#exo1

[yeast-papers]

Chk2 homologue Mek1 limits Exo1-dependent DNA end resection during meiotic recombination in S. cerevisiae

BioRxiv: http://dlvr.it/T5RgyL

[actiasdara]

DNA Repair and Recombination

DNA Maintenance

DNA replication → inheritance

DNA repair → genome stability and integrity

DNA recombination → variety in organism

Why are DNA lesions lethal

Structural damage → prevent replication/transcription stalling of replication fork

Harmful mutations → impair survival of organism mutation in tumor suppressor gene (gene that prevent proliferation wildly, pro cell survival)

If unrepaired:

Senescence (cellular aging)

Apoptosis

Aberrant cell division cancer

Not all DNA lesions create cell death, but in some part they do

Culprits

Endogenous

Replication error

Reactive oxygen species

Defective repair system

Exogenous

Radiation

Interchelating agent

Carcinogen

Viruses (integrate genome to host)

Types of DNA Lesions

Single base changes

Damages on nucleobases or nucleotide

Examples:

Cytosine hydrolysis and become uracil (deamination)

Guanine methylation (add methyl group to guanine)

Guanine oxidation (may only create 2 hydrogen bond with C)

Depurination (lost of purin)

alkylation/methylation (protecting nucleotide)/oxidation

Repair:

Base excision repair

recognition of damage base and remove it (DNA glycosylase)

AP (area that don’t have nucleobase)

AP endonuclease (remove nucleotide of AP)

DNA Polymerase and ligase will fill the gap (divided into short and long “up to 10 nucleotides”)

Structural distortion

Bulky DNA lesions (include covalent bond “T dimer” triggered commonly by UV radiation)

Repair:

Nucleotide excision repair

Multicomplex nuclease (recognize and cut the bulky section)

DNA Helicase (the cut strand)

DNA polymerase and ligase (fill the gap)

DNA Mismatch

Repair

Mismatch excision repair

MutSalpha (MSH2-MSH6 heterodimer) recognize and recruit other protein

PCNA clamp, RFC, and Exo1 (cut the mismatch area)

Fill the gap

ligation

DNA backbone damage

Can occur when single strand break is not fixed

Strategies:

Homologous recombination (HR)

Active only in S-G2 phase

Require homologous chromosomes

Less efficient repair

Lead to faithful repair outcomes

Protein

MRN complex (cut and create ssDNA “overhang”)

Exo1 exonuclease (expose the overhang)

Rad51 Bind to 3’ ssDNA overhangs and help migrate

BRCA1 aids Rad51 search and invade homologous sequence

DNA polymerase

May end with crossover

Non-homologous end joining (NHEJ)

JUST JOIN THE END

Active throughout the cell cycle (last choice)

Could create small mutation (change DNA sequence, frame shift)

Ku protein (Ku70-Ku80), recognize and binds to DNA DSB ends

Protect and stabilize DNA ends

Recruit additional protein

Bring to ends together

Artemis (additional DNA end processing)

DNA-PK (kinase, add phosphate) and DNA ligase

Alternative End Joining

PARP1 → Recognize, binds, and match

Match with 2-20 nucleotide base pairing

PolQ (polymerase)

DNA Lesion Comes from Different Forms

Base pair mismatch (you get the idea, single base changes, most common)

Repair with mismatch repair

Single strand break (break of the phosphodiester bond on one strand, DNA backbone damage)

Single strand break repair

Structural base pair distortion (match with its own strand

Nucleotide excision repair (removal of entire nucleotide)

Nucleotide alteration (can change the helical structure)

Base excision repair

Double strand break

Homologous recombination

Non-homologous end joining

Genetic Recombination - Cross overs

Often happen in fertilization process

Morgan & Sturtevant

Types of Mutation

Silent mutation (mutation but same product, except when it create splicing region)

Missense mutation (produce different product, but same function)

Nonsense mutation (produce stop codon)

Frameshift (shift of translation frame)

Variation = Polymorphism

Single nucleotide polymorphism

Variation at single position in DNA sequence among individual

Single nucleotide variation

More than 1% of the population carries this sequence

Copy number variations

Variation in copy number of particular DNA sequence among individual

Structural Variation

[km3solutions]

Been away for a minute, but now I'm back Under investigation for #russiancollusion with @battlecocktactical ! #izmash prototype #pdw? Maybe just a bad ass @firecontrolunit #exo1 #bakeliteallthethings #fakelite #fakelite #fcu #firecontrolunit #nailedthatcerakoteshit #cerakote #pdw #pistol #badass #kalashlife #kalash #wwmkd #cyberpunk #futurepast

[kpopfluffauthor]

Precious

Title: Precious

Paring reader x Lay/Yixing

Word count: 307

Genre: fluff

A/N: @xiulayhasmyheart, seems to think that she is worthless, her mutals and Yixing seem to think different

Precious [presh-uh s] adj. Highly esteemed for some spiritual, nonmaterial, or moral quality

N. A dearly beloved person; darling

You come home and throw your bag on the floor clearly upset, slumping onto the couch as you sigh loudly. Yixing walks into the room from the kitchen throwing a towel over his shoulder. “What's wrong honey?” He says the words in a soft tone as he sits next to you. You can smell a sweet, almost savory, smell coming off of him, and you know he has been cooking.

“I am just tired of being told how worthless I am at work, the managers keep telling me that I would be easy to replace.” You sound slightly defeated as you speak the words. “Every holiday they overwork me and I don't feel valued”

Yixing scoffs at you. “Pft, I value you more than you know Y/N, there is no one that I value more.” He stops a moment to think about his next words. “I hope you know I am not the only person that finds you truly a dearly beloved person.” He smiles, rubbing your back before he gasps and runs to your kitchen in the next room. After about a minute he comes back camly and sits down next to you again.

You look over at him confused, the towel is no longer draped across his shoulder. You ignore what just happened, assuming it has to do with whatever he is cooking. “You may feel that way but I don’t”

Yixing puts his hand in yours and leans in kissing you. “Y/N, you need to know your are the exact opposite, the antonym, if you will, of worthless. You are precious.” He pulls you into the kitchen where is adding a few last seasonings to your favorite meal. The two of you continue to talk into the wee hours of the night, Yixing as always finds a way to cheer you up.

[peachixfn]

[bigspoonkyungsoo]

00:21:46:02 : .//EXO1-99 #12 004-8 SYSTEM ERROR. PROCESSING... PLEASE STANDBY.

[videomitch]

As Snow Falls

Commuting Montreal Style

Montréal-Ouest, the 2nd stop from Montreal’s Lucien-L’Allier Terminus on the (former) Canadian Pacific main line. It sees services from lines exo1 Vaudreuil–Hudson, exo2 Saint-Jérôme & exo4 Candiac lines.

[myysi]

YSI EXO-S Series Overview from YSIinc on Vimeo.

Introducing the EXO-S Series Multiparameter Water Quality Sondes (ysi.com/exo). The EXO-S sondes are shorter, lighter, more affordable, and more sustainable versions of our industry-leading EXO sondes.

These sondes are purpose-built without a battery compartment and provide the same sensor payload and best-in-class performance for applications where external power is available. These battery-less sondes offer several advantages to standard EXO-S as long as external power can be provided. The first and most obvious is the smaller footprint, which means the sonde can fit into tight spaces and be more easily hidden. These are also lighter sondes that are better suited for integration with AUVs, drones, and buoys where weight is a factor.

Perhaps most compelling is the lower price point. With these sondes it is more affordable than ever to adopt the EXO platform, and you don't have to worry about replacing and disposing of alkaline batteries.

With reduced size, weight, and cost, the EXO-S sondes are a great option for discreet sampling applications. For example, the EXO1s is perfect for spot-checking water quality with a handheld. In addition to popular water quality parameters such as conductivity, pH, dissolved oxygen, and turbidity, YSI offers unique sensors including total algae plus chlorophyll, fDOM, Rhodamine, and the NitraLED UV nitrate sensor which is exclusive to the EXO platform.

Big things really do come in small packages. And with the EXO-S series, you have more options than ever for reliable water quality data collection.

[theguncollective]

Got a quick hands on with the EXO1 p320 chassis! Interesting concept! @echo5training #guns #freedom #shotshow2018 #theguncollective

[alvis2160]

【活動REPO】夏祭り＝沒好事！

今年夏天的ファフナー活動。從一開始就有種多災多難的感覺。

包括活動開始前１個月才放出時間地點，

活動開始前半個月才開始售票，

完全沒有安排物販，

明明是主役，但石井跟松本竟然是活動發表後才說會來之類的

總之就是你們到底想不想狠狠的坑一下島民們啊。問號。

但我還是去了。很拼命的安排兩天一夜急行軍行程。

這次的會場安排成夏季祭典的樣子。

開場前快拍1張。

1. 開場

先放個PV。

2. 來賓出場

包含MC在內全體來賓穿浴衣出場。MC是King Record的製作人，開場介紹的時候聽得出很緊張，然後他其實有點拉不住這群不受控制的來賓（特別是某些人）……

喜安先生是第一個，出場時還先從布簾後面探頭出來。接著依序是石井、松本、白石、新井和石川。

喜安自我介紹時，後面的大螢幕上放的是上面那個PV中小總（14）歲一臉得意的鏡頭，觀眾大笑，

喜安「奇怪，我不過就是自報名號而已，大家為什麼笑？」

但他轉頭的時候螢幕已經換成拍現場。

接下來是石井，後面放的是黑色長外套的一騎，觀眾反應很正常

喜安「 為什麼反應差這麼多，剛才我後面放什麼？是小的嗎？」

松本放的是戰鬥畫面的真矢，感想是「好普通」

白石放的是系統裡中年發福版的劍司，觀眾又大笑

白石「他跟他裡面的人越來越接近了」

新井跟石川放的則是玩兒子的咲良，還有戰鬥中的美三香。

3.  名場面回顧+現場配音

無印1話「我們要去哪裡」「樂園」

無印10話「fafner跟我們哪個重要」

無印16話「5秒待て」

無印23話（總士X9）

無印26話「只要我跟你就一定能飛」

HAE（開頭跟結��）

EXO1話(招待糖果跟煮皆城燉菜)

EXO9話「你做了和平的夢嗎」及「で、それだけか」還有「這就是我的祝福」

EXO10話「向我跟遠見道歉」

EXO25話「回歸於無吧」

EXO26話一騎和總士的最後道別

以下是花絮

3-1（無印1話及10話）

大家談14年前的表現跟作畫(特別是總士頭髮飛起來那邊)

喜安(不愧是寫劇本的)分析一大串，結果松本只說一句「是因為年輕吧」。

3-2（無印10話）

松本「這邊的一騎講的台詞很女孩子氣」

石井「工作跟我哪個重要？之類的」

松本「因為你最喜歡人家」

石井「啊所以那是因為」

松本「喜歡對吧」

石井「啊所以那個」

松本「大家看他拼命辯解耶」

3-3（ 無印23話）

石井「當初的劇本是寫半狂亂狀態」

喜安「這邊怎麼聽怎麼發毛」

石井「這場景你（總士）已經不在了，應該不會聽到才對」

喜安「可是喜安會聽到呀！你當初包含事前練習排練修正，到OK為止至少錄了4遍，激昂度都完全一樣！」

3-4（EXO9話）

石井「一點也不和平」

3-5（EXO9話）

這邊大家談到劇本，喜安把他那一份的劇本打開讓攝影機拍總士那句「で、それだけか」，因為上面有他自己做筆記的痕跡，大家就開始談自己做筆記的習慣。像新井是會畫起來。

松本「蒼穹是我第一部動畫配音作品，當初我加入時真的完全都搞不懂，所以我就會在現場像這樣（偷瞄旁邊），看別人怎麼作筆記就怎麼寫，現在呢我已經達到專業水準了。」

石川會在有自己台詞的地方做很多筆記。

松本「變成球之後也有台詞嗎？」

石川「沒有！可是還是會幫忙！」

3-6

從名場面列表就會發現，所有的現場錄音都是石井跟喜安上去唸，而且不是一直站著，而是念完兩三段之後下來，聊一下，再被叫上去唸，因此兩人抗議

松本「fafner就是主角要多做點事」

白石跟新井跟石川坐旁邊看戲。

  4. 上新圖時間

眾人開始對BEYOND的圖品頭論足。

4-1 大家都看慣的舊首頁圖

喜安「那個背景應該要有ゴゴゴゴゴ、或者オラオラオラオラ」

白石「變成別的作品了！」

松本「所以你是配上面那個還是下面那個？」

喜安「兩個都是呀！」

松本「所以這個你也可以？」

喜安「可以」 

4-2 新的首頁圖

松本「後面那是幽靈嗎？」

石井「總士真的很喜歡穿領子很高的衣服」

白石「那個瓦礫看來有夠不祥」

4-3新圖（小總（2歲）趴在一騎的背上睡覺）

松本「喜安，你有練習嗎？」

喜安「有哇！」

松本「所以這個小的你也可以？」

喜安「不，這個沒有排我」

松本「你明明就有兩年可以練習」

喜安「有啦！(發出鼾聲)」

5. THE BE 音頭

MC「接下來這個單元，是石井先生」

（台下騷動：他要RAP了要RAP了）

石井「我這次還有配歌喔！」

然後他就唱了一大段ファフナー  ザ ビ音頭，中間混雜RAP，場上每個來賓都點到名，比方說「劍司妳是怎麼回事」或者「咲良當了媽」之類的。

喜安坐在後面一臉虛無，新井跟白石猛拍扇子看戲。

音頭唱完後

松本「認真點好嗎？你看你最重要的那個人一臉悲傷的樣子（鏡頭照喜安），你看看他的眼神多難過（鏡頭又照喜安）完全就是受傷的樣子（鏡頭繼續照喜安）」

石井「耶，我傷到他了嗎」

松本「一騎，去跟他道歉」

石井（走到喜安背後）「總士，對不起，我傷到你了，我要怎麼做你才會原諒我呢？看起來我好像只有這樣才行（伸手要去抱喜安肩膀）」

這時有人出聲打斷（好像是白石，但因為話題沒接下去，石井又伸手要去抱喜安肩膀

松本「（站起來）一騎」

石井「遠見！？」

松本「啊，抱歉，我打斷你們」

喜安「（爆發）向我和遠見道歉！」

石井「我的遠見？」

喜安「我和遠見！」

松本「皆城，你要好好支持一騎」

喜安「（怒）就是因為你在那邊猶豫不決才會變成這樣！」

松本「沒事的，一騎，坐下，皆城，說句話吧」 

喜安（裝模作樣地重重歎一口氣） 

6. 再度開始現場配音

這回上場的是白石跟新井，配無印21話劍司跟咲良告白的景，還有EXO19話二人結婚的段落，白石跟新井一面配一面笑場。

白石「站上去才知道有多羞恥！」

7. 紀念逝去的同伴

這裡族繁不及備載，全都是EXO的，沒有無印，從廣登、暉，一直到最終話的弓子跟艾梅莉都有收錄。

這裡最狠毒的莫過於在所有便當片段都結束之後才放第17話結尾卡農消失的段落，放到這裡時四面八方都響起抽泣聲。我算是撐最久的，但是還是在最後巧克力高聲長吠的時候陷落（泣）。

8. 神秘嘉賓：angela

愛すること

ファフナー ザ ビ音頭

Shangri-La

atsuko「 蒼穹當然就應該要有angela！ 我們今天稍早在紅磚倉庫那邊喝檸檬沙瓦，然後接到電話說你們現在有空嗎？所以我們就來了！」

katsu「 以上純屬虛構，不是真實！」

atsuko「我來時發現我要在那麼悲傷的段落(卡農)後面出場，壓力好大！還有，我在後台聽到石井唱音頭，想說這人這樣行嗎，所以我也來學他一下！」

katsu「以前石井唱RAP，把蒼穹のファフナー變成肉球のファフニャー的時候我就想說這應該到頂了，沒想到今年他又超越了！他明明以前不是這樣的人啊！」

9. 來點新情報

9-1 THE BEYOND主題曲決定是angela

atsuko「音頭嗎？」

katsu「不行！」

9-2 究極的CDBOX跟DVD BOX

石井「該不會連那些角色歌都有收？」

MC「就是全部都有收！」

9-3 HEAVEN AND EARTH 4D

9-4  1229總士生誕祭

喜安「小總不是說12月初嗎，總士本人是1227怎麼活動還往後延！」

MC「抱歉，場地檔期喬不出來」

松本「（拉住石井）欸我從之前就覺得不公平，為什麼只有皆城用那麼大的場地，啊我們呢？」

白石&新井「你們有啥好抱怨看看我們好嗎我們哪有活動連角色歌都沒有耶」

（現場吵成一團）

10. 收場（每個人都講很多，主要是回顧14年的歷史，但我大多都忘了）

11. THE BEYOND 明年開始上映，共12話

[peachixfn]

i lobe him s o much i can't believe i saw him in person, his forehead looks so much better in person, he was literally glowing. HE WAVED AT ME! I PUT UP MY PHONE AND MY LIGHTSTICK AND YELLED OUT CHEN SO LOUD MY VOICE CRACKED and looked a t me and WAVED. i literally died and wanted to cry on my gf. HE'S ALSO SUPER SKINNy his legs, man and his butt all a+ i have pictures where he was yelling and jumping but they're all blurry :( this is the only photo i got and im never deleting it bc his forehead shows and he's doin his lil smile but that is all, i will make one abt sehun where he didnt notice me and i pretended not to b hurt abt it

[tachtutor]

Avoidance of Ribonucleotide-Induced Mutations by RNase H2 and Srs2-Exo1 Mechanisms

Avoidance of Ribonucleotide-Induced Mutations by RNase H2 and Srs2-Exo1 Mechanisms

[ad_1] https://www.ncbi.nlm.nih.gov/pubmed/24896181 [ad_2]

[videomitch]

Gare Lucien-L’Allier, Montreal

Terminus on the (former) Canadian Pacific main line. It sees services from lines exo1 Vaudreuil–Hudson, exo2 Saint-Jérôme & exo4 Candiac lines.

Built on part of the former Gare Windsor, most of which was consumed by the Centre Bell. Passenger facilities are minimal!

[cancersfakianakis1]

A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics

The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterize this heterogeneous disease by combining transcriptomics and genomics data, with the aim of revealing convergent pathway dependencies with the potential for treatment intervention. A Bayesian algorithm was used to integrate molecular profiles in two TNBC cohorts, followed by validation using five independent cohorts (n = 1,168), including three clinical trials. A four-gene decision tree signature was identified, which robustly classified TNBCs into six subtypes. All four genes in the signature (EXO1, TP53BP2, FOXM1, and RSU1) are associated with either genomic instability, malignant growth, or treatment response. One of the six subtypes, MC6, encompassed the largest proportion of tumors (~50%) in early diagnosed TNBCs. In TNBC patients with metastatic disease, the MC6 proportion was reduced to 25%, and was independently associated with a higher response rate to platinum-based chemotherapy. In TNBC cell line data, platinum sensitivity was recapitulated, and a sensitivity to the inhibition of the phosphatase PPM1D was revealed. Molecularly, MC6-TNBCs displayed high levels of telomeric allelic imbalances, enrichment of CD4+ and CD8+ immune signatures, and reduced expression of genes negatively regulating the MAPK signaling pathway. These observations suggest that our integrative classification approach may identify TNBC patients with discernible and theoretically pharmacologically tractable features that merit further studies in prospective trials.

http://bit.ly/2AAVQIf

[borntocode42-blog]

Day 02

Je repars, determinée en mode warrior. Je termine le day 00 et le push.. un bon 5/20 se pointe dû a un espace oublié et a un saut de ligne en trop. Je recommence et je re-push la meme.. sachant qu'il y avait une faute au niveau des octets sur une ligne d'un de mes codes mais la moulinette a fait passer ça pour un OK.. Apparemment la moulinette a toujours raison mais mes trois correcteurs ont, jusqu'a present, compter faux.. je ne sais plus qui croire, ni quoi faire. J'attends demain pour que la moulinette passe une seconde fois sur mon day 00. Un peu compliqué. Je push mon day 01 egalement mais bien evidemment.. mon correcteur arrive pour me corriger et a mon exo1 grosse faute. Un oubli de s pour le “sed”.. mettons ça sur le compte de la fatigue. En fin d'apres midi, on sait dis qu'on allait regarder des videos sur du C. Car bien evidemment avec les day 02 & 03 commence le langage C. J'ai vu plus flou que pour le Shell. Clairement !! Je n'y comprends absolument R-I-E-N. Sachant que nous avons notre premier exam machin 00 ce Vendredi soir durant 4 heures sur di C et que nous avons un rush ce week-end en C toujours.. je crains le pire.. •"La réussite est liée à la patience mais elle dépend également de beaucoup de bonne volonté.“ -Gilbert Brévart.

[epigen-papers]

Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners.

Pubmed: http://dlvr.it/QdSwQW