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For Those Times When You Just Really Hate Something




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Have You Met Donald Trump's Imaginary Friend Jim?

It's been a fun week for political memes. While Donald Trump's friend "Jim" has been the subject of skepticism since as early as 2016, the marvelous mystery has once again been thrust into the spotlight by the Associated Press. Their July 13th piece, "Trump in Paris: The curious case of his friend Jim" was covered by outlets such as HuffPo and the AV Club, and inspired a healthy number of Twitter jokes. We've put together the most noteworthy Jim jokes from the past year, for your convenient viewing pleasure. 




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'Today Years Old' Revelations That Might Teach Something New

The saying "you learn something new every day" may not always feel true, but on Twitter, that's definitely the case. People are very eager to share surprising and little-known facts that blow their minds - whether they're political or about something as trivial as the flavor of green Haribo gummy bears. These facts might not be revelatory for everyone, but they definitely aren't common knowledge. And it's nice to make that brain feel a little bigger. 




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Are women really no better off in the workplace after #MeToo?

The #MeToo movement seemed poised to help us create more equitable workplaces — where women thrive as much as men. Unfortunately, we have yet to see this come to fruition in any significant way. And, in some cases, the backlash has made it even more difficult for women to get ahead. The hashtag #MeToo was […]

The post Are women really no better off in the workplace after #MeToo? appeared first on DiversityJobs.com.




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The Best Way to Remove Coffee and Tea Stains from Mugs: Foolproof Methods Revealed

Discover simple yet effective methods to remove coffee and tea stains from mugs, maintaining their shine and cleanliness. Our article offers practical steps and household products you can use, helping you enjoy your beverages stain-free. Goodbye, stubborn stains!

The post The Best Way to Remove Coffee and Tea Stains from Mugs: Foolproof Methods Revealed appeared first on Unclutterer.




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Bitcoin pushes past $90K amid meteoric 24-hour rally




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An all-new 650 hp Cadillac, Hertz is selling off more EVs, and something weird at Tesla

On today’s exciting episode of Quick Charge, we’ve got the Vistiq! It’s all-new, three row SUV from Cadillac that packs 650 hp and can go from 0-60 mph in under 3.5 seconds, a serious word from Rivian, and something fishy at Tesla. We’ve also got word that Hertz is selling off even more of its…




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'Crumb trails' of meteoroids could reveal potentially dangerous comets years before they reach Earth

Potentially dangerous comets could be spotted many years in advance by following the meteoroid trails they leave near Earth, new research shows.




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Computing orientation with complex multiplication but without trigonometric function

Today’s methods for computing orientation are quaternion and rotation matrix. However, their efficiencies are tarnished by the complexity of the rotation matrix and the counterintuitivity of quaternion. A better method is presented here. It uses complex multiplication for rotating vectors in 3D space and can compute orientation without angle and trigonometric functions, which is simple,...




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Trajectory of ‘Oumuamua and wandering Sun, alien asteroids and comets detected by SOHO

The apparent non‑gravitational acceleration the extra-solar-system ‘Oumuamua exhibits is puzzling. We find that when the position and velocity of the Sun is correctly set in computing the predicted orbit, ‘Oumuamua’s trajectory can be explained with gravity and we have reproduced the unexpected gap by computation. We also propose to search for new extra-solar-system high speed...




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Transforming Our Complaints into Something Generative

By Leo Babauta Something that has long been a struggle for me is when people complain a lot — I really don’t love the negative energy, and I tend to turn away from people who are complaining. So I’ve been examining this in recent years … and I’ve been learning a lot about myself. The […]

The post Transforming Our Complaints into Something Generative appeared first on zen habits.



  • Intimacy & Whole-Hearted Connection

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The First Time You'll Want to Click On Something About the Movie 'Pixel'




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Shaded Metallic Thread Sets – They’re Fabulous!

Last week, I briefly mentioned the shaded metallic thread sets from Au Ver a Soie that I’m so happy to …




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Meta Quest 3 Pre-Order Bonuses

Best Buy

https://cag.vg/metaquest3

 

Newegg

 

 

Asgard’s Wrath 2 free when you buy Meta Quest 3*

Also, get a 6-month trial of BBY’s VR subscription included when you purchase a 512GB headset**

Offer ends 1/27/24; terms apply.

**Eligibility and auto-renewal terms apply for trial subscription. See full terms.

 

 




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Meta Quest Deals & Discussion

I thought I'd just start a new topic since they changed from Oculus to Meta nearly two years ago.

 

At any rate, meta was kind enough to give us a few weekly deals.




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Impact of antiretroviral therapy on liver disease progression and mortality in patients co-infected with HIV and hepatitis C: systematic review and meta-analysis

Systematic review produced by the EPPI-Centre in 2015.This systematic review aimed to evaluate the effect of HAART and ARV monotherapy on liver disease progression and liver-related mortality in individuals co-infected with HIV and hepatitis C, including in patients with haemophilia.




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F&S zijn blij met hun fatbike (NRC, vr, 23-08-24)




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F&S gaan stoppen met foksuk.nl (NRC, ma, 09-09-24)




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McAlvany Precious Metals

This substack is brought to you by McAlvany Precious Metals




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Elevate Your Curtains Instantly with This Simple Pelmet DIY

Sometimes the best hacks are the ones hiding in plain sight, just waiting for a bright spark to shine light on it. Süreyya Tuncer of @sues_daily took a simple IKEA MOSSLANDA picture ledge and turned it into an affordable curtain pelmet. I’ve come across lots of picture ledge hacks over the years but this is the first time I’ve seen it used this way. It’s a straightforward repurposing of the ledge yet this simple twist made a stark difference. Süreyya […]

The post Elevate Your Curtains Instantly with This Simple Pelmet DIY appeared first on IKEA Hackers.





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Leonid meteor shower 2024: How to spot 'shooting stars' and 'fireballs' over the US this week

The Leonid meteor shower peaks in North America overnight from Nov. 17 to 18, with fast-moving fireballs possible in US skies.




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South Korea Fines Meta $15.67M for Illegally Sharing Sensitive User Data with Advertisers

Meta has been fined 21.62 billion won ($15.67 million) by South Korea's data privacy watchdog for illegally collecting sensitive personal information from Facebook users, including data about their political views and sexual orientation, and sharing it with advertisers without their consent. The country's Personal Information Protection Commission (PIPC) said Meta gathered information such as




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“Sometimes We Can’t See Ourselves As What We Are”: Director Naoko Yamada On Why She Made ‘The Colors Within’

"It’s wonderful to find somebody who can show us this positive side of ourselves," Yamada says of the idea behind her new film.




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Check Out: New Helmets, Knee Pads, Alloy Wheels, High Rise Bars, & More



A look at the latest gear to cross our desks.
( Photos: 18, Comments: 88 )




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Mega meteorite tore up seabed and boiled Earth's oceans

It was 200 times bigger than the one that wiped out the dinosaurs nearly three billion years later.




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Skies to clear for Taurid meteor shower peak on Monday

The Northern Taurids are at their peak on 11-12 November - but will the clouds part to let us see them?




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'Dreams do come true': When Riley met Ryan Reynolds

Riley, who has cancer, is surprised after an online appeal to meet the Marvel star.




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The full list of major US companies slashing staff this year, including Goldman Sachs, Meta, and Chegg

Companies have continued to cut jobs in 2024 after a wave of layoffs last year. Meta, Goldman Sachs, Google, and Tesla are among those shedding staff.





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News24 | Fraser's Phala Phala claims something from a movie, but baseless, says Ramaphosa's lawyer

President Cyril Ramaphosa's lawyers say former spy boss Arthur Fraser's claims about the Phala Phala break-in are like something from a movie - but are founded on nothing more than baseless speculation.




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The singularity probability of a random symmetric matrix is exponentially small

Marcelo Campos, Matthew Jenssen, Marcus Michelen and Julian Sahasrabudhe
J. Amer. Math. Soc. 38 (), 179-224.
Abstract, references and article information




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A novel method produces native light-harvesting complex II aggregates from the photosynthetic membrane revealing their role in nonphotochemical quenching [Bioenergetics]

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.




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Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources]

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.




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Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...




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Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).




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Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function [Signal Transduction]

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phosphorylated on IQGAP1 when phosphotyrosine phosphatase activity was inhibited in cells. IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. To investigate the biological sequelae of phosphorylation, we generated a nonphosphorylatable IQGAP1 construct by replacing Tyr-1510 with alanine. The ability of hepatocyte growth factor, the ligand for MET, to promote AKT activation and cell migration was significantly greater when IQGAP1-null cells were reconstituted with IQGAP1 Y1510A than when cells were reconstituted with WT IQGAP1. Collectively, our data suggest that phosphorylation of Tyr-1510 of IQGAP1 alters cell function. Because increased MET signaling is implicated in the development and progression of several types of carcinoma, IQGAP1 may be a potential therapeutic target in selected malignancies.




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Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources




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Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research




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In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy

Ivan Matic
Jan 1, 2008; 7:132-144
Research




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Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




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Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research




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Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics

William M. Old
Oct 1, 2005; 4:1487-1502
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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Parts per Million Mass Accuracy on an Orbitrap Mass Spectrometer via Lock Mass Injection into a C-trap

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology




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#MeToo, A Year On




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Undercurrents: Episode 20 - #MeToo and the Power of Women's Anger




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Cybersecurity Series: Exploring Methods of Internet Censorship and Control