Isotropy of Cosmic Rays beyond 10

We report an estimation of the injected mass composition of ultrahigh energy cosmic rays (UHECRs) at energies higher than 10 EeV. The composition is inferred from an energy-dependent sky distribution of UHECR events observed by the Telescope Array surface detector by comparing it to the Large Scale Structure of the local Universe. In the case of negligible extragalactic magnetic fields (EGMFs), the results are consistent with a relatively heavy injected composition at E∼10 EeV that becomes lighter up to E∼100 EeV, while the composition at E>100 EeV is very heavy. The latter is true even in the presence of highest experimentally allowed extragalactic magnetic fields, while the composition at lower energies can be light if a strong EGMF is present. The effect of the uncertainty in the galactic magnetic field on these results is subdominant.

Frailty Trajectories and Its Associated Factors in Japanese Older Adults.

BACKGROUND: Associated factors for frailty development according to age group remain unclear. OBJECTIVES: To identify frailty score trajectories among community-dwelling older Japanese individuals and examine their associated factors. DESIGN: 13-year longitudinal study. SETTING: Kusatsu Town in Gunma Prefecture, Japan. PARTICIPANTS: 1706 older adults aged ≥ 65 years who completed an annual frailty assessment at least once between 2007 and 2019. MEASUREMENTS: Frailty status was determined using an index based on the Fried frailty phenotype criteria. Potential associated factors for frailty trajectory included physical, biological, lifestyle-related, and psychological factors, as well as comorbidities. RESULTS: We identified five trajectory patterns in the frailty score from age of 65 to 90 years -individuals who were robust (Group 1, 10.5%) as well as individuals with late-onset frailty (Group 2, 16.1%), middle-onset frailty (Group 3, 25.6% and Group 4, 35.2%), and early-onset frailty (Group 5, 12.7%). Compared with the other groups, the early-onset group showed a higher prevalence of cerebrovascular diseases, bone and joint diseases, poor nutrition, sarcopenia, hospitalization, low cognitive function, and smoking at the end of follow-up. Associated factors in the middle-onset group largely overlapped with those of the early-onset group. The late-onset frailty group tended to have a higher association with heart disease and bone and joint diseases compared with the robust group. CONCLUSION: Our findings from a 13-year longitudinal study identified five frailty trajectory patterns and seven associated factors for frailty trajectory. Proposed effective population-based frailty prevention strategies in each age group may contribute to effective strategies to extend healthy life expectancy in aging, aged, and super-aged communities.

Georectified polygon database of ground-mounted large-scale solar photovoltaic sites in the United States.

Over 4,400 large-scale solar photovoltaic (LSPV) facilities operate in the United States as of December 2021, representing more than 60 gigawatts of electric energy capacity. Of these, over 3,900 are ground-mounted LSPV facilities with capacities of 1 megawatt direct current (MWdc) or more. Ground-mounted LSPV installations continue increasing, with more than 400 projects appearing online in 2021 alone; however, a comprehensive, publicly available georectified dataset including spatial footprints of these facilities is lacking. The United States Large-Scale Solar Photovoltaic Database (USPVDB) was developed to fill this gap. Using US Energy Information Administration (EIA) data, locations of 3,699 LSPV facilities were verified using high-resolution aerial imagery, polygons were digitized around panel arrays, and attributes were appended. Quality assurance and control were achieved via team peer review and comparison to other US PV datasets. Data are publicly available via an interactive web application and multiple downloadable formats, including: comma-separated value (CSV), application programming interface (API), and GIS shapefile and GeoJSON.

An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

Muscle Evaluation and Hospital-Associated Disability in Acute Hospitalized Older Adults.

OBJECTIVES: We aimed to examine the association of muscle evaluation, including muscle ultrasound, with hospital-associated disability (HAD), focusing on ADL categories. DESIGN: A prospective observational cohort study. SETTING AND PARTICIPANTS: We recruited patients aged 65 years or older who were admitted to the geriatric ward of an acute hospital between October 2019 and September 2021. MEASUREMENTS: Handgrip strength, bioimpedance analyzer-determined skeletal muscle mass, bilateral thigh muscle thickness (BATT), and the echo intensity of the rectus femoris on muscle ultrasound were performed as muscle assessments. HAD was evaluated separately for mobility impairments and self-care impairments. RESULTS: In total, 256 individuals (mean age, 85.2 years; male sex, 41.8%) were analyzed. HAD in mobility was more common than HAD in self-care (37.5% vs. 30.0%). Only BATT was independently associated with HAD in mobility in multiple logistic regression analysis. There was no significant association between muscle indicators and HAD in self-care. CONCLUSION: A lower BATT was associated with a higher prevalence of HAD in mobility, suggesting the need to reconsider muscle assessment methods in hospitalized older adults. In addition, approaches other than physical may be required, such as psychosocial and environmental interventions to improve HAD in self-care.

Structure-activity relationships of antifungal phenylpropanoid derivatives and their synergy with n-dodecanol and fluconazole.

trans-Anethole (anethole) is a phenylpropanoid; with other drugs, it exhibits synergistic activity against several fungi and is expected to be used in new therapies that cause fewer patient side effects. However, the detailed substructure(s) of the molecule responsible for this synergy has not been fully elucidated. We investigated the structure-activity relationships of phenylpropanoids and related derivatives, with particular attention on the methoxy group and the double bond of the propenyl group in anethole, as well as the length of the p-alkyl chain in p-alkylanisoles. Antifungal potency was largely related to p-alkyl chain length and the methoxy group of anethole, but not to the double bond of its propenyl group. Production of reactive oxygen species also played a role in these fungicidal activities. Inhibition of drug efflux was associated with the length of the p-alkyl chain and the double bond of the propenyl group in anethole, but not with the methoxy group. Although a desirable synergy was observed between n-dodecanol and anethole or p-alkylanisoles with a length of C2-C6 in alkyl chains, it cannot be explained away as being solely due to the inhibition of drug efflux. Similar results were obtained when phenylpropanoid derivatives were combined with fluconazole against Candida albicans.

The Green Light on Buying a Car: How Consumer Decision-Making Interacts with Environmental Attributes in the New Vehicle Purchase Process.

Although it is commonly understood that the average U.S. new vehicle buyer ranks price and safety above environmental attributes, a stated ranking of one shopping criterion above another is not necessarily maintained when consumers make an actual purchase decision. In fact, the distribution of shopping criteria rankings is not well understood, and it is unclear how rankings translate to the attributes of purchased vehicles. This raises several related questions: What is the distribution of shopping criteria rankings across the U.S. and how do they differ among demographic groups and purchasers of different vehicle fuel types or body styles?How do consumers weigh their purchase criteria?How does the environmental impact of a vehicle rank as a purchase criterion for U.S. new vehicle buyers, and its importance differ among gender, age, or income groups?Do purchase criteria differ for consumers who state that they value the environment?Is a consumer's shopping criteria ranking of environmental attributes reflected in the vehicles they consider and ultimately purchase? We explore these issues using data from an extensive survey of new vehicle buyers in 2014, 2015, and 2016 (approximately 250,000 respondents per year). We broadly find the environmental criterion outranked by preference for safety and performance, but different patterns emerge across groups defined by household income, purchased vehicle fuel type, and other measures of respondent attitude toward the environment. Stated preferences for environmental attributes align with higher fuel economy and greater likelihood of electric or hybrid fuel type within considered and purchased vehicles.

Exploring rare cellular activity in more than one million cells by a transscale scope.

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.

Prognostic impact of six versus eight cycles of standard regimen in patients with diffuse large B-cell lymphoma: propensity score-matching analysis.

BACKGROUND: R-CHOP-21 has been the standard treatment for diffuse large B-cell lymphoma (DLBCL), but there is a paucity of evidence focusing on the number of cycles of regimens. PATIENTS AND METHODS: We conducted a retrospective study to compare the effectiveness of six cycles of standard regimens versus eight cycles for overall survival (OS) in DLBCL patients using propensity score matching, in consideration of relative dose intensity (RDI). RESULTS: A total of 685 patients with newly diagnosed DLBCL were identified in three institutions from 2007 to 2017. Patients treated using six cycles of standard regimens were matched by propensity scores with those treated using eight cycles. A 1 : 1 propensity score matching yielded 138 patient pairs. Eight cycles did not significantly improve OS in the conventional Cox proportional hazards model (hazard ratio 0.849, 95% confidence interval 0.453-1.588, P = 0.608). Restricted cubic spline Cox models for OS confirmed that the effect of the number of cycles was not modified by total average RDI, the International Prognostic Index, and age. Occurrence of adverse events did not differ between six and eight cycles. CONCLUSION: Even considering the impact of RDI, six cycles of the initial standard regimen for DLBCL is not inferior to eight cycles.

Construction and validation of a scoring system to predict resistance to chemotherapeutic drugs using gene expression profiles in canine lymphoma.

The present study aimed to verify the changes in the expression levels of 13 candidate genes associated with chemotherapy resistance and to construct a scoring system to predict resistance to these drugs. The expression levels of the 13 candidate genes were compared between 20 dogs with lymphoma that were sensitive to drugs used in CHOP-based protocol and 16 dogs with lymphoma that were resistant to these drugs. The expression levels of six genes; ASNS, CCR3, CALCA, FCER1A, LOC448801, and EDNRB were significantly different between the two groups. A scoring system to predict resistance to cyclophosphamide, doxorubicin and vincristine, which are used in CHOP-based protocol, was constructed based on expression levels of the six genes in these 36 dogs using logistic regression models. After internal validation, sensitivity and specificity of the scoring system were 0.759 and 0.853, respectively. External validation was conducted in another cohort of 33 dogs with lymphoma, and sensitivity and specificity of the scoring system were 0.800 and 0.696, respectively. In conclusion, this study identified six genes associated with resistance to drugs used in CHOP-based protocol in canine lymphoma and proposed a novel scoring system to predict resistance to these drugs. This system might be beneficial in selecting the most appropriate chemotherapy protocol for individual dogs with lymphoma.

Enhancing the fungicidal activity of amphotericin B via vacuole disruption by benzyl isothiocyanate, a cruciferous plant constituent.

Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+ -permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections.

Severe Dirac Mass Gap Suppression in Sb2Te3-Based Quantum Anomalous Hall Materials.

The quantum anomalous Hall (QAH) effect appears in ferromagnetic topological insulators (FMTIs) when a Dirac mass gap opens in the spectrum of the topological surface states (SSs). Unaccountably, although the mean mass gap can exceed 28 meV (or ∼320 K), the QAH effect is frequently only detectable at temperatures below 1 K. Using atomic-resolution Landau level spectroscopic imaging, we compare the electronic structure of the archetypal FMTI Cr0.08(Bi0.1Sb0.9)1.92Te3 to that of its nonmagnetic parent (Bi0.1Sb0.9)2Te3, to explore the cause. In (Bi0.1Sb0.9)2Te3, we find spatially random variations of the Dirac energy. Statistically equivalent Dirac energy variations are detected in Cr0.08(Bi0.1Sb0.9)1.92Te3 with concurrent but uncorrelated Dirac mass gap disorder. These two classes of SS electronic disorder conspire to drastically suppress the minimum mass gap to below 100 µeV for nanoscale regions separated by <1 µm. This fundamentally limits the fully quantized anomalous Hall effect in Sb2Te3-based FMTI materials to very low temperatures.

Publisher Correction: A New Landscape of Multiple Dispersion Kinks in a High-Tc Cuprate Superconductor.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Atomic-scale electronic structure of the cuprate pair density wave state coexisting with superconductivity.

The defining characteristic of hole-doped cuprates is d-wave high temperature superconductivity. However, intense theoretical interest is now focused on whether a pair density wave state (PDW) could coexist with cuprate superconductivity [D. F. Agterberg et al., Annu. Rev. Condens. Matter Phys. 11, 231 (2020)]. Here, we use a strong-coupling mean-field theory of cuprates, to model the atomic-scale electronic structure of an eight-unit-cell periodic, d-symmetry form factor, pair density wave (PDW) state coexisting with d-wave superconductivity (DSC). From this PDW + DSC model, the atomically resolved density of Bogoliubov quasiparticle states [Formula: see text] is predicted at the terminal BiO surface of Bi2Sr2CaCu2O8 and compared with high-precision electronic visualization experiments using spectroscopic imaging scanning tunneling microscopy (STM). The PDW + DSC model predictions include the intraunit-cell structure and periodic modulations of [Formula: see text], the modulations of the coherence peak energy [Formula: see text] and the characteristics of Bogoliubov quasiparticle interference in scattering-wavevector space [Formula: see text] Consistency between all these predictions and the corresponding experiments indicates that lightly hole-doped Bi2Sr2CaCu2O8 does contain a PDW + DSC state. Moreover, in the model the PDW + DSC state becomes unstable to a pure DSC state at a critical hole density p*, with empirically equivalent phenomena occurring in the experiments. All these results are consistent with a picture in which the cuprate translational symmetry-breaking state is a PDW, the observed charge modulations are its consequence, the antinodal pseudogap is that of the PDW state, and the cuprate critical point at p* ≈ 19% occurs due to disappearance of this PDW.

Accuracy of mandible-independent maxillary repositioning using pre-bent locking plates: a pilot study.

The double splint method is considered the gold standard for maxillary repositioning, but the procedure is lengthy and prone to error. Recent splintless methods have shown high repositioning accuracy; however, high costs and technical demands make them inaccessible to many patients. Therefore, a new cost-effective method of mandible-independent maxillary repositioning using pre-bent locking plates is proposed. Plates are bent on maxillary models in the planned position prior to surgery. The locations of the plate holes are replicated during surgery using osteotomy guides made from thermoplastic resin sheets. Pre-bent plates are subsequently fitted onto the maxilla, and plate holes are properly set to reposition the maxilla. The purpose of this study was to evaluate the accuracy of this method for maxillary repositioning and the reproducibility of the plate holes. Fifteen orthognathic surgery patients were evaluated retrospectively by superimposing preoperative simulations over their postoperative computed tomography models. The median deviations in maxillary repositioning and plate hole positioning between the preoperative plan and postoperative results were 0.43mm (range 0-1.55mm) and 0.33mm (range 0-1.86mm), respectively. There was no significant correlation between these deviations, suggesting that the method presented here allows highly accurate and reliable mandible-independent maxillary repositioning.

Postoperative stability of conventional bimaxillary surgery compared with maxillary impaction surgery with mandibular autorotation for patients with skeletal class II retrognathia.

We aimed to compare the postoperative stability of conventional bimaxillary surgery (with bilateral sagittal split osteotomy) with that of maxillary impaction surgery (with mandibular autorotation without bilateral sagittal split osteotomy) in patients with skeletal class II retrognathia. Patients were assigned to have conventional bimaxillary surgery (conventional group, n=6) or mandibular autorotation (experimental group, n=7). Measurements were made using serial lateral cephalometric radiographs taken immediately preoperatively (T0), immediately postoperatively (T1), and one year later (T2) to assess the variation in operative change (T1-T0) and relapse (T2-T1). There was no significant difference in median (range) surgical change in the anterior movement at point B (conventional group, 4.5 (3.0-11.0) mm; experimental group 4.1 (2.1-6.4) mm). However, there was a significant difference in median (range) surgical posterior movement relapse at point B (conventional group -1.7 (-2.3 to -0.5) mm; experimental group -0.6 (-1.0 to 1.0) mm; p=0.032). Mandibular advancement with mandibular autorotation is therefore a more stable procedure than mandibular advancement with bilateral sagittal split osteotomy in patients with skeletal class II retrognathia.

Enhancement of paraben-fungicidal activity by sulforaphane, a cruciferous vegetable-derived isothiocyanate, via membrane structural damage in Saccharomyces cerevisiae.

Parabens have been widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, foods and beverages. Commonly, methyl-, ethyl-, propyl- and butylparaben are used independently or in combination to maintain the quality of industrial products, and they are considered to have low toxicity. However, recent evidence has suggested that parabens are toxic in mammalian cells, and parabens have been associated with allergic-contact dermatitis, breast cancer and changes in testosterone levels. Sulforaphane, a cruciferous vegetable-derived isothiocyanate, was effective in decreasing the growth inhibitory concentrations of ethyl-, propyl-, butyl- and methylparaben in the yeast Saccharomyces cerevisiae. The sulforaphane-enhanced fungicidal effects of methylparaben were deemed to be caused by drastic cell membrane damage and the leakage of internal substances, such as nucleotides, from S. cerevisiae cells. Moreover sulforaphane markedly decreased the minimum concentration of methyl- and ethylparaben required to inhibit the growth of various microbes, such as the pathogenic yeast that causes severe mycosis, Candida albicans; the filamentous fungi Aspergillus niger; and the Gram-negative bacterium Escherichia coli. Enhanced antimicrobial activity from the beneficial components of edible plants may increase paraben efficacy at low concentrations and minimize preservative-induced side effects in consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: Sulforaphane, a natural and beneficial cruciferous vegetable-derived isothiocyanate, increased the ability of parabens to disrupt fungal cell membranes. Paraben-containing products have been reported to cause allergic contact dermatitis and drug hypersensitivity; therefore, methods to preserve organic products that may reduce the concentrations of parabens are both timely and necessary. In this study, we found that the combined antimicrobial effects of sulforaphane and parabens had the potential to reduce the paraben concentration needed to preserve organic products, thereby indicating that paraben toxicity may be reduced without affecting its activity as a preservative.

Reduced marine phytoplankton sulphur emissions in the Southern Ocean during the past seven glacials.

Marine biogenic sulphur affects Earth's radiation budget and may be an indicator of primary productivity in the Southern Ocean, which is closely related to atmospheric CO2 variability through the biological pump. Previous ice-core studies in Antarctica show little climate dependence of marine biogenic sulphur emissions and hence primary productivity, contradictory to marine sediment records. Here we present new 720,000-year ice core records from Dome Fuji in East Antarctica and show that a large portion of non-sea-salt sulphate, which was traditionally used as a proxy for marine biogenic sulphate, likely originates from terrestrial dust during glacials. By correcting for this, we make a revised calculation of biogenic sulphate and find that its flux is reduced in glacial periods. Our results suggest reduced dimethylsulphide emissions in the Antarctic Zone of the Southern Ocean during glacials and provide new evidence for the coupling between climate and the Southern Ocean sulphur cycle.

Machine learning in electronic-quantum-matter imaging experiments.

For centuries, the scientific discovery process has been based on systematic human observation and analysis of natural phenomena1. Today, however, automated instrumentation and large-scale data acquisition are generating datasets of such large volume and complexity as to defy conventional scientific methodology. Radically different scientific approaches are needed, and machine learning (ML) shows great promise for research fields such as materials science2-5. Given the success of ML in the analysis of synthetic data representing electronic quantum matter (EQM)6-16, the next challenge is to apply this approach to experimental data-for example, to the arrays of complex electronic-structure images17 obtained from atomic-scale visualization of EQM. Here we report the development and training of a suite of artificial neural networks (ANNs) designed to recognize different types of order hidden in such EQM image arrays. These ANNs are used to analyse an archive of experimentally derived EQM image arrays from carrier-doped copper oxide Mott insulators. In these noisy and complex data, the ANNs discover the existence of a lattice-commensurate, four-unit-cell periodic, translational-symmetry-breaking EQM state. Further, the ANNs determine that this state is unidirectional, revealing a coincident nematic EQM state. Strong-coupling theories of electronic liquid crystals18,19 are consistent with these observations.