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Glacial cycles of the late Quaternary are controlled by the asymmetrically varying mass balance of continental ice sheets in the Northern Hemisphere. Surface mass balance is governed by processes of ablation and accumulation. Here two ablation schemes, the positive-degree-day (PDD) method and the surface energy balance (SEB) approach, are compared in transient simulations of the last glacial cycle with the Earth system model of intermediate complexity CLIMBER-2. The standard version of the CLIMBER-2 model incorporates the SEB approach and simulates ice volume variations in reasonable agreement with paleoclimate reconstructions during the entire last glacial cycle. Using results from the standard CLIMBER-2 model version, we simulated ablation with the PDD method in offline mode by applying different combinations of three empirical parameters of the PDD scheme. We found that none of the parameter combinations allow us to simulate a surface mass balance of the American and European ice sheets that is similar to that obtained with the standard SEB method. The use of constant values for the empirical PDD parameters led either to too much ablation during the first phase of the last glacial cycle or too little ablation during the final phase. We then substituted the standard SEB scheme in CLIMBER-2 with the PDD scheme and performed a suite of fully interactive (online) simulations of the last glacial cycle with different combinations of PDD parameters. The results of these simulations confirmed the results of the offline simulations: no combination of PDD parameters realistically simulates the evolution of the ice sheets during the entire glacial cycle. The use of constant parameter values in the online simulations leads either to a buildup of too much ice volume at the end of glacial cycle or too little ice volume at the beginning. Even when the model correctly simulates global ice volume at the last glacial maximum (21 ka), it is unable to simulate complete deglaciation during the Holocene. According to our simulations, the SEB approach proves superior for simulations of glacial cycles.

The nonmesonic weak decay of Λ hypernuclei is studied within a microscopic diagrammatic approach which is extended to include the three-nucleon induced mechanism. We adopt a nuclear matter formalism which, through the local density approximation, allows us to model finite hypernuclei, a one-meson-exchange weak transition potential and a Bonn nucleon–nucleon strong potential. One-, two- and three-nucleon induced weak decay rates are predicted for CΛ12 by including ground state correlations up to second order in the nucleon–nucleon potential and the recoil of the residual nucleus. Three-nucleon stimulated decays, ΛNNN→nNNN (N=n or p), are considered here for the first time. The obtained decay rates compare well with the latest KEK and FINUDA data. The three-nucleon induced rate turns out to be dominated by nnp- and npp-induced decays, it amounts to ∼7% of the total nonmesonic rate and it is ∼1/2 of the neutron-induced decay rate. The reduction effect of the nuclear recoil is particularly relevant for the three-nucleon induced rates (∼15%), less important for the two-nucleon induced rates (∼4%) and negligible for the one-nucleon induced rates. Given the non-negligible size of the three-nucleon induced contribution and consequently its importance in the precise determination of the complete set of decay rates, new measurements and/or experimental analysis are encouraged.

Nanostructuring has been considered an effective approach to enhance the thermoelectric (TE) performance of materials by reducing their lattice thermal conductivity. In the present study, we show the influence of a process control agent (PCA) for ball milling, Stearic acid (SA), on the nano- and microstructure and thermoelectric properties of type-I clathrates in the Ba–Cu–Si system, which are promising candidates for TE applications. The SA effectively reduces cold welding and prevents particle agglomeration during ball milling. Consequently, it increases the powder yield and the milling efficiency. Smaller grain/crystallite sizes are obtained in the as-milled powders than without SA. Importantly, the SA forms nano-layers around the clathrate particles, which inhibit the grain growth during the hot pressing process used for powder compaction. Therefore, smaller grain sizes are also obtained in the hot-pressed samples. They show increased hardness and reduced thermal conductivity but also increased electrical resistivity. However, as the phonon transport is more strongly degraded than the charge transport, we observe 15% enhancement in the dimensionless thermoelectric figure of merit ZT by adding the PCA. Keywords: Nanostructured materials, Clathrates, Mechanical milling, Thermoelectric properties, Hardness, Microstructure

Evaluating how populations are connected by migration is important for understanding species resilience because gene flow can facilitate recovery from demographic declines. We therefore investigated the extent to which migration may have contributed to the global recovery of the Antarctic fur seal (Arctocephalus gazella), a circumpolar distributed marine mammal that was brought to the brink of extinction by the sealing industry in the eighteenth and nineteenth centuries. It is widely believed that animals emigrating from South Georgia, where a relict population escaped sealing, contributed to the re-establishment of formerly occupied breeding colonies across the geographical range of the species. To investigate this, we interrogated a genetic polymorphism (S291F) in the melanocortin 1 receptor gene, which is responsible for a cream-coloured phenotype that is relatively abundant at South Georgia and which appears to have recently spread to localities as far afield as Marion Island in the sub-Antarctic Indian Ocean. By sequencing a short region of this gene in 1492 pups from eight breeding colonies, we showed that S291F frequency rapidly declines with increasing geographical distance from South Georgia, consistent with locally restricted gene flow from South Georgia mainly to the South Shetland Islands and Bouvetøya. The S291F allele was not detected farther afield, suggesting that although emigrants from South Georgia may have been locally important, they are unlikely to have played a major role in the recovery of geographically more distant populations.

No contexto da temática da avaliação de desempenho, vida útil, degradação e diagnóstico de patologias, tem-se observado que os edifícios construídos em Brasília vêm apresentando elevados casos de manifestações patológicas nas fachadas. Esses fenômenos vêm sendo observados em edifícios nas mais diferentes idades, induzindo a questionamentos importantes na parte técnica, relacionados à compatibilidade dos materiais constituintes do sistema de revestimento, técnicas construtivas, degradação dos materiais e projeto. Neste sentido, o objetivo deste estudo consiste em apresentar uma metodologia de inspeção, identificação e quantificação das manifestações patológicas que ocorrem com maior frequência nas fachadas dos edifícios. A metodologia proposta consiste em uma sistematização do processo de inspeção, com identificação, mapeamento e quantificação das manifestações patológicas em uma amostra de 90 fachadas. Essa metodologia permite estabelecer índices de intensidade de ocorrência de danos em função da orientação solar e da idade, bem como permite determinar a intensidade de manifestação patológica em diferentes regiões das fachadas (paredes contínuas, aberturas, sacadas, cantos e extremidades, juntas, transição entre pavimentos e topo). A amostragem é tomada no contexto dos edifícios de Brasília com idade na faixa de 5 a 48 anos. Os resultados mostram elevado fator de dano de descolamento cerâmico e evidenciam que os valores mais elevados dos fatores de danos foram observados nas fachadas Norte e Oeste e ainda nas fachadas com idade acima de 10 anos. Os resultados mostram também que os danos ocorrem com maior frequência na região das paredes contínuas. Este estudo visa contribuir com a necessidade de sistematização da identificação, classificação e quantificação dos danos em fachadas com revestimento cerâmico.

Possible feedback effects between aeolian dust, climate and ice sheets are studied for the first time with an Earth system model of intermediate complexity over the late Pleistocene period. Correlations between climate and dust deposition records suggest that aeolian dust potentially plays an important role for the evolution of glacial cycles. Here climatic effects from the dust direct radiative forcing (DRF) caused by absorption and scattering of solar radiation are investigated. Key elements controlling the dust DRF are the atmospheric dust distribution and the absorption-scattering efficiency of dust aerosols. Effective physical parameters in the description of these elements are varied within uncertainty ranges known from available data and detailed model studies. Although the parameters can be reasonably constrained, the simulated dust DRF spans a~wide uncertainty range related to the strong nonlinearity of the Earth system. In our simulations, the dust DRF is highly localized. Medium-range parameters result in negative DRF of several watts per square metre in regions close to major dust sources and negligible values elsewhere. In the case of high absorption efficiency, the local dust DRF can reach positive values and the global mean DRF can be insignificantly small. In the case of low absorption efficiency, the dust DRF can produce a significant global cooling in glacial periods, which leads to a doubling of the maximum glacial ice volume relative to the case with small dust DRF. DRF-induced temperature and precipitation changes can either be attenuated or amplified through a feedback loop involving the dust cycle. The sensitivity experiments suggest that depending on dust optical parameters, dust DRF has the potential to either damp or reinforce glacial–interglacial climate changes.

In this talk, we summarize the work in progress toward a full characterization of strange star−strange star (SS−SS) mergers related to the GW/GRB/kilonova events. In addition, we show that the a priori probability constructed from the observed neutron star mass distribution points toward an asymmetric binary system as the progenitor of the GW170817 event.

General circulation models' (GCMs) estimates of the liquid water path adjustment to anthropogenic aerosol emissions differ in sign from other lines of evidence. This reduces confidence in estimates of the effective radiative forcing of the climate by aerosol–cloud interactions (ERFaci). The discrepancy is thought to stem in part from GCMs' inability to represent the turbulence–microphysics interactions in cloud-top entrainment, a mechanism that leads to a reduction in liquid water in response to an anthropogenic increase in aerosols. In the real atmosphere, enhanced cloud-top entrainment is thought to be the dominant adjustment mechanism for liquid water path, weakening the overall ERFaci. We show that the latest generation of GCMs includes models that produce a negative correlation between the present-day cloud droplet number and liquid water path, a key piece of observational evidence supporting liquid water path reduction by anthropogenic aerosols and one that earlier-generation GCMs could not reproduce. However, even in GCMs with this negative correlation, the increase in anthropogenic aerosols from preindustrial to present-day values still leads to an increase in the simulated liquid water path due to the parameterized precipitation suppression mechanism. This adds to the evidence that correlations in the present-day climate are not necessarily causal. We investigate sources of confounding to explain the noncausal correlation between liquid water path and droplet number. These results are a reminder that assessments of climate parameters based on multiple lines of evidence must carefully consider the complementary strengths of different lines when the lines disagree.

Brown carbon (BrC) is an absorbing organic aerosol (OA), primarily emitted through biomass burning (BB), which exhibits light absorption unique to both black carbon (BC) and other organic aerosols. Despite many field and laboratory studies seeking to constrain BrC properties, the radiative forcing (RF) of BrC is still highly uncertain. To better understand its climate impact, we introduced BrC to the One-Moment Aerosol (OMA) module of the GISS ModelE Earth system model (ESM). We assessed ModelE sensitivity to primary BrC processed through a novel chemical aging scheme and to secondary BrC formed from biogenic volatile organic compounds (BVOCs). Initial results show that BrC typically contributes a top-of-the-atmosphere (TOA) radiative effect of 0.04 W m−2. Sensitivity tests indicate that explicitly simulating BrC (separating it from other OAs), including secondary BrC, and simulating chemical bleaching of BrC contribute distinguishable radiative effects and should be accounted for in BrC schemes. This addition of prognostic BrC to ModelE allows greater physical and chemical complexity in OA representation with no apparent trade-off in model performance, as the evaluation of ModelE aerosol optical depth against Aerosol Robotic Network (AERONET) and Moderate Resolution Imaging Spectroradiometer (MODIS) retrieval data, with and without the BrC scheme, reveals similar skill in both cases. Thus, BrC should be explicitly simulated to allow more physically based chemical composition, which is crucial for more detailed OA studies like comparisons to in situ measurement campaigns. We include a summary of best practices for BrC representation within ModelE at the end of this paper.

The composition of soil dust aerosols derives from the mineral abundances in the parent soils that vary across dust source regions. Nonetheless, Earth system models (ESMs) have traditionally represented mineral dust as a globally homogeneous species. The growing interest in modeling dust mineralogy, facilitated by the recognized sensitivity of the dust climate impacts to composition, has motivated state-of-the-art ESMs to incorporate the mineral speciation of dust along with its effect upon the dust direct radiative effect (DRE). In this work, we enable the NASA Goddard Institute for Space Studies ModelE2.1 to calculate the shortwave (SW) DRE accounting for the regionally varying soil mineralogy. Mineral–radiation interaction at solar wavelengths is calculated according to two alternative coupling schemes: (1) external mixing of three mineral components that are optically distinguished, one of which contains embedded iron oxides; (2) a single internal mixture of all dust minerals with a dynamic fraction of iron oxides that varies regionally and temporally. We link dust absorption to the fractional mass of iron oxides based on recent chamber measurements using natural dust aerosol samples. We show that coupled mineralogy overall enhances the scattering by dust, and thus the global cooling, compared to our control run with globally uniform composition. According to the external mixing scheme, the SW DRE at the top of atmosphere (TOA) changes from −0.25 to -0.30Wm-2, corresponding to a change in the net DRE, including the longwave effect, from −0.08 to -0.12Wm-2. The cooling increase is accentuated when the internal mixing scheme is configured: the SW DRE at the TOA becomes -0.34Wm-2 with a net DRE of -0.15Wm-2. The varying composition modifies the regional distribution of single scattering albedo (SSA), whose variations in specific regions can be remarkable (above 0.03) and significantly modify the regional SW DRE. Evaluation against the AErosol RObotic NETwork (AERONET) shows that explicit representation of soil mineralogy and its regional variations reduces the low bias of model dust SSA while improving the range of variability across stations and calendar months. Despite these improvements, the moderate spatiotemporal correlation with AERONET reveals remaining modeling challenges and the need for more accurate measurements of mineral fractions in soils.

European iron ore production is primarily sourced from magnetite dominated iron oxide-apatite ore deposits in the northern Norrbotten ore province of northernmost Sweden. The Malmberget iron oxide-apatite deposit is at present the largest iron ore resource in Europe and is an amphibolite facies grade analogue of the world-famous Kiirunavaara iron oxide-apatite deposit. The Malmberget rock association is characterised by multiple phases of deformation, metamorphism, and alteration that resulted in a geometrically and petrologically complex deposit that is genetically ambiguous. Primary ore textures and emplacement structures of the Malmberget iron oxide-apatite deposit have largely been recrystallised during metamorphic overprinting and now comprise dominantly medium- to coarse-grained granoblastic magnetite. However, isotopic characteristics are preserved and when combined with trace element chemistry, these can be used to understand magmatic vs. hydrothermal origin of the deposit. To unravel the primary origin of the Malmberget magnetite ore, we combined magnetite trace element chemistry and Fe-O stable isotopes to investigate the massive magnetite in the Fabian-Kapten and ViRi ore bodies of the Malmberget iron oxide-apatite deposit. Trace element correlations indicate a high-temperature magmatic to a transitional high-temperature magmatic-hydrothermal origin of the Malmberget iron oxide-apatite ore deposit, with data plotting into fields of clear magmatic affinity in trace element discrimination diagrams. Fe-O data fall into established magmatic fields regardless of subsequent metamorphic modifications, underlining a dominantly (ortho-)magmatic origin of the investigated deposits. Despite an overall magmatic to magmatic-hydrothermal origin for the two ore bodies studied, Fe-O isotope equilibrium calculations of the magnetite suggest a possible temperature discrepancy between the Fabian-Kapten ore body and the ViRi ore body, the latter showing a more pronounced magmatic character. These variations in trace element contents and Fe-O isotopes can be explained by the proximity of the more magmatic signatures to the centre of the ore forming magmatic system.

Abstract Long noncoding RNAs (lncRNAs) play crucial roles in maintaining cell homeostasis and function. However, it remains largely unknown whether and how neuronal activity impacts the transcriptional regulation of lncRNAs, or if this leads to synapse-related changes and contributes to the formation of long-term memories. Here, we report the identification of a lncRNA, SLAMR, which becomes enriched in CA1-hippocampal neurons upon contextual fear conditioning but not in CA3 neurons. SLAMR is transported along dendrites via the molecular motor KIF5C and is recruited to the synapse upon stimulation. Loss of function of SLAMR reduces dendritic complexity and impairs activity-dependent changes in spine structural plasticity and translation. Gain of function of SLAMR, in contrast, enhances dendritic complexity, spine density, and translation. Analyses of the SLAMR interactome reveal its association with CaMKIIα protein through a 220-nucleotide element also involved in SLAMR transport. A CaMKII reporter reveals a basal reduction in CaMKII activity with SLAMR loss-of-function. Furthermore, the selective loss of SLAMR function in CA1 disrupts the consolidation of fear memory in male mice, without affecting their acquisition, recall, or extinction, or spatial memory. Together, these results provide new molecular and functional insight into activity-dependent changes at the synapse and consolidation of contextual fear.

ABSTRACTPurpose Medical school educators face challenges determining which new and emerging topics to incorporate into medical school curricula, and how to do so. A study was conducted to gain a better understanding of the integration of emerging topics related to microbiology and immunology in the undergraduate medical curriculum (UME).Methods An anonymous survey with 17 questions was emailed to medical school faculty who teach immunology and/or microbiology through the DR-Ed listserv, the American Society for Microbiology (ASM) Connect listserv, and attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop. Participants were asked about experiences, perceptions, and the decision-making process regarding integrating emerging topics into UME.Results The top emerging topics that were added to the curriculum or considered for addition in the last 10 years included COVID-19, Zika virus, mRNA vaccines, and Mpox (formerly known as monkeypox). Most respondents reported lectures and active learning as the major methods for topic delivery, with most faculty indicating that formative assessment was the best way to assess emerging topics. Content experts and course directors were the most cited individuals making these decisions. Top reasons for incorporating emerging topics into curricula included preparing students for clinical treatment of cases, followed by demonstrating the importance of basic science, and opportunities to integrate basic science into other disciplines. Challenges for incorporating these topics included making room in an already crowded curriculum, followed by content overload for students.Conclusions This study describes the rationale for integrating emerging topics related to microbiology and immunology into UME, and identifies the current new and emerging topics, as well as the main methods of integration and assessment. These results may be used by medical educators to inform curricular decisions at their institutions. Future studies will include developing innovative learning modules that overcome barriers to integration.

This paper analyzes the use of recycled construction and demolition debris as aggregate for the construction of concrete blocks to be used in sealing masonry. Initial studies addressed the definition of parameters used in the mix of conventional materials (traditionally used in the production of concrete blocks), involving cylindrical test specimens (100x200 mm), molded with the help of a vibratory table. In addition to these definitions, and based on the mixes showing the best results, a new granulometric range was established, against which the granulometry of the recycled aggregates was adjusted. After the initial studies, concrete blocks were molded with the following dimensions: 100x190x390 mm). Studies have determined the behavior of aggregates in relation to mold humidity specific mass, water absorption, and compression resistance in view of the percentage of recycled debris that composes the total aggregate. For the most part, results suggest that construction and demolition debris can potentially be used in the production of concrete blocks, as well as in other pre-molded artefacts.

Abstract In the face of a changing climate, the understanding, predictions, and projections of natural and human systems are increasingly crucial to prepare and cope with extremes and cascading hazards, determine unexpected feedbacks and potential tipping points, inform long‐term adaptation strategies, and guide mitigation approaches. Increasingly complex socio‐economic systems require enhanced predictive information to support advanced practices. Such new predictive challenges drive the need to fully capitalize on ambitious scientific and technological opportunities. These include the unrealized potential for very high‐resolution modeling of global‐to‐local Earth system processes across timescales, reduction of model biases, enhanced integration of human systems and the Earth Systems, better quantification of predictability and uncertainties; expedited science‐to‐service pathways, and co‐production of actionable information with stakeholders. Enabling technological opportunities include exascale computing, advanced data storage, novel observations and powerful data analytics, including artificial intelligence and machine learning. Looking to generate community discussions on how to accelerate progress on U.S. climate predictions and projections, representatives of Federally‐funded U.S. modeling groups outline here perspectives on a six‐pillar national approach grounded in climate science that builds on the strengths of the U.S. modeling community and agency goals. This calls for an unprecedented level of coordination to capitalize on transformative opportunities, augmenting and complementing current modeling center capabilities and plans to support agency missions. Tangible outcomes include projections with horizontal spatial resolutions finer than 10 km, representing extremes and associated risks in greater detail, reduced model errors, better predictability estimates, and more customized projections to support next generation climate services.

The Advanced X-ray Imaging Satellite (AXIS) promises revolutionary science in the X-ray and multi-messenger time domain. AXIS will leverage excellent spatial resolution (80× that of Swift), and a large collecting area (5–10× that of Chandra) across a 24-arcmin diameter field of view at soft X-ray energies (0.3–10.0 keV) to discover and characterize a wide range of X-ray transients from supernova-shock breakouts to tidal disruption events to highly variable supermassive black holes. The observatory’s ability to localize and monitor faint X-ray sources opens up new opportunities to hunt for counterparts to distant binary neutron star mergers, fast radio bursts, and exotic phenomena like fast X-ray transients. AXIS will offer a response time of

Abstract Robust estimates of historical changes in aerosols are key for accurate constraints on climate sensitivity. Dry deposition is a primary sink of aerosols from the atmosphere. However, most global climate models do not accurately represent observed strong dependencies of dry deposition following turbulent transport on aerosol size. It is unclear whether there is a substantial impact of mischaracterized aerosol deposition velocities on historical aerosol changes. Here we describe improved mechanistic representation of aerosol dry deposition in the NASA Goddard Institute for Space Studies (GISS) global climate model, ModelE, and illustrate the impact on 1850–2000 changes in global aerosol burdens as well as aerosol direct and cloud albedo effects using a set of 1850 and 2000 time slice simulations. We employ two aerosol configurations of ModelE (a “bulk” mass‐based configuration and a configuration that more explicitly represents aerosol size distributions, internal mixing, and microphysics) to explore how model structural differences in aerosol representation alter the response to representation of dry deposition. Both configurations show larger historical increases in the global burdens of non‐dust aerosols with the new dry deposition scheme, by 11% in the simpler mass‐based configuration and 23% in the more complex microphysical configuration. Historical radiative forcing responses, which vary in magnitude from 5% to 12% as well as sign, depend on the aerosol configuration.

Climate change and evolution are topics at the forefront of political discussions, debates, and the public sphere. Regardless of evidence on both topics, the public as a whole still believes they are under debate. It is imperative that the public have access to correct and easy-to-digest information on these topics to make informed environmental and ecological decisions. To date, scientifically accurate digital platforms aimed at informing the public on these topics are overly complex and jargon-ridden. Time Scavengers (www.timescavengers.blog) was created to address these issues and is maintained by a group of academics, graduate students, avocational scientists, and educators. The site includes many informational pages about geology, climate change, and evolution, all written for the public with useful descriptions and figures. To make the process of science more transparent, the site includes blogs to provide insight into data collection and interpretation, field work, and public outreach. The site also includes additional pages with links to relevant content and activities appropriate for K-12 classrooms. The overarching goals of the site are to bridge the gap between scientists and the public through engaging, informational pages and personal experiences and to increase science literacy through easy-to-digest content.

Quaternary chalcogenide compounds Cu2+xZnSn1−xSe4 (0 ≤ x ≤ 0.15) were prepared by solid state synthesis. Rietveld powder X-ray diffraction (XRD) refinements combined with Electron Probe Micro Analyses (EPMA, WDS-Wavelength Dispersive Spectroscopy) and Raman spectra of all samples confirmed the stannite structure (Cu2FeSnS4-type) as the main phase. In addition to the main phase, small amounts of secondary phases like ZnSe, CuSe and SnSe were observed. Transport properties of all samples were measured as a function of temperature in the range from 300 K to 720 K. The electrical resistivity of all samples decreases with an increase in Cu content except for Cu2.1ZnSn0.9Se4, most likely due to a higher content of the ZnSe. All samples showed positive Seebeck coefficients indicating that holes are the majority charge carriers. The thermal conductivity of doped samples was high compared to Cu2ZnSnSe4 and this may be due to the larger electronic contribution and the presence of the ZnSe phase in the doped samples. The maximum zT = 0.3 at 720 K occurs for Cu2.05ZnSn0.95Se4 for which a high-pressure torsion treatment resulted in an enhancement of zT by 30% at 625 K.

Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2–4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse.

We present an analysis of the Atacama Large Millimeter-submillimeter Array (ALMA) multiband dust continuum observations for 28 spectroscopically confirmed bright Lyman break galaxies at 5 < z < 8. Our sample consists of 11 galaxies at z ∼ 6 newly observed in our ALMA program, which substantially increases the number of 5 < z < 8 galaxies with both rest-frame 88 and 158 μ m continuum observations, allowing us to simultaneously measure the IR luminosity and dust temperature for a statistical sample of z ≳ 5 galaxies for the first time. We derive the relationship between the ultraviolet (UV) slope ( β _UV ) and infrared excess (IRX) for the z ∼ 6 galaxies, and find a shallower IRX– β _UV relation compared to the previous results at z ∼ 2–4. Based on the IRX– β _UV relation consistent with our results and the β _UV – M _UV relation including fainter galaxies in the literature, we find a limited contribution of the dust-obscured star formation to the total star formation rate density, ∼30% at z ∼ 6. Our measurements of the dust temperature at z ∼ 6–7, ${T}_{\mathrm{dust}}={40.9}_{-9.1}^{+10.0}\,{\rm{K}}$ on average, support a gentle increase of T _dust from z = 0 to z ∼ 6–7. Using an analytic model with parameters consistent with recent James Webb Space Telescope results, we discuss that the observed redshift evolution of the dust temperature can be reproduced by an ∼0.6 dex decrease in the gas depletion timescale and ∼0.4 dex decrease in the metallicity. The variety of T _dust observed at high redshifts can also be naturally explained by scatters around the star formation main sequence and average mass–metallicity relation including an extremely high dust temperature of T _dust > 80 K observed in a galaxy at z = 8.3.

We present a catalog of hard X-ray serendipitous sources detected in the first 80 months of observations by the Nuclear Spectroscopic Telescope Array (NuSTAR). The NuSTAR serendipitous survey 80 month (NSS80) catalog has an unprecedented ∼62 Ms of effective exposure time over 894 unique fields (a factor of 3 increase over the 40 month catalog, NSS40), with an areal coverage of ∼36 deg ^2 , larger than all NuSTAR extragalactic surveys. NSS80 provides 1274 hard X-ray sources in the 3−24 keV band (822 new detections compared to the previous NSS40). Approximately 76% of the NuSTAR sources have lower-energy (

“Changing-look” active galactic nuclei (CL-AGNs) challenge our basic ideas about the physics of accretion flows and circumnuclear gas around supermassive black holes. Using first-year Sloan Digital Sky Survey V (SDSS-V) repeated spectroscopy of nearly 29,000 previously known active galactic nuclei (AGNs), combined with dedicated follow-up spectroscopy, and publicly available optical light curves, we have identified 116 CL-AGNs where (at least) one broad emission line has essentially (dis-)appeared, as well as 88 other extremely variable systems. Our CL-AGN sample, with 107 newly identified cases, is the largest reported to date, and includes ∼0.4% of the AGNs reobserved in first-year SDSS-V operations. Among our CL-AGNs, 67% exhibit dimming while 33% exhibit brightening. Our sample probes extreme AGN spectral variability on months to decades timescales, including some cases of recurring transitions on surprisingly short timescales (≲2 months in the rest frame). We find that CL events are preferentially found in lower-Eddington-ratio ( f _Edd ) systems: Our CL-AGNs have a f _Edd distribution that significantly differs from that of a carefully constructed, redshift- and luminosity-matched control sample (Anderson–Darling test yielding p _AD ≈ 6 × 10 ^−5 ; median f _Edd ≈ 0.025 versus 0.043). This preference for low f _Edd strengthens previous findings of higher CL-AGN incidence at lower f _Edd , found in smaller samples. Finally, we show that the broad Mg ii emission line in our CL-AGN sample tends to vary significantly less than the broad H β emission line. Our large CL-AGN sample demonstrates the advantages and challenges in using multi-epoch spectroscopy from large surveys to study extreme AGN variability and physics.

We present Atacama Large Millimeter/submillimeter Array (ALMA) deep spectroscopy for a lensed galaxy at z _spec = 8.496 with $\mathrm{log}({M}_{\mathrm{star}}/{M}_{\odot })\sim 7.8$ whose optical nebular lines and stellar continuum are detected by JWST/NIRSpec and NIRCam Early Release Observations in the field of SMACS J0723.3–7327. Our ALMA spectrum shows [O iii ] 88 μ m and [C ii ] 158 μ m line detections at 4.0 σ and 4.5 σ , respectively. The redshift and position of the [O iii ] line coincide with those of the JWST source, while the [C ii ] line is blueshifted by 90 km s ^−1 with a spatial offset of 0.″5 (≈0.5 kpc in the source plane) from the centroid of the JWST source. The NIRCam F444W image, including [O iii ] λ 5007 and H β line emission, spatially extends beyond the stellar components by a factor of >8. This indicates that the z = 8.5 galaxy has already experienced strong outflows as traced by extended [O iii ] λ 5007 and offset [C ii ] emission, which would promote ionizing photon escape and facilitate reionization. With careful slit-loss corrections and the removal of emission spatially outside the galaxy, we evaluate the [O iii ] 88 μ m/ λ 5007 line ratio, and derive the electron density n _e by photoionization modeling to be ${220}_{-130}^{+230}$ cm ^−3 , which is comparable with those of z ∼ 2–3 galaxies. We estimate an [O iii ] 88 μ m/[C ii ] 158 μ m line ratio in the galaxy of >4, as high as those of known z ∼ 6–9 galaxies. This high [O iii ] 88 μ m/[C ii ] 158 μ m line ratio is generally explained by the high n _e as well as the low metallicity ( ${Z}_{\mathrm{gas}}/{Z}_{\odot }={0.04}_{-0.02}^{+0.02}$ ), high ionization parameter ( $\mathrm{log}U\gt -2.27$ ), and low carbon-to-oxygen abundance ratio (log(C/O) = [−0.52: −0.24]) obtained from the JWST/NIRSpec data; further [C ii ] follow-up observations will constrain the covering fraction of photodissociation regions.

Background and aims: Postpolypectomy syndrome (PPS) is a relevant adverse event that can appear after polypectomy. Several publications mention postpolypectomy syndrome using different criteria to define it. The aim of this study is to detect potential risk factors and predictors for developing PPS and to define the main criteria of PPS. Methods: In this retrospective monocentric study, 475 out of 966 patients who underwent colonoscopy with polypectomy from October 2015 to June 2020 were included. The main criterion of PPS is defined as the development of postinterventional abdominal pain lasting more than six hours. Results: A total of 9.7% of the patients developed PPS, which was defined as local abdominal pain around the polypectomy area after six hours. A total of 8.6% of the study population had abdominal pain within six hours postintervention. A total of 3.7% had an isolated triad of fever, leukocytosis, and increased CRP in the absence of abdominal pain. Increased CRP combined with an elevated temperature over 37.5 °C seems to be a positive predictor for developing PPS. Four independent risk factors could be detected: serrated polyp morphology, polypoid configurated adenomas, polyp localization in the cecum, and the absence of intraepithelial neoplasia. Conclusions: Four independent risk factors for developing PPS were detected. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology. As expected, the increasing use of cold snare polypectomies will reduce the incidence of this syndrome. Key summary: Our monocentric study on 966 patients detected four independent risk factors for developing PPS: pedunculated polyp, resected polyps in the cecum, absence of IEN, and serrated polyp morphology. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology.

We present results of [C ii ] 158 μ m emission line observations, and report the spectroscopic redshift confirmation of a strongly lensed ( μ ∼ 20) star-forming galaxy, MACS0308-zD1 at z = 6.2078 ± 0.0002. The [C ii ] emission line is detected with a signal-to-noise ratio >6 within the rest-frame UV-bright clump of the lensed galaxy (zD1.1) and exhibits multiple velocity components; the narrow [C ii ] has a velocity full width half maximum (FWHM) of 110 ± 20 km s ^−1 , while broader [C ii ] is seen with an FWHM of 230 ± 50 km s ^−1 . The broader [C ii ] component is blueshifted (−80 ± 20 km s ^−1 ) with respect to the narrow [C ii ] component, and has a morphology that extends beyond the UV-bright clump. We find that, while the narrow [C ii ] emission is most likely associated with zD1.1, the broader component is possibly associated with a physically distinct gas component from zD1.1 (e.g., outflowing or inflowing gas). Based on the nondetection of λ _158 _μ _m dust continuum, we find that MACS0308-zD1's star formation activity occurs in a dust-free environment indicated by a strong upper limit of infrared luminosity ≲9 × 10 ^8 L _⊙ . Targeting this strongly lensed faint galaxy for follow-up Atacama Large Millimeter/submillimeter Array and JWST observations will be crucial to characterize the details of typical galaxy growth in the early Universe.

Accreting supermassive black holes (SMBHs) located at the centers of galaxies are typically surrounded by large quantities of gas and dust. The structure and evolution of this circumnuclear material can be studied at different wavelengths, from the submillimeter to the X-ray. Recent X-ray studies have shown that the covering factor of the obscuring material tends to decrease with increasing Eddington ratio, likely due to radiative feedback on dusty gas. Here we study a sample of 549 nearby ( z ≲ 0.1) hard X-ray (14–195 keV) selected nonblazar active galactic nuclei (AGN) and use the ratio between the AGN infrared and bolometric luminosity as a proxy of the covering factor. We find that, in agreement with what has been found by X-ray studies of the same sample, the covering factor decreases with increasing Eddington ratio. We also confirm previous findings that showed that obscured AGN typically have larger covering factors than unobscured sources. Finally, we find that the median covering factors of AGN located in different regions of the column density–Eddington ratio diagram are in good agreement with what would be expected from a radiation-regulated growth of SMBHs.

Abstract: To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

Abstract: Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9–mediated disruption of DNA regulatory elements that repress γ-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and β-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rγ −/−/Kit W41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies.