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© Copyright 2022. Sociedad Meteorológica Estadounidense (AMS). Para obtener permiso para reutilizar cualquier parte de este Trabajo, comuníquese con permisos@ametsoc. org . Cualquier uso del material en este Trabajo que se determine como "uso justo" según la Sección 107 de la Ley de derechos de autor de EE. UU. (17 Código de EE. UU. § 107) o que cumpla las condiciones especificadas en la Sección 108 de la Ley de derechos de autor de EE. ) no requiere el permiso de la AMS. La republicación, la reproducción sistemática, la publicación en forma electrónica, como en un sitio web o en una base de datos de búsqueda, u otros usos de este material, excepto los exentos de la declaración anterior, requieren un permiso por escrito o una licencia de la AMS. Todas las publicaciones periódicas y monográficas de AMS están registradas en el Centro de Autorización de Derechos de Autor (https://www.copyright.com ). Se proporcionan detalles adicionales en la declaración de política de derechos de autor de AMS, disponible en el sitio web de AMS ( https://www.ametsoc.org/PUBSCopyrightPolicy ) ., In 2021, both social and economic activities began to return towards the levels preceding the COVID-19 pandemic for some parts of the globe, with others still experiencing restrictions. Meanwhile, the climate has continued to respond to the ongoing increase in greenhouse gases and resulting warming. La Niña, a phenomenon which tends to depress global temperatures while changing rainfall patterns in many regions, prevailed for all but two months of the year. Despite this, 2021 was one of the six-warmest years on record as measured by global mean surface temperature with an anomaly of between +0.21° and +0.28°C above the 1991–2020 climatology., Lake surface water temperatures from satellite data have been generated within the GloboLakes project funded by the UK National Environment Research Council (NE/J023345/2), with extensions funded by the EU Copernicus Climate Change Service (C3S) programme...

Ageing is driven by the accumulation of diverse types of damage that leads to a decline in function over time. In unicellular organisms, in addition to this damage accumulation within individuals, asymmetric partitioning of damage at cell division might also play a crucial role in shaping demographic ageing patterns. Despite empirical single-cell studies providing quantitative data at the molecular and demographic level, a comprehensive understanding of how cellular damage production and partition propagate and influence demographic patterns is still lacking. To address this gap, we present a generic and flexible damage model using a stochastic differential equation approach which incorporates stochastic damage accumulation and asymmetric damage partitioning at cell divisions. We provide an analytical approximation linking cellular and damage parameters to demographic ageing patterns. Interestingly, we observe that the lifespan of the cells follows an inverse-gaussian distribution whose statistical properties can be expressed with cellular and damage parameters, as well as easily inferred from empirical single-cell data. Furthermore, we demonstrate how stochasticity (noise) in damage production and asymmetry in damage partitioning contribute to shaping lifespans. Applying the model to empiricalE.colidata reveals non-exponential scaling in mortality rates, which cannot be captured by classical Gompertz-Makeham models. Additionally, we highlight the essential role of stochastic division times in shaping lifespans. Our findings provide a deeper understanding of how fundamental processes contribute to cellular damage dynamics and generate demographic patterns. The generic nature and flexibility of our damage model offer a valuable framework for investigating ageing in diverse biological systems.

Detection and attribution of climate extremes in Africa has predominantly focused on univariate analysis of drought events and heat waves in different regions of the continent, although there have been unusual extreme events such as the Ethiopian heavy rainfall and flooding events in 2020, the 2022 flood in Nigeria and the 2020-2022 persistent drought event over Eastern Africa. Furthermore, the compounding of such type of extremes has not been investigated on the African continent so far.Decision makers and climate practitioners need context-specific and reliable information about the magnitude of climate risk for humans, socioeconomic and environmental sectors. Compound climate extremes (different combinations of heavy precipitation, floods, heat waves, droughts, and high discharge) are known for their large devastating impacts resulting from their concurrent or in-close-succession occurrence. Furthermore, the conventional univariate risk assessment can lead to under underestimated risk. Although risk analysis for compound extremes is a recent research topic globally, lack of such information is more acute for developing regions.Therefore, in this study, we conduct a detection and attribution study on the recent extreme events using a univariate analysis. In addition, we assess whether there was compounding of multiple extremes events using event coincidence analysis in different regions of the African continent. We use bivariate fraction of attributable risk method to take dependence between compounding events into account. We also assess sector-specific risks of compound climate extremes in the historical period and in the future using climate projections over Africa. Our risk analysis will be based on the recently proposed bottom-up approach and multi-criteria risk assessment, and follow procedures: prioritizing specific aspects of a sector of interest based on national and regional priorities, examining relevant climate and societal drivers, defining compound extremes, vulnerability assessment, preliminary analysis of risk assessment and refining the analysis for a detailed risk assessment. Keywords: detection and attribution, risk and vulnerability assessment, compound climate extremes, heat waves, droughts, floods, climate change

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted AR nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of liver X receptor (LXR)-β, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC.Significance:These results suggest that macrophage-targeted therapies can be combined with androgen deprivation therapy to treat patients with prostate cancer by limiting cholesterol bioavailability and the production of intratumoral androgens.See related commentary by Al-Janabi and Lewis, p. 5399

Key resources

Abundance of lipids in macrophages and importance of mevalonate pathway in prostate cancer cells

Additional details on LC-MS/MS sample preparation and RNA sequencing

Historically, observational information about atmospheric temperature has been limited due to a lack of suitable measurements. Recent advances in satellite observations provide new insight into the fine structure of the free atmosphere, with the upper troposphere and lower stratosphere comprising essential components of the climate system. This is a prerequisite for understanding the complex processes of this part of the atmosphere, which is also known to have a large impact on surface climate. With unprecedented resolution, latest climate observations reveal a dramatic warming of the atmosphere. The tropical upper troposphere has already warmed about 1 K during the first two decades of the 21st century. The tropospheric warming extends into the lower stratosphere in the tropics and southern hemisphere mid-latitudes, forming a prominent hemispheric asymmetry in the temperature trend structure. Together with seasonal trend patterns in the stratosphere, this indicates a possible change in stratospheric circulation.

SUMMARYInborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. Few genes are assigned to both IEM and IEI, but immunometabolic demands suggest functional overlap is underestimated. We applied CRISPR screens to test IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable crossover. Analysis of IEM showed N-linked glycosylation and thede novohexosamine synthesis enzyme,Gfpt1, are critical for T cell expansion and function. Interestingly,Gfpt1-deficient TH1 cells were more affected than TH17 cells, which had increasedNagkfor salvage UDP-GlcNAc synthesis. Screening IEI genes showed the transcription factorBcl11bpromotes CD4+T cell mitochondrial activity andMcl1expression necessary to prevent metabolic stress. These data illustrate a high degree of functional overlap of IEM and IEI genes and point to potential immunometabolic mechanisms for a previously unappreciated set of these disorders.HIGHLIGHTSInborn errors of immunity and metabolism have greater overlap than previously knownGfpt1deficiency causes an IEM but also selectively regulates T cell subset fateLoss ofBcl11bcauses a T cell deficiency IEI but also harms mitochondrial functionMany IEM may have immune defects and IEI may be driven by metabolic mechanisms

The Earth climate system is out of energy balance, and heat has accumulated continuously over the past decades, warming the ocean, the land, the cryosphere, and the atmosphere. According to the Sixth Assessment Report by Working Group I of the Intergovernmental Panel on Climate Change, this planetary warming over multiple decades is human-driven and results in unprecedented and committed changes to the Earth system, with adverse impacts for ecosystems and human systems. The Earth heat inventory provides a measure of the Earth energy imbalance (EEI) and allows for quantifying how much heat has accumulated in the Earth system, as well as where the heat is stored. Here we show that the Earth system has continued to accumulate heat, with 381±61 ZJ accumulated from 1971 to 2020. This is equivalent to a heating rate (i.e., the EEI) of 0.48±0.1 W m−2. The majority, about 89 %, of this heat is stored in the ocean, followed by about 6 % on land, 1 % in the atmosphere, and about 4 % available for melting the cryosphere. Over the most recent period (2006–2020), the EEI amounts to 0.76±0.2 W m−2. The Earth energy imbalance is the most fundamental global climate indicator that the scientific community and the public can use as the measure of how well the world is doing in the task of bringing anthropogenic climate change under control. Moreover, this indicator is highly complementary to other established ones like global mean surface temperature as it represents a robust measure of the rate of climate change and its future commitment. We call for an implementation of the Earth energy imbalance into the Paris Agreement's Global Stocktake based on best available science. The Earth heat inventory in this study, updated from von Schuckmann et al. (2020), is underpinned by worldwide multidisciplinary collaboration and demonstrates the critical importance of concerted international efforts for climate change monitoring and community-based recommendations and we also call for urgently needed actions for enabling continuity, archiving, rescuing, and calibrating efforts to assure improved and long-term monitoring capacity of the global climate observing system. The data for the Earth heat inventory are publicly available, and more details are provided in Table 4.

We apply a causal inference-based framework to test and quantify previously suggested causalrelationships between Northern Hemisphere blocking, upward wave-activity fluxes and stratospheric polarvortex (SPV) variability using reanalysis data. We show that the influence of blocking on the polar vortex isentirely mediated by upward wave-activity fluxes, as the classical view would suggest. However, the causalpathway is not completely straightforward. In contrast to the vortex-weakening effect of European blocking,the vortex-strengthening effect of west Pacific blocking on lower stratospheric wave-activity fluxes is onlypartially mediated by upper tropospheric wave-activity fluxes. In addition, only two-thirds of the effectof upper tropospheric wave-activity fluxes on polar vortex variability is mediated by lower stratosphericwave-activity fluxes. We also show that sudden stratospheric warmings are not entirely explainable in terms ofupward wave-activity fluxes. These findings help clarify the pathways of influence between blocking and SPVvariability.

Extreme climatic events may influence individual-level variability in phenotypes, survival, and reproduction, and thereby drive the pace of evolution. Here, we quantify how experiencing major hurricanes influences individual life courses in the Cayo Santiago rhesus macaques. Our results show that major hurricanes increase heterogeneity in reproductive life courses despite an average reduction in mean fertility and survival, i.e. shortened life courses. In agreement with this, the population is expected to achieve stable population dynamics faster after a hurricane. Our work suggests that natural disasters force individuals into new niches to potentially reduce strong competition during poor environments where mean reproduction and survival are compromised. We also demonstrate that variance in lifetime reproductive success and longevity are differently affected by hurricanes, and such variability is mostly driven by survival.

SummaryObesity is a leading risk factor for progression and metastasis of many cancers1,2, yet can also promote improved survival for some cancers3-5and enhance responses to some immune checkpoint blockade therapies6-8. The role of the immune system in the obesity-cancer connection and how obesity influences immunotherapy, however, remain unclear. While PD-1 expression by macrophages has been described9-12, we found that obesity selectively induced PD-1 on macrophages and that PD-1 directly impaired macrophage function. Single cell RNA sequencing of murine colorectal carcinoma tumors showed obesity remodeled myeloid and T cell populations, with fewer clonally expanded effector T cells and increased abundance of PD-1+tumor-associated macrophages (TAM). Cytokines and molecules associated with obesity, including IL-6, leptin, and insulin, and the unsaturated fatty acid palmitate, induced PD-1 expression on macrophages in a glycolysis-dependent manner. PD-1+TAMs had increased mitochondrial respiration and expression of genes regulating oxidative phosphorylation, lipid uptake and cell cycle while PD-1-TAMs showed greater signatures of phagocytosis and antigen presentation to T cells. These patterns were directly regulated by PD-1, as recombinant PD-L1 reduced macrophage glycolysis and phagocytic capacity, and this was reversed with blocking PD-1 antibody. Conversely, PD-1-deficientPdcd1-/-TAMs had high rates of glycolysis, phagocytosis, and expression of MHC-II. Myeloid-specific PD-1 deficiency correlated with slower tumor growth, enhanced TAM antigen presentation capability, and increased CD8 T cell activation together with reduced markers of exhaustion. These findings show metabolic signaling in obesity induces PD-1-mediated suppression of TAM function and reveal a unique macrophage-specific mechanism to modulate immune tumor surveillance and checkpoint blockade. This may contribute to increased cancer risk yet improved response to PD-1 blockade in TAM-enriched tumors and obesity.

Providing comprehensive regional- and local-scale information on changes observed in the climate system plays a vital role in planning effective and efficient climate change adaptation options, specifically over resource-limited regions. Here, we assess changes in temperature and heat waves over different regions of the African continent, with a focus on spatiotemporal trends and the time of emergence of change in hot extremes from natural variability. We analyse absolute and relative threshold indices. Data sets include temperatures from observations (CRUTS4.03 and BEST) and from three representative state-of-the-art reanalyses (ERA5, MERRA2 and JRA-55) for the common period 1980–2018. Statistically significant warming is observed over all regions of Africa in temperature time series from CRU observations and reanalysis data, although the trend strength varies between data sets. Also, extreme temperatures and heat wave indices from BEST observations and all reanalysis data sets reveal increasing trends over all regions of the African continent. However, there are differences in both trend strength and time evolution of heat wave indices between different reanalysis data sets. Most data sets agree in identifying 2010 as a peak heat year over Northern and Western Africa while Eastern and Southern Africa experienced the highest heat wave occurrence in 2016. Our results clearly reveal that heat wave occurrences have emerged from natural climate variability in Africa. The earliest time of emergence takes place in the Northern Africa region in the early 2000s while in the other African regions emergence over natural variability is found mainly after 2010. This also depends on the respective index metrics, where indices based on more consecutive days show later emergence of heat wave trends. Overall, significant warming and an increase in heat wave occurrence is found in all regions of Africa and has emerged from natural variability in the past one or two decades.

We compare atmospheric temperature changes in satellite data and in older and newer multi-model and single-model ensembles performed under phases 5 and 6 of the Coupled Model Intercomparison Project (CMIP5 and CMIP6). In the lower stratosphere, multi-decadal stratospheric cooling during the period of strong ozone depletion is smaller in newer CMIP6 simulations than in CMIP5 or satellite data. In the troposphere, however, despite differences in the forcings and climate sensitivity of the CMIP5 and CMIP6 ensembles, their ensemble-average global warming over the satellite era is remarkably similar. We also examine four well-understood properties of tropical behavior governed by basic physical processes. The first three properties are ratios between trends in water vapor (WV) and trends in sea surface temperature (SST), the temperature of the lower troposphere (TLT), and the temperature of the mid- to upper troposphere (TMT). The fourth property is the ratio between TMT and SST trends. All four trend ratios are tightly constrained in CMIP simulations. Observed ratios diverge markedly when calculated with SST, TLT, and TMT trends produced by different groups. Observed data sets with larger warming of the tropical ocean surface and tropical troposphere yield atmospheric moistening that is closer to model results. For the TMT/SST ratio, model-data consistency depends on the selected combination of observed data sets used to estimate TMT and SST trends. If model expectations of these four covariance relationships are realistic, one interpretation of our findings is that they reflect a systematic low bias in satellite tropospheric temperature trends. Alternately, the observed atmospheric moistening signal may be overestimated. Given the large structural uncertainties in observed tropical TMT and SST trends, and because satellite WV data are available from one group only, it is difficult to determine which interpretation is more credible. Nevertheless, our analysis illustrates the diagnostic power of simultaneously considering multiple complementary variables and points towards possible problems with certain observed data sets.

Purpose: The cemented Exeter V40 stem is known to migrate distally. Several previous studies have reported on the extent of stem migration and its influence on clinical outcome. However, no studies have investigated the influence of stem migration on Patient Reported Outcome Measures (PROM). Methods: One hundred and twelve total hip arthroplasties (THA) were included in a 2-year follow-up using Radiostereometric Analysis (RSA). Patients were evaluated using the Oxford Hip Score (OHS) and EQ-5D-3L PROMs. The purpose of this study was to assess the influence of stem migration, measured by Maximum Total Point Motion (MTPM), on the 2-year postoperative score (OHS and EQ-5D). Furthermore, the influence of pre-operative PROM, age, gender, acetabular component and BMI was associated with the 2-year postoperative OHS and EQ-5D scores. Results: MTPM was a non-significant predictor of the 2-year postoperative OHS (regression coefficient (B) = − 2.38 (CI − 5.44;.69)) and of the 2-year postoperative EQ-5D (B = − .01 (CI − .04;.02)). The only significant predictor of the 2-year postoperative OHS and 2-year postoperative EQ-5D was gender (B = 8.71 (CI 3.52; 13.90)) and (B =.13 (CI.07;.18)), respectively. Conclusion: Stem migration did not significantly influence PROMs at 2 years post-operatively. Using a patient-focused approach, our results seem to corroborate results reported by previous studies, showing that slow migration of the Exeter V40 stem does not seem to influence the clinical outcome.

Launched in 2006, the Formosa Satellite Mission 3–Constellation Observing System for Meteorology, Ionosphere and Climate (FORMOSAT-3/COSMIC) was the first constellation of microsatellites carrying global positioning system (GPS) radio occultation (RO) receivers. Radio occultation is an active remote sensing technique that provides valuable information on the vertical variations of electron density in the ionosphere, and temperature, pressure, and water vapor in the stratosphere and troposphere. COSMIC has demonstrated the great value of RO data in ionosphere, climate, and meteorological research and operational weather forecasting. However, there are still challenges using RO data, particularly in the moist lower troposphere and upper stratosphere. A COSMIC follow-on constellation, COSMIC-2, was launched into equatorial orbit in 2019. With increased signal-to-noise ratio (SNR) from improved receivers and digital beam steering antennas, COSMIC-2 will produce at least 5,000 high-quality RO profiles daily in the tropics and subtropics. In this paper, we summarize 1) recent (since 2011 when the last review was published) contributions of COSMIC and other RO observations to weather, climate, and space weather science; 2) the remaining challenges in RO applications; and 3) potential contributions to research and operations of COSMIC-2.

Historically, retrieving the detailed structure of atmospheric temperature trends from observations has been demanding. For decades, observations of upper-air temperature have either lacked the necessary vertical resolution, or the horizontal coverage. This has resulted in limited knowledge about the important transition zone around the tropopause. Recent advances in satellite measurement techniques provide new insight into the thermal structure of the upper troposphere/lower stratosphere region. This is a prerequisite for understanding the complex processes of this part of the atmosphere. With unprecedented resolution, latest climate observations from GPS Radio Occultation satellites reveal a significant warming of the atmosphere. The tropical upper troposphere has already warmed about 1 K in the 21st century alone, and the stratospheric trend structure indicates a possible change in stratospheric circulation.

Introduction: There is increasing need for renal replacement therapy associated with the aging population and dramatic increases in diabetes prevalence. Despite an increasing clinical vascular access workload, there are significant unanswered research questions and a paucity of high quality trials to guide clinical practice. To address where future research in vascular access should be directed, we conducted a Priority Setting Partnership involving multiple disciplines, specialties, patients and carers. Methods: In collaboration with the James Lind Alliance, four rounds of surveys were circulated to identify and score professional and patient priorities in vascular access research. Finally, in a consensus workshop attended by patients and professionals, priorities were discussed and a ranked top 10 list was produced using a nominal group technique. Results: A total of 1,813 research priorities were submitted within all areas of vascular surgery. Following removal of duplicates, consolidation and categorisation, 15 patient and professional priorities in vascular access research were taken forward to the consensus workshop. The workshop produced a ranked top 10 list of vascular access research priorities relating to: optimising access function, preventing access complications and education of patients and healthcare staff. Conclusions: These research priorities should help to direct and contextualise future research in vascular access.

In the aeronautical industry, the specification and design choices of flight assistance functions are strongly guided by the control of the workload (WL) that their use induces. In fact, the WL is often defined as a criterion determining the success or failure of the function and must be taken into account from the first steps of design. Quantifying WL through physiological measures is not straightforward and few models exist to explain the mechanisms behind it [1]. Indeed, the effectiveness of assistive devices depends on the understanding of the sensorimotor system, specifically, movement optimality (OPM). OPM represents how the nervous system manages the trade-off between action performance and the cognitive cost (or cognitive WL) related in its execution. It can be quantified through biomechanical criteria also called \"cost functions\" [2] The objective of this study is twofold. It aims (1) to identify the relationship between task difficulty (ID) and OPM, and (2) to compare biomechanical criteria of OPM to subjective measures of WL, more classically used in the field of ergonomics, in different ID conditions. To do this, two groups of 20 participants performed a reciprocal version of Fitts\' task [3]. Placed in a speed-accuracy trade-off situation, the participants were instructed to control the movement of an object in a virtual environment by operating a sidestick along the medial-lateral axis. Each group controls the movement of the object according to a specific law (position or speed). During two sessions, each participant performs the experiment in a specific frame of reference (geocentric vs egocentric). For each session (geocentric or egocentric), 5 levels of ID are tested. Several cost functions are calculated from kinematic and EMG recordings made on the participant\'s arm. The main results show that with the increase of the ID we observe (1) a decrease of the performance (increase of the movement time, undershoot and overshoot), (2) the appearance of nonlinearities in the kinematics of the object, (3) a more important quantity of noise in the distribution of coactivation of the EMG signal. These results verify Fitts\' law and validate the hypothesis that biomechanical criteria of movement can be used to quantify more accurately cognitive workload at different levels of analysis in addition to the subjective measures of WL classically used in system design ergonomics. References [1] Zhang, X., Qu, X., Xue, H., Zhao, H., Li, T., Tao, D. (2019). Modeling pilot mental workload using information theory. The Aeronautical Journal, 123(1264), 828-839. doi:10.1017/aer.2019.13. [2] Berret, B., Chiovetto, E., Nori, F., Pozzo, T. (2011). Evidence for composite cost functions in arm movement planning: an inverse optimal control approach. PLoS computational biology, 7(10), e1002183. [3] Fitts P.M., Peterson J.R.,(1964), Information capacity of discrete motor responses, Journal of Experimental Psychology 67, 103112.

Global warming has clearly affected the occurrence of extreme events in recent years. Here, we assess changes in the frequency of temperature extremes and their causes, using percentile-based indices. Cold extremes are defined as temperatures below the 10th percentile of daily minimum (TN10) and maximum (TX10) temperatures while hot extremes exceed the 90th percentile of daily minimum (TN90) and maximum (TX90) temperatures. We analyze Berkeley Earth Surface Temperature (BEST) for observed changes in the last four decades 1981-2020, for two extended seasons, boreal summer April–September (AMJJAS) and boreal winter October–March (ONDJFM), and evaluate results using several reanalysis data sets. For the attribution of causes we use CMIP6 climate model simulations, analyzing natural-only and anthropogenic-only forcings. We use an attribution method that accounts for climate modeling uncertainty in both amplitude and pattern of responses.The observations show detectable changes in both cold and hot extreme temperatures. Hot extremes have increased in all regions and in both seasons while cold extremes have decreased over the past decades. Our attribution analysis revealed anthropogenic forcings are robustly detectable and the main drivers of observed changes in all indices for all regions, consistently in all data sets. Contributions from natural forcings are found small and detectable only in a few regions mainly for daytime cold extremes in ONDJFM. Anthropogenic forcing contributed to an increase of 3.4 days per decade in TN90 and of 2.7 days per decade in TX90, on average, at the global scale. Regionally, the anthropogenic contribution caused a range of decrease of 2–4.7 days per decade in TN10, 1.5–3.6 days per decade in TX10 while it caused an increase of 2.2–4.8 days per decade for TN90 and 2–3.3 days per decade in TX90. Anthropogenic-only warming in ONDJFM is slightly less than in AMJJAS.

The ability to measure the fiber orientation in fiber reinforced polymers plays a vital role in process and part design. Recently, it has been discovered that carbon fibers polarize light, providing an opportunity to detect the fiber orientation in carbon fiber-reinforced polymer parts. The Fraunhofer Institute for Integrated Circuits has developed a polarization camera system capable of measuring the polarization state of light reflected from objects in real-time. In this work, the camera system is used to measure the surface fiber orientation in carbon fiber reinforced Sheet Molding Compound semi-finished products at several stages of the processing chain. First, the fiber orientation of carbon fiber-reinforced Sheet Molding Compound semi-finished product is measured during continuous production, enabling real-time quality control and complete digitization of the material's fiber orientation information. Second, the measurement system is used to characterize static flat pressed carbon fiber reinforced Sheet Molding Compound specimens. In addition, the technique is widely applicable to many other carbon fiber based raw material forms (e.g. preforms, prepregs, tapes) and even composite parts.

Description, Continued rise of the tropopause after 2000 in the Northern Hemisphere is mainly due to tropospheric warming., Tropopause height (H) is a sensitive diagnostic for anthropogenic climate change. Previous studies showed increases in H over 1980–2000 but were inconsistent in projecting H trends after 2000. While H generally responds to temperature changes in the troposphere and stratosphere, the relative importance of these two contributions is uncertain. Here, we use radiosonde balloon observations in the Northern Hemisphere (NH) over 20°N to 80°N to reveal a continuous rise of H over 1980–2020. Over 2001–2020, H increases at 50 to 60 m/decade, which is comparable to the trend over 1980–2000. The GPS radio occultation measurements from satellites and homogenized radiosonde records are in good agreement with those results. The continuous rise of the tropopause in the NH after 2000 results primarily from tropospheric warming. A large trend in H remains after major natural forcings for H are removed, providing further observational evidence for anthropogenic climate change.

We investigate climate change impacts transferred via foreign trade to Germany, a country that is heavily engaged in international trade. Specifically, we look at temperature changes and the associated labour productivity losses at a global scale until 2050. We assess the effects on Germany’s imports and exports by means of a global computable general equilibrium (CGE) model. To address uncertainty, we account for three Shared Socioeconomic Pathways (SSP1, SSP2 and SSP3) and two Representative Concentration Pathways (RCP4.5 and RCP8.5) using projections from five global climate models. We find that average annual labour productivity for high intensity work declines by up to 31% for RCP4.5 (and up to 38% for RCP8.5) in Southeast Asia and the Middle East by 2050, all relative to a 2050 baseline without climate change. As a consequence, for RCP8.5, Germany’s imports from regions outside Europe are lower by up to 2.46%, while imports from within Europe partly compensate this reduction. Also, Germany’s exports to regions outside Europe are lower, but total exports increase by up to 0.16% due to higher exports to EU regions. Germany’s GDP and welfare, however, are negatively affected with a loss of up to − 0.41% and − 0.46%, respectively. The results highlight that overall positive trade effects for Germany constitute a comparative improvement rather than an absolute gain with climate change.

Jellyfish blooms are conspicuous demographic events with significant ecological and socio-economic impact. Despite worldwide concern about an increased frequency and intensity of such mass occurrences, predicting their booms and busts remains challenging. Forecasting how jellyfish populations may respond to environmental change requires considering their complex life histories. Metagenic life cycles, which include a benthic polyp stage, can boost jellyfish mass occurrences via asexual recruitment of pelagic medusae. Here we present stage-structured matrix population models with monthly, individual-based demographic rates of all life stages of the moon jellyfish Aurelia aurita L. (sensu stricto). We investigate the life stage-dynamics of these complex populations under low and high food conditions to illustrate how changes in medusa density depend on non-medusa stage dynamics. We show that increased food availability can be an important ecological driver of jellyfish mass occurrences, as it can temporarily shift the population structure from polyp- to medusa-dominated. Projecting populations for a winter warming scenario additionally enhanced the booms and busts of jellyfish blooms. We identify demographic key variables that control the intensity and frequency of jellyfish blooms in response to environmental drivers such as habitat eutrophication and climate change. By contributing to an improved understanding of mass occurrence phenomena, our findings provide perspective for future management of ecosystem health.

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted AR nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of liver X receptor (LXR)-β, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC. Significance: These results suggest that macrophage-targeted therapies can be combined with androgen deprivation therapy to treat patients with prostate cancer by limiting cholesterol bioavailability and the production of intratumoral androgens. See related commentary by Al-Janabi and Lewis, p. 5399

Tolerance and persistence are states that allow non-genetically resistant bacterial cells to survive periods of bactericidal concentrations. Compared to resistance, tolerance and persistence appear to be more diverse in their mechanisms but are less studied. Here we report, using a high throughput microfluidic single-cell microfluidic device, selection for and phenomenological characteristics of cells exposed to recurring exposure to antibiotics. We find a high fraction of tolerant cells, these cells reduce their growth rate but do not go into slow growth or growth arrest, a characteristic previously reported on. Here, tolerance is induced by antibiotic exposure and not caused by a stochastic switch or predetermined state. The tolerance state only weakly depends on the applied concentration of the antibiotic and post-antibiotic exposure there is no fast resumption of growth contrasting again with previous studies. Tolerant cells remain susceptible to antibiotic exposure suggesting recurrent selection for tolerance. Selection also did not act primarily on cells showing relatively high growth rates, as often assumed under exposure to a β-lactam antibiotic. The cells with relatively high growth rates, but still reduced growth compared to prior antibiotic exposure conditions, showed equal mortality risk than cells that were in growth arrest or shrank, slowly growing cells showed the lowest mortality risk. Relatively fast-growing cells and non-growing or shrinking cells exhibited less robust growth patterns compared to slowly, but constantly, growing cells. Our findings suggest a type of tolerance that differs from previously described tolerance and persister characteristics. The high frequency of such tolerant cells, in combination with the fact that they do not arise from growth arrested cells and do not go into growth arrest under antibiotic exposure, suggest that they might play an important role for the evolution to resistance and for antibiotic treatment failure of recurring infections.

Both sudden stratospheric warming (SSW) events and tropospheric blocking events can have a significant influence on winter extratropical surface weather. Upward propagating planetary waves from the troposphere can interact with the stratospheric mean flow and disrupt the stratospheric polar vortex, which is associated with an SSW event. Blocking has often been suggested as one of the tropospheric precursors for anomalous upward propagating wave activity flux. It remains an open question to what extent upward wave activity caused by blocking is related to SSW events. In the present study, we examine the evolution of the Eliassen-Palm fluxes during blocking events that precede SSWs. We use Global Navigation Satellite System radio occultation measurements for this analysis to provide accurate and vertically well-resolved information on the wave coupling between these two phenomena in the upper troposphere and stratosphere. First results will be presented and discussed.Keywords: sudden stratospheric warming, Eliassen-Palm flux, blocking

In this study, we aim at quantifying the contribution of different forcings to changes in temperature extremes over 1981–2020 using CMIP6 climate model simulations. We first assess the changes in extreme hot and cold temperatures defined as days below 10% and above 90% of daily minimum temperature (TN10 and TN90) and daily maximum temperature (TX10 and TX90). We compute the change in percentage of extreme days per season for October-March (ONDJFM) and April-September (AMJJAS). Spatial and temporal trends are quantified using multi-model mean of all-forcings simulations. The same indices will be computed from aerosols-, greenhouse gases- and natural-only forcing simulations. The trends estimated from all-forcings simulations are then attributed to different forcings (aerosols-, greenhouse gases-, and natural-only) by considering uncertainties not only in amplitude but also in response patterns of climate models. The new statistical approach to climate change detection and attribution method by Ribes et al. (2017) is used to quantify the contribution of human-induced climate change. Preliminary results of the attribution analysis show that anthropogenic climate change has the largest contribution to the changes in temperature extremes in different regions of the world.Keywords: climate change, temperature, extreme events, attribution, CMIP6 Acknowledgement: This work was funded by the Austrian Science Fund (FWF) under Research Grant W1256 (Doctoral Programme Climate Change: Uncertainties, Thresholds and Coping Strategies)

Simple demographic events, the survival and reproduction of individuals, drive population dynamics. These demographic events are influenced by genetic and environmental parameters, and are the focus of many evolutionary and ecological investigations that aim to predict and understand population change. However, such a focus often neglects the stochastic events that individuals experience throughout their lives. These stochastic events also influence survival and reproduction and thereby evolutionary and ecological dynamics. Here, we illustrate the influence of such non-selective demographic variability on population dynamics using population projection models of an experimental population of Plantago lanceolata. Our analysis shows that the variability in survival and reproduction among individuals is largely due to demographic stochastic variation with only modest effects of differences in environment, genes, and their interaction. Common expectations of population growth, based on expected lifetime reproduction and generation time, can be misleading when demographic stochastic variation is large. Large demographic stochastic variation exhibited within genotypes can lower population growth and slow evolutionary adaptive dynamics. Our results accompany recent investigations that call for more focus on stochastic variation in fitness components, such as survival, reproduction, and functional traits, rather than dismissal of this variation as uninformative noise.

Objective In order to isolate and identify bacteria that produce potentially novel bactericidal/bacteriostatic compounds, two ponds on the campus of the Rochester Institute of Technology (RIT) were targeted as part of a bioprospecting effort. Results One of the unique isolates, RIT 452 was identified as Exiguobacterium sp. and subjected to whole-genome sequencing. The genome was assembled and in silico analysis was performed to predict the secondary metabolite gene clusters, which suggested the potential of Exiguobacterium RIT452 for producing antibiotic compounds. Extracts of spent growth media of RIT452 were active in disc diffusion assays performed against four reference strains, two Gram-negative (E. coli ATCC 25922 and P. aeruginosa ATCC 27853) and two Gram-positive (B. subtilis BGSC 168 and S. aureus ATCC 25923). Differential extraction and liquid chromatography was used to fractionate the extracts. Efforts to identify and elucidate the structure of the active compound(s) are still ongoing.

In 2015 the United Nations proposed the Sustainable Development Goals (SDGs), a set of universal goals for meeting the urgent environmental, political and economic challenges in the world. Universities play an important role to support and contribute to the SDGs mainly through education and research. To evaluate the contributions through research, universities aim at relating their scientific publications to SDGs, and automatically quantify the connectedness of these publications to the detailed targets and the unique indicators under SDGs. In this paper, we apply deep learning techniques to estimate the unknown indicators (third level) and targets (second level) for each publication, and output all its possible goals (first level). Specifically, we first exploit the dependency of categories at different levels (goals, targets, and indicators) to extract the dependent label features. Then we calculate the degree of matching between categories and publications in a bottom-up way and design a hierarchical structure to transfer such matching information level by level until obtaining the predicted SDGs of the publications. This is the first application of a deep learning method on this SDG prediction task and our experiments clearly demonstrate the good performance of our model on this real-world SDGs matching task, the extraction of key information as well as the prediction of potential sub-categories. As auxiliary analysis, we visualize the extraction of key semantic information and the probability of the hierarchical SDG categories.