Hot off Twitter.  Prices may be fluctuating and cards may go in and out of stock.
 

From 11/17 until 12/14, get $25 off future grocery purchase when you buy $150+ in gift cards. Includes PSN, xbox, gamestop, and other random retailers.

16.6% discount on gaming credit if you were getting groceries anyway. Promos are usually valid at all regional Albertson affiliates. Star Market, Acme, Vons, etc.

Eneba has $70 Xbox Gift Card (Digital Delivery) for around $59 after applying code X70US in cart.

• Note: Price is after service fees and applying code X70US in cart.

You can purchase the code(s) and redeem to add balance to your Microsoft account.

• Both the Microsoft and Xbox cards work just the same. Once redeemed to your Microsoft account, you can spend your balance at Microsoft Store online, on Windows, and on Xbox. You can get the latest apps, games, movies, TV shows, and Surface, Xbox, and accessories. (Source)

Add balance to your Microsoft account and use to purchase items from Microsoft Store online. Black Friday deals from Microsoft Store can be found here.
 

Note:

• Price is after service fees and applying discount code X70US.
• Deals ends tonight.
• Eneba codes usually sell out fast.
• Xbox Gift cards do not currently work at physical Microsoft Stores.
• You currently cannot buy Microsoft 365 with a gift card.

Eneba has Xbox Game Pass Ultimate – 3 Month Membership (Digital Delivery) on sale for around $28 when you follow the instructions below.

• Note: You can stack up to three years of Game Pass Ultimate Membership.

Deal Instructions:

• Visit the product page
• Click 'Buy Now' to add the item to cart
• Click on "Got discount code?" Apply discount code GamePassBF
• Proceed to checkout
• Select a payment method: PayPal or Credit Card (a service fee will be applied on this step)
• Price after discount and service fee will be ~$28
• Note: Price is subject to change by a few cents due to currency exchange rate volatility
• After purchase, redeem the Membership code at Microsoft

​

Eneba also has $100 Amazon Gift Card (Digital Delivery) on sale for around $94 when you follow the instructions below.

Deal Instructions:

• Visit the product page
• Click 'Buy Now' to add the item to cart
• Click on "Got discount code?" Apply discount code USBFAMZ
• Proceed to checkout
• Select a payment method: PayPal or Credit Card (a service fee will be applied on this step)
• Price after discount and service fee will be ~$94
  • Note: Price is subject to change by a few cents due to currency exchange rate volatility
• After purchase, redeem the Gift Card code at Amazon

Eneba has $99 Nintendo eShop Gift Card (Digital Delivery) on sale for around $85 when you follow the instructions below.

Eneba also has $50 PlayStation Network Gift Card (Digital Delivery) on sale for around $43 when you follow the instructions below.

Deal Instructions:

• Visit the product page
• Click 'Buy Now' to add the item to cart
• Click on "Got discount code?" Apply discount code USBFPSN
• Proceed to checkout
• Select a payment method: PayPal or Credit Card (a service fee will be applied on this step)
• Price after discount and service fee will be ~$43
  • Note: Price is subject to change by a few cents due to currency exchange rate volatility
• After purchase, redeem the Gift Card code at PlayStation

About:

• Buy a PlayStation Store gift card and redeem for anything on PlayStation Store: games, add-ons, subscriptions and more. Codes can be redeemed on the PlayStation Store via console, any web browser or on the PlayStation App.
• Please note that PlayStation Store digital gift cards are not redeemable at direct.playstation.com

Princeton University will present the honors at Alumni Day, scheduled for Feb. 22, 2025.

England's Laurie Canter tells BBC Sport's Iain Carter he feels "lucky" to be in the mix to win one of 10 lucrative PGA Tour cards at the DP World Tour's season finale in Dubai.

Latest scorecard from the Women's Big Bash League match between Sydney Thunder and Perth Scorchers at Sydney's Drummoyne Oval.

Molly McGregor, 29, was fined £450 for not showing her railcard during a rail journey in May.

She likes Kamala's polices enough to put a lawn sign up on her property, but when one toll with a postcard personalizes those policies... she loses it.

The post Harris Supporter Outraged By Postcard Trolling… Did They Go Too Far? appeared first on Clash Daily.

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

Expert

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N and C termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N and C terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LC variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LC processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.

Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications. Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, for example HexNAc(2)Hex(5) rather than man5. Even at this level, however, glycopeptide analysis poses challenges:  finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.  Here we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues. Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, for example, at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, for example, ± 0.01 Daltons. Also new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans. Finally the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications. We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Deaths from cardiovascular disease have surged among adults ages 25 to 64 living in rural areas, a new study shows.

The fantastic Supercomputing 2024 show is coming back to Atlanta this year. If last year was any indication, there will be plenty of coffee flowing and lots of discussions around […]

The post Top500 Wild Cards Could Add Thrills to Supercomputing 2024 Show appeared first on HPCwire.

What does food mean to you, your community and our planet? With ​​personal accounts from the kitchen to the operating room, chef and content creator Jon Kung and cardiologist Uma Valeti unpack how food cultivates creativity and offers opportunities to connect with and blend cultures. Exploring Valeti’s experiences developing a healthier meat alternative, they discuss what it takes to overcome the impossible — whether that’s saving a patient’s life or transforming ideas around traditional foods — and how we can all make steps towards more sustainable cooking.

The state, which earned a B, saw its educational strength buoyed by strong performance in areas that measure socioeconomic factors that can affect the educational environment.

The state, which earned a B-plus, led the nation in K-12 achievement rankings and outperformed other states in several key academic indicators, but fell short on funding equity.

The state, which earned a D-plus, was weak on socioeconomic factors that can affect the educational environment, and also in the school finance area.

The state, which earned a D-plus, has struggled with school finance issues and endured teacher strikes and battles over pay, but also earned B-plus for funding equity.

The state, which earned a B, is one of the nation’s wealthiest and turned in strong performances in the school finance arena and in areas such as preschool and kindergarten enrollment.

Best known in education circles for its performance assessment, New Hampshire is a hotbed of innovation around personalized learning, writes Adriana Martinez of the Innovation Lab Network.

86 Sergei Bobrovsky, 85 Cole Perfetti, and 85 Alexandar Goergiev among new cards

The state, which earned a D-plus, scored low on the Chance for Success Index, which tracks a host of socioeconomic factors that can affect the educational environment.

It was Louisville women's basketball vs UT Martin at the Kathleen and Tom Elam Center. See score updates and highlights from the road clash.

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.

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

Elections Nova Scotia is investigating PC candidate Susan Corkum-Greek's campaign to determine whether it broke the law by handing out gift cards on Saturday outside a Tim Hortons in Lunenburg, N.S. 

A box found in a Saskatchewan attic, potentially holding millions of dollars worth of hockey cards, is going back up for auction after the original winning bidder never paid up, according to the auction company.

The oft-discussed wild-card setup at the national championships took centre stage again Monday with the release of updated rankings that appeared to determine the play-in game matchup at the Scotties Tournament of Hearts.

While the Trump administration proposal would not strip student eligibility for Head Start, the federal school lunch program, or the Individual with Disabilities Education Act, it could still affect millions of school-aged children who live with immigrant parents.

The first season of the Netflix political potboiler was rich with education-policy plotlines, and we're hoping for more of the same.

This interactive map offers a quick way to examine state-by-state grades and summary data.

Penn State Hazleton Benefiting THON, the campus’ THON chapter, will host a designer purse and gift card bingo on Sunday, Oct. 20. Doors open at 1 p.m. and games will start at 2 p.m. in the Dr. Thomas M. Caccese Gymnasium in the Physical Education Building. The event is open to the public. 

The arts, geography, economics, and foreign languages will lose their place in the testing line-up as the National Assessment of Educational Progress is being streamlined to cut costs.

Street evangelism - that’s how Nicolas ended up carrying a 2 meter high cardboard coffin on a bus across Santiago, Chile.

Ishq was directed by Indra Kumar

Attorney General Kathy Jennings today co-led a coalition of attorneys general from across the nation in denouncing four of the world’s largest credit card companies for walking back their commitment to implement a new merchant code for gun sales that would help prevent mass shootings and curb gun violence. “Gun violence has become so endemic in our country that it is now the leading cause of childhood death. […]

Read the in depth Review of NVIDIA RTX 3080 Graphics Card PC Components. Know detailed info about NVIDIA RTX 3080 Graphics Card configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Read the in depth Review of AMD Radeon RX 6800 XT Graphics Card PC Components. Know detailed info about AMD Radeon RX 6800 XT Graphics Card configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.