Ketamine is a glutamate receptor antagonist that was developed over 50 years ago as an anesthetic agent. At subanesthetic doses, ketamine and some metabolites are analgesics and fast-acting antidepressants, presumably through targets other than glutamate receptors. We tested ketamine and its metabolites for activity as allosteric modulators of opioid receptors expressed as recombinant receptors in heterologous systems and with native receptors in rodent brain; signaling was examined by measuring GTP binding, β-arrestin recruitment, MAPK activation, and neurotransmitter release. Although micromolar concentrations of ketamine alone had weak agonist activity at μ opioid receptors, the combination of submicromolar concentrations of ketamine with endogenous opioid peptides produced robust synergistic responses with statistically significant increases in efficacies. All three opioid receptors (μ, , and ) showed synergism with submicromolar concentrations of ketamine and either methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk), and/or dynorphin A17 (Dyn A17), albeit the extent of synergy was variable between receptors and peptides. S-ketamine exhibited higher modulatory effects compared with R-ketamine or racemic ketamine, with ~100% increase in efficacy. Importantly, the ketamine metabolite 6-hydroxynorketamine showed robust allosteric modulatory activity at μ opioid receptors; this metabolite is known to have analgesic and antidepressant activity but does not bind to glutamate receptors. Ketamine enhanced potency and efficacy of Met-enkephalin signaling both in mouse midbrain membranes and in rat ventral tegmental area neurons as determined by electrophysiology recordings in brain slices. Taken together, these findings support the hypothesis that some of the therapeutic effects of ketamine and its metabolites are mediated by directly engaging the endogenous opioid system.

ABSTRACTIntroduction:Emergency contraceptive pills (ECPs) are effective and can be used safely at any age repeatedly within the same cycle. They are often favored by youth yet are underutilized. Private facilities can increase ECP access but present barriers including cost. Identifying effective public-sector ECP distribution models can help ensure equitable access. The Malawi Ministry of Health developed a strategy to improve ECP access in 2020. We documented ECP provision through select public, youth-serving channels recommended by the strategy: general and youth-specific outreach, paid and unpaid community health workers (CHWs), and youth clubs.Methods:We conducted this mixed methods study from November 2022–March 2023 in 2 rural districts (Mchinji and Phalombe) implementing the strategy. We conducted qualitative interviews with 10 national stakeholders, 46 providers, and 24 clients aged 15–24 years about ECP service delivery. Additionally, 25 providers collected quantitative tally data about clients seeking ECPs. We analyzed qualitative data using grounded theory and quantitative data descriptively.Results:Stakeholders and providers reported ECP uptake increased in geographies where the strategy was implemented, especially among youth. Providers documented 3,988 client visits for ECPs over 3 months. Of these visits, 26% were from male clients, 36% were from clients aged younger than 20 years, and 64% received ECPs for the first time. Across channels, youth club leaders and unpaid CHWs reported the most client visits per provider and served the youngest clients. However, no ECPs were dispensed during 29% of visits due to stock-outs. While many providers were supportive of youth accessing ECPs, most held unfavorable attitudes toward repeat use.Conclusion:ECP access should be expanded through provision in the studied channels, especially youth clubs and CHWs. However, to meet demand, the supply chain must be strengthened. We recommend addressing providers’ attitudes about repeat use to ensure informed method choice.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurologic phenotypes. Piperine derivative 8015 promoted mitochondrial fusion and motility in Mfn2-deficient cells in a mitofusin-dependent manner and reversed mitochondrial dysfunction in cultured fibroblasts and reprogrammed motor neurons from a human CMT2A patient carrying the MFN2 T105M mutation. Like previous mitofusin activators, 8015 exhibited stereospecific functionality, but the more active stereoisomer, 8015-P2, is unique in that it has subnanomolar potency and undergoes entero-hepatic recirculation which extends its in vivo half-life. Daily administration of 8015-P2 to Mfn2 T105M knock-in mice for 6 weeks normalized neuromuscular and sensory dysfunction and corrected histological/ultrastructural neurodegeneration and neurogenic myoatrophy. These studies describe a more clinically relevant mouse model of CMT2A and an improved mitofusin activator derived from piperine. We posit that 8015-P2 and other piperine derivatives may benefit CMT2A or other neurodegenerative conditions wherein mitochondrial dysdynamism plays a contributory role.

Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/β-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRAB_eCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level.

[¹⁷⁷Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [¹⁷⁷Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [¹⁷⁷Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer–associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0–6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3–16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer–associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [¹⁷⁷Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence–based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

Over 4 decades of research support the link between Alzheimer disease (AD) and somatostatin [somatotropin-releasing inhibitory factor (SRIF)]. SRIF and SRIF-expressing neurons play an essential role in brain function, modulating hippocampal activity and memory formation. Loss of SRIF and SRIF-expressing neurons in the brain rests at the center of a series of interdependent pathological events driven by amyloid-β peptide (Aβ), culminating in cognitive decline and dementia. The connection between the SRIF and AD further extends to the neuropsychiatric symptoms, seizure activity, and inflammation, whereas preclinical AD investigations show SRIF or SRIF receptor agonist administration capable of enhancing cognition. SRIF receptor subtype-4 activation in particular presents unique attributes, with the potential to mitigate learning and memory decline, reduce comorbid symptoms, and enhance enzymatic degradation of Aβ in the brain. Here, we review the links between SRIF and AD along with the therapeutic implications.

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders.

BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

The respiratory literature, both written and in online formats, is growing exponentially. Capturing quality content, to meet the learning needs of those working in all fields of respiratory medicine and delivering it in a palatable, accessible format is challenging but paramount. In this article we discuss ways to determine the information content and review different methods of delivering this content to those who need it.

Tim Miller hopes Amazon's anthology series will help viewers appreciate the "blood, sweat, and tears" Firewalk Studios put into the scrapped game.

Two runners saved by the same public defibrillator appeal for all the life-saving devices to be publicly available. Tens of thousands of defibs are unregistered so ‘invisible’ in an emergency.

Chris just wants to ride a chocobo and get a headshot, but he's old and fingers hurt. Speaking of, Kelley's Digimon died of old age. Meanwhile, Josh five hours The Good Life and goes to fight a bear (as in rawr). And the whole cast travels to the world of Pinocchisouls.

The post RPG Cast – Episode 608: “Sentient Potatoes” appeared first on RPGamer.

Paul Cousins presents a multi-channel installation in which the listener becomes the performer.

The post Patch Notes: Atomised Listening appeared first on Fact Magazine.

Call of Duty: Black Ops 6 in its third week remained in first place on the Steam Weekly Top Sellers chart (excluding revenue generated by free games) for Week 46, 2024, which ended November 12, 2024.

There were two new releases in the top 10 this week. Planet Coaster 2 debuted in fourth place, while Farming Simulator 25 came in fifth place.

Steam Deck is up two spots to second place, while Baldur's Gate 3 re-entered the top 10 in third place. EA Sports FC 25 is up two spots to sixth place, Cyberpunk 2077 re-entered the top 10 in seventh place, and Dragon Age: The Veilguard fell from second to eighth place.

Ahead of its release next week pre-orders for S.T.A.L.K.E.R. 2: Heart of Chornobyl came in ninth place.

Here are the Steam Weekly Top Sellers by revenue for the week (excluding free games):

1. Call of Duty: Black Ops 6
2. Steam Deck
3. Baldur's Gate 3
4. Planet Coaster 2 - NEW
5. Farming Simulator 25 - NEW
6. EA Sports FC 25
7. Cyberpunk 2077
8. Dragon Age: The Veilguard
9. S.T.A.L.K.E.R. 2: Heart of Chornobyl - Pre-orders
10. The Binding of Isaac: Rebirth

Here are the Steam Weekly Top Sellers by revenue for the week (including free games):

1. PUBG: Battlegrounds
2. Counter-Strike 2
3. Call of Duty: Black Ops 6
4. Apex legends
5. Throne and Liberty
6. Steam Deck
7. Baldur's Gate 3
8. Dota 2
9. Planet Coaster 2 - NEW
10. Farming Simulator 25 - NEW

The Steam charts are ordered by revenue, include pre-order numbers, and hardware. If a game appears multiple times it is because it has multiple editions.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463048/planet-coaster-2-and-farming-simulator-25-debut-on-the-steam-charts/

Stationeers and Icarus developers RocketWerkz are making a spiritual successor to beloved space sim Kerbal Space Program, which is currently titled "Kitten Space Agency" in a flagrant display of adherence to wholesome internet trends. It's based on an actual Kerbal Space Program 2 pitch the studio threw at Take-Two subsidiary Private Division back in the day. RocketWerkz CEO and original DayZ creator Dean Hall has hired several former KSP and KSP2 developers to work on the game, and is describing it on social media as a "KSP killer".

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Inflexion Games are closing their UK office, laying off staff and restructuring their main Canadian studio after failing to find commercial success with their Victorian fantasy survival game Nightingale. Reportedly, at least 22 people have been let go.

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Twitch have introduced a new "Politics and Sensitive Social Issues" label for streams that "focus" on topics like "elections, civic integrity, and war or military conflict". As with the streaming giant's existing labels for M-rated material, sexual themes or depictions of gambling, the idea is that viewers can filter out such streams in advance by altering their settings.

Advertisers, similarly, can "make better choices about the content they want to advertise next to" - in other words, pull their ads from a whole swathe of material if they don't want to be associated with anything controversial. Twitch's hope is that "the labels will allow advertisers to have more context to inform which types of streams they show their ads alongside, which we expect to increase brands’ confidence in running ads on Twitch, and could bring new advertisers to our service."

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Back in the misty reaches of time (March) popular farming sim Stardew Valley got a big update that added more pets to the game (it also let you drink mayonaise but let's not get sidetracked). Those new cats, dogs, and turtles had the cute distinction of being able to wear hats, should you choose to kit your wee friends out. Now, following many months of smaller updates to the game, it seems those hats are causing a problem. "[If] you are experiencing performance issues in Stardew Valley 1.6, remove all hats from pets," said creator Eric Barone in a xeet. When asked the lore-accurate cause of this problem, he blamed: "a strange rash".

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The dominion of hated Super Earth threatens to expand afresh as Arrowhead CEO Johan Pilestedt toys openly with the prospect of Helldivers 2 cross-over games, beginning with tabletop wargame Trench Crusade and extending to, well, take your pick. Arrowhead's appetite for other licenses appears insatiable. It's the kind of sheer expansionism you'd expect from Earth's loathsome regime, whose "managed democracy" propaganda continues to enthrall thousands of hapless disposable imperialists. Pilestedt even wants to make a Fifth Element game! Milla Jovovich is spinning in her grave. Milla Jovovich isn't dead, you say? Well, that's good news at least.

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Could tower defence be the ultimate "it's Friday and I am here in body only" genre? I haven't really thought about it before, but Rift Riff's effusively laidback crowd control has me pondering those optimal moments in any tower defender when the incoming horde hits the flamer-MG triangle just right, and you can settle back comfortably into the role of clockwatcher.

Rift Riff encourages this behaviour by being nice to look at. Created by a trio of developers including Hidden Folks designer Adriaan de Jongh, it's a world of spacey, sun-carved mountains, forests and monoliths. The towers resemble the sacred architecture of Monument Valley, and the colour scheme and general ambience remind me of Cocoon. There's a demo, if you fancy it.

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Let’s try and get you up to speed on the fascinating oddity that is simulation game Ecosystem, on the off chance that Nate's coverage of it hasn't stuck with you like an unwelcome brain parasite you’re nonetheless unwilling to get removed for fear of the lingering emptiness it might cause (he once described an eel as “a quaver with erectile dysfunction”). Broadly speaking, this game is Spore’s evolutionary-biology-degree-having cousin. It’s been in early access for about three years now, but with the latest "Crustacean" update, it’s just hit 1.0. Once again, carcinization has come for all things.

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In a basement beneath City St George's, University of London, senior NATO leaders watch on as four research teams demonstrate the latest in AI-controlled, autonomous drone technolo0gy

Our Future Chronicles column explores an imagined history of inventions and developments yet to come. This time, Rowan Hooper takes us to the early 2030s, when a technological step change enabled us to produce all the food we needed without the use of animals

We're trying to avert Judgment Day yet again – this time in an anime series for Netflix. But striking visuals can't make up for shortcomings in narrative and character development

Hours after Donald Trump wins the most conclusive mandate in 40 years, Mitch McConnell engineers a coup against his agenda by calling early leadership elections in the senate.

The company behind Pornhub and other popular pornographic sites broke Canadian privacy law by allowing intimate images to be shared on its websites without the direct knowledge or consent of everyone depicted, the federal privacy commissioner has ruled. The Office of the Privacy Commissioner’s (OPC) investigation into Aylo (formerly MindGeek), one of the world’s largest […]

And the Epic Games Achievements system will start to roll out next week.

Flu and other respiratory viruses seem to barely exist outside of winter, but covid-19 cases have consistently risen every summer over the past few years

A multi-country Salmonella outbreak in Europe linked to tomatoes from Italy has sickened more than 250 people. From January 2023 to November 2024, 266 confirmed cases of Salmonella Strathcona have been identified in 16 European countries and the United Kingdom. Croatia, Czech Republic, Denmark, Estonia, Finland, France, Ireland, Luxembourg, the... Continue Reading

Senator-elect Jim Justice's office has clarified reports that his famous pooch Babydog was banned from the Senate floor, saying Justice never intended to bring the dog onto the floor.

Quantum computing is a devilishly complex technology, with many technical hurdles impacting its development. Of these challenges two critical issues stand out: miniaturization and qubit quality.

IBM has adopted the superconducting qubit road map of reaching a 1,121-qubit processor by 2023, leading to the expectation that 1,000 qubits with today’s qubit form factor is feasible. However, current approaches will require very large chips (50 millimeters on a side, or larger) at the scale of small wafers, or the use of chiplets on multichip modules. While this approach will work, the aim is to attain a better path toward scalability.

Now researchers at MIT have been able to both reduce the size of the qubits and done so in a way that reduces the interference that occurs between neighboring qubits. The MIT researchers have increased the number of superconducting qubits that can be added onto a device by a factor of 100.

“We are addressing both qubit miniaturization and quality,” said William Oliver, the director for the Center for Quantum Engineering at MIT. “Unlike conventional transistor scaling, where only the number really matters, for qubits, large numbers are not sufficient, they must also be high-performance. Sacrificing performance for qubit number is not a useful trade in quantum computing. They must go hand in hand.”

The key to this big increase in qubit density and reduction of interference comes down to the use of two-dimensional materials, in particular the 2D insulator hexagonal boron nitride (hBN). The MIT researchers demonstrated that a few atomic monolayers of hBN can be stacked to form the insulator in the capacitors of a superconducting qubit.

Just like other capacitors, the capacitors in these superconducting circuits take the form of a sandwich in which an insulator material is sandwiched between two metal plates. The big difference for these capacitors is that the superconducting circuits can operate only at extremely low temperatures—less than 0.02 degrees above absolute zero (-273.15 °C).

Superconducting qubits are measured at temperatures as low as 20 millikelvin in a dilution refrigerator.Nathan Fiske/MIT

In that environment, insulating materials that are available for the job, such as PE-CVD silicon oxide or silicon nitride, have quite a few defects that are too lossy for quantum computing applications. To get around these material shortcomings, most superconducting circuits use what are called coplanar capacitors. In these capacitors, the plates are positioned laterally to one another, rather than on top of one another.

As a result, the intrinsic silicon substrate below the plates and to a smaller degree the vacuum above the plates serve as the capacitor dielectric. Intrinsic silicon is chemically pure and therefore has few defects, and the large size dilutes the electric field at the plate interfaces, all of which leads to a low-loss capacitor. The lateral size of each plate in this open-face design ends up being quite large (typically 100 by 100 micrometers) in order to achieve the required capacitance.

In an effort to move away from the large lateral configuration, the MIT researchers embarked on a search for an insulator that has very few defects and is compatible with superconducting capacitor plates.

“We chose to study hBN because it is the most widely used insulator in 2D material research due to its cleanliness and chemical inertness,” said colead author Joel Wang, a research scientist in the Engineering Quantum Systems group of the MIT Research Laboratory for Electronics.

On either side of the hBN, the MIT researchers used the 2D superconducting material, niobium diselenide. One of the trickiest aspects of fabricating the capacitors was working with the niobium diselenide, which oxidizes in seconds when exposed to air, according to Wang. This necessitates that the assembly of the capacitor occur in a glove box filled with argon gas.

While this would seemingly complicate the scaling up of the production of these capacitors, Wang doesn’t regard this as a limiting factor.

“What determines the quality factor of the capacitor are the two interfaces between the two materials,” said Wang. “Once the sandwich is made, the two interfaces are “sealed” and we don’t see any noticeable degradation over time when exposed to the atmosphere.”

This lack of degradation is because around 90 percent of the electric field is contained within the sandwich structure, so the oxidation of the outer surface of the niobium diselenide does not play a significant role anymore. This ultimately makes the capacitor footprint much smaller, and it accounts for the reduction in cross talk between the neighboring qubits.

“The main challenge for scaling up the fabrication will be the wafer-scale growth of hBN and 2D superconductors like [niobium diselenide], and how one can do wafer-scale stacking of these films,” added Wang.

Wang believes that this research has shown 2D hBN to be a good insulator candidate for superconducting qubits. He says that the groundwork the MIT team has done will serve as a road map for using other hybrid 2D materials to build superconducting circuits.

Will Apple keep one of the few single-fee alternatives to Photoshop available?

Republican Senators huddled for over two hours Tuesday night for a family meeting over who will take the reins from Sen. Mitch McConnell (R-KY).

The post Republican Senators Hold Leader Candidate Forum Hours Before Consequential Vote appeared first on Breitbart.

While initial rumors suggested that Kinberg’s trilogy might continue the iconic Skywalker Saga, insiders have clarified that the upcoming series will chart new territory within the ‘Star Wars’ universe

The Connecticut Democrat suddenly thinks Democrats need to listen to people outside their coalition.

Meta has long been at loggerheads with European Union officials over its approach to targeted Facebook and Instagram ads. The company is hoping to placate regulators with some changes to its ad model in the bloc, which includes lowering the price of its ad-free subscription. Starting November 13, the plan will cost 40 percent less — €6 ($6.36) per month for signups via the web and €8 ($8.48) for those who subscribe on an iOS or Android device. The fee for each additional Facebook and Instagram account is €4 per month on the web and €5 via mobile.

The company will automatically drop current subscribers down to the lower pricing. It says that it will once again ask users in the bloc if they'd like to sign up.

When they see this prompt (which can only be ignored for a certain period of time), there will be a third option for EU Facebook and Instagram users to choose from. Those who don't want to pay for a subscription can instead opt to only view ads that are based on what they see in a given session in the apps. Meta will also factor in a few key data markers such as "a person’s age, location, gender and how a person engages with ads."

These less-personalized ads naturally won't be as tailored to a given user's interests, the company notes. As such, people are perhaps less likely to click on such ads. To make up for that (and make sure this option doesn't hit Meta in the pocket too hard), folks who choose the less-personalized ads option will sometimes encounter unskippable ads. According to The Wall Street Journal, these will be displayed full screen.

"Such ad breaks are common across other services, and are already offered by many of our competitors," Meta argues. "This change will help us continue to provide value to advertisers which ensures we can offer people a less personalized ads experience at no charge."

Targeted ads are Meta's biggest revenue driver, but EU officials have reportedly been pressuring the company to offer a free, less-personalized option in its apps. Meta has argued that would negatively impact its bottom line. Although it has seemingly caved to officials' requests, the unskippable ad aspect may be construed as malicious compliance, as it worsens the user experience.

Meta claims that these changes to its ad model "meet EU regulator demands and go beyond what’s required" by the bloc's laws. The company introduced its ad-free subscription a year ago to comply with laws such as the Digital Markets Act (DMA), as well as stricter interpretations of the General Data Protection Regulation. It was previously ordered to seek permission from users in the bloc before showing them personalized ads.

The EU didn't take too kindly to the paid ad-free approach, however. An investigation into the "consent or pay" model is ongoing. In July, the EU said that in its preliminary findings, Meta was violating the DMA with this plan.

These latest changes are said to be Meta's attempt to settle the case, but according to the Journal, the EU's discussions with the company haven't concluded. The bloc's regulatory body has until late March to finish its investigation and make a final decision. If it determines that Meta has indeed violated the DMA, the company could be on the hook for a fine of up to 10 percent of its annual global revenue. Based on its total revenue for 2023, it could have to pay up as much as $13 billion or so.

Canada's intelligence agency amassed a sizable file on Abousfian Abdelrazik's suspected terrorism ties in the early 2000s, although the validity of that intelligence was called into question during the Montreal man's Federal Court case.

Former Liberal senator Sean Edwards has continued to fuel speculation he is set to make a bid to enter state politics.

Une découverte biochimique intrigante pourrait permettre d’identifier rapidement les patients à haut risque.

The Subject Expert Committee (SEC), which advises the national drug regulator on matters related to approval of new drugs and medical devices and clinical trials, has recommended grant of market authorisation for

Olivia Friett, editor of Medical Plastics News takes a look at the current regulatory landscape.

Regulatory experts LFH Regulatory have announced their attendance at MEDICA 2024 to provide insights and support to healthcare innovators facing the complexities of the UK and EU markets.

• Johnson & Johnson Innovative Medicines gives a peek inside its $43 billion gross-to-net bubble

• Optum Rx joins the private label biosimilar bandwagon

• Biosimilars boom for provider-administered drugs

• Fresh evidence of how copay accumulators hurt patients

There’s still time to request an invite to the inaugural Drug Channels Leadership Forum. Attendance will be highly limited. We have already begun extending invitations, so apply now to be considered. Click here to view the full agenda.