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Vāzhahnāmah-i Pābīkā (shāmil-i Dū hazār va chahār ṣad lughat-i mushtarak-i Bakhtiyārī - Ingilīsī hamrāh bā tarjumah va tafsīr).

Location: Main Library- PK6393.L67S58 2015




mr

Resistive switching : from fundamentals of nanoionic redox processes to memristive device applications

Location: Engineering Library- TK7874.84.R47 2016




mr

Gene Proximity to Nuclear Speckles Drives Efficient mRNA Splicing

Nuclear architecture investigation provides insights into the role of nuclear bodies in RNA processing.



  • News
  • News & Opinion

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Nats second baseman Danny Espinosa undergoes MRIs

Nationals second baseman Danny Espinosa underwent MRIs on both his left shoulder and his right wrist on Wednesday.




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British period dramedy Mrs. Harris Goes to Paris tries a bit too hard to win over its audience

There's a fine line between sweet and cloying, and the British dramedy Mrs. Harris Goes to Paris crosses it a little too often…



  • Screen/Movie Reviews


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Mr. Fix SOS: la plataforma para encontrar técnicos




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PERFORMANCE / TOUR: Rick Bogart Releases 5th Album 'Rick Bogart Sings Mr. Paganini' - Debut Performance at Backstage Tavern on Friday, November 8

Acclaimed jazz clarinetist and vocalist Rick Bogart is thrilled to announce the release of his highly anticipated new album as a tribute to Ella Fitzgerald, Rick Bogart Sings Mr. Paganini, now available on all streaming platforms...




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SEMrush IPO (SEMR)

On Wednesday SEMrush priced their IPO at $14 a share & listed Thursday.

There have been many marketing and online advertising companies which are publicly traded, but few that were so focused specifically on SEO while having a sizeable market cap. According to this SeekingAlpha post at the IPO price SEMrush had a valuation of about $1.95 to $1.99 billion. For comparison sake, here are some other companies & valuations.

  • Facebook acquired Instagram for $1 billion.
  • Google acquired YouTube for $1.65 billion.
  • Yelp trades at around a $2.9 billion market cap.
  • Yahoo! was acquired by Verizon for $4.48 billion.
  • Hubspot has a market cap of around $20.4 billion.

A couple years ago Gannett bought AdWords reseller WordStream. A few years before that they bought ReachLocal. The Hearst publishing empire also bought iCrossing long ago. Marin Software remains publicly traded, but they are only valued at about $20 million.

Newspapers reselling Google AdWords ads isn't really SEO though. Beyond those sorts of deals, many of the publicly traded SEO stuff has been only tangentially relevant to SEO, or crap.

There are some quality category-leading publishers which use SEO as a means of distribution but are not necessarily an SEO service provider like TripAdvisor, BankRate, and WebMD. Over time many of these sorts of companies have been gobbled up by Red Ventures or various private equity firms. Zillow, Yelp and TripAdvisor are some of the few examples which still exist as independent companies.

So that puts most of the publicly traded SEO stuff in one of the following categories...

  • small scale - does anyone other than Andy Beal & Mike Grehan still remember KeywordRanking / WebSourced / Think Interactive / MarketSmart Interactive?
  • hope and nope - sites like Business.com were repeatedly acquired but never really gained lasting relevance.
  • affiliate networks - which reliant on partners with SEO traffic like Quinstreet & Commission Junction. many affiliate networks were hit hard as the barrier to entry in SEO increased over the years. Quinstreet is doing well in some verticals but sold their education division to Education Dynamics for $20 million. CJ was part of the Publicis Groupe acquisition of Epsilon.
  • pump and dump scams - Demand Media, owner of eHow, which later rebranded as Leaf Group & still trades at a small fraction of their IPO price.

[Editorial note: 8 days after writing this post LEAF announced a $304.3 million all cash buyout offer from Graham Holdings at 21% above current market prices and was trading at $8.63 a share. If you bought shares at $40 or $30 or $20 and hoped it would at some point come back - nope - the losses are crystalized on a take out. Graham Holdings formerly owned the Washington Post but sold it to Jeff Bezos 8 years ago for $250 million.]

The one lasting counter-example to the above is Barry Diller's IAC. [edit: added ... here is the WSJ recommending the stock 3 months later, even after a big run]

IAC's innovation ecosystem is surreal. Across time & across markets Diller is the best creator of vertical leading properties later spun off as their own companies. He's owned Expedia, TripAdvisor, LendingTree, HomeAdvisor, Match.com, TicketMaster and so many other category leaders.

His buying of Ask.com did not pan out as well as hoped as web browsers turned the address bar into a search box, his ability to differentiate the service went away after they shut down the engine in 2008, he was locked out of mobile search marketshare by default placement contracts & Google pushed back against extension bundling, but just about everything else he touched turned to gold.

A lot of IAC's current market cap is their ownership of Vimeo, which by itself is valued at $6 billion.

[Added a section on Vimeo here since it was spun out after this post was originally published.] Vimeo was a throw in when IAC bought CollegeHumor owner Connected Ventures. IAC was willing to sell Vimeo to Kodak for around $10 million over a decade ago, but there was no transaction. Around that time I ran a membership website here and we were going to use Vimeo for delivery of our videos but they deleted our paid subscription claiming Vimeo wasn't for businesses and was just for artistic uses. They probably did that hundreds or thousands of times over the years and then realized ... wait, we should allow businesses to use this, everyone else will just upload to YouTube. So they switched focus to business use, YouTube kept increasing ad load, and Vimeo kept becoming more appealing on a relative basis. This year YouTube updated their terms of service allowing them to monetize and and all uploaded videos, which only makes Vimeo look that much more appealing to businesses which are on the fence about paying a small monthly subscription for video hosting. When IAC spun out Vimeo this year (VMEO) it was valued at north of $6 billion. Someone like Microsoft could buy it and promote it in Bing search results the way Google does YouTube.

What is the most recent big bet for Barry Diller? MGM. Last August he bet $1 billion on the growth of online gambling. And he was willing to bet another billion to help them acquire Entain:

IAC has to date invested approximately US$1 billion in MGM with an initial investment thesis of accelerating MGM’s penetration of the $450 billion global gaming market. IAC notes in its letter of intent that IAC continues to strongly support this objective for MGM whether or not a transaction with Entain is consummated.

Barry Diller not only accurately projects future trends, but he also has the ability to rehab broken companies past their due dates.

The New York Times bought About.com for $410 million in 2005 & did little with it as its relevance declined over time as its content got stale, Wikipedia grew and search engines kept putting more scraped content in the search results. The relentless growth of Wikipedia and Google launching "universal search" in 2007 diminished the value of About.com even as web usage was exploding.

IAC bought About.com from the New York Times for $300 million in August of 2012. They tried to grow it through improving usability, content depth and content quality but ultimately decided to blow it up.

They were bold enough to break it into vertical category branded sites. They've done amazingly well with it and in many cases they rank 2, 3, 4 times in the SERPs with different properties like TheSpruce, TheBalance, Investopedia, etc. As newspapers chains keep consolidating or going under, IAC is one of the few constant "always wins" online publishers.

At its peak TheBalance was getting roughly 2/3 the traffic About.com generated.

Part of the decline in the chart there was perhaps a Panda hit, but the reason traffic never fully recovered is they broke some of these category sites into niche sites using sub-brands.

All the above search traffic estimate trend charts are from SEMrush. :)

I could do a blog post titled 1001 ways to use SEMrush if you would like me to, though I haven't yet as I already have affiliate ads for them here and don't want to come across as a shill by overpromoting a tool I love & use regularly.

I tend to sort of "not get" a lot of SaaS stocks in terms of prices and multiples, though they seem to go to infinity and beyond more often than not. I actually like SEMrush more than most though & think they'll do well for years to come. I get the sense with both them and Ahrefs that they were started by programmers who learned marketing rather than started by marketers who cobbled together offerings which they though would sell. If you ever have feedback on ways to improve SEMrush they are fast at integrating it, or at least were in the past whenever I had feedback.

When SEMrush released their S-1 Dan Barker did a quick analysis on Twitter.

Some stats from the S-1: $144 million in annual recurring revenues @ 50% compound annual growth rate, 76% gross margins, nearly 1,000 employees and over 67,000 paying customers.

At some point a lot of tool suits tend to overlap because much of their data either comes from scraping Google or crawling the open web. If something is strong enough of a point of differentiation to where it is widely talked about or marketed then competitors will try to clone it. Thus spending a bit extra on marketing to ensure you have the brand awareness to be the first tool people try is wise. Years ago when I ran a membership site here I paid to license the ability to syndicate some SEMrush data for our members & I have promoted them as an affiliate for what seems like a decade now.

When Dan Barker did his analysis of the S-1 it made me think SEMrush likely has brighter prospects than many would consider. A few of the reasons I could think of off the top of my head:

  • each day their archive of historical data is larger, especially when you consider they crawl many foreign markets which some other competitive research tools ignore
  • increasing ad prices promote SEO by making it relatively cheaper
  • keyword not provided on organic search means third party competitive analysis tools are valuable not only for measuring competitors but also measuring your own site
  • Google Ads has recently started broadening ad targeting further and hiding some keyword data so advertisers are paying for clicks where they are not even aware what the keyword was

That last point speaks to Google's dominance over the search ecosystem. But it is also so absurd that even people who ran AdWords training workshops point out the absurdity.

In Google maximizing their income some nuance is lost for the advertiser who must dig into N-Gram analysis or look at historical data to find patterns to adjust:

The account overall has a CPA in the $450 range. If the word ‘how’ is in the query, our CPA is over double. If someone searches for ‘quote,’ our CPA is under $300. If they ask a question about cost, the CPA is over $1000. Obviously, looking for quotes versus cost data is very different in the eyes of a user, but not in the matching search terms of Google.

Every ad network has incentive to overstate its contribution to awareness and conversions so that more ad budget is allocated to them.

  • Facebook kept having to restate their ad stats around video impressions, user reach, etc.
  • Facebook gave themselves a 28 day window for credit for some app installs.
  • Google AMP accidentally double counted unique users on Google Analytics (drives adoption = good).
  • Google Analytics came with last click attribution, which over-credits the search channel you use near the end of a conversion journey.

There are a lot of Google water carriers who suggest any and all of their actions are at worst benevolent, but when I hear about hiding keyword data I am reminded of the following quote from the Texas AG Google lawsuit.

"Google employees agreed that, in the future, they should not directly lie to publishers, but instead find ways to convince publishers to act against their interest and remove header bidding on their own."

That lawsuit details the great lengths Google went to in order to leverage their search monopoly to keep monopoly profit margins on their display ad serving business.

AMP was created with the explicit intent to kill header bidding as header bidding shifted power and profit margins to publishers. Some publishers saw a 50% rise in ad revenues from header bidding.

Remember how Google made companywide bonuses depend on the performance of the Google Facebook clone named Google+? Google later literally partnered with Facebook on a secret ad deal to prevent Facebook from launching a header bidding solution. The partnership agreement with Facebook explicitly mentioned antitrust repeatedly.

When a company partners with its biggest direct competitor on a bid rigging scheme you can count on it that the intent is to screw others.

So when you see Google talk about benevolence, remember that they promise to no longer lie in the future & only deceive others into working against themselves via other coercive measures.

We went from the observation that you can't copyright facts to promoting opinion instead:

to where after many thousands of journalists have been laid off now the "newspaper of record" is promoting ponzi scheme garbage as a performance art piece:

Is it any wonder people have lost trust in institutions?

The decline of About.com was literally going to be terminal without the work of Barry Diller to revive it. That slide reflected how over time a greater share of searches never actually leave Google:

Of those 5.1T searches, 33.59% resulted in clicks on organic search results. 1.59% resulted in clicks on paid search results. The remaining 64.82% completed a search without a direct, follow-up click to another web property. Searches resulting in a click are much higher on desktop devices (50.75% organic CTR, 2.78% paid CTR). Zero-click searches are much higher on mobile devices (77.22%)

The data from the above study came from SimilarWeb, which is another online marketing competitive research tool planning on going public soon.

Google "debunked" Rand's take by focusing on absolute numbers instead of relative numbers. But if you keep buying default placements in a monopoly ecosystem where everyday more people have access to a computer in their pocket you would expect your marketshare and absolute numbers to increase even if the section of pie other publishers becomes a smaller slice of a bigger pie.

Google's take there is disingenuous at the core. It reminds me of the time when they put out a study claiming brand bidding was beneficial and that it was too complex and expensive for advertisers to set up a scientific study, without any mention of the fact the reason that would be complex and expensive is because Google chooses not to provide those features in their ad offering. That parallels the way they now decide to hide keyword data even from paying advertisers in much the same way they hide ad fees and lie to publishers to protect their ad income.

Google suggests they don't make money from news searches, but if they control most of the display ads technology stack & used search to ram AMP down publishers throats as a technological forced sunk cost while screwing third party ad networks and news publishers, Google can both be technically true in their statement and lying in spirit.

"Google employees agreed that, in the future, they should not directly lie to publishers, but instead find ways to convince publishers to act against their interest and remove header bidding on their own."

There are many more treats in store for publishers.

Google Chrome stopped sending full referrals for most web site visitors late last year. Google will stop supporting third party cookies in Chrome next year. They've even floated the idea of hiding user IP addresses from websites (good luck to those who need to prevent fraud!).

Google claims they also going to stop selling ads where targeting is based on tracking user data across websites:

"Google plans to stop selling ads based on individuals’ browsing across multiple websites, a change that could hasten upheaval in the digital advertising industry. The Alphabet Inc. company said Wednesday that it plans next year to stop using or investing in tracking technologies that uniquely identify web users as they move from site to site across the internet. ... Google had already announced last year that it would remove the most widely used such tracking technology, called third-party cookies, in 2022. But now the company is saying it won’t build alternative tracking technologies, or use those being developed by other entities, to replace third-party cookies for its own ad-buying tools. ... Google says its announcement on Wednesday doesn’t cover its ad tools and unique identifiers for mobile apps, just for websites."

Google stated they would make no replacement for the equivalent of the third party cookie tracking of individual users:

"we continue to get questions about whether Google will join others in the ad tech industry who plan to replace third-party cookies with alternative user-level identifiers. Today, we’re making explicit that once third-party cookies are phased out, we will not build alternate identifiers to track individuals as they browse across the web, nor will we use them in our products. We realize this means other providers may offer a level of user identity for ad tracking across the web that we will not — like PII graphs based on people’s email addresses. We don’t believe these solutions will meet rising consumer expectations for privacy, nor will they stand up to rapidly evolving regulatory restrictions, and therefore aren’t a sustainable long term investment."

On the above announcement, other ad networks tanked, with TheTradeDesk falling 20% in two days.

Competing ad networks wonder if Google will play by their own rules:

“One clarification I’d like to hear from them is whether or not it means there’ll be no login for DBM [a historic name for Google’s DSP], no login for YouTube and no login for Google properties. I’m looking for them to play by the same rules that they so generously foisted upon the rest of the industry,” Magnite CTO Tom Kershaw said.

Regulators are looking into antitrust implications:

"Google’s plan to block a popular web tracking tool called “cookies” is a source of concern for U.S. Justice Department investigators who have been asking advertising industry executives whether the move by the search giant will hobble its smaller rivals, people familiar with the situation said."

The web will continue to grow more complicated, but it isn't going to get any more transparent anytime soon.

"Google employees agreed that, in the future, they should not directly lie to publishers, but instead find ways to convince publishers to act against their interest and remove header bidding on their own."

As the Attention Merchants blur the ecosystem while shifting free clicks over to paid and charging higher ad rates on their owned and operated properties it increases the value of neutral third party measurement services.

The trend is not too hard to notice if you are remotely awake.

While I was writing this post Google announced the launch of a "best things" scraper website featuring their scraped re-representations of hot selling items. And they are cross-promoting competitors in "knowledge" panels to dilute brand values & force the brand ad buy.

Shortly after Google launched their thin affiliate scraper site full of product ads they announced an update to demote other product review sites.

Where Google can get away with it, they will rig things in their favor to rip off other players in the ecosystem:

Google for years operated a secret program that used data from past bids in the company’s digital advertising exchange to allegedly give its own ad-buying system an advantage over competitors, according to court documents filed in a Texas antitrust lawsuit. The program, known as “Project Bernanke,” wasn’t disclosed to publishers who sold ads through Google’s ad-buying systems.

If I could give you one key takeaway here, it would be this:

"Google employees agreed that, in the future, they should not directly lie to publishers, but instead find ways to convince publishers to act against their interest and remove header bidding on their own."

Categories: 




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WMM presents Brock Wilbur & Nick Spacek of The Pitch + Damron Russel Armstrong of The Black Repertory Theatre of Kansas City

Wednesday MidDay Medley Produced and Hosted by Mark Manning Wednesday, November 13, 2024 Brock Wilbur & Nick Spacek of The Pitch + Damron Russel Armstrong of The Black Repertory Theatre […]

The post WMM presents Brock Wilbur & Nick Spacek of The Pitch + Damron Russel Armstrong of The Black Repertory Theatre of Kansas City appeared first on KKFI.




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Connor Bedard, Damar Hamlin, Prince Harry's book, Ozempic, Dry January, portable MRNA vaccine factories & more

Connor Bedard's former coach says the World Junior hockey phenom is something special; how Buffalo is rallying together after Damar Hamlin's near death on the football field; how the bid to keep Prince Harry's memoir from leaking plays into the hype; seriously though, what exactly is Ozempic?; Toronto bartender mixes alcohol-free cocktails for Dry January and beyond; why BioNTech's plan to ship prefabricated mRNA vaccine factories to Rwanda is controversial; and more.



  • Radio/Day 6

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stormrider

But in this process, we must remember something important: life is not meant to be rushed through. It is not a race, nor is it a problem to be solved. It is an experience to be lived, and living well requires presence. To focus on one thing deeply, to give it your full attention, is to experience it fully. And when we do this, something remarkable happens. Time, which so often feels like it is slipping through our fingers, begins to slow. Moments become rich, textured. Even the simplest of tasks takes on a new significance when approached with care, with attention.




mr

Inheritance Fund Scam - Mrs. Martha Moran Sanz

An inheritance fund scammer that requires you to eat the documents to get the funds.




mr

Charity Scam - From Mrs Sulak

Mrs Sulak is dying, but she will always stay alive, long enough for someone to reply. That's 419 scam law!




mr

Lottery Scam - CONTACT MR. MARK VAN JAS

You need to contact Mr Mark Van Jas... but what if you are under the age of 18?




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BHCS MRI Machine Now Fully Operational

Bermuda HealthCare Services [BHCS] announced that their MRI machine is “now fully operational following recent recovery efforts after Hurricane Ernesto’s impact.” A spokesperson said, “With essential services restored, BHCS is ready to accept clients for MRI procedures.” Dr. Ewart Brown, Chairman of BHCS, remarked, “We are delighted to inform the community that our MRI services […]




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BMRA’s Open Track & Race School On Saturday

Motorcycle racing enthusiasts are encouraged to attend the Bermuda Motorcycle Racing Association’s open track and race school on Saturday [April 23]. The event, which starts at 1 pm, will be held at the Rubis Southside Raceway in St David’s. Existing and new members will be able to renew their membership. Related Stories Aeziah Divine Reflects […]




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62 Million Views On Mr Beast Bermuda Video

American YouTuber Mr Beast has filmed one of his popular challenges on the island, entitled: “I buried treasure in the Bermuda Triangle.” Mr Beast, whose real name is Jimmy Donaldson, is one of the biggest social media influencers in the world, with 167 million subscribers on YouTube, 85 million followers on TikTok and 39 million […]




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Ve věku 76 let zemřela bývalá ministryně spravedlnosti Marie Benešová

Ve věku 76 let zemřela bývalá ministryně spravedlnosti a místopředsedkyně sociální demokracie Marie Benešová. České televizi to potvrdila někdejší ústecká hejtmanka Jana Vaňhová, o úmrtí advokátky na síti X informoval také předseda Rady ČTK David Soukup. Benešová se ministryní spravedlnosti stala ve vládě Jiřího Rusnoka od července 2013 do ledna 2014, a potom znovu ve vládě Andreje Babiše od dubna 2019 do prosince 2021, tehdy už ale jako nestranička za hnutí ANO.




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Tragické osudy horolezkyň: Japonku nechali kolegové umrznout, Američanka zemřela s úsměvem na rtech

Sportem ku zdraví, říká se. A k trvalé invaliditě, dodávají jiní. V případě horolezectví to ale může dopadnout mnohem hůř. Všechny ty světově známé vrcholky mají svůj smutný seznam těch, kteří padli při jejich zdolávání. A pochopitelně mezi nimi nechybí ani ženy. Hannelore Schmatz se měla stát první Němkou, která zdolala Mount Everest. Na vrchol se dostala i se svým manželem Gerhardem, jakožto nejstarším pokořitelem hory. Jenže u Everestu je pořádně zrádná i cesta dolů. Hannelore se nakonec stala osudnou.




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Mrowrowr




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Дэн Фэллоуз: Мы до сих пор не можем разобраться с AMR24

Сезон 2024 года складывается для Aston Martin весьма неудачно, и Дэн Фэллоуз, технический директор команды, попытался объяснить, с чем это связано...




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Why Virat Kohli, Jasprit Bumrah were missing from Perth nets; India ramp up privacy amid Manchester United-like security - Hindustan Times

  1. Why Virat Kohli, Jasprit Bumrah were missing from Perth nets; India ramp up privacy amid Manchester United-like security  Hindustan Times
  2. Virat Kohli in focus: Intense net session begins for upcoming Test series against Australia  The Times of India
  3. Virat Kohli in Australia for BGT: A timeline  India Today
  4. Black veil of secrecy: India begin training in privacy in Perth  ESPNcricinfo
  5. India to play intra-squad warm-up match at WACA on Friday ahead of Australia Tests but BCCI denies public viewing  Hindustan Times




mr

mr clompers high five

Today on Married To The Sea: mr clompers high five


This RSS feed is brought to you by Drew and Natalie's podcast Garbage Brain University. Our new series Everything Is Real explores the world of cryptids, aliens, quantum physics, the occult, and more. If you use this RSS feed, please consider supporting us by becoming a patron. Patronage includes membership to our private Discord server and other bonus material non-patrons never see!




mr

ABN Amro Interest Income, Impairment Releases Drive Profit Beat




mr

Mr. Watson — come here — I want to see you

On this day in 1876, shortly after making history, Alexander Graham Bell wrote the following letter to his father. To read his diary entry from that same day, visit Diaries of Note. And don’t forget to sign up for the Letters of Note newsletter. Born in Scotland in 1847, Alexander Graham Bell hailed from a




mr

Werbeaktivitäten der Fraktionen, Sturmreif, “Nius” stockt auf

1. Bundestag will die Öffentlichkeitsarbeit der Fraktionen neu regeln (netzpolitik.org, Martin Schwarzbeck) Der Bundestag plane, noch vor der nächsten Wahl die Regeln für die Öffentlichkeitsarbeit der Fraktionen zu überarbeiten. Der Bundesrechnungshof habe festgestellt, dass viele Social-Media-Aktivitäten der Fraktionen, die eigentlich die parlamentarische Arbeit darstellen sollen, in der Vergangenheit parteipolitische Werbung enthielten. Eine breite Mehrheit der […]



  • 6 vor 9

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Discordant Protein and mRNA Expression in Lung Adenocarcinomas

Guoan Chen
Apr 1, 2002; 1:304-313
Research




mr

Mapping invisible epitopes by NMR spectroscopy [Molecular Biophysics]

Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.




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Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins [Protein Structure and Folding]

Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics.




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Impact of 18F-FDG PET/MRI on Therapeutic Management of Women with Newly Diagnosed Breast Cancer: Results from a Prospective Double-Center Trial

Visual Abstract




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Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI

Visual Abstract




mr

NSun2 promotes cell migration through methylating autotaxin mRNA [Cell Biology]

NSun2 is an RNA methyltransferase introducing 5-methylcytosine into tRNAs, mRNAs, and noncoding RNAs, thereby influencing the levels or function of these RNAs. Autotaxin (ATX) is a secreted glycoprotein and is recognized as a key factor in converting lysophosphatidylcholine into lysophosphatidic acid (LPA). The ATX-LPA axis exerts multiple biological effects in cell survival, migration, proliferation, and differentiation. Here, we show that NSun2 is involved in the regulation of cell migration through methylating ATX mRNA. In the human glioma cell line U87, knockdown of NSun2 decreased ATX protein levels, whereas overexpression of NSun2 elevated ATX protein levels. However, neither overexpression nor knockdown of NSun2 altered ATX mRNA levels. Further studies revealed that NSun2 methylated the 3'-UTR of ATX mRNA at cytosine 2756 in vitro and in vivo. Methylation by NSun2 enhanced ATX mRNA translation. In addition, NSun2-mediated 5-methylcytosine methylation promoted the export of ATX mRNA from nucleus to cytoplasm in an ALYREF-dependent manner. Knockdown of NSun2 suppressed the migration of U87 cells, which was rescued by the addition of LPA. In summary, we identify NSun2-mediated methylation of ATX mRNA as a novel mechanism in the regulation of ATX.




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Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane [Research]

Protein synthesis on the endoplasmic reticulum (ER) requires the dynamic coordination of numerous cellular components. Together, resident ER membrane proteins, cytoplasmic translation factors, and both integral membrane and cytosolic RNA-binding proteins operate in concert with membrane-associated ribosomes to facilitate ER-localized translation. Little is known, however, regarding the spatial organization of ER-localized translation. This question is of growing significance as it is now known that ER-bound ribosomes contribute to secretory, integral membrane, and cytosolic protein synthesis alike. To explore this question, we utilized quantitative proximity proteomics to identify neighboring protein networks for the candidate ribosome interactors SEC61β (subunit of the protein translocase), RPN1 (oligosaccharyltransferase subunit), SEC62 (translocation integral membrane protein), and LRRC59 (ribosome binding integral membrane protein). Biotin labeling time course studies of the four BioID reporters revealed distinct labeling patterns that intensified but only modestly diversified as a function of labeling time, suggesting that the ER membrane is organized into discrete protein interaction domains. Whereas SEC61β and RPN1 reporters identified translocon-associated networks, SEC62 and LRRC59 reporters revealed divergent protein interactomes. Notably, the SEC62 interactome is enriched in redox-linked proteins and ER luminal chaperones, with the latter likely representing proximity to an ER luminal chaperone reflux pathway. In contrast, the LRRC59 interactome is highly enriched in SRP pathway components, translation factors, and ER-localized RNA-binding proteins, uncovering a functional link between LRRC59 and mRNA translation regulation. Importantly, analysis of the LRRC59 interactome by native immunoprecipitation identified similar protein and functional enrichments. Moreover, [35S]-methionine incorporation assays revealed that siRNA silencing of LRRC59 expression reduced steady state translation levels on the ER by ca. 50%, and also impacted steady state translation levels in the cytosol compartment. Collectively, these data reveal a functional domain organization for the ER and identify a key role for LRRC59 in the organization and regulation of local translation.




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Endovascular treatment for acute ischaemic stroke in routine clinical practice: prospective, observational cohort study (MR CLEAN Registry)




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Rammya Mathew: GPs have to be able to request MRI scans for patients in primary care

At a recent clinical meeting, I heard that GPs local to me are about to lose the ability to request magnetic resonance imaging (MRI) scans for patients presenting with musculoskeletal symptoms. We’re instead advised to refer our patients to a musculoskeletal clinical assessment and triage service (CATS)—staffed largely by musculoskeletal advanced practitioners, who will assess our patients and determine whether imaging is warranted.The hope is that fewer patients will have unnecessary imaging and that this will reduce the potential harms of overdiagnosis. Radiologists rarely report musculoskeletal MRI scans as entirely normal, and it can be hard to know what to do with abnormal findings on an MRI. More often than not, patients with abnormal scans are referred to orthopaedic teams, even though there may not necessarily be a surgical target.At a population level, this is problematic on two fronts. Firstly, MRI scans are expensive and need to be used judiciously....




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Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.




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Diagnostic Accuracy of [18F]FDG PET/MRI in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Metaanalysis

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.




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Mapping Human Cortical Areas In Vivo Based on Myelin Content as Revealed by T1- and T2-Weighted MRI

Matthew F. Glasser
Aug 10, 2011; 31:11597-11616
BehavioralSystemsCognitive




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A Novel Directed Seed-Based Connectivity Analysis Toolbox Applied to Human and Marmoset Resting-State FMRI

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the language-network that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis.




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AMR Multi-Stakeholder Partnership Platform - Creating a movement for change through engaging multiple actors and voices

The Tripartite organizations (FAO, OIE, WHO) invite partners to join public discussion on the establishment of the AMR Multi-Stakeholder Partnership Platform.




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Cardiac MRI of an animal that has undergone photosynthetic therapy

Cardiac MRI of an animal that has undergone photosynthetic therapy. CREDIT: Stanford University School of Medicine, Department of Cardiothoracic Surgery




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Revisiting the Unknown Soldier: How a grassroots campaign brought a fallen comrade home

Monday marks the first Remembrance Day ceremony at the National War Memorial in St. John's to include the tomb of the Unknown Soldier. We're proud to present again two documentaries that tell a remarkable story.



  • News/Canada/Nfld. & Labrador

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Mr Plankton Review: The K-Drama Is A Mixed Bag Which Is More Frustrating Than Fulfilling

Mr Plankton Review - The K-drama has the potential to be tighter but the pacing suffers from unnecessary delays and moments of repetitiveness that only serve to dilute the stakes.




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Amrita Rao Celebrates 25 Years In The Entertainment Industry, Cuts Beautiful Cake. Watch

The cake topper read "25 years," and the bottom tier featured snapshots of Amrita's famous movie characters




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Crazy Viral: Shilpa Shetty's Famjam Post With Mr Beast, Logan Paul And KSI

Shilpa Shetty’s son Viaan was excited to meet the social media powerhouses




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Dhadak 2: Triptii Dimri, Siddhant Chaturvedi Start Shooting For Sequel To 2018 Film. See Viral Pics

The first movie released in 2018 and featured Janhvi Kapoor and Ishaan Khatter in the lead roles




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Nimrat Kaur's Latest Insta Entry Is All About Setting Intentions: "Become Clear On What It Is You Wish To Manifest"

She reshared a thoughtful note on the significance of 11/11, a day believed by many to amplify manifestations and focus on setting clear intentions




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Who Was Gursimran Kaur, Indian Teen Found Dead In Walmart Oven

A 19-year-old Indian girl was found burnt to death in a walk-in oven at a Walmart in Halifax on October 19.




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DDR5 12.8Gbps MRDIMM IP: Powering the Future of AI, HPC, and Data Centers

The demand for higher-performance computing is greater than ever. Cutting-edge applications in artificial intelligence (AI), big data analytics, and databases require high-speed memory systems to handle the ever-increasing volumes and complexities of data. Advancements in cloud computing and machine virtualization are stretching the limits of current capabilities. AI applications hosted in the cloud rely on fast access and reduced latency in memory systems, which is amplified by an increasing number of CPU and GPU cores.

Introducing the DDR5 Multiplexed Rank DIMM (MRDIMM), the next-generation memory module technology designed to meet the needs of high-performance computing (HPC) and AI in cloud applications. By leveraging existing DDR5 DRAM memory devices, MRDIMM modules not only double the DRAM data rate but also maintain the RAS capabilities of the industry-proven RDIMM modules, setting a new precedent for memory module performance.

Let’s compare RDIMM and MRDIMM modules using the same DRAM parts. Today, high-speed production DDR5 RDIMM modules run at 5600Mbps. Those modules use DDR5 DRAM parts, which also run at 5600Mbps. An MRDIMM module using the same DDR5 5600Mbps DRAM parts will run at a blazing 11.2Gbps.

One key metric for best-in-class performance, low bit error rate (BER), and ease of adoption is the eye diagram. The eye diagram illustrates at-speed system margin and accurately represents DDR system quality when captured with a pseudo-random binary sequence (PRBS)-like pattern. The diagram below illustrates Cadence’s 3nm silicon write eye diagram for DDR5 MRDIMM IP running at 12.8Gbps.

Cadence 3nm DDR5 MRDIMM 12.8Gbps test chip write eye diagram, design kit is available today

The eye diagram is captured using a PRBS-like pattern, incorporating a package and system board representative of a typical MRDIMM channel. Using PRBS-like patterns is crucial for capturing accurate eye diagrams. Repetitive clock-like data patterns create deceptively “open eyes” that do not reflect the real system performance. Effects like intersymbol interference, simultaneous switching, reflections, and crosstalk are not accurately reflected in the eye diagrams for parallel interfaces like DDR using non-random data streams. Relying on improperly captured eye diagrams inevitably leads to a significantly worse real system BER than conveyed by that eye diagram.

Doubling the DDR5 RDIMM data rate is challenging. Achieving high performance while optimizing for area and power requires multiple design techniques. Feed-forward equalization (FFE), decision feedback equalization (DFE), continuous-time linear equalization (CTLE), and T-coils are required to reach 12.8Gbps MRDIMM data rates in multi-channel systems. Building a production-worthy 12.8Gbps DDR5 MRDIMM IP requires engineering expertise that comes from many generations of memory interface design and production experience. Cadence has developed this expertise through multiple DDR5/4, LPDDR5X/5, and GDDR6 designs in different technology nodes and foundries. For instance, Cadence’s GDDR6 IP is available in three foundries and ten process nodes, with mass production at speeds exceeding 22Gbps.

For your next project, consider DDR5 12.8Gbps MRDIMM, a technology that not only doubles the bandwidth of DDR5 RDIMM but also promises rapid proliferation into next-generation AI, data center, HPC, and enterprise applications. With its cutting-edge capabilities, the Cadence DDR5 12.8Gbps MRDIMM IP is ready to power the future of computing.