For clean-room technologies such as isolators and restricted access barrier systems (RABS), decontamination using hydrogen peroxide (H₂O₂) is increasingly attractive to fulfill regulatory requirements. Several approaches are currently used, ranging from manual wipe disinfection to vapor phase hydrogen peroxide (VPHP) or automated nebulization sanitization. Although the residual airborne H₂O₂ concentration can be easily monitored, detection of trace H₂O₂ residues in filled products is rather challenging. To simulate the filling process in a specific clean room, technical runs with water for injection (WfI) are popular. Thus, the ability to detect traces of H₂O₂ in water is an important prerequisite to ensure a safe and reliable use of H₂O₂ for isolator or clean room decontamination. The objective of this study was to provide a validated quantitative, fluorometric Amplex UltraRed assay, which satisfies the analytical target profile of quantifying H₂O₂ in WfI at low nanomolar to low micromolar concentrations (ppb range) with high accuracy and high precision. The Amplex UltraRed technology provides a solid basis for this purpose; however, no commercial assay kit that fulfills these requirements is available. Therefore, a customized Amplex UltraRed assay was developed, optimized, and validated. This approach resulted in an assay that is capable of quantifying H₂O₂ in WfI selectively, sensitively, accurately, precisely, and robustly. This assay is used in process development and qualification approaches using WfI in H₂O₂-decontaminated clean rooms and isolators.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (K_i) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated K_i of 3.93 μM. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low.

SIGNIFICANCE STATEMENT

The authors used the endogenous biomarker coproporphyrin I (CP-I) and identified abiraterone as a moderate inhibitor of organic anion transporting polypeptide (OATP) 1B3 in vitro. Subsequent physiologically based pharmacokinetic (PBPK) simulations and clinical observations suggested an absence of OATP1B-mediated interaction between abiraterone and CP-I among prostate cancer patients. This multipronged study concluded that the interaction risk between abiraterone acetate and substrates of OATP1Bs is low, demonstrating the application of PBPK-CP-I modeling in predicting OATP1B-mediated interaction implicating abiraterone.

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2–57 days old) and human hepatocytes (pediatric liver tissue donors: age 2–12 months) by determining uptake clearance of 4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide (ASP+) as a known rOct/hOCT probe substrate. mRNA expression was determined in rat liver tissue corresponding to rat ages used in the functional studies, while hOCT1 mRNA expressions were determined in the same hepatocyte batches as those used for uptake studies. Maturation of rOct/hOCT activity and expression were evaluated by comparing values obtained at the various ages to the adult values. Relative to adult values (at 8 weeks), ASP⁺ uptake clearance in suspended rat hepatocytes aged 0, 1, 2, 3, 4, 5, and 6 weeks reached 26%, 29%, 33%, 37%, 72%, 63%, and 71%, respectively. Hepatic Oct1 mRNA expression was consistent with Oct activity (correlation coefficient of 0.92). In human hepatocytes, OCT1 activity was age dependent and also correlated with mRNA levels (correlation coefficient of 0.88). These data show that Oct1/OCT1 activities and expression mature gradually in rat/human liver, thereby mirroring the expression pattern of organic anion transporting polypeptide in rat. These high-resolution transporter ontogeny profiles will allow for more accurate prediction of the pharmacokinetics of OCT1/Oct1 substrates in pediatric populations and juvenile animals.

SIGNIFICANCE STATEMENT

Organic cation transporter-1 (OCT1) represents a major drug uptake transporter in human liver. This study provides high-resolution data regarding the age-dependent function of OCT1 in the liver, based on in vitro experiments with rat and human hepatocytes obtained from donors between birth and adulthood. These ontogeny profiles will inform improved age-specific physiologically based pharmacokinetic models for OCT1 drug substrates in neonates, infants, children, and adults.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2.

SIGNIFICANCE STATEMENT

The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.

Pregnane X receptor (PXR) belongs to the nuclear receptor superfamily that plays a crucial role in hepatic physiologic and pathologic conditions. Phase separation is a process in which biomacromolecules aggregate and condense into a dense phase as liquid condensates and coexist with a dilute phase, contributing to various cellular and biologic functions. Until now, whether PXR could undergo phase separation remains unclear. This study aimed to investigate whether PXR undergoes phase separation. Analysis of the intrinsically disordered regions (IDRs) using algorithm tools indicated a low propensity of PXR to undergo phase separation. Experimental assays such as hyperosmotic stress, agonist treatment, and optoDroplets assay demonstrated the absence of phase separation for PXR. OptoDroplets assay revealed the inability of the fusion protein of Cry2 with PXR to form condensates upon blue light stimulation. Moreover, phase separation of PXR did not occur even though the mRNA and protein expression levels of PXR target, cytochrome P450 3A4, changed after sorbitol treatment. In conclusion, for the first time, these findings suggested that exogenous PXR does not undergo phase separation following activation or under hyperosmotic stress in nucleus of cells.

SIGNIFICANCE STATEMENT

PXR plays a critical role in hepatic physiological and pathological processes. The present study clearly demonstrated that exogenous PXR does not undergo phase separation after activation by agonist or under hyperosmotic stress in nucleus. These findings may help understand PXR biology.

The antitumor effect of cardiotonic steroids (CTS) has stimulated the search for new methods to evaluate both kinetic and thermodynamic aspects of their binding to Na⁺/K⁺-ATPase (IUBMB Enzyme Nomenclature). We propose a real-time assay based on a chromogenic substrate for phosphatase activity (pNPPase activity), using only two concentrations with an inhibitory progression curve, to obtain the association rate (k_on), dissociation rate (k_off), and equilibrium (K_i) constants of CTS for the structure-kinetics relationship in drug screening. We show that changing conditions (from ATPase to pNPPase activity) resulted in an increase of K_i of the cardenolides digitoxigenin, essentially due to a reduction of k_on. In contrast, the K_i of the structurally related bufadienolide bufalin increased much less due to the reduction of its k_off partially compensating the decrease of its k_on. When evaluating the kinetics of 15 natural and semisynthetic CTS, we observed that both k_on and k_off correlated with K_i (Spearman test), suggesting that differences in potency depend on variations of both k_on and k_off. A rhamnose in C3 of the steroidal nucleus enhanced the inhibitory potency by a reduction of k_off rather than an increase of k_on. Raising the temperature did not alter the k_off of digitoxin, generating a H (k_off) of –10.4 ± 4.3 kJ/mol, suggesting a complex dissociation mechanism. Based on a simple and inexpensive methodology, we determined the values of k_on, k_off, and K_i of the CTS and provided original kinetics and thermodynamics differences between CTS that could help the design of new compounds.

SIGNIFICANCE STATEMENT

This study describes a fast, simple, and cost-effective method for the measurement of phosphatase pNPPase activity enabling structure-kinetics relationships of Na⁺/K⁺-ATPase inhibitors, which are important compounds due to their antitumor effect and endogenous role. Using 15 compounds, some of them original, this study was able to delineate the kinetics and/or thermodynamics differences due to the type of sugar and lactone ring present in the steroid structure.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

SIGNIFICANCE STATEMENT

This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors.

Cannabinoid and opioid receptor activities can be modulated by a variety of post-translational mechanisms including the formation of interacting complexes. This study examines the involvement of endogenous and exogenous chaperones in modulating the abundance and activity of cannabinoid CB₁ receptor (CB₁R), opioid receptor (DOR), and CB₁R-DOR interacting complexes. Focusing on endogenous protein chaperones, namely receptor transporter proteins (RTPs), we examined relative mRNA expression in the mouse spinal cord and found RTP4 to be expressed at higher levels compared with other RTPs. Next, we assessed the effect of RTP4 on receptor abundance by manipulating RTP4 expression in cell lines. Overexpression of RTP4 causes an increase and knock-down causes a decrease in the levels of CB₁R, DOR, and CB₁R-DOR interacting complexes; this is accompanied by parallel changes in signaling. The ability of small molecule lipophilic ligands to function as exogenous chaperones was examined using receptor-selective antagonists. Long-term treatment leads to increases in receptor abundance and activity with no changes in mRNA supporting a role as pharmacological chaperones. Finally, the effect of cannabidiol (CBD), a small molecule ligand and a major active component of cannabis, on receptor abundance and activity in mice was examined. We find that CBD administration leads to increases in receptor abundance and activity in mouse spinal cord. Together, these results highlight a role for chaperones (proteins and small molecules) in modulating levels and activity of CB₁R, DOR, and their interacting complexes potentially through mechanisms including receptor maturation and trafficking.

SIGNIFICANCE STATEMENT

This study highlights a role for chaperones (endogenous and small membrane-permeable molecules) in modulating levels of cannabinoid CB₁ receptor, delta opioid receptor, and their interacting complexes. These chaperones could be developed as therapeutics for pathologies involving these receptors.

Intrapatient intermetastatic heterogeneity (IIH) has been demonstrated in metastatic castration-resistant prostate cancer (mCRPC) patients and is of the utmost importance for radiopharmaceutical therapy (RPT) eligibility. This study was designed to determine the prevalence of IIH and RPT eligibility in mCRPC patients through a triple-tracer PET imaging strategy. Methods: This was a multisite prospective observational study in which mCRPC patients underwent both ¹⁸F-FDG and ⁶⁸Ga-prostate-specific membrane antigen (PSMA)–617 PET/CT scans. A third scan with ⁶⁸Ga-DOTATATE, a potential biomarker of neuroendocrine differentiation, was performed if an ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found. Per-tracer lesion positivity was defined as having an uptake at least 50% above that of the liver. IIH prevalence was defined as the percentage of participants having at least 2 lesions with discordant features on multitracer PET. Results: IIH was observed in 81 patients (82.7%), and at least 1 ¹⁸F-FDG–positive/⁶⁸Ga-PSMA–negative lesion was found in 45 patients (45.9%). Of the 37 participants who also underwent ⁶⁸Ga-DOTATATE PET/CT, 6 (16.2%) had at least 1 ⁶⁸Ga-DOTATATE–positive lesion. In total, 12 different combinations of lesion imaging phenotypes were observed. On the basis of our prespecified criteria, 52 (53.1%) participants were determined to be eligible for PSMA RPT, but none for DOTATATE RPT. Patients with IIH had a significantly shorter median overall survival than patients without IIH (9.5 mo vs. not reached; log-rank P = 0.03; hazard ratio, 2.7; 95% CI, 1.1–6.8). Conclusion: Most mCRPC patients showed IIH, which was associated with shorter overall survival. On the basis of a triple-tracer PET approach, multiple phenotypic combinations were found. Correlation of these imaging phenotypes with genomics and treatment response will be relevant for precision medicine.

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3' region of the last exon of PDX1 was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.

Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol–cytochrome c reductase, are particularly rare in humans. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.

Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.

Back in the mists of 2021, No Man's Sky revealed its very own Normandy SR1 space frigate. "The Normandy in No Man's Sky?" you cry. "Why, that's a Mass Effect vessel. Some mistake here surely?" 1) My name's not Shirley, and 2) Indeed it is a Mass Effect ship, but HelloGames struck a time-limited deal with BioWare to create a version for their own space sim.

"Blast, if only I'd noticed this at the time and acquired one," you mourn. "Ah, so many years I have wasted." Be of good cheer, my friend, for No Man's Sky has a Normandy once again, just in time for the latest N7 Day of assorted Mass Effect celebrations. For the next two weeks, you'll be able to get a-hold of it by way of a revised version of 2021's Beachhead Expedition. Tray-tray, away!

Read more

It is thought that humans can only maintain relationships with around 150 people, a figure known as Dunbar's number, but it seems that AI models can outstrip this and reach consensus in far bigger groups

A lithium-ion battery made from three droplets of hydrogel is the smallest soft battery of its kind – and it could be used in biocompatible and biodegradable implants

ROGER FEDERER has explained why he gets injured less than rivals Rafael Nadal and Novak Djokovic..

Imagine pulling up to a refueling station and filling your vehicle’s tank with liquid hydrogen, as safe and convenient to handle as gasoline or diesel, without the need for high-pressure tanks or cryogenic storage. This vision of a sustainable future could become a reality if a Calgary, Canada–based company, Ayrton Energy, can scale up its innovative method of hydrogen storage and distribution. Ayrton’s technology could make hydrogen a viable, one-to-one replacement for fossil fuels in existing infrastructure like pipelines, fuel tankers, rail cars, and trucks.

The company’s approach is to use liquid organic hydrogen carriers (LOHCs) to make it easier to transport and store hydrogen. The method chemically bonds hydrogen to carrier molecules, which absorb hydrogen molecules and make them more stable—kind of like hydrogenating cooking oil to produce margarine.

A researcher pours a sample of Ayrton’s LOHC fluid into a vial.Ayrton Energy

The approach would allow liquid hydrogen to be transported and stored in ambient conditions, rather than in the high-pressure, cryogenic tanks (to hold it at temperatures below -252 ºC) currently required for keeping hydrogen in liquid form. It would also be a big improvement on gaseous hydrogen, which is highly volatile and difficult to keep contained.

Founded in 2021, Ayrton is one of several companies across the globe developing LOHCs, including Japan’s Chiyoda and Mitsubishi, Germany’s Covalion, and China’s Hynertech. But toxicity, energy density, and input energy issues have limited LOHCs as contenders for making liquid hydrogen feasible. Ayrton says its formulation eliminates these trade-offs.

Safe, Efficient Hydrogen Fuel for Vehicles

Conventional LOHC technologies used by most of the aforementioned companies rely on substances such as toluene, which forms methylcyclohexane when hydrogenated. These carriers pose safety risks due to their flammability and volatility. Hydrogenious LOHC Technologies in Erlanger, Germany and other hydrogen fuel companies have shifted toward dibenzyltoluene, a more stable carrier that holds more hydrogen per unit volume than methylcyclohexane, though it requires higher temperatures (and thus more energy) to bind and release the hydrogen. Dibenzyltoluene hydrogenation occurs at between 3 and 10 megapascals (30 and 100 bar) and 200–300 ºC, compared with 10 MPa (100 bar), and just under 200 ºC for methylcyclohexane.

Ayrton’s proprietary oil-based hydrogen carrier not only captures and releases hydrogen with less input energy than is required for other LOHCs, but also stores more hydrogen than methylcyclohexane can—55 kilograms per cubic meter compared with methylcyclohexane’s 50 kg/m³. Dibenzyltoluene holds more hydrogen per unit volume (up to 65 kg/m³), but Ayrton’s approach to infusing the carrier with hydrogen atoms promises to cost less. Hydrogenation or dehydrogenation with Ayrton’s carrier fluid occurs at 0.1 megapascal (1 bar) and about 100 ºC, says founder and CEO Natasha Kostenuk. And as with the other LOHCs, after hydrogenation it can be transported and stored at ambient temperatures and pressures.

Judges described [Ayrton's approach] as a critical technology for the deployment of hydrogen at large scale.” —Katie Richardson, National Renewable Energy Lab

Ayrton’s LOHC fluid is as safe to handle as margarine, but it’s still a chemical, says Kostenuk. “I wouldn’t drink it. If you did, you wouldn’t feel very good. But it’s not lethal,” she says.

Kostenuk and fellow Ayrton cofounder Brandy Kinkead (who serves as the company’s chief technical officer) were originally trying to bring hydrogen generators to market to fill gaps in the electrical grid. “We were looking for fuel cells and hydrogen storage. Fuel cells were easy to find, but we couldn’t find a hydrogen storage method or medium that would be safe and easy to transport to fuel our vision of what we were trying to do with hydrogen generators,” Kostenuk says. During the search, they came across LOHC technology but weren’t satisfied with the trade-offs demanded by existing liquid hydrogen carriers. “We had the idea that we could do it better,” she says. The duo pivoted, adjusting their focus from hydrogen generators to hydrogen storage solutions.

“Everybody gets excited about hydrogen production and hydrogen end use, but they forget that you have to store and manage the hydrogen,” Kostenuk says. Incompatibility with current storage and distribution has been a barrier to adoption, she says. “We’re really excited about being able to reuse existing infrastructure that’s in place all over the world.” Ayrton’s hydrogenated liquid has fuel-cell-grade (99.999 percent) hydrogen purity, so there’s no advantage in using pure liquid hydrogen with its need for subzero temperatures, according to the company.

The main challenge the company faces is the set of issues that come along with any technology scaling up from pilot-stage production to commercial manufacturing, says Kostenuk. “A crucial part of that is aligning ourselves with the right manufacturing partners along the way,” she notes.

Asked about how Ayrton is dealing with some other challenges common to LOHCs, Kostenuk says Ayrton has managed to sidestep them. “We stayed away from materials that are expensive and hard to procure, which will help us avoid any supply chain issues,” she says. By performing the reactions at such low temperatures, Ayrton can get its carrier fluid to withstand 1,000 hydrogenation-dehydrogenation cycles before it no longer holds enough hydrogen to be useful. Conventional LOHCs are limited to a couple of hundred cycles before the high temperatures required for bonding and releasing the hydrogen breaks down the fluid and diminishes its storage capacity, Kostenuk says.

Breakthrough in Hydrogen Storage Technology

In acknowledgement of what Ayrton’s nontoxic, oil-based carrier fluid could mean for the energy and transportation sectors, the U.S. National Renewable Energy Lab (NREL) at its annual Industry Growth Forum in May named Ayrton an “outstanding early-stage venture.” A selection committee of more than 180 climate tech and cleantech investors and industry experts chose Ayrton from a pool of more than 200 initial applicants, says Katie Richardson, group manager of NREL’s Innovation and Entrepreneurship Center, which organized the forum. The committee based its decision on the company’s innovation, market positioning, business model, team, next steps for funding, technology, capital use, and quality of pitch presentation. “Judges described Ayrton’s approach as a critical technology for the deployment of hydrogen at large scale,” Richardson says.

As a next step toward enabling hydrogen to push gasoline and diesel aside, “we’re talking with hydrogen producers who are right now offering their customers cryogenic and compressed hydrogen,” says Kostenuk. “If they offered LOHC, it would enable them to deliver across longer distances, in larger volumes, in a multimodal way.” The company is also talking to some industrial site owners who could use the hydrogenated LOHC for buffer storage to hold onto some of the energy they’re getting from clean, intermittent sources like solar and wind. Another natural fit, she says, is energy service providers that are looking for a reliable method of seasonal storage beyond what batteries can offer. The goal is to eventually scale up enough to become the go-to alternative (or perhaps the standard) fuel for cars, trucks, trains, and ships.

It looks like SNK is celebrating the 30th anniversary of the superb The King of Fighters series with a big …

Continue reading "All of SNK’s The King of Fighters ACA NeoGeo Games Are Discounted on iOS and Android, Switch Later Today"

Prime Minister Justin Trudeau sounded an upbeat note Tuesday on the prospect of working with U.S. president-elect Donald Trump, saying Canada has dealt with his trade threats before and can do so again.

Consultations on the reclassification of two progestogen-only contraceptive pills from prescription-only to pharmacy medicines have been launched.

Neurogene’s Rett syndrome gene therapy has preliminary data supporting safety and efficacy of the one-time treatment. But a late-breaking report of a serious complication in a patient who received the high dose sent shares of the biotech downward.

The post Neurogene Gene Therapy Shows Signs of Efficacy in Small Study, But an Adverse Event Spooks Investors appeared first on MedCity News.

Sep 2, 2023

Amid the global energy transition, investors are anxious to pour billions of dollars into many of these countries to turn the new fossil fuel finds into hydrogen. The element is the key feedstock for fuel cells, which use chemical reactions to generate electricity cleanly, with water as the main byproduct. Notwithstanding the considerable technological challenges ahead, demand for the gas in Europe and elsewhere is widely expected to surge as vehicles, factories, and other energy users seek to reduce greenhouse gas emissions.

For Southern Rim nations, however, this tantalizing opportunity for economic development risks turning into just another Sahara mirage. That’s because the hype surrounding hydrogen may continue to distract the regions’ leaders from addressing the tough domestic social issues that are behind the migration crisis. If the technology does become viable, revenue from hydrogen exports to Europe could just perpetuate rent-seeking behavior by political and economic elites at the expense of their own citizens.

Mar 26, 2024

India aims to become a leading producer of green hydrogen by the next decade as part of its broader industrial and decarbonization strategies. This brief provides an overview of India's current hydrogen strategy, as well as the challenges - land and water scarcity, infrastructure gaps, and financing gaps - that must be addressed in order for India to achieve its ambitious goals.

Jul 8, 2024

Green, grey, blue, turquoise, pink, yellow, orange – Nicola De Blasio provides a guide to the color codes used to classify hydrogen produced from different sources.

NEXITY CONJONCTURE LOGEMENT - DATA MARCHE ET CHIFFRES NEXITY

Les tendances du march� neuf

Neutrogena� Launches See What�s Possible

Rowenta Brand Ambassador Dr. Noreen Khan-Mayberry discusses how allergens affect our health, and the importance of removing them from our homes.

Magic Denim - Camille Seydoux for Roger Vivier

Brad & Jenny Lost 400 lbs. Together

Ask About the Curve Public Service Announcement

A lithium-ion battery made from three droplets of hydrogel is the smallest soft battery of its kind – and it could be used in biocompatible and biodegradable implants

Wrecky minion Aryn took this photo October 23rd:

OCTOBER 23RD.

So this bakery is selling Christmas cakes two major holidays before Christmas. Which would be awesome for pranking that friend who passed out after drinking too much, but otherwise... da heck?

 

And if you think Christmas Creep is bad, wait'll you see Easter Creep:

A pink Easter Egg cake... made October 19th.

Because it's never too early to stock up on "decorated" egg cakes in October, you guys.

 

It actually gets worse when bakeries try to be seasonally appropriate:

Orange icing + crappy turtle pancake = "Fall!"

 

White pointy-headed "ghosts" + anything = FAIL!

Seriously, let's talk about all the ways this is a bad idea.

Oh yes, please, put them on white cupcakes. THAT HELPS SO MUCH.

 

Speaking of not helping, let's talk creepy clowns.

This was also spotted last week.

::shudder::

 

Although at least the clown is recognizable. What about this thing?

It was out last week, so... Dapper Halloween Alien? Count Unibrow? Evil Mystic Muppet?

Oooh, "Evil Mystic Muppet" would be an awesome band name.

 

Thanks to Aryn W., Elizabeth C., Robbie C., Anony M., Julie R., Alexa M., & Jenny E for reminding us it's just two more months 'til Christmas.

*****

The only way I approve of celebrating Christmas this early is by wearing one of these:

Unisex Ugly Christmas Sweaters

Look closely at the "chestnuts" on the right, bahaha. There are tons more to choose from at the link, so happy browsing.

*****

And from my other blog, Epbot:

Experts from UVA Health are issuing a warning about mushroom gummies marketed to enhance brain function, as they may contain the illegal hallucinogen

Highlights: Vaginal estrogen during prolapse surgery did not improve the outcomes of post-operative prolapse M

The five Partner States of the Kavango Zambezi Transfrontier Conservation Area (KAZA TFCA) have joined forces with IWMI to manage groundwater resources spanning an area larger than Austria and Germany.

The post New project brings five African countries together to jointly manage region’s groundwater first appeared on International Water Management Institute (IWMI).

Optineurin, or OPTN protein when present in the cells it restricts the spread of HSV-1, the herpes simplex virus type 1. The study finds a potential direct

Implementing high-ambition nitrogen interventions can benefit the environment and medlinkpublic health/medlink, suggests a new study. h2Is Earth's

A new study, published in the August 28, 2024, online issue of Neurology, the medical journal of the American Academy of Neurology, suggests that the

Periodontal disease or periodontitis is a significant inflammatory condition triggered by an infection from periodontal pathogens. This condition not

A recent study featured in the iInternational Journal of Sports Medicine/i titled "Inhalation of Hydrogen-Rich Gas Before Acute Exercise Alleviates

Scientists in /medlink Bonn pinpoint uncommon genetic mutations linked to male-pattern hair loss. From receding hairlines to the iconic horseshoe baldness

Innovative semaglutide hydrogel may revolutionize diabetes treatment by reducing the need for injections to just once a month, improving patient convenience.

A recent discovery led by the University of Maryland could pave the way for new and enhanced treatments for Hutchinson-Gilford progeria syndrome (HGPS),

Increasing ketone levels in the blood through a medlinkketogenic diet/medlink or supplements may help regulate irregular medlinkmenstrual cycles/medlink

The World Health Organization (WHO) released a new study identifying 17 endemic pathogens in urgent need of vaccines (!--ref1--). The study published