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Abstract To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells’ capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.

Abstract Micropatterned dry adhesive systems are a promising alternative to conventional handling solutions. However, the use of these gripping systems still requires precise manual adjustment of the gripping parameters. To address this limitation, a coil‐based sensor is designed to enable automatic detection of the attachment process. The sensor consists of three sensing, one transmitting coil, a conductive film, and a compliant layer. The components are optimized to achieve reproducible, precise measurements, and minimize hysteresis effects of the components. A mathematical concept to calculate the geometrical relations between the gripping object and the gripper is established based on triangulation. The functionality of the sensor system is demonstrated in contact experiments with a glass substrate under different tilt angles, and an accuracy of 0.042 degree is achieved. The sensor system not only allows precise detection of the misalignment angle but also fast estimation of the qualitative direction of misalignment with minimal compression. This is interesting for scaling the sensor system to industrial pick‐and‐place applications as it promises to speed up the handling times and reliability of the fibrillary adhesives. In the future, the system needs to be extended to capture more complex objects and properties to be applicable to more handling problems.

Fluctuations in the size of taurine cattle (Bos taurus) have been regularly demonstrated using archaeozoological data from across time and space in Europe, and have been linked to cultural, social and economic changes, but little is known about whether phenotypic change is accompanied by changes in genetic diversity. Here, we performed PCR-typed analysis of the partial mtDNA d-loop fragments of 99 cattle from the Neolithic to Early Medieval times from a number of different sites across Switzerland, combining newly presented data with previously published data (n = 20). We found that most cattle included (84) were members of the common European macro-haplogroup T3. However, cattle belonging to the haplogroups T1, T2, Q and P were identified as early as the Neolithic period, before 2690 cal. BCE. The highest diversity was found in the Neolithic period, during the 1st century CE and during the 7th–8th centuries CE. Bottleneck phases with low genetic diversity were detected during the Late Iron Age and from the fifth to the seventh century CE. Based on the FST values, Horgen, Corded Ware and cattle populations from the seventh to the ninth century CE were plotted away from the clusters of all other populations. The periods with larger-sized cattle correspond with those of high mtDNA d-loop diversity. Phenotype and genotype both appear to respond to the same socio-economic and cultural processes.

BackgroundNeurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD).MethodsWe analyzed individual participant data from studies of children evaluated with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI).ResultsAmong 1770 subjects from 22 institutions, assessed at age 14.5 ± 3.7 months, PDIs and MDIs (77.6 ± 18.8 and 88.2 ± 16.7, respectively) were lower than normative means (each P < .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P ≤ .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P < .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02).ConclusionsEarly neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources.

UnlabelledIncident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.IntroductionVertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.MethodsVF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.ResultsSixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017).ConclusionsThe incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the Drosophila aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic in vivo experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased Cirl1 expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.

As part of an interdisciplinary research project on the Late La Tène period settlement at Basel-Gasfabrik, ceramic sherds, animal bones and archaeological sediments from different archaeological structures (one large pit, two ditches and four archaeological layers) were examined in respect of 21 taphonomic features (proxies). These proxies, in turn, were linked to different processes that can leave traces on objects or sediments: primary use, mechanical stress, heat impact, water, redeposition, exposure, covering and postdepositional processes. The different proxies were compared using a statistical procedure. Our results show significant differences between the different features with regard to taphonomic alteration. For example, ceramic sherds and animal bones from archaeological layers show severe alteration due to exposure, whilst a good and uniform preservation within the pit points to its rapid filling. Furthermore, there is evidence of middens which probably served as material depots. Our results suggest that waste was not simply seen as rubbish, but was stored as a resource. Therefore, materials could take different "paths", each of which resulted in specific taphonomic processes (alterations). The interdisciplinary approach taken in this project has provided new insight into the complex but probably clearly defined handling of various materials at Basel-Gasfabrik, thus allowing us to visualise part of the cultural biography of things.

Aims. This study is aimed at assessing the association of previously developed indices of glucose homeostasis derived from principal component analysis (PCA) with parameters of insulin action, secretion, and beta cell function during pregnancy. Methods. In this prospective longitudinal study, an oral glucose tolerance test was performed in sixty-seven pregnant women at two prepartum (12+0 to 22+6 and 24+0 to 28+6) and one postpartum (2 to 11 months) visits. Three principal component scores (PCS) were calculated based on measurements of glucose, insulin, C-peptide, age, and BMI to assess their association with fasting and dynamic indices of insulin action, secretion, and β-cell function. Results. PCS1 was positively associated with fasting and dynamic parameters of insulin sensitivity (Matsuda index: r=0.93, p

Abstract Bariatric surgery (BS) is regarded to be the most effective treatment of obesity with long lasting beneficial effects including weight loss and improvement of metabolic disorders. A considerable number of women undergoing BS are at childbearing age. Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS. Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.

This paper investigates the resonant behaviour of silicon-based micro-oscillators with a length of 3600 µm, a width of 1800 µm and a thickness of 10 µm over a wide range of ambient gas (N2) pressures, extending over six orders of magnitude from 10−3 mbar to 900 mbar. The oscillators are actuated piezoelectrically by a thin-film aluminium-nitride (AlN) layer, with the cantilever coverage area being varied from 33% up to 100%. The central focus is on nonlinear Duffing effects, occurring at higher oscillation amplitudes. A theoretical background is provided. All relevant parameters describing a Duffing oscillator, such as stiffness parameters for each coverage size as well as for different bending modes and more complex modes, are extracted from the experimental data. The so-called 2nd roof-tile-shaped mode showed the highest stiffness value of −97.3∙107 m−2s−2. Thus, it was chosen as being optimal for extended range pressure measurements. Interestingly, both a spring softening effect and a spring hardening effect were observed in this mode, depending on the percentage of the AlN coverage area. The Duffing-effect-induced frequency shift was found to be optimal for obtaining the highest pressure sensitivity, while the size of the hysteresis loop is also a very useful parameter because of the possibility of eliminating the temperature influences and long-term drift effects of the resonance frequency. An reasonable application-specific compromise between the sensitivity and the measurement range can be selected by adjusting the excitation voltage, offering much flexibility. This novel approach turns out to be very promising for compact, cost-effective, wide-range pressure measurements in the vacuum range.

The membrane-bound C4-dicarboxylate (C4DC) sensor kinase DcuS of Escherichia coli typically forms a protein complex with the C4DC transporter DctA. The DctA × DcuS complex is able to respond to C4DCs, whereas DcuS without DctA is in the permanent ON state. In DctA, the C-terminal helix 8b (H8b) serves as the site for interaction with DcuS. Here the interaction site in DcuS and the related structural and functional adaptation in DcuS were determined. The Linker connecting transmembrane helix 2 (TM2) and the cytosolic PASC (Per-ARNT-SIM) domain of DcuS, was identified as the major site for interaction with DctA-H8b by in vivo interaction studies. The Linker is known to convert the piston-type transmembrane signaling of TM2 to a tilting motion which relies on a resolution of the Linker-Linker’ homodimer in the presence of C4DCs. Absence of DctA caused decreased cross-linking in the Linker, as identified by oxidative Cys-cross-linking. This response resembled structurally and functionally that of fumarate activation in the DctA × DcuS complex. Overall, formation of the DctA × DcuS complex is based on the interaction of the DcuS Linker with DctA H8b; the interaction is required to set DcuS in the C4DC-responsive state by stabilizing the linker-linker’ homodimer in DcuS. This work identifies DctA as a structural co-regulator of DcuS sensor kinase.

A single ^40 Ca ion is confined in the harmonic potential of a Paul trap and cooled to a temperature of a few mK, with a wave packet of sub- μ m spatial and sub-m s ^−1 velocity uncertainty. Deterministically extracted from the Paul trap, the single ion is propagating over a distance of 0.27 m and detected. By engineering the ion extraction process on the initial wave packet, theoretically modeling the ion trajectories, and studying experimentally the time-of-flight distribution, we directly infer the state of the previously trapped ion. This analysis allows for accurate remote sensing of the previous motional excitation in the trap potential, both coherently or incoherently. Our method paves a way to extract, manipulate and design quantum wave packets also outside of the Paul trap.

Large-scale introduction of electric vehicles (EVs) to the market sets outstanding requirements for battery performance to extend vehicle driving range, prolong battery service life, and reduce battery costs. There is a growing need to accurately and robustly model the performance of both individual cells and their aggregated behavior when integrated into battery packs. This paper presents a novel methodology for Lithium-ion (Li-ion) battery pack simulations under actual operating conditions of an electric mining vehicle. The validated electrochemical-thermal models of Li-ion battery cells are scaled up into battery modules to emulate cell-to-cell variations within the battery pack while considering the random variability of battery cells, as well as electrical topology and thermal management of the pack. The performance of the battery pack model is evaluated using transient experimental data for the pack operating conditions within the mining environment. The simulation results show that the relative root mean square error for the voltage prediction is 0.7–1.7% and for the battery pack temperature 2–12%. The proposed methodology is general and it can be applied to other battery chemistries and electric vehicle types to perform multi-objective optimization to predict the performance of large battery packs.

Background In neonates with single ventricle, smaller ascending aorta diameter is associated with cerebral white matter (WM) microstructural abnormalities. We sought to determine whether this association persists into adolescence. Methods and Results Ascending aorta Z scores were obtained from first postnatal echocardiogram. Brain magnetic resonance imaging with diffusion tensor imaging was acquired in adolescence and used to obtain fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity in 33 WM tract regions of interest. Partial Pearson correlation coefficients were evaluated for associations between ascending aorta Z scores and WM microstructure measures, adjusting for sex, age at magnetic resonance imaging, scanner field strength, and Norwood status. Among 42 single ventricle patients aged 10 to 19 years, 31 had undergone the Norwood procedure as neonates. Lower ascending aorta Z scores were associated with lower fractional anisotropy in bilateral pontine crossing tracts (P=0.02), inferior fronto‐occipital fasciculus (P=0.02), and inferior longitudinal fasciculus (P=0.01); left cingulum–cingulate bundle (P=0.01), superior longitudinal fasciculus (P=0.04), and superior longitudinal fasciculus–temporal component (P=0.01); and right cingulum–hippocampal bundle (P=0.009) and inferior cerebellar peduncle (P=0.01). Lower ascending aorta Z scores were associated with higher radial diffusivity and mean diffusivity in a similar regional pattern but not with axial diffusivity. Conclusions In adolescents with single ventricle, smaller aorta diameter at birth is associated with abnormalities of WM microstructure in a subset of WM tracts, mostly those located in deeper brain regions. Our findings suggest that despite multiple intervening medical or surgical procedures, prenatal cerebral blood flow may have a lasting influence on WM microstructure in single‐ventricle patients.

The aim of this study was to assess the association between OGTT glucose levels and requirement of pharmacotherapy in GDM patients classified by the IADPSG criteria. This study included 203 GDM patients (108 managed with lifestyle modification and 95 requiring pharmacotherapy). Clinical risk factors and OGTT glucose concentrations at 0 (G0), 60 (G60), and 120 min (G120) were collected. OGTT glucose levels were significantly associated with the later requirement of pharmacotherapy (ROC-AUC: 71.1, 95% CI: 63.8–78.3). Also, the combination of clinical risk factors (age, BMI, parity, and pharmacotherapy in previous gestation) showed an acceptable predictive accuracy (ROC-AUC: 72.1, 95% CI: 65.0–79.2), which was further improved when glycemic parameters were added (ROC-AUC: 77.5, 95% CI: 71.5–83.9). Random forest analysis revealed the highest variable importance for G0, G60, and age. OGTT glucose measures in addition to clinical risk factors showed promising properties for risk stratification in GDM patients classified by the recently established IADPSG criteria.

Smoking during pregnancy is a persistent public health problem that has been linked to later adverse outcomes. The neonatal period--the first month of life--carries substantial developmental change in regulatory skills and is the period when tobacco metabolites are cleared physiologically. Studies to date mostly have used cross-sectional designs that limit characterizing potential impacts of prenatal tobacco exposure on the development of key self-regulatory processes and cannot disentangle short-term withdrawal effects from residual exposure-related impacts. In this study, pregnant participants (N = 304) were recruited prospectively during pregnancy, and smoking was measured at multiple time points, with both self-report and biochemical measures. Neonatal attention, irritable reactivity, and stress dysregulation were examined longitudinally at three time points during the first month of life, and physical growth indices were measured at birth. Tobacco-exposed infants showed significantly poorer attention skills after birth, and the magnitude of the difference between exposed and nonexposed groups attenuated across the neonatal period. In contrast, exposure-related differences in irritable reactivity largely were not evident across the 1st month of life, differing marginally at 4 weeks of age only. Third-trimester smoking was associated with pervasive, deleterious, dose-response impacts on physical growth measured at birth, whereas nearly all smoking indicators throughout pregnancy predicted level and growth rates of early attention. The observed neonatal pattern is consistent with the neurobiology of tobacco on the developing nervous system and fits with developmental vulnerabilities observed later in life. (Contains 7 tables, 1 footnote and 1 figure.)

We present a feasibility study with several magnetic field configurations for creating spin-dependent forces that can split a low-energy ion beam by the Stern–Gerlach (SG) effect. To the best of our knowledge, coherent spin-splittings of charged particles have yet to be realised. Our proposal is based on ion source parameters taken from a recent experiment that demonstrated single-ion implantation from a high-brightness ion source combined with a radio-frequency Paul trap. The inhomogeneous magnetic fields can be created by permanently magnetised microstructures or from current-carrying wires with sizes in the micron range, such as those recently used in a successful implementation of the SG effect with neutral atoms. All relevant forces (Lorentz force and image charges) are taken into account, and measurable splittings are found by analytical and numerical calculations.

Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G x E) on important outcomes (A. Caspi & T. E. Moffitt, 2006). It is also important to consider the possibility that these G x E effects may vary across development, particularly for constructs like self-regulation that emerge slowly, depend on brain regions that change qualitatively in different developmental periods, and thus may be manifested differently. To illustrate one approach to exploring such developmental patterns, the relation between variation in the "Taq"IA polymorphism, related to D[subscript 2] dopamine receptor expression and availability, and prenatal exposure to tobacco was examined in two exploratory studies. First, in 4-week-old neonates, genotype-exposure interactions were observed for attention and irritable reactivity, but not for stress dysregulation. Second, in preschool children, genotype was related to Preschool Trail Making Test (K. A. Espy and M. F. Cwik, 2004) task performance on conditions requiring executive control; children with both the A1+ genotype and a history of prenatal tobacco exposure displayed disproportionately poor performance. Despite study limitations, these results illustrate the importance of examining the interplay between genetic and prenatal environmental factors across development. (Contains 3 tables, 3 figures, and 2 footnotes.)