Second-order optimization strategies for neural network quantum states.

The Variational Monte Carlo (VMC) method has recently seen important advances through the use of neural network quantum states. While more and more sophisticated ansatze have been designed to tackle a wide variety of quantum many-body problems, modest progress has been made on the associated optimization algorithms. In this work, we revisit the Kronecker-Factored Approximate Curvature (KFAC), an optimizer that has been used extensively in a variety of simulations.

Response of stratospheric water vapour to warming constrained by satellite observations.

Future increases in stratospheric water vapour risk amplifying climate change and slowing down the recovery of the ozone layer. However, state-of-the-art climate models strongly disagree on the magnitude of these increases under global warming. Uncertainty primarily arises from the complex processes leading to dehydration of air during its tropical ascent into the stratosphere.

Stratospheric water vapor affecting atmospheric circulation.

Water vapor plays an important role in many aspects of the climate system, by affecting radiation, cloud formation, atmospheric chemistry and dynamics. Even the low stratospheric water vapor content provides an important climate feedback, but current climate models show a substantial moist bias in the lowermost stratosphere. Here we report crucial sensitivity of the atmospheric circulation in the stratosphere and troposphere to the abundance of water vapor in the lowermost stratosphere.

Expression of the Transient Receptor Potential Vanilloid 1 ion channel in the supramammillary nucleus and the antidepressant effects of its antagonist AMG9810 in mice.

The Transient Receptor Potential Vanilloid 1 (TRPV1) non-selective cation channel predominantly expressed in primary sensory neurons of the dorsal root and trigeminal ganglia mediates pain and neurogenic inflammation. TRPV1 mRNA and immunoreactivity were described in the central nervous system (CNS), but its precise expression pattern and function have not been clarified. Here we investigated Trpv1 mRNA expression in the mouse brain using ultrasensitive RNAScope in situ hybridization.

Responses of Arctic sea ice to stratospheric ozone depletion.

The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades, particularly in 1997, 2011 and 2020. However, the impact of this stratospheric ozone depletion on the climate system remains poorly understood. Here we show that the stratospheric ozone depletion causes significant reductions in the sea ice concentration (SIC) and the sea ice thickness (SIT) over the Kara Sea, Laptev Sea and East Siberian Sea from spring to summer.

Integrated ozone depletion as a metric for ozone recovery.

The Montreal Protocol is successfully protecting the ozone layer. The main halogen gases responsible for stratospheric ozone depletion have been regulated under the Protocol, their combined atmospheric abundances are declining and ozone is increasing in some parts of the atmosphere. Ozone depletion potentials, relative measures of compounds' abilities to deplete stratospheric ozone, have been a key regulatory component of the Protocol in successfully guiding the phasing out in the manufacture of the most highly depleting substances.

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia.

Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878.

Two strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3 × 10 to 30 CFU/mouse, followed by aerosol infection with Mtb (H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3 × 10-3000 CFU (BALB/c) and 3 × 10-300 CFU (CB6F1). Whereas, a significant protection was seen in both strains of mice with BCG doses at 3 × 10-300 CFU when infected with H37Rv.

The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice.

Hydrogen sulfide (HS) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which HS triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(NaS) and slow-releasing (GYY4137) HS donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in knockout () and wild-type () mice.

Regional Features of Long-Term Exposure to PM Air Quality over Asia under SSP Scenarios Based on CMIP6 Models.

This study investigates changes in fine particulate matter (PM) concentration and air-quality index (AQI) in Asia using nine different Coupled Model Inter-Comparison Project 6 (CMIP6) climate model ensembles from historical and future scenarios under shared socioeconomic pathways (SSPs). The results indicated that the estimated present-day PM concentrations were comparable to satellite-derived data. Overall, the PM concentrations of the analyzed regions exceeded the WHO air-quality guidelines, particularly in East Asia and South Asia.

Identifying Surrogates for Heart and Ipsilateral Lung Dose to Guide Field Placement and Treatment Modality Selection during Virtual Simulation of Breast Radiotherapy.

Aims: Virtual simulation (VSim) of tangential photon fields is a common method of field localisation for breast radiotherapy. Heart and ipsilateral lung dose is unknown until the dosimetric plan is produced. If heart and ipsilateral lung tolerance doses are exceeded, this can prolong the pre-treatment pathway, particularly if a change of technique is required.

Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining.

Tuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information.

Reconciling the climate and ozone response to the 1257 CE Mount Samalas eruption.

The 1257 CE eruption of Mount Samalas (Indonesia) is the source of the largest stratospheric injection of volcanic gases in the Common Era. Sulfur dioxide emissions produced sulfate aerosols that cooled Earth's climate with a range of impacts on society. The coemission of halogenated species has also been speculated to have led to wide-scale ozone depletion.

Delay in recovery of the Antarctic ozone hole from unexpected CFC-11 emissions.

The Antarctic ozone hole is decreasing in size but this recovery will be affected by atmospheric variability and any unexpected changes in chlorinated source gas emissions. Here, using model simulations, we show that the ozone hole will largely cease to occur by 2065 given compliance with the Montreal Protocol. If the unusual meteorology of 2002 is repeated, an ozone-hole-free-year could occur as soon as the early 2020s by some metrics.

Prescribing Zonally Asymmetric Ozone Climatologies in Climate Models: Performance Compared to a Chemistry-Climate Model.

Three different methods of specifying ozone in an atmosphere-only version of the HadGEM3-A global circulation model are compared to the coupled chemistry configuration of this model. These methods include a specified zonal-mean ozone climatology, a specified 3-D ozone climatology, and a calculated-asymmetry scheme in which a specified zonal-mean ozone field is adapted online to be consistent with dynamically produced zonal asymmetries. These simulations all use identical boundary conditions and, by construction, have the same climatological zonal-mean ozone, that of the coupled chemistry configuration of the model.

Dysregulated IL-1β-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine.

Background: Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF.

Tail-Cuff Technique and Its Influence on Central Blood Pressure in the Mouse.

Background: Reliable measurement of blood pressure in conscious mice is essential in cardiovascular research. Telemetry, the "gold-standard" technique, is invasive and expensive and therefore tail-cuff, a noninvasive alternative, is widely used. However, tail-cuff requires handling and restraint during measurement, which may cause stress affecting blood pressure and undermining reliability of the results.

Intravital multiphoton imaging of mouse tibialis anterior muscle.

Intravital imaging by multiphoton microscopy is a powerful tool to gain invaluable insight into tissue biology and function. Here, we provide a step-by-step tissue preparation protocol for imaging the mouse tibialis anterior skeletal muscle. Additionally, we include steps for jugular vein catheterization that allow for well-controlled intravenous reagent delivery.

Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions.

The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice.

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse.

Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.

Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis.

Background: The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice.

The tachykinin NK1 receptor was suggested to be involved in psychiatric disorders, but its antagonists have failed to be effective as antidepressants in clinical trials. Hemokinin-1 (HK-1), the newest tachykinin, is present in several brain regions and activates the NK1 receptor similarly to substance P (SP), but acts also through other mechanisms. Therefore, we investigated the roles of the Tac4 gene-derived HK-1 in comparison with SP and neurokinin A (NKA) encoded by the Tac1 gene, as well as the NK1 receptor in anxiety and depression-like behaviors in mice.

Investigating how the attributes of self-associated drug complexes influence the passive transport of molecules through biological membranes.

Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p<0.

The application of local hypobaric pressure - A novel means to enhance macromolecule entry into the skin.

The local application of controlled hypobaric stress represents a novel means to facilitate drug delivery into the skin. The aims of this work were to understand how hypobaric stress modified the properties of the skin and assess if this penetration enhancement strategy could improve the percutaneous penetration of a macromolecule. Measurements of skin thickness demonstrated that the topical application of hypobaric stress thinned the tissue (p<0.