence the target gene. These molecules can mediate gene silencing in vivo, especially in tissues that receive local drug administration, e.g., eyes. However, limited efficacy and potential off-target effects may be observed with these modalities. For example, Kleinman and colleagues23 observed that bevasiranib and AGN211745 triggered significant activation of toll-like receptor 3 (TLR3) and its adapter molecule TRIF, inducing the secretion of interleukin-12 and interferon-γ. Bevasiranib and AGN211745 are siRNA therapeutics developed for the treatment of age-related macular degeneration.24 The VEGFA-targeting bevasiranib25 and VEGFR1-targeting AGN21174526 are unmodified and slightly modified siRNAs, respectively. Moreover, Kleinman and colleagues further demonstrated that siRNA classes with sequences of 21 nucleotides or longer, regardless of which genes they target, can suppress CNV in mice compared to bevasiranib and AGN211745. These findings eventually led to the termination of the clinical investigation of bevasiranib in 2009.

Chemically modified siRNAs, such as siRNAs with substitution of the 2′-OH with a 2′-O-methyl (2′-OMe)27 or 2′-methoxyethyl (2′-MOE)28 group or the substitution of certain nucleotides with locked nucleic acid (LNA),29 unlocked nucleic acid (UNA)30 or glycol nucleic acid (GNA)31 (Fig. 2), can efficiently suppress immunostimulatory siRNA-driven innate immune activation, enhance activity and specificity, and reduce off-target-induced toxicity. To enhance the potency and reduce the potential toxicity of siRNA, numerous chemical modification geometries have been established and tested.32

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