Electrification of Heating-Requirements for Successful Wide-Scale Deployment.

Electrification is potentially the most efficient method of decarbonization of space, water, and in certain instances, process heating through the deployment of electrically driven heat pumps. However, challenges are noted in terms of electricity network capacity that ultimately must influence a holistic approach to building/process heating demand reductions which in turn must influence heat pump development, heat pump operations, heat pump capital cost, and the role of thermal storage. Approaches to these challenges are presented from a global and, a UK and Ireland perspective, as for the UK and Ireland, it is often muted that the electricity network is less well suited to addressing the electrification of heating.

The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

Thymoma-Associated Multiorgan Autoimmunity (TAMA) Presenting as a Graft Versus Host Disease-Like Erythroderma.

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare paraneoplastic disorder that presents similarly to graft versus host disease (GVHD). We report a unique case of TAMA presenting as a GVHD-like erythroderma in an elderly male with a history of benign thymoma. Cutaneous histopathological findings demonstrated vacuolar interface dermatitis with numerous dyskeratotic keratinocytes, exocytosis of lymphocytes, and a mildly acanthotic epidermis, which can be seen in several different disease processes.

Development and validation of PBPK models for genistein and daidzein for use in a next-generation risk assessment.

Introduction: All cosmetic ingredients must be evaluated for their safety to consumers. In the absence of data, systemic concentrations of ingredients can be predicted using Physiologically based Pharmacokinetic (PBPK) models. However, more examples are needed to demonstrate how they can be validated and applied in Next-Generation Risk Assessments (NGRA) of cosmetic ingredients.

Physiological liver microtissue 384-well microplate system for preclinical hepatotoxicity assessment of therapeutic small molecule drugs.

Hepatotoxicity can lead to the discontinuation of approved or investigational drugs. The evaluation of the potential hepatoxicity of drugs in development is challenging because current models assessing this adverse effect are not always predictive of the outcome in human beings. Cell lines are routinely used for early hepatotoxicity screening, but to improve the detection of potential hepatotoxicity, in vitro models that better reflect liver morphology and function are needed.

High-fidelity teleportation of a logical qubit using transversal gates and lattice surgery.

Quantum state teleportation is commonly used in designs for large-scale quantum computers. Using Quantinuum's H2 trapped-ion quantum processor, we demonstrate fault-tolerant state teleportation circuits for a quantum error correction code-specifically the Steane code. The circuits use up to 30 qubits at the physical level and employ real-time quantum error correction.

Effect of vehicle on the in vitro penetration and metabolism of genistein and daidzein in ex vivo skin explants and the Phenion full-thickness skin model.

In a read-across assessment of the safety of genistein and daidzein in cosmetic products, additional information was required to account for differences in their systemic exposure after topical application in a typical body lotion formulation. Therefore, we measured the penetration and metabolism of two doses (3 and 30 nmoles/cm) of genistein and daidzein applied in ethanol and in a body formulation to fresh pig skin, fresh and frozen human skin, and PhenionFT models. Both chemicals readily penetrated all skin models when applied in ethanol.

Fault-tolerant one-bit addition with the smallest interesting color code.

Fault-tolerant operations based on stabilizer codes are the state of the art in suppressing error rates in quantum computations. Most such codes do not permit a straightforward implementation of non-Clifford logical operations, which are necessary to define a universal gate set. As a result, implementations of these operations must use either error-correcting codes with more complicated error correction procedures or gate teleportation and magic states, which are prepared at the logical level, increasing overhead to a degree that precludes near-term implementation.

Next-generation risk assessment read-across case study: application of a 10-step framework to derive a safe concentration of daidzein in a body lotion.

We performed an exposure-based Next Generation Risk Assessment case read-across study using New Approach Methodologies (NAMs) to determine the highest safe concentration of daidzein in a body lotion, based on its similarities with its structural analogue, genistein. Two assumptions were: (1) daidzein is a new chemical and its dietary intake omitted; (2) only data were used for daidzein, while and legacy data for genistein were considered. The 10-step tiered approach evaluating systemic toxicity included toxicokinetics NAMs: PBPK models and biokinetics measurements in cells used for toxicogenomics and toxicodynamic NAMs: pharmacology profiling (i.

Evidence of scaling advantage for the quantum approximate optimization algorithm on a classically intractable problem.

The quantum approximate optimization algorithm (QAOA) is a leading candidate algorithm for solving optimization problems on quantum computers. However, the potential of QAOA to tackle classically intractable problems remains unclear. Here, we perform an extensive numerical investigation of QAOA on the low autocorrelation binary sequences (LABS) problem, which is classically intractable even for moderately sized instances.

Performance Prediction and Optimization of Nanofluid-Based PV/T Using Numerical Simulation and Response Surface Methodology.

A numerical investigation was carried out in ANSYS Fluent on a photovoltaic/thermal (PV/T) system with MXene/water nanofluid as heat transfer fluid (HTF). The interaction of different operating parameters (nanofluid mass fraction, mass flow rate, inlet temperature and incident radiation) on the output response of the system (thermal efficiency, electrical efficiency, thermal exergy efficiency, and electrical exergy efficiency) was studied using a predictive model generated using response surface methodology (RSM). The analysis of variance (ANOVA) method was used to evaluate the significance of input parameters affecting the energy and exergy efficiencies of the nanofluid-based PV/T system.

Proposals for new spray drift exposure values in orchards and vineyards for residents and bystanders.

In the EU, predicted exposure to spray drift for residents and bystanders from applications in orchards and vineyards is based on data from one study published in 1987, where one downwind distance (8 m) was considered. CropLife Europe conducted sixteen new GLP compliant studies in 4 EU countries, 8 in orchards, 8 in vineyards with early and late season applications, using adult and child mannequins located 5, 10 and 15 m downwind from the last row to measure dermal and inhalation exposures. The resulting "Bystander Resident Orchard Vineyard (BROV)" database comprises 288 observations and offers a more comprehensive option for exposure prediction.

In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters.

As part of the safety assessment of salicylate esters in cosmetics, we developed a metabolism factor based on in vitro to in vivo extrapolation (IVIVE) to provide a better estimation of the aggregate internal exposure to the common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring salicylic acid formation from 31 substances. Four control substances, not defined as salicylic esters but which could be mistaken as such due to their nomenclature, did not form salicylic acid.

Proposals for new transfer coefficient (TC) values for worker re-entry activities in grape vineyards.

New transfer coefficient (TC) values were derived for vineyard workers handling treated grapevines during harvesting and crop maintenance activities. Re-entry exposure and dislodgeable foliar residue (DFR) studies were performed in Europe, covering hand harvesting, pruning/training, pruning/tying and pruning/shoot lifting. Foliar applications of fungicides (iprovalicarb, dimethomorph, dithianon, pyrimethanil and fenbuconazole) were made and 73 workers at 16 sites were monitored over one working day.

Ambient air concentrations of plant protection products: Data collection for the combined air concentration database and associated risk assessment.

CropLife Europe collected literature values from monitoring studies measuring air concentrations of Plant Protection Products (PPPs) that may be inhaled by humans located in rural areas but not immediately adjacent to PPP applications. The resulting "Combined Air Concentration Database" (CACD) was used to determine whether air concentrations of PPPs reported by the French "Agency for Food, Environmental and Occupational Health & Safety" (ANSES) are consistent with those measured by others to increase confidence in values of exposure to humans. The results were put into risk assessment context.

Use of in vitro ADME methods to identify suitable analogs of homosalate and octisalate for use in a read-across safety assessment.

Case studies are needed to demonstrate the use of human-relevant New Approach Methodologies in cosmetics ingredient safety assessments. For read-across assessments, it is crucial to compare the target chemical with the most appropriate analog; therefore, reliable analog selection should consider physicochemical properties, bioavailability, metabolism, as well as the bioactivity of potential analogs. To complement in vitro bioactivity assays, we evaluated the suitability of three potential analogs for the UV filters, homosalate and octisalate, according to their in vitro ADME properties.

Next generation risk assessment: an case study to assess the systemic safety of the cosmetic ingredient, benzyl salicylate, after dermal exposure.

We performed an next-generation risk assessment (NGRA) for a fragrance ingredient, benzyl salicylate (BSal), to demonstrate how cosmetic ingredients can be evaluated for systemic toxicity endpoints based on non-animal approaches. New approach methodologies (NAMs) used to predict the internal exposure included skin absorption assays, hepatocyte metabolism, and physiologically based pharmacokinetic (PBPK) modeling, and potential toxicodynamic effects were assessed using pharmacology profiling, ToxProfiler cell stress assay, transcriptomics in HepG2 and MCF-7 cells, ReproTracker developmental and reproductive toxicology (DART) assays, and cytotoxicity assays in human kidney cells. The outcome of the NGRA was compared to that of the traditional risk assessment approach based on animal data.

Urban residential building stock synthetic datasets for building energy performance analysis.

The urban building stock dataset consists of synthetic input and output data for the energy simulation of one million buildings. The dataset consists of four different residential types, namely: terraced, detached, semi-detached, and bungalow. Constructing this buildings dataset requires conversion, categorization, extraction, and analytical processes.

Safety assessment for nail cosmetics: Framework for the estimation of systemic exposure through the nail plate.

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited.

Molecular annotation of G protein variants in a neurological disorder.

Heterotrimeric G proteins transduce extracellular chemical messages to generate appropriate intracellular responses. Point mutations in GNAO1, encoding the G protein α subunit, have been implicated in a pathogenic condition characterized by seizures, movement disorders, intellectual disability, and developmental delay (GNAO1 disorder). However, the effects of these mutations on G protein structure and function are unclear.

Predictors and Risk Factors of Treatment-Resistant Depression: A Systematic Review.

To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD). Online databases (PubMed, MEDLINE, Embase, and APA PsycNet) and relevant conference sources were searched from inception up to January 24, 2022. The following keywords were used: , , , , and .

Application of a skin and liver Chip2 microphysiological model to investigate the route-dependent toxicokinetics and toxicodynamics of consumer-relevant doses of genistein.

The HUMMIC skin-liver Chip2 microphysiological system using EpiDerm™ and HepaRG and stellate liver spheroids was used to evaluate the route-specific metabolism and toxicodynamic effects of genistein. Human-relevant exposure levels were compared: 60 nM representing the plasma concentration expected after topical application of a cosmetic product and 1 μM representing measured plasma concentrations after ingesting soya products. Genistein was applied as single and repeated topical and/or systemic doses.