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Serial crystallography (SX) is a cutting-edge technique in structural biology, involving the systematic collection of X-ray diffraction data from numerous randomly oriented microcrystals. To extract comprehensive three-dimensional information about the studied system, SX utilises thousands of measured diffraction patterns. As such, SX takes advantages of the properties of modern X-ray sources, including Free Electron Lasers (FELs) and third and fourth generation synchrotrons, as well as contemporary high-repetition-rate detectors. Efficient analysis of the extensive datasets generated during SX experiments demands fast and effective algorithms. The FDIP library offers meticulously optimised functions tailored for preprocessing data obtained in SX experiments. This encompasses tasks such as background subtraction, identification and masking of parasitic streaks, elimination of unwanted powder diffraction (e.g., from ice or salt crystals), and pinpointing useful Bragg peaks in each diffraction pattern. The library is equipped with a user-friendly graphical interface for facile parameter adjustment tailored to specific datasets. Compatible with popular SX processing software like OnDA, Cheetah, CrystFEL, and Merge3D, the FDIP library enhances the capabilities of these tools for streamlined and precise serial crystallography analyses., Helmholtz Association of German Research Centres

Purpose: Surgical stabilization of rib fractures (SSRF) improves outcomes in certain patient populations. The Chest Wall Injury Society (CWIS) began a new initiative to recognize centers who epitomize their mission as CWIS Collaborative Centers (CWIS-CC). We sought to describe incidence and epidemiology of SSRF at our institutions. Methods: A retrospective registry evaluation of all patients (age > 15 years) treated at international trauma centers from 1/1/20 to 7/30/2021 was performed. Variables included: age, gender, mechanism of injury, injury severity score, abbreviated injury severity score (AIS), emergency department disposition, length of stay, presence of rib/sternal fractures, and surgical stabilization of rib/sternal fractures. Classification and regression tree analysis (CART) was used for analysis. Results: Data were collected from 9 centers, 26,084 patient encounters. Rib fractures were present in 24% (n = 6294). Overall, 2% of all patients underwent SSRF and 8% of patients with rib fractures underwent SSRF. CART analysis of SSRF by AIS-Chest demonstrated a difference in management by age group. AIS-Chest 3 had an SSRF rate of 3.7, 7.3, and 12.9% based on the age ranges (16–19; 80–110), (20–49; 70–79), and (50–69), respectively (p = 0.003). AIS-Chest > 3 demonstrated an SSRF rate of 9.6, 23.3, and 39.3% for age ranges (16–39; 90–99), (40–49; 80–89), and (50–79), respectively (p = 0.001). Conclusion: Anticipated rate of SSRF can be calculated based on number of rib fractures, AIS-Chest, and age. The disproportionate rate of SSRF in patients age 50–69 with AIS-Chest 3 and age 50–79 with AIS-Chest > 3 should be further investigated, as lower frequency of SSRF in the other age ranges may lead to care inequalities.

The ability to extract material parameters of perovskite from quantitative experimental analysis is essential for rational design of photovoltaic and optoelectronic applications. However, the difficulty of this analysis increases significantly with the complexity of the theoretical model and the number of material parameters for perovskite. Here we use Bayesian optimization to develop an analysis platform that can extract up to 8 fundamental material parameters of an organometallic perovskite semiconductor from a transient photoluminescence experiment, based on a complex full physics model that includes drift-diffusion of carriers and dynamic defect occupation. An example study of thermal degradation reveals that the carrier mobility and trap-assisted recombination coefficient are reduced noticeably, while the defect energy level remains nearly unchanged. The reduced carrier mobility can dominate the overall effect on thermal degradation of perovskite solar cells by reducing the fill factor, despite the opposite effect of the reduced trap-assisted recombination coefficient on increasing the fill factor. In future, this platform can be conveniently applied to other experiments or to combinations of experiments, accelerating materials discovery and optimization of semiconductor materials for photovoltaics and other applications., Comment: The work is published in Energy & Environmental Science (DOI: 10.1039/D4EE00911H). This work is supported by the Australian Centre for Advanced Photovoltaics (ACAP) and received funding from the Australian Renewable Energy Agency (ARENA). H.Z. acknowledges the support of the ACAP Fellowship. H.Z. thanks Pawsey for providing the Nimbus Research Cloud Service

We present the first direct observations of acoustic waves in warm dense matter. We analyze wavenumber- and energy-resolved X-ray spectra taken from warm dense methane created by laser-heating a cryogenic liquid jet. X-ray diffraction and inelastic free electron scattering yield sample conditions of 0.3$\pm$0.1 eV and 0.8$\pm$0.1 g/cm$^3$, corresponding to a pressure of $\sim$13 GPa and matching the conditions predicted in the thermal boundary layer between the inner and outer envelope of Uranus. Inelastic X-ray scattering was used to observe the collective oscillations of the ions. With a highly improved energy resolution of $\sim$50 meV, we could clearly distinguish the Brillouin peaks from the quasi-elastic Rayleigh feature. Data at different wavenumbers were used to obtain a sound speed of 5.9$\pm$0.5 km/s, which enabled us to validate the use of Birch's law in this new parameter regime., Comment: 7 pages, 4 figures with supplementary information

"Sacrificing Indian Childrens' Rights""Paleface Paternalism""Justice Massacred""Ethnic Errancy""Rose Parade Indian-givers""Slaves to the tribe""Tribal bigotry""Kids pay the price for tribes"The phrases listed above are published titles of newspaper editorials and op-ed essays challenging the legitimacy of the federal Indian Child Welfare Act ("ICWA") in the last 40 years. ICWA is a federal law originally passed in 1978 to address the high rate of removal (and subsequent adoption) of Indian children by state authorities. In passing the law, Congress found "there is no resource that is more vital to the continued existence and integrity of Indian tribes than their children." While there was no significant controversy about the law when it was drafted and passed with unanimous consent in 1978, the application of the law over the past 40 years, the law has come under sustained attack from scholars, attorneys, legislators, think tanks, adoption agencies, and judges. Moreover, while most child custody cases impacted by ICWA are so conventional that they don't warrant any particular attention, almost all national news coverage of ICWA emanates from a few specific high-profile cases in which mainstream news outlets usually characterize ICWA as cultivating unfair battles between Tribal Nations and prospective adoptive parents. Editorials, though, often go further than that, using words like "sacrificing", "massacre", and "slaves" to describe both tribal citizens and tribal nations. This article focuses on how these high-profile cases are characterized in newspaper editorials and op-eds; namely how these authors explicate their colonial views about ICWA, Indian identity, tribal sovereignity, and the virtues of adoption.

Biodiversity is in crisis, and insects are no exception. To understand insect population and community trends globally, it is necessary to identify and synthesize diverse datasets representing different taxa, regions, and habitats. The relevant literature is, however, vast and challenging to aggregate. The Entomological Global Evidence Map (EntoGEM) project is a systematic effort to search for and catalogue studies with long-term data that can be used to understand changes in insect abundance and diversity. Here, we present the overall EntoGEM framework and results of the first completed subproject of the systematic map, which compiled sources of information about changes in dragonfly and damselfly (Odonata) occurrence, abundance, biomass, distribution, and diversity. We identified 45 multi-year odonate datasets, including 10 studies with data that span more than 10 years. If data from each study could be gathered or extracted, these studies could contribute to analyses of long-term population trends of this important group of indicator insects. The methods developed to support the EntoGEM project, and its framework for synthesizing a vast literature, have the potential to be applied not only to other broad topics in ecology and conservation, but also to other areas of research where data are widely distributed.

The study is designed to assist police and other law enforcement agencies, as well as local government officials, in planning new burglary prevention activities and modifying existing ones. Information was compiled from (1) a survey of 50 United States police departments, (2) site visits to 12 departments with operating burglary prevention programs, (3) a literature review, and (4) meetings with offenders, victims, and law enforcement, business, and citizen groups. The study's major findings and recommendations are presented in chapter 2, covering problems that communities face in preventing burglaries and in developing prevention programs. Chapter 3 identifies burglary prevention activities currently used in the 50 cities surveyed. Several of those activities are discussed in detail in chapters 4 through 8: crime-patterns and vulnerability analysis and evaluation, community education, premise security surveys, property marking programs, patrol and surveillance activities, and anti-fencing operations. Tables provide statistics on burglaries and crime prevention programs. Appended materials (28 pages) describe: various police crime prevention training programs, the Minnesota Crime Watch program, Oakland and Los Angeles (California) security ordinances, A Model for Estimating Aggregate Deterence and Apprehension Effects, and a two-page bibliography. (BP)

The project, which utilized a series of workshops and supervisory visits to successfully plan a curriculum in the work ethic for grades 4-6, originated in response to a concern expressed by western Massachusetts educators and employers as to the attitudes toward work of their students and employees. The project report includes: (1) project, teacher, and student objectives; (2) a financial statement; (3) list of participants; (4) an introduction which briefly describes project philosophy, participant selection and responsibilities, implementations, and suggestions for continuation; (5) workshop schedules; and (6) a three-page list of materials purchased for the project. The bulk of the document (106 pages) contains detailed teacher developed units for the three grade levels. Teachers involved in the project found they needed to focus on the interrelationships between work attitudes, self-esteem, and the interdependence of individuals. The units are composed of specific self-awareness and career awareness activities with objectives, teaching procedures, and student materials or lists of material sources. The report also contains a project evaluation form for use by the 24 participating teachers and a copy of a brochure describing the project. (Author/MS)

Polymer passivation layers can improve the open-circuit voltage of perovskite solar cells when inserted at the perovskite–charge transport layer interfaces. Unfortunately, many such layers are poor conductors, leading to a trade-off between passivation quality (voltage) and series resistance (fill factor, FF). Here, we introduce a nanopatterned electron transport layer that overcomes this trade-off by modifying the spatial distribution of the passivation layer to form nanoscale localized charge transport pathways through an otherwise passivated interface, thereby providing both effective passivation and excellent charge extraction. By combining the nanopatterned electron transport layer with a dopant-free hole transport layer, we achieved a certified power conversion efficiency of 21.6% for a 1-square-centimeter cell with FF of 0.839, and demonstrate an encapsulated cell that retains ~91.7% of its initial efficiency after 1000 hours of damp heat exposure.

Plant–animal interactions are key to sustaining whole communities and ecosystem function. However, their complexity may limit our understanding of the underlying mechanisms and the species involved. The ecological effects of epizoochory remain little known compared to other seed dispersal mechanisms given the few vectors identified. In addition, epizoochory is mostly considered non-mutualistic since dispersers do not obtain nutritional rewards. Here, we show a widespread but unknown mutualistic interaction between parrots and plants through epizoochory. Combining our observations with photos from web-sources, we recorded nearly 2000 epizoochory events in 48 countries across five continents, involving 116 parrot species and nearly 100 plant species from 35 families, including both native and non-native species. The viscid pulp of fleshy fruits and anemochorous structures facilitate the adherence of tiny seeds (mean 3.7 × 2.56 mm) on the surface of parrots while feeding, allowing the dispersion of these seeds over long distances (mean = 118.5 m). This parrot–plant mutualism could be important in ecosystem functioning across a wide diversity of environments, also facilitating the spread of exotic plants. Future studies should include parrots for a better understanding of plant dispersal processes and for developing effective conservation actions against habitat loss and biological invasions.

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested alreadyapproved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.

Perceived lack of tools, and fears of the sensitivity of DNA data, should not be obstacles

While most of the knowledge on invasive species focuses on their impacts, little is known about their potential positive effects on other species. Invasive ecosystem engineers can disrupt recipient environments; however, they may also facilitate access to novel resources for native species. The monk parakeet (Myiopsitta monachus) is a worldwide invader and the only parrot that builds its own communal nests, which can be used by other species. However, the ecological effects of these interspecific interactions are barely known. We compared the role of the monk parakeet as a nest-site facilitator in different rural and urban areas, both invaded and native, across three continents and eight breeding seasons. A total of 2690 nests from 42 tenant species, mostly cavity-nesting birds, were recorded in 26% of 2595 monk parakeet nests. Rural and invaded areas showed the highest abundance and richness of tenant species. Multispecies communal nests triggered interspecific aggression between the monk parakeet host and its tenants, but also a cooperative defense against predators. Despite the positive effects for native species, monk parakeets also facilitate nesting opportunities to other non-native species and may also transmit diseases to tenants, highlighting the complexity of biotic interactions in biological invasions.

Plant–animal interactions are key to sustaining whole communities and ecosystem function. However, their complexity may limit our understanding of the underlying mechanisms and the species involved. The ecological effects of epizoochory remain little known compared to other seed dispersal mechanisms given the few vectors identified. In addition, epizoochory is mostly considered non-mutualistic since dispersers do not obtain nutritional rewards. Here, we show a widespread but unknown mutualistic interaction between parrots and plants through epizoochory. Combining our observations with photos from web-sources, we recorded nearly 2000 epizoochory events in 48 countries across five continents, involving 116 parrot species and nearly 100 plant species from 35 families, including both native and non-native species. The viscid pulp of fleshy fruits and anemochorous structures facilitate the adherence of tiny seeds (mean 3.7 2.56 mm) on the surface of parrots while feeding, allowing the dispersion of these seeds over long distances (mean = 118.5 m). This parrot–plant mutualism could be important in ecosystem functioning across a wide diversity of environments, also facilitating the spread of exotic plants. Future studies should include parrots for a better understanding of plant dispersal processes and for developing effective conservation actions against habitat loss and biological invasions

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale. There is thus a need for a more complex package of policy and practical responses. We undertook a solution scan to identify and collate 161 possible options for reducing the risks of further epidemic disease transmission from animals to humans, including potential further SARS-CoV-2 transmission (original or variants). We include all categories of animals in our responses (i.e. wildlife, captive, unmanaged/feral and domestic livestock and pets) and focus on pathogens (especially viruses) that, once transmitted from animals to humans, could acquire epidemic potential through high rates of human-to-human transmission. This excludes measures to prevent well-known zoonotic diseases, such as rabies, that cannot readily transmit between humans. We focused solutions on societal measures, excluding the development of vaccines and other preventive therapeutic medicine and veterinary medicine options that are discussed elsewhere. We derived our solutions through reading the scientific literature, NGO position papers, and industry guidelines, collating our own experiences, and consulting experts in different fields. Herein, we review the major zoonotic transmission pathways and present an extensive list of options. The potential solutions are organised according to the key stages of the trade chain and encompass solutions that can be applied at the local

While most of the knowledge on invasive species focuses on their impacts, little is known about their potential positive effects on other species. Invasive ecosystem engineers can disrupt recipient environments; however, they may also facilitate access to novel resources for native species. The monk parakeet (Myiopsitta monachus) is a worldwide invader and the only parrot that builds its own communal nests, which can be used by other species. However, the ecological effects of these interspecific interactions are barely known. We compared the role of the monk parakeet as a nest-site facilitator in different rural and urban areas, both invaded and native, across three continents and eight breeding seasons. A total of 2690 nests from 42 tenant species, mostly cavity-nesting birds, were recorded in 26% of 2595 monk parakeet nests. Rural and invaded areas showed the highest abundance and richness of tenant species. Multispecies communal nests triggered interspecific aggression between the monk parakeet host and its tenants, but also a cooperative defense against predators. Despite the positive effects for native species, monk parakeets also facilitate nesting opportunities to other non-native species and may also transmit diseases to tenants, highlighting the complexity of biotic interactions in biological invasions.

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Asynchrony is a critical cue informing the brain whether sensory signals are caused by a common source and should be integrated or segregated. This psychophysics‐electroencephalography (EEG) study investigated the influence of asynchrony on how the brain binds audiotactile (AT) signals to enable faster responses in a redundant target paradigm. Human participants actively responded (psychophysics) or passively attended (EEG) to noise bursts, ‘taps‐to‐the‐face’, and their AT combinations at seven AT asynchronies: 0, ±20, ±70, and ±500ms. Behaviourally, observers were faster at detecting AT than unisensory stimuli within a temporal integration window: the redundant target effect was maximal for synchronous stimuli and declined within a ≤70ms AT asynchrony. EEG revealed a cascade of AT interactions that relied on different neural mechanisms depending on AT asynchrony. At small (≤20ms) asynchronies, AT interactions arose for evoked response potentials (ERPs) at 110ms and ~400ms post‐stimulus. Selectively at ±70ms asynchronies AT interactions were observed for the P200 ERP, theta‐band inter‐trial coherence (ITC) and power at ~200ms poststimulus. In conclusion, AT binding was mediated by distinct neural mechanisms depending on the asynchrony of the AT signals. Early AT interactions in ERPs and theta‐band ITC and power were critical for the behavioural response facilitation within a ≤±70ms temporal integration window

Instability in perovskite solar cells is the main challenge for the commercialization of this solar technology. Here, a contactless, nondestructive approach is reported to study degradation across perovskite and perovskite/silicon tandem solar cells. The technique employs spectrally and spatially resolved absorptivity at sub-bandgap wavelengths of perovskite materials, extracted from their luminescence spectra. Parasitic absorption in other layers, carrier diffusion, and photon smearing phenomena are all demonstrated to have negligible effects on the extracted absorptivity. The absorptivity is demonstrated to reflect real degradation in the perovskite film and is much more robust and sensitive than its luminescence spectral peak position, representing its optical bandgap, and intensity. The technique is applied to study various common factors which induce and accelerate degradation in perovskite solar cells including air and heat exposure and light soaking. Finally, the technique is employed to extract the individual absorptivity component from the perovskite layer in a monolithic perovskite/silicon tandem structure. The results demonstrate the value of this approach for monitoring degradation mechanisms in perovskite and perovskite/silicon tandem cells at early stages of degradation and various fabrication stages.

Synthesizing evidence is an essential part of scientific progress, but it is often done in a slow and uncoordinated manner, sometimes producing misleading conclusions. Here, we propose the idea of an ‘open synthesis community’ to resolve this pressing issue.

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

The European XFEL (EuXFEL) is a 3.4-km long X-ray source, which produces femtosecond, ultrabrilliant and spatially coherent X-ray pulses at megahertz (MHz) repetition rates. This X-ray source has been designed to enable the observation of ultrafast processes with near-atomic spatial resolution. Time-resolved crystallographic investigations on biological macromolecules belong to an important class of experiments that explore fundamental and functional structural displacements in these molecules. Due to the unusual MHz X-ray pulse structure at the EuXFEL, these experiments are challenging. Here, we demonstrate how a biological reaction can be followed on ultrafast timescales at the EuXFEL. We investigate the picosecond time range in the photocycle of photoactive yellow protein (PYP) with MHz X-ray pulse rates. We show that difference electron density maps of excellent quality can be obtained. The results connect the previously explored femtosecond PYP dynamics to timescales accessible at synchrotrons. This opens the door to a wide range of time-resolved studies at the EuXFEL.

The new European X-ray Free-Electron Laser (European XFEL) is the first X-ray free-electron laser capable of delivering intense X-ray pulses with a megahertz interpulse spacing in a wavelength range suitable for atomic resolution structure determination. An outstanding but crucial question is whether the use of a pulse repetition rate nearly four orders of magnitude higher than previously possible results in unwanted structural changes due to either radiation damage or systematic effects on data quality. Here, separate structures from the first and subsequent pulses in the European XFEL pulse train were determined, showing that there is essentially no difference between structures determined from different pulses under currently available operating conditions at the European XFEL.

A crystallographic indexing algorithm,pinkIndexer, is presented for the analysisof snapshot diffraction patterns. It can be used in a variety of contexts includingmeasurements made with a monochromatic radiation source, a polychromaticsource or with radiation of very short wavelength. As such, the algorithm isparticularly suited to automated data processing for two emerging measurementtechniques for macromolecular structure determination: serial pink-beam X-raycrystallography and serial electron crystallography, which until now lackedreliable programs for analyzing many individual diffraction patterns fromcrystals of uncorrelated orientation. The algorithm requires approximateknowledge of the unit-cell parameters of the crystal, but not the wavelengthsassociated with each Bragg spot. The use ofpinkIndexeris demonstrated byobtaining 1005 lattices from a published pink-beam serial crystallography dataset that had previously yielded 140 indexed lattices. Additionally, in tests onexperimental serial crystallography diffraction data recorded with quasi-monochromatic X-rays and with electrons the algorithm indexed more patternsthan other programs tested.

China’s Belt and Road Initiative has led to an efflorescence of interest in the heritage of the “Silk Road,” both in China and abroad. In this article, I approach the BRI and its associated “Silk Road fever” ethnographically, discussing its effects on a particular region of China. What was once characterized in official discourse as a “remote border region” is now recovering its history of camel-based connectivity, and using this to imagine its future development. I situate this Silk Road discourse within the context of the politics of land, ethnicity, and the environment in a Chinese border region. Drawing on 18 months of ethnographic fieldwork in this region, and analysis of local publications, the article shows how this discourse provides ethnic Mongol elites in the west of the Inner Mongolia Autonomous Region with resources to defend pastoralist livelihoods threatened by the state’s recent grassland conservation policies. I thus show how the BRI’s spatial imaginary is “domesticated” in a particular part of China, and shine a light on the spatial politics which this imaginary – and the nonhumans involved in it – affords.

The new European X-ray Free-Electron Laser (European XFEL) is the first X-ray free-electron laser capable of delivering intense X-ray pulses with a megahertz interpulse spacing in a wavelength range suitable for atomic resolution structure determination. An outstanding but crucial question is whether the use of a pulse repetition rate nearly four orders of magnitude higher than previously possible results in unwanted structural changes due to either radiation damage or systematic effects on data quality. Here, separate structures from the first and subsequent pulses in the European XFEL pulse train were determined, showing that there is essentially no difference between structures determined from different pulses under currently available operating conditions at the European XFEL.

To date X-ray protein crystallography is the most successful technique available for the determination of high-resolution 3D structures of biological molecules and their complexes. In X-ray protein crystallography the structure of a protein is refined against the set of observed Bragg reflections from a protein crystal. The resolution of the refined protein structure is limited by the highest angle at which Bragg reflections can be observed. In addition, the Bragg reflections alone are typically insufficient (by a factor of two) to determine the structure ab initio, and so prior information is required. Crystals formed from an imperfect packing of the protein molecules may also exhibit continuous diffraction between and beyond these Bragg reflections. When this is due to random displacements of the molecules from each crystal lattice site, the continuous diffraction provides the necessary information to determine the protein structure without prior knowledge, to a resolution that is not limited by the angular extent of the observed Bragg reflections but instead by that of the diffraction as a whole. This article presents an iterative projection algorithm that simultaneously uses the continuous diffraction as well as the Bragg reflections for the determination of protein structures. The viability of this method is demonstrated on simulated crystal diffraction.

X-ray free electron lasers (XFELs) create new possibilities for structural studies of biological objects that extend beyond what is possible with synchrotron radiation. Serial femtosecond crystallography has allowed high-resolution structures to be determined from micro-meter sized crystals, whereas single particle coherent X-ray imaging requires development to extend the resolution beyond a few tens of nanometers. Here we describe an intermediate approach: the XFEL imaging of biological assemblies with helical symmetry. We collected X-ray scattering images from samples of microtubules injected across an XFEL beam using a liquid microjet, sorted these images into class averages, merged these data into a diffraction pattern extending to 2 nm resolution, and reconstructed these data into a projection image of the microtubule. Details such as the 4 nm tubulin monomer became visible in this reconstruction. These results illustrate the potential of single-molecule X-ray imaging of biological assembles with helical symmetry at room temperature.

Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.

The new European X-ray Free-Electron Laser (European XFEL) is the first X-ray free-electron laser capable of delivering intense X-ray pulses with a megahertz interpulse spacing in a wavelength range suitable for atomic resolution structure determination. An outstanding but crucial question is whether the use of a pulse repetition rate nearly four orders of magnitude higher than previously possible results in unwanted structural changes due to either radiation damage or systematic effects on data quality. Here, separate structures from the first and subse- quent pulses in the European XFEL pulse train were determined, showing that there is essentially no difference between structures deter- mined from different pulses under currently available operating conditions at the European XFEL.

Background: Evidence on the association between sitting for extended periods (i.e. prolonged sedentary time (PST)) and cardio-metabolic health is inconsistent in children. We aimed to estimate the differences in cardio-metabolic health associated with substituting PST with non-prolonged sedentary time (non-PST), light (LIPA) or moderate-to-vigorous physical activity (MVPA) in children. Methods: Cross-sectional data from 14 studies (7 countries) in the International Children's Accelerometry Database (ICAD, 1998-2009) was included. Accelerometry in 19,502 participants aged 3-18 years, together with covariate and outcome data, was pooled and harmonized. Iso-temporal substitution in linear regression models provided beta coefficients (95%CI) for substitution of 1 h/day PST (sedentary time accumulated in bouts > 15 min) with non-PST, LIPA or MVPA, for each study, which were meta-analysed. Results: Modelling substitution of 1 h/day of PST with non-PST suggested reductions in standardized BMI, but estimates were > 7-fold greater for substitution with MVPA (- 0.44 (- 0.62; - 0.26) SD units). Only reallocation by MVPA was beneficial for waist circumference (- 3.07 (- 4.47; - 1.68) cm), systolic blood pressure (- 1.53 (- 2.42; - 0.65) mmHg) and clustered cardio-metabolic risk (- 0.18 (- 0.3; - 0.1) SD units). For HDL-cholesterol and diastolic blood pressure, substitution with LIPA was beneficial; however, substitution with MVPA showed 5-fold stronger effect estimates (HDL-cholesterol: 0.05 (0.01; 0.10) mmol/l); diastolic blood pressure: - 0.81 (- 1.38; - 0.24) mmHg). Conclusions: Replacement of PST with MVPA may be the preferred scenario for behaviour change, given beneficial associations with a wide range of cardio-metabolic risk factors (including adiposity, HDL-cholesterol, blood pressure and clustered cardio-metabolic risk). Effect estimates are clinically relevant (e.g. an estimated reduction in waist circumference of ≈1.5 cm for 30 min/day replacement). Repl

The article commences with a review focusing on three critical aspects of the perovskite/Si tandem technology: the evolution of efficiencies to date, comparisons of Si subcell choices, and the interconnection design strategies. Building on this review, a clear route is provided for minimizing optical losses aided by optical simulations of a recently reported high‐efficiency perovskite/Si tandem system, optimizations which result in tandem current densities of ≈20 mAcm−2 with front‐side texture. The primary focus is on electrical modeling on the Si‐subcell, in order to understand the efficiency potential of this cell under filtered light in a tandem configuration. The possibility of increasing the Si subcell efficiency by 1% absolute is offered through joint improvements to the bulk lifetime, which exceeds 4 ms, and improves surface passivation quality to saturation current densities below 10 fA cm−2. Polycrystalline‐Si/SiOx passivating contacts are proposed as a promising alternative to partial‐area rear contacts, with the potential for further simplifying cell fabrication and improving device performance. A combination of optical modeling of the complete tandem structure alongside electrical modeling of the Si‐subcell, both with state‐of‐the‐art modeling tools, provides the first complete picture of the practical efficiency potential of perovskite/Si tandems.