We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected ...children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extension of previous findings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.
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•Identification of rare inherited variants associated with ASD and 16 new ASD risk genes•Inherited risk reveals both new biological pathways and shared PPI with known genes•We develop and validate a machine learning algorithm (ARC) to remove WGS artifacts•NR3C2 mutations define a novel syndromic form of ASD, which we model in zebrafish
Whole-genome sequencing from families with multiple ASD-affected children allows identification of rare inherited variants associated with disease and definition of a syndromic form of disease caused by mutations in NR3C2.
Spatial covariance in the simulated temperature evolution over the past millennium has been reported to exceed that of multiproxy‐based reconstructions. Here we use tree ring‐based temperature ...reconstructions and state‐of‐the‐art climate model simulations to assess temporal changes in Northern Hemisphere intercontinental temperature covariance during the last 1000 years. Tree ring‐only approaches reveal stronger agreement with model simulations compared to multiproxy networks. Although simulated temperatures exhibit a substantial spread among individual models, intercontinental temperature coherency is mainly driven by the cooling of large volcanic eruptions in 1257, 1452, 1600, and 1815 Common Era. The coherence of these synchronizing events appears to be elevated in several climate simulations relative to their own unforced covariance baselines and in comparison to the proxy reconstructions. This suggests that some models likely overestimate the amplitude of abrupt summer cooling in response to volcanic eruptions, particularly at larger spatial scales.
Key Points
Tree ring‐based summer temperature reconstructions show higher intercontinental covariance than multiproxy approaches
Volcanic eruptions cause periods of high intercontinental summer temperature covariance
Model simulations tend to overestimate the amplitude of volcanic‐induced summer cooling
Information about past volcanic impact on climate is mostly derived from historic documentary data and sulfate depositions in polar ice sheets. Although these archives have provided important ...insights into the Earth's volcanic eruption history, the climate forcing and exact dating of many events is still vague. Here we apply a new method of break detection to the first millennium-length maximum latewood density reconstruction of Northern Hemisphere summer temperatures to develop an alternative record of large volcanic eruptions. The analysis returns fourteen outstanding cooling events, all of which agree well with recently developed volcanic forcing records from high-resolution bipolar ice cores. In some cases, however, the climatic impact detected with our new method peaks in neighboring years, likely due to either dating errors in the polar ice cores or uncertainty in the interpretation of atmospheric aerosol transport to polar ice core locations. The most apparent mismatches between forcing and cooling estimates occur in the 1450s and 1690s. Application of the algorithm to two additional and recently developed reconstructions that blend maximum latewood density and ring width data reproduces twelve of the detected events among which eight are retrieved in all three of the dendroclimatic reconstructions. Collectively, the new estimates of volcanic activity with precise age control provide independent evidence for forcing records during the last millennium. Evaluating the cooling magnitude in response to detected events yields an upper benchmark for the volcanic impact on climate. The average response to the ten major events in the density derived reconstruction is −0.60 °C ± 0.13 °C. Other last millennium temperature records from proxies and model simulations reveal higher cooling estimates, which is, to some degree, related to the very different high frequency variance in these timeseries.
X‐ray microdensitometry on annually resolved tree‐ring samples has gained an exceptional position in last‐millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also ...increasingly through other density parameters. For 50 years, X‐ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light‐based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree‐ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh “long‐standing wisdom” but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume‐based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree‐ring density data. Finally, we provide recommendations expected to facilitate futureinter‐comparability and interpretations for global change research.
Plain Language Summary
Paleoclimatology, the study of how the climate has changed throughout earth history, is an important component of climate change research. The wood density of tree rings is a widely used parameter to study past temperature changes. Despite wood density being widely used and considered excellent for this type of research, deriving comparable measurements at different laboratories and using a variety of techniques are proving challenging. This review compiles the current understanding and merits of wood density as a proxy in paleoclimate research. We further describe and review prevalent measurement techniques and associated analytical measurement challenges. The review is also complemented with a careful comparison of a set of new measurements derived at 17 laboratories, using several different techniques. We find that there are substantial differences in measurements performed among laboratories. The main challenge is associated with the analytical resolution when measuring small features such as the density of the latewood. We provide recommendations for future work to overcome systematic differences and towards the prospect of combining measurements from different techniques in integrative studies.
Key Points
We review the merits and state of the art of tree‐ring wood microdensitometry and its associated analytical challenges
We show that systematic level offsets in mean wood density from different techniques and laboratories require correction
Measurement resolution—notoriously difficult to control—is identified as the major challenge for future research applications
Loneliness is typically defined in terms of feeling states. In this review, we take a somewhat different approach, describing loneliness in terms of perceived social isolation. Vulnerabilities to ...perceived social isolation differ across the lifespan. Unique properties of adolescence are identified that carry special risk for perceived social isolation. These include (but are not limited to) developmental changes in companions, developmental changes in autonomy and individuation, identity exploration, cognitive maturation, developmental changes in social perspective taking, and physical maturation. Scholars are encouraged to consider loneliness through the lens of perceived social isolation so as to better understand how the experience of physical isolation varies across adolescence.
Abstract
Photovoltaics (PV) is one of the important technologies for electricity generation from renewable energies today and has an excellent environmental sustainability. It is a fast-growing ...market worldwide and also offers opportunities for aviation to intensify the use of renewable sources. Although the efficiency of PV systems has increased to a certain extent in recent years, a predominant part of solar radiation acting on a PV system is still lost to the environment through reflection and convection as well as heat radiation from the heated PV system. In addition, the efficiency of these systems decreases with increasing heating. Possible solutions for energy harvesting of this energy loss through thermoelectric (TE) have been investigated theoretically and in part experimentally in various cases but have not yet been transferred to larger PV systems. At the same time, cooling the PV system through thermogenerators (TEG) allows its efficiency to be increased. This contribution presents first results from investigations into the design and testing of hybrid PV/TEG systems, which aim to increase the efficiency and improve economic manufacturability of such systems. Among others, important design aspects of hybrid PV/TEG systems and integration of IoT elements (Internet of Things) are addressed and the development of an analytical model to optimise hybrid systems is presented.
Ni–Ti alloys are used as functional materials in numerous sectors such as aerospace, automotive engineering, medical technology, and consumer goods. Their properties in terms of shape memory effect ...and superelasticity offer a great potential for innovative smart products. However, forming and machining of these alloys into concrete products is challenging. Assembling plain structures by laser welding to complex product shapes offers an economical alternative in many cases, but can be associated with negative effects, such as reduction of strength, development of brittle intermetallic compounds, alteration of transformation temperatures, and modification of shape memory effects and superelastic behavior. Against this background, investigations on laser welding of Ni55/Ti45 foil with a thickness of 125
µ
m by a fiber laser were conducted. Supported by methods of design of experiments, optimal parameters were determined with respect to laser power, welding speed, focus position, and beam oscillation, and the welding results were analyzed concerning the microstructure and mechanical characteristics of the welded joints. The effect of laser beam oscillation was investigated for the first time for the welding of this alloy. Due to the very low thickness, the preparation of the foils for the microstructure characterization is quite demanding. Best results were obtained by ion milling. Fracture surfaces and the influence of the welding were also investigated.
Resource Control Theory (Hawley, 1999) posits a group of bistrategic popular youth who attain status through coercive strategies while mitigating fallout via prosociality. This study identifies and ...distinguishes this bistrategic popular group from other popularity types, tracing the adjustment correlates of each. Adolescent participants (288 girls, 280 boys; Mage = 12.50 years) completed peer nominations in the Fall and Spring of the seventh and eighth grades. Longitudinal latent profile analyses classified adolescents into groups based on physical and relational aggression, prosocial behavior, and popularity. Distinct bistrategic, aggressive, and prosocial popularity types emerged. Bistrategic popular adolescents had the highest popularity and above average aggression and prosocial behavior; they were viewed by peers as disruptive and angry but were otherwise well‐adjusted.
Tree-ring stable isotopes, providing insight into drought-induced eco-physiological mechanisms, are frequently used to reconstruct past changes in growing season temperature and precipitation. Their ...climatic response is, however, still not fully understood, particularly for data originating from non-extreme, mid-latitude environments with differing ecological conditions. Here, we assess the response of δ(13)C, δ(18)O and tree-ring width (TRW) from a temperate mountain forest in the Austrian pre-Alps to climate and specific drought events. Variations in stem growth and isotopic composition of Norway spruce, common beech and European larch from dry, medium and moist sites are compared with records of sunshine, temperature, moisture, precipitation and cloud cover. Results indicate uniform year-to-year variations in δ(13)C and δ(18)O across sites and species, but distinct differences in TRW according to habitat and species. While the climate sensitivity of TRW is overall weak, the δ(13)C and δ(18)O chronologies contain significant signals with a maximum sensitivity to cloud cover changes (r = -0.72 for δ(18)O). The coherent inter-annual isotopic variations are accompanied by substantial differences in the isotopic signatures with offsets up to ∼3‰ for δ(13)C, indicating species-specific physiological strategies and varying water-use efficiencies. During severe summer drought, beech and larch benefit from access to deeper and moist soils, allowing them to keep their stomata open. This strategy is accompanied by an increased water loss through transpiration, but simultaneously enables enhanced photosynthesis. Our findings indicate the potential of tree-ring stable isotopes from temperate forests to reconstruct changes in cloud cover, and to improve knowledge on basic physiological mechanisms of tree species growing in different habitats to cope with soil moisture deficits.
Background For children with diabetes, metabolic control typically declines across the adolescent years.
The longitudinal interplay between supportive relationships with parents and metabolic control ...were investigated in families that differ in parents' restrictiveness.
The time-dependent links between perceived parental social support and metabolic control were investigated in a sample of 109 German adolescents with diabetes. 3 waves of data were collected at annual intervals; metabolic control (indexed by HbA1c) was assayed by physicians annually.
Family restrictiveness moderated longitudinal associations between metabolic control and perceived social support. For adolescents reporting high family restrictiveness, poorer initial metabolic control predicted greater subsequent declines in perceived parent social support, and lower initial perceived parental social support predicted greater subsequent deterioration in metabolic control.
The findings add to the growing body of work suggesting that restrictiveness is a risk factor that exacerbates problems associated with low perceived parental support.
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