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We introduced a new class of gas diffusion electrodes (GDEs) with adjustable pore morphology. We fabricated intrinsically conductive polymer-composite membranes containing carbon filler, enabling a pore structure variation through film casting cum phase separation protocols. We further selectively functionalized specific pore regions of the membranes with Cu by a NaBH4-facilitated coating strategy. The as-obtained GDEs can facilitate the electrochemical CO2 reduction reaction (CO2RR) at Cu active sites that are presented inside a defined and electrically conductive pore system. When employing them as free-standing cathodes in a CO2 flow electrolyzer, we achieved >70% Faradaic efficiencies for CO2RR products at up to 200 mA/cm2. We further demonstrated that deposition of a dense Cu layer on top of the membrane leads to obstruction of the underlying pore openings, inhibiting an excessive wetting of the pore pathways that transport gaseous CO2. However, the presentation of Cu inside the pore system of our novel membrane electrodes increased the C2H4/CO selectivity by a factor of up to 3 compared to Cu presented in the dense layer on top of the membrane. Additionally, we found that gaseous CO2 could still access Cu in macropores after wetting with electrolyte, while CO2RR was completely suppressed in wetted nm-scale pores., (© 2024 Wiley‐VCH GmbH.)

A new concept for the synthesis of dialkyl chloronium cations [R‒Cl‒R]+ is described (R = CH3, CH2CF3), that allows the formation of fluorinated derivatives. By utilizing the xenonium salt [XeOTeF5][M(OTeF5)n] (M = Sb, n = 6; M = Al, n = 4) chlorine atoms of chloroalkanes or the deactivated chlorofluoroalkane CH2ClCF3 are oxidized and removed as ClOTeF5 leading to the isolation of the corresponding chloronium salt. Since the resulting highly electrophilic cation [Cl(CH2CF3)2]+ is able to alkylate weak nucleophiles, this compound can be utilized for the introduction of a fluorinated alkyl group to those. In addition, the fluorinated alkyl chloronium cation displays a high hydride ion affinity, enabling the activation of linear hydrocarbons by hydride abstraction even at low temperatures ultimately leading to the formation of branched carbocations., (© 2024 Wiley‐VCH GmbH.)

Nanoscopic magnetic domain walls (DWs), via their absence or presence, enable highly interesting binary data bits. The current-controlled, high-speed, synchronous motion of sequences of chiral DWs in magnetic nanoconduits induced by current pulses makes possible high-performance spintronic memory and logic devices. The closer the spacing between neighboring DWs in an individual conduit or nanowire, the higher the data density of the device, but at the same time, the more difficult it is to read the bits. Here, we show how the DW spacing can be dynamically varied to facilitate reading for otherwise closely packed bits. In the first method, the current density is increased in portions of the conduit that, thereby, locally speeds up the DWs, decompressing them and making them easier to read. In the second method, a localized bias current is used to compress and decompress the DW spacing. Both of these methods are demonstrated experimentally and validated by micromagnetic simulations. DW compression and decompression rates as high as 88% are shown. These methods can increase the density with which DWs can be packed in future DW-based spintronic devices by more than an order of magnitude.

We developed a novel method to fabricate copper nanorods in situ in a poly(ether sulfone) (15 wt %) casting solution by a sonochemical reduction of Cu 2+ ions with NaBH 4 . The main twist is the addition of ethanol to remove excess NaBH 4 through Cu(0) catalyzed ethanolysis. This enabled the direct use of the resulting copper-containing casting dispersions for membrane preparation by liquid nonsolvent-induced phase separation and led to full utilization of the copper source, generating zero metal waste. We characterized the copper nanorods as presented in the membranes via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV/vis spectroscopy. We could demonstrate that the rapid immobilization from reducing conditions led to the membrane incorporation of copper nanorods in a state of high reactivity, which also promoted the complete oxidation to CuO after fabrication. We further observed a large aspect ratio and crystal straining of the nanorods, likely resulting from growth around the matrix polymer. The entanglement with poly(ether sulfone) further facilitated a selective presentation at the pore surface of the final CuO-decorated membranes. The membranes also exhibit high water permeances of up to 2800 L/m 2 hbar. Our catalytic membranes achieved exceptionally high activities in the aqueous flow-through reduction of p -nitrophenol ( p -NP), with turnover frequencies of up to 115 h -1 , even surpassing those of other state-of-the-art catalytic membranes that incorporate Pd or Ag. Additionally, we demonstrated that catalytic hydrolysis of the reducing agent in water can lead to hydrogen gas formation and blocking of active sites during continuous catalytic p -NP hydrogenation. We illustrated that the accompanying conversion loss can be mitigated by facilitated gas transport in the water-filled pores, which is dependent on the orientation of the pore size gradient and the flow direction.

Herein we report on the formation of the adduct salts [Xe(OTeF 5 )(py F )][Al(OTeF 5 ) 4 ] (py F = C 5 F 5 N, C 5 H 3 F 2 N) by abstraction of an -OTeF 5 group from Xe(OTeF 5 ) 2 with the Lewis superacid Al(OTeF 5 ) 3 and subsequent adduct formation of the generated [XeOTeF 5 ] + cation with fluorinated pyridines. These salts represent the first xenonium cations with the weakly coordinating [Al(OTeF 5 ) 4 ] - anion. The strong oxidizing property of these compounds is further assessed.

Biogenic vapors form new particles in the atmosphere, affecting global climate. The contributions of monoterpenes and isoprene to new particle formation (NPF) have been extensively studied. However, sesquiterpenes have received little attention despite a potentially important role due to their high molecular weight. Via chamber experiments performed under atmospheric conditions, we report biogenic NPF resulting from the oxidation of pure mixtures of β-caryophyllene, α-pinene, and isoprene, which produces oxygenated compounds over a wide range of volatilities. We find that a class of vapors termed ultralow-volatility organic compounds (ULVOCs) are highly efficient nucleators and quantitatively determine NPF efficiency. When compared with a mixture of isoprene and monoterpene alone, adding only 2% sesquiterpene increases the ULVOC yield and doubles the formation rate. Thus, sesquiterpene emissions need to be included in assessments of global aerosol concentrations in pristine climates where biogenic NPF is expected to be a major source of cloud condensation nuclei.

The straightforward synthesis of polyamide-derived statistical copolymers with catechol, amine, amide and hydroxy residues via free radical polymerization is presented. In particular, catechol, amine and amide residues are present in natural mussel foot proteins, enabling strong underwater adhesion due to synergistic effects where cationic residues displace hydration and ion layers, followed by strong short-rang hydrogen bonding between the catechol or primary amides and SiO 2 surfaces. The present study is aimed at investigating whether such synergistic effects also exist for statistical copolymer systems that lack the sequence-defined positioning of functional groups in mussel foot proteins. A series of copolymers is established and the adsorption in saline solutions on SiO 2 is determined by quartz crystal microbalance measurements and ellipsometry. These studies confirm a synergy between cationic amine groups with catechol units and primary amide groups via an increased adsorptivity and increased polymer layer thicknesses. Therefore, the free radical polymerization of catechol, amine and amide monomers as shown here may lead to simplified mussel-inspired adhesives that can be prepared with the readily scalable methods required for large-scale applications.

Medical Assisted Reproduction proved its efficacy to treat the vast majority forms of infertility. One of the key procedures in this treatment is the selection and transfer of the embryo with the highest developmental potential. To assess this potential, clinical embryologists routinely work with static images (morphological assessment) or short video sequences (time-lapse annotation). Recently, Artificial Intelligence models were utilized to support the embryo selection procedure. Even though they have proven their great potential in different in vitro fertilization settings, there is still considerable room for improvement. To support the advancement of algorithms in this research field, we built a dataset consisting of static blastocyst images and additional annotations. As such, Gardner criteria annotations, depicting a morphological blastocyst rating scheme, and collected clinical parameters are provided. The presented dataset is intended to be used to train deep learning models on static morphological images to predict Gardner's criteria and clinical outcomes such as live birth. A benchmark of human expert's performance in annotating Gardner criteria is provided., (© 2023. The Author(s).)

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a "normal" range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.

Dendrites receive the vast majority of a single neuron's inputs, and coordinate the transformation of these signals into neuronal output. Ex vivo and theoretical evidence has shown that dendrites possess powerful processing capabilities, yet little is known about how these mechanisms are engaged in the intact brain or how they influence circuit dynamics. New experimental and computational technologies have led to a surge in interest to unravel and harness their computational potential. This review highlights recent and emerging work that combines established and cutting-edge technologies to identify the role of dendrites in brain function. We discuss active dendritic mediation of sensory perception and learning in neocortical and hippocampal pyramidal neurons. Complementing these physiological findings, we present theoretical work that provides new insights into the underlying computations of single neurons and networks by using biologically plausible implementations of dendritic processes. Finally, we present a novel brain-computer interface task, which assays somatodendritic coupling to study the mechanisms of biological credit assignment. Together, these findings present exciting progress in understanding how dendrites are critical for in vivo learning and behavior, and highlight how subcellular processes can contribute to our understanding of both biological and artificial neural computation., (Copyright © 2022 the authors.)

Magnetosensitive elastomers respond to external magnetic fields by changing their stiffness and shape. These effects result from interactions among magnetized inclusions that are embedded within an elastic matrix. Strong external magnetic fields induce internal restructuring, for example the formation of chain-like aggregates. However, such reconfigurations affect not only the overall mechanical properties of the elastomers but also the transport through such systems. We concentrate here on the transport of heat, that is thermal conductivity. For flat, thin model systems representing thin films or membranes and modeled by bead-spring discretizations, we evaluate the internal restructuring in response to magnetization of the particles. For each resulting configuration, we evaluate the associated thermal conductivity. We analyze the changes in heat transport as a function of the strength of magnetization, particle number, density of magnetizable particles (at fixed overall particle number), and aspect ratio of the system. We observe that varying any one of these parameters can induce pronounced changes in the bulk thermal conductivity. Our results motivate future experimental and theoretical studies of systems with magnetically tunable thermal but also electric conductivity-both of which have only rarely been addressed so far., (Creative Commons Attribution license.)

The data provided allows other research groups to numerically investigate the flame wall interactions of an experimental test bench at the University of the Bundeswehr Munich. Numerical simulations can then be compared to the experimental results to test new models. Three data sets are available. The first data set contains the inflow boundary conditions created by the burner into the test section. The fields of interest are the velocity and RMS-velocity fields. Large-Eddy-Simulation (LES) using ANSYS Fluent was used to collect this data. The second data set provides the inflow boundary condition from the fuel injector into the test section using methane at a momentum ratio of I = 10. LES using OpenFOAM was used to create this data. The third data set provides the temperature distribution at the wall of the test section when injecting methane at a momentum ratio of I = 10. The temperature is provided along the wall ranging from +/- 25 mm in the lateral and 0 - 220 mm in the axial direction. The data was derived from wall-embedded thermocouples by applying the inverse heat conduction method using MATLAB and COMSOL., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2022 The Authors. Published by Elsevier Inc.)

Background: Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect., Questions/purposes: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma?, Methods: We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals., Results: Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity., Conclusion: Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture., Level of Evidence: Level III, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

For the first time, the direct synthesis of 1-methyl-phosphininium salts has been achieved by reacting aromatic λ 3 ,σ 2 -phosphinines with the readily available dimethyl chloronium salt [(CH 3 ) 2 Cl] + [Al(OTeF 5 ) 4 ] - . The remarkably high electrophilicity of the alkylation reagent in combination with the weakly coordinating pentafluoro-orthotelluratoaluminate anion offers excellent conditions for this one-step approach. Our simple and quantitative access to 1-methyl-phosphininium salts will pave the way to explore the chemistry of such reactive species in more detail.

Separating and labeling each nuclear instance (instance-aware segmentation) is the key challenge in nuclear image segmentation. Deep Convolutional Neural Networks have been demonstrated to solve nuclear image segmentation tasks across different imaging modalities, but a systematic comparison on complex immunofluorescence images has not been performed. Deep learning based segmentation requires annotated datasets for training, but annotated fluorescence nuclear image datasets are rare and of limited size and complexity. In this work, we evaluate and compare the segmentation effectiveness of multiple deep learning architectures (U-Net, U-Net ResNet, Cellpose, Mask R-CNN, KG instance segmentation) and two conventional algorithms (Iterative h-min based watershed, Attributed relational graphs) on complex fluorescence nuclear images of various types. We propose and evaluate a novel strategy to create artificial images to extend the training set. Results show that instance-aware segmentation architectures and Cellpose outperform the U-Net architectures and conventional methods on complex images in terms of F1 scores, while the U-Net architectures achieve overall higher mean Dice scores. Training with additional artificially generated images improves recall and F1 scores for complex images, thereby leading to top F1 scores for three out of five sample preparation types. Mask R-CNN trained on artificial images achieves the overall highest F1 score on complex images of similar conditions to the training set images while Cellpose achieves the overall highest F1 score on complex images of new imaging conditions. We provide quantitative results demonstrating that images annotated by under-graduates are sufficient for training instance-aware segmentation architectures to efficiently segment complex fluorescence nuclear images.

Purpose: To assess the mechanical properties, tendon resistance to suture cutout, and knot size of a broad variety of high-strength sutures and tapes available for arthroscopic rotator cuff repair., Methods: Nine different types of high-strength sutures and tapes for arthroscopic rotator cuff repair were studied: 6 were tapes (FiberTape, Hi-Fi Tape, Permatape, SutureTape, UltraTape, and XBraid TT), and 3 were sutures (Dynacord, FiberWire, and Ultrabraid). First, mechanical tensile testing of suture loops (n = 6) was performed. Second, the suture material was passed through an intact human cadaveric rotator cuff tendon (supraspinatus or infraspinatus), and cyclic as well as load-to-failure testing was performed, 8 times for each suture or tape. Statistical analysis of groups (tapes vs sutures) and between each suture and each tape was performed., Results: Material testing revealed significant differences with superior mechanical properties of tapes compared with sutures regarding load for 3 mm of displacement (201 N vs 84 N, P < .0001), displacement at 200 N (3.6 mm vs 6.6 mm, P  < .0001), stiffness (46 N/mm vs 25 N/mm, P < .0001), and ultimate load to failure (509 N vs 288 N, P < .0001). FiberTape showed the highest ultimate load to failure (805.5 ± 36.1 N), the highest load necessary for 3 mm of displacement (376.2 ± 19.1 N), and the lowest displacement at a 200-N load (2 ± 0.1 mm). Permatape had the highest stiffness (58.5 ± 5.3 N/mm). FiberTape had the highest knot height (9.5 ± 1.3 mm) and knot width (3.8 ± 0.7 mm) of a suture loop with 7 square knots. The typical failure mode in the cadaveric study part was tendon cut through., Conclusions: Biomechanical in vitro testing showed that high-strength suture tapes compared with regular high-strength sutures have significantly better mechanical properties in both dry-laboratory testing and human cadaveric rotator cuff tendon pullout testing. FiberTape outperformed the other tapes and the sutures used in this analysis. Nonetheless, differences in tendon testing appeared to be less substantial than in dry-laboratory testing, and FiberTape had the highest knot height and width., Clinical Relevance: FiberTape revealed the most favorable biomechanical performance in dry-laboratory and rotator cuff tendon testing. It may provide the best repair strength in vivo; however, it also has the largest knot size., (© 2021 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

Purpose: Swept Source Optical coherence tomography angiography (SS-OCTA) is a novel technique to visualize perfusion and vascular changes like ischemia in patients with diabetic retinopathy. The aim of this study was to compare non-perfusion areas on conventional fluorescein angiography (FA) with those on SS-OCTA using detailed manual annotation in patients with diabetic macular edema (DME) and to evaluate possible artifacts caused by DME on SS-OCTA., Methods: 27 eyes of 21 patients with DME were analyzed in this prospective, cross-sectional study; on all, standard ophthalmological examination, SS-OCTA and FA imaging were performed. Early-phase FA and SS-OCTA images were analyzed for capillary dropout and foveal avascular zone (FAZ) was measured on both modalities. Artifacts in SS-OCTA imaging caused by DME were marked and analyzed., Results: The mean age of the patients was 62.6 ± 11.5 years. On FA the mean size of the annotated non-perfusion areas was 0.14 ± 0.31 mm2 whereas the mean size in SS-OCTA was 0.04 ± 0.13 mm2; areas marked on FA were statistically significantly larger than on SS-OCTA (p<0.01). Mean size of FAZs was similar between FA and OCTA images. (p = 0.91). Seven eyes (25.9 percent) showed imaging artifacts due to DME in SS-OCTA., Conclusion: SS-OCTA is a valid tool to analyze capillary perfusion status of patients with DME, although areas of non-perfusion were measured smaller than in conventional FA. More non-perfusion areas were found on SS-OCTA images. FAZ measurements were similar using the two modalities. However, SS-OCTA is prone to artifacts and therefore requires reviewing of imaging results: up to 25 percent of the analyzed eyes showed artifacts on OCTA, which occurred in the areas of diabetic macular edema and did not correspond to capillary drop out., Competing Interests: “Lukas Fischer is an employee at the company Software Competence Center Hagenberg GmbH. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare that there is no conflict of interest regarding the publication of this paper.

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) ( p = 0.012), higher porosity of the outer transitional zone (OTZ) ( p = 0.006), inner transitional zone (ITZ) ( p = 0.043) and the compact-appearing cortex (CC) ( p = 0.023) while trabecular vBMD was lower ( p = 0.002). At the distal tibia, cases also had a smaller cortical CSA ( p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower ( p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ ( p = 0.028), ITZ ( p = 0.030) not CC ( p = 0.054). Trabecular vBMD was lower ( p = 0.041). Distal tibial porosity was higher in the OTZ ( p = 0.035), ITZ ( p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

In Graeco-Roman times in the Lower-Egyptian Fayoum region, a painted portrait was traditionally placed over the face of a deceased individual. These mummy portraits show considerable inter-individual diversity. This suggests that those portraits were created separately for each individual. In the present study, we investigated a completely wrapped young infant mummy with a typical mummy portrait by whole body CT analysis. This was used to obtain physical information on the infant and provided the basis for a virtual face reconstruction in order to compare it to the mummy portrait. We identified the mummy as a 3-4 years old male infant that had been prepared according to the typical ancient Egyptian mummification rites. It most probably suffered from a right-sided pulmonary infection which may also be the cause of death. The reconstructed face showed considerable similarities to the portrait, confirming the portrait's specificity to this individual. However, there are some differences between portrait and face. The portrait seems to show a slightly older individual which may be due to artistic conventions of that period., Competing Interests: One of the authors (LF) is an employee of the commercial company 3-D-Construct, Cologne. The funder provided support in the form of salaries for this authors (LF), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the “Author contributions” section. There are no other relevant declarations relating to employment, consultancy,patents, products in development, or marketed products, etc. Furthermore, we declare, that this commercial affiliation does not alter our adherence to PLOS One policies on sharing data and material.

Catechol and amine residues, both abundantly present in mussel adhesion proteins, are known to act cooperatively by displacing hydration barriers before binding to mineral surfaces. In spite of synthetic efforts toward mussel-inspired adhesives, the effect of positioning of the involved functional groups along a polymer chain is not well understood. By using sequence-defined oligomers grafted to soft hydrogel particles as adhesion probes, we study the effect of catechol-amine spacing, as well as positioning relative to the oligomer terminus. We demonstrate that the catechol-amine spacing has a significant effect on adhesion, while shifting their position has a small effect. Notably, combinations of non-charged amides and catechols can achieve similar cooperative effects on adhesion when compared to amine and catechol residues. Thus, these findings provide a blueprint for the design of next generation mussel-inspired adhesives., Competing Interests: The authors filed a patent application DE 102019208832.5 “Polymere für die Behandlung von Oberflächen”., (This journal is © The Royal Society of Chemistry.)

Fully-automated nuclear image segmentation is the prerequisite to ensure statistically significant, quantitative analyses of tissue preparations,applied in digital pathology or quantitative microscopy. The design of segmentation methods that work independently of the tissue type or preparation is complex, due to variations in nuclear morphology, staining intensity, cell density and nuclei aggregations. Machine learning-based segmentation methods can overcome these challenges, however high quality expert-annotated images are required for training. Currently, the limited number of annotated fluorescence image datasets publicly available do not cover a broad range of tissues and preparations. We present a comprehensive, annotated dataset including tightly aggregated nuclei of multiple tissues for the training of machine learning-based nuclear segmentation algorithms. The proposed dataset covers sample preparation methods frequently used in quantitative immunofluorescence microscopy. We demonstrate the heterogeneity of the dataset with respect to multiple parameters such as magnification, modality, signal-to-noise ratio and diagnosis. Based on a suggested split into training and test sets and additional single-nuclei expert annotations, machine learning-based image segmentation methods can be trained and evaluated.

To better understand the role of aromatic hydrocarbons in new-particle formation, we measured the particle-phase abundance and volatility of oxidation products following the reaction of aromatic hydrocarbons with OH radicals. For this we used thermal desorption in an iodide-adduct Time-of-Flight Chemical-Ionization Mass Spectrometer equipped with a Filter Inlet for Gases and AEROsols (FIGAERO-ToF-CIMS). The particle-phase volatility measurements confirm that oxidation products of toluene and naphthalene can contribute to the initial growth of newly formed particles. Toluene-derived (C 7 ) oxidation products have a similar volatility distribution to that of α-pinene-derived (C 10 ) oxidation products, while naphthalene-derived (C 10 ) oxidation products are much less volatile than those from toluene or α-pinene; they are thus stronger contributors to growth. Rapid progression through multiple generations of oxidation is more pronounced in toluene and naphthalene than in α-pinene, resulting in more oxidation but also favoring functional groups with much lower volatility per added oxygen atom, such as hydroxyl and carboxylic groups instead of hydroperoxide groups. Under conditions typical of polluted urban settings, naphthalene may well contribute to nucleation and the growth of the smallest particles, whereas the more abundant alkyl benzenes may overtake naphthalene once the particles have grown beyond the point where the Kelvin effect strongly influences the condensation driving force.

The putative generalization of the thermodynamic uncertainty relation (TUR) to underdamped dynamics is still an open problem. So far, bounds that have been derived for such a dynamics are not particularly transparent and they do not converge to the known TUR in the overdamped limit. Furthermore, it was found that there are restrictions for a TUR to hold such as the absence of a magnetic field. In this article we first analyze the properties of driven free diffusion in the underdamped regime and show that it inherently violates the overdamped TUR for finite times. Based on numerical evidence, we then conjecture a bound for one-dimensional driven diffusion in a potential which is based on the result for free diffusion. This bound converges to the known overdamped TUR in the corresponding limit. Moreover, the conjectured bound holds for observables that involve higher powers of the velocity as long as the observable is odd under time reversal. Finally, we address the applicability of this bound to underdamped dynamics in higher dimensions.

Background: The objective of this study was to analyze prognostic factors and risk stratification in patients with pulmonary arterial hypertension (PAH) and comorbidities., Methods: Patients with invasively diagnosed PAH were included in the analysis. Comorbidities were clinically diagnosed as proposed in the 6th World Symposium of pulmonary hypertension. Uni- and multivariate analysis were employed for identification of factors predicting survival and time to first clinical worsening (TTCW). Risk stratification was based on parameters from ESC/ERS-guidelines 2015., Results: In total 142 patients were enrolled in the study, 90 of them were diagnosed as PAH without and 52 with comorbidities. All patients received targeted PAH therapy and were followed for 3.3 ± 2.4 years. In PAH patients without comorbidities survival and TTCW were significantly associated with reduced 6-min walking distance (6MWD), elevated N-terminal pro brain natriuretic peptide (NT-proBNP), WHO-functional class (WHO-FC) and right atrial (RA) area. In the multivariate analysis, 6MWD was an independent predictor for survival (p = 0.002) and WHO-FC for TTCW (p = 0.001). In patients with PAH and comorbidities these parameters had no significant association with survival and TTCW. Average risk score was significantly associated with survival (p = 0.001) and TTCW (p = 0.013) in PAH but not in PAH with comorbidities (both p > 0.05; figure 1)., Conclusion: Risk stratification based on ESC/ERS-guidelines could only be confirmed in patients without comorbidities, but not in patients with PAH and comorbidities. The data of this study suggest, that a different risk stratification needs to be applied to PAH patients with comorbidities. Further studies are needed to confirm these results., Trial Registration: Not applicable, retrospective registry.

The process by which visual information is incorporated into the brain's spatial framework to represent landmarks is poorly understood. Studies in humans and rodents suggest that retrosplenial cortex (RSC) plays a key role in these computations. We developed an RSC-dependent behavioral task in which head-fixed mice learned the spatial relationship between visual landmark cues and hidden reward locations. Two-photon imaging revealed that these cues served as dominant reference points for most task-active neurons and anchored the spatial code in RSC. This encoding was more robust after task acquisition. Decoupling the virtual environment from mouse behavior degraded spatial representations and provided evidence that supralinear integration of visual and motor inputs contributes to landmark encoding. V1 axons recorded in RSC were less modulated by task engagement but showed surprisingly similar spatial tuning. Our data indicate that landmark representations in RSC are the result of local integration of visual, motor, and spatial information., Competing Interests: LF, RM, FB, MH No competing interests declared, (© 2020, Fischer et al.)

Multiple Sclerosis (MS) is the most common chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), which can lead to severe cognitive impairment over time. Magnetic resonance imaging (MRI) is currently the best available biomarker to track MS pathophysiology in vivo and examine the link to clinical disability. However, conventional MRI metrics have limited sensitivity and specificity to detect direct associations between symptoms and their underlying CNS substrates. In this study, we aimed to investigate structural and resting state functional connectomes and subnetworks associated with neuropsychological (NP) performance using a graph theoretical approach. A comprehensive NP test battery was administered in a sample of patients with relapsing remitting MS (RRMS) and mild disability [n = 33, F/M = 20/13, age = 40.9 ± 9.7, median [Expanded Disability Status Scale] (EDSS) = 2, range =0-4] and compared to healthy controls (HC) [n = 29, F/M = 19/10, age = 41.0 ± 8.5] closely matched for age, sex, and level of education. The NP battery comprised the most relevant domains of cognitive dysfunction in MS including attention, processing speed, verbal and spatial learning and memory, and executive function. While standard MRI metrics showed good correlations with TAP Alertness test, disease duration and neurological exams, structural networks showed closer associations with 9-hole peg test and cognitive performances. Decreased graph strength was associated with two out of the 5 NP tests in the spatial learning and memory domain specified by BVMT [Sum 1-3] and BVMT [Recall], and with also SDMT which is one out of the 9 NP tests in the attention/processing speed domain, while no correlation was found between these scores and functional connectivity. Nodal strength was decreased in all subnetworks based on Yeo atlas in patients compared to HC; however, no difference was observed in nodal level of functional connectivity between the groups. The difference in structural and functional nodal connectivity between the groups was also observed in the relationship between structural and functional connectivity within the groups; the relationship between nodal degree and nodal strength was reversed in patients but positive in controls. On a nodal level, structural and functional networks (mainly the default mode network) were correlated with more than one cognitive domain rather than one specific network for each domain within patients. Interestingly, poorer cognitive performance was mostly correlated with increased functional connectivity but decreased structural connectivity in patients. Increased functional connectivity in the default mode network had both positive as well as negative associations with verbal and spatial learning and memory, possibly indicating adaptive and maladaptive mechanisms. In conclusion, our results suggest that cognitive performance, even in patients with RRMS and very mild disability, may reflect a loss of structural connectivity. In contrast, widespread increases in functional connectivity may be the result of maladaptive processes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Solid phase synthesis (SPS) is well established for the synthesis of biomacromolecules such as peptides, oligonucelotides, and oligosaccharides, and today is also used for the synthesis of synthetic macromolecules and polymers. The key feature of this approach is the stepwise assembly of building blocks on solid support, enabling monodispersity and monomer sequence control. However, in order to achieve such control, a high excess of building blocks is required during the reaction. Herein, the recovery, purification, and reusability of building blocks used in SPS, including representative examples of tailor-made building blocks, Fmoc-protected amino acids, and functionalized carbohydrate ligands, are reported for the first time. Results demonstrate the general applicability with recovery in high yields and high purity. Furthermore, the described recovery process can be applied in both manual and automated synthesis using a standard peptide synthesizer. Overall, this process is envisioned to be applicable for a large variety of building blocks used in the SPS of different types of molecules, and to contribute to more resourceful SPS syntheses., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Isoprene is emitted from the biosphere into the atmosphere, and may strengthen the defense mechanisms of plants against oxidative and thermal stress. Once in the atmosphere, isoprene is rapidly oxidized, either to isoprene-hydroxy-hydroperoxides (ISOPOOH) at low levels of nitrogen oxides, or to methyl vinyl ketone (MVK) and methacrolein at high levels. Here we combine uptake rates and deposition velocities that we obtained in laboratory experiments with observations in natural forests to show that 1,2-ISOPOOH deposits rapidly into poplar leaves. There, it is converted first to cytotoxic MVK and then most probably through alkenal/ one oxidoreductase (AOR) to less toxic methyl ethyl ketone (MEK). This detoxification process is potentially significant globally because AOR enzymes are ubiquitous in terrestrial plants. Our simulations with a global chemistry-transport model suggest that around 6.5 Tg yr - of MEK are re-emitted to the atmosphere. This is the single largest MEK source presently known, and recycles 1.5% of the original isoprene flux. Eddy covariance flux measurements of isoprene and MEK over different forest ecosystems confirm that MEK emissions can reach 1-2% those of isoprene. We suggest that detoxification processes in plants are one of the most important sources of oxidized volatile organic compounds in the atmosphere., Competing Interests: Competing interests The authors declare no competing interests.

We use a real-time temperature-programmed desorption chemical-ionization mass spectrometer (FIGAERO-CIMS) to measure particle-phase composition and volatility of nucleated particles, studying pure α-pinene oxidation over a wide temperature range (-50 °C to +25 °C) in the CLOUD chamber at CERN. Highly oxygenated organic molecules are much more abundant in particles formed at higher temperatures, shifting the compounds toward higher O/C and lower intrinsic (300 K) volatility. We find that pure biogenic nucleation and growth depends only weakly on temperature. This is because the positive temperature dependence of degree of oxidation (and polarity) and the negative temperature dependence of volatility counteract each other. Unlike prior work that relied on estimated volatility, we directly measure volatility via calibrated temperature-programmed desorption. Our particle-phase measurements are consistent with gas-phase results and indicate that during new-particle formation from α-pinene oxidation, gas-phase chemistry directly determines the properties of materials in the condensed phase. We now have consistency between measured gas-phase product concentrations, product volatility, measured and modeled growth rates, and the particle composition over most temperatures found in the troposphere.

Magnetic gels and elastomers are promising candidates to construct reversibly excitable soft actuators, triggered from outside by magnetic fields. These magnetic fields induce or alter the magnetic interactions between discrete rigid particles embedded in a soft elastic polymeric matrix, leading to overall deformations. It is a major challenge in theory to correctly predict from the discrete particle configuration the type of deformation resulting for a finite-sized system. Considering an elastic sphere, we here present such an approach. The method is in principle exact, at least within the framework of linear elasticity theory and for large enough interparticle distances. Different particle arrangements are considered. We find, for instance, that regular simple cubic configurations show elongation of the sphere along the magnetization if oriented along a face or space diagonal of the cubic unit cell. Contrariwise, with the magnetization along the edge of the cubic unit cell, they contract. The opposite is true in this geometry for body- and face-centered configurations. Remarkably, for the latter configurations but the magnetization along a face or space diagonal of the unit cell, contraction was observed to revert to expansion with decreasing Poisson ratio of the elastic material. Randomized configurations were considered as well. They show a tendency of elongating the sphere along the magnetization, which is more pronounced for compressible systems. Our results can be tested against actual experiments for spherical samples. Moreover, our approach shall support the search of optimal particle distributions for a maximized effect of actuation.

Salts of the weakly coordinating anions [Ga(OTeF 5 ) 4 ] - as well as [Ga(Et)(OTeF 5 ) 3 ] - and the neutral Ga 2 (Et) 3 (OTeF 5 ) 3 were synthesized and characterized by spectroscopic methods and single-crystal X-ray diffraction. Ga 2 (Et) 3 (OTeF 5 ) 3 was formed by treating GaEt 3 with pentafluoroorthotelluric acid (HOTeF 5 ) and reacted with PPh 4 Cl and CPh 3 Cl to [PPh 4 ][Ga(Et)(OTeF 5 ) 3 ] and [CPh 3 ][Ga(Et)(OTeF 5 ) 3 ]. In contrast, Ag[Ga(OTeF 5 ) 4 ] was prepared from AgOTeF 5 and GaCl 3 and was used as a versatile starting material for further reactions. Starting with Ag[Ga(OTeF 5 ) 4 ] the substrates [PPh 4 ][Ga(OTeF 5 ) 4 ] and [CPh 3 ][Ga(OTeF 5 ) 4 ] were formed from PPh 4 Cl and CPh 3 Cl., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Clinical decision-making in cancer and other diseases relies on timely and cost-effective genome-wide testing. Classical bioinformatic algorithms, such as Rawcopy, can support genomic analysis by calling genomic breakpoints and copy-number variations (CNVs), but often require manual data curation, which is error prone, time-consuming, and thus substantially increasing costs of genomic testing and hampering timely delivery of test results to the treating physician. We aimed to investigate whether deep learning algorithms can be used to learn from genome-wide single-nucleotide polymorphism array (SNPa) data and improve state-of-the-art algorithms. We developed, applied, and validated a novel deep neural network (DNN), DeepSNP. A manually curated data set of 50 SNPa analyses was used as truth-set. We show that DeepSNP can learn from SNPa data and classify the presence or absence of genomic breakpoints within large genomic windows with high precision and recall. DeepSNP was compared with well-known neural network models as well as with Rawcopy. Moreover, the use of a localization unit indicates the ability to pinpoint genomic breakpoints despite their exact location not being provided while training. DeepSNP results demonstrate the potential of DNN architectures to learn from genomic SNPa data and encourage further adaptation for CNV detection in SNPa and other genomic data types.

In this study, we present reactions of NH 4 + with a series of analytes (A): acetone (C 3 H 6 O), methyl vinyl ketone (C 4 H 6 O), methyl ethyl ketone (C 4 H 8 O), and eight monoterpene isomers (C 10 H 16 ) using a Selective Reagent Ionization Time-of-Flight Mass Spectrometer (SRI-ToF-MS). We studied the ion-molecule reactions at collision energies of 55 and 80 meV. The ketones, having a substantially lower proton affinity than NH 3 , produce only cluster ions NH 4 + (A) in detectable amounts at 55 meV. At 80 meV, no cluster ions were detected meaning that these adduct ions are formed by strongly temperature dependent association reactions. Bond energies of cluster ions and proton affinities for most monoterpenes are not known and were estimated by high level quantum chemical calculations. The calculations reveal monoterpene proton affinities, which range from slightly smaller to substantially higher than the proton affinity of NH 3 . Proton affinities and cluster bond energies allow to group the monoterpenes as a function of the enthalpy for the dissociation reaction N H 4 + A → A H + + N H 3 . We find that this enthalpy can be used to predict the NH 4 + (A) cluster ion yield. The present study explains product ion formation involving NH 4 + ion chemistry. This is of importance for chemical ionization mass spectrometry (CIMS) utilizing NH 4 + as well as NH 4 + (H 2 O) as reagent ions to quantitatively detect atmospherically important organic compounds in real-time.

The thermodynamic uncertainty relation provides a universal lower bound on the product of entropy production and the fluctuations of any current. While proven for Markov dynamics on a discrete set of states and for overdamped Langevin dynamics, its status for underdamped dynamics is still open. We consider a two-dimensional harmonically confined charged particle in a magnetic field under the action of an external torque. We show analytically that, depending on the sign of the magnetic field, the thermodynamic uncertainty relation does not hold for the currents associated with work and heat. A strong magnetic field can effectively localize the particle with concomitant bounded fluctuations and low dissipation. Numerical results for a three-dimensional variant and for further currents suggest that the existence of such a bound depends crucially on the specific current.

A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NO x ) and sulfur oxides (SO x ) from fossil fuel combustion, as well as ammonia (NH 3 ) from livestock and fertilizers. Here, we show how NO x suppresses particle formation, while HOMs, sulfuric acid, and NH 3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.

Background: The objective of this study was to assess, whether right atrial (RA) and ventricular (RV) size is related to RV pump function at rest and during exercise in patients with pulmonary arterial hypertension (PAH)., Methods: We included 54 patients with invasively diagnosed PAH that had been stable on targeted medication. All patients underwent clinical assessments including right heart catheterization and echocardiography at rest and during exercise. RV output reserve was defined as increase of cardiac index (CI) from rest to peak exercise (∆CI exercise ). Patients were classified according to the median of RA and RV-area. RV pump function and further clinical parameters were compared between groups by student's t-test. Uni- and multivariate Pearson correlation analyses were performed., Results: Patients with larger RA and/or RV-areas (above a median of 16 and 20cm 2 , respectively) showed significantly lower ∆CI exercise , higher mean pulmonary arterial pressure, pulmonary vascular resistance at rest and NT-proBNP levels. Furthermore, patients with higher RV-areas presented with a significantly lower RV stroke volume and pulmonary arterial compliance at peak exercise than patients with smaller RV-size. RV area was identified as the only independent predictor of RV output reserve., Conclusion: RV and RA areas represent valuable and easily accessible indicators of RV pump function at rest and during exercise. Cardiac output reserve should be considered as an important clinical parameter. Prospective studies are needed for further evaluation.

α-Pinene (C 10 H 16 ) represents one of the most important biogenic emissions in the atmosphere. Its oxidation products can significantly contribute to the secondary organic aerosol (SOA) formation. Here, we report on the formation mechanism of C 19 and C 20 accretion products from α-pinene oxidation, which are believed to be efficient SOA precursors. Measurements have been performed in a free-jet flow system. Detection of RO 2 radicals and accretion products was carried out by recent mass spectrometric techniques using different ionization schemes. Observed C 10 -RO 2 radicals from α-pinene ozonolysis were O,O-C 10 H 15 (O 2 ) x O 2 with x = 0, 1, 2, 3 and from the OH radical reaction HO-C 10 H 16 (O 2 ) α O 2 with α = 0, 1, 2. All detected C 20 accretion products can be explained via the accretion reaction RO 2 + R'O 2 → ROOR' + O 2 starting from the measured C 10 -RO 2 radicals. We speculate that C 19 accretion products are formed in an analogous way assuming CH 2 O elimination. Addition of isoprene (C 5 H 8 ), producing C 5 -RO 2 radicals, leads to C 15 accretion products formed via cross-reactions with C 10 -RO 2 radicals. This process is competing with the formation of C 19 /C 20 products from the pure α-pinene oxidation. A similar behavior has been observed for ethylene additives that form C 12 accretion products. In the atmosphere, a complex accretion product spectrum from self- and cross-reactions of available RO 2 radicals can be expected. Modeling atmospheric conditions revealed that C 19 /C 20 product formation is only reduced by a factor of 1.2 or 3.6 in isoprene-dominated environments assuming a 2- or 15-fold isoprene concentration over α-pinene, respectively, as present in different forested areas.

Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from [Formula: see text]C to [Formula: see text]C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

The integration of visual stimuli and motor feedback is critical for successful visually guided navigation. These signals have been shown to shape neuronal activity in the primary visual cortex (V1), in an experience-dependent manner. Here, we examined whether visual, reward, and self-motion-related inputs are integrated in order to encode behaviorally relevant locations in V1 neurons. Using a behavioral task in a virtual environment, we monitored layer 2/3 neuronal activity as mice learned to locate a reward along a linear corridor. With learning, a subset of neurons became responsive to the expected reward location. Without a visual cue to the reward location, both behavioral and neuronal responses relied on self-motion-derived estimations. However, when visual cues were available, both neuronal and behavioral responses were driven by visual information. Therefore, a population of V1 neurons encode behaviorally relevant spatial locations, based on either visual cues or on self-motion feedback when visual cues are absent., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hydrocarbons are emitted into the Earth's atmosphere in very large quantities by human and biogenic activities. Their atmospheric oxidation processes almost exclusively yield RO 2 radicals as reactive intermediates whose atmospheric fate is not yet fully unraveled. Herein, we show that gas-phase reactions of two RO 2 radicals produce accretion products composed of the carbon backbone of both reactants. The rates for accretion product formation are very high for RO 2 radicals bearing functional groups, competing with those of the corresponding reactions with NO and HO 2 . This pathway, which has not yet been considered in the modelling of atmospheric processes, can be important, or even dominant, for the fate of RO 2 radicals in all areas of the atmosphere. Moreover, the vapor pressure of the formed accretion products can be remarkably low, characterizing them as an effective source for the secondary organic aerosol., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Employing large deviation theory, we explore current fluctuations of underdamped Brownian motion for the paradigmatic example of a single particle in a one-dimensional periodic potential. Two different approaches to the large deviation function of the particle current are presented. First, we derive an explicit expression for the large deviation functional of the empirical phase space density, which replaces the level 2.5 functional used for overdamped dynamics. Using this approach, we obtain several bounds on the large deviation function of the particle current. We compare these to bounds for overdamped dynamics that have recently been derived, motivated by the thermodynamic uncertainty relation. Second, we provide a method to calculate the large deviation function via the cumulant generating function. We use this method to assess the tightness of the bounds in a numerical case study for a cosine potential.

Spatial learning requires estimates of location that may be obtained by path integration or from positional cues. Grid and other spatial firing patterns of neurons in the superficial medial entorhinal cortex (MEC) suggest roles in behavioral estimation of location. However, distinguishing the contributions of path integration and cue-based signals to spatial behaviors is challenging, and the roles of identified MEC neurons are unclear. We use virtual reality to dissociate linear path integration from other strategies for behavioral estimation of location. We find that mice learn to path integrate using motor-related self-motion signals, with accuracy that decreases steeply as a function of distance. We show that inactivation of stellate cells in superficial MEC impairs spatial learning in virtual reality and in a real world object location recognition task. Our results quantify contributions of path integration to behavior and corroborate key predictions of models in which stellate cells contribute to location estimation., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

We have developed and characterized the novel PTR3, a proton transfer reaction-time-of-flight mass spectrometer (PTR-TOF) using a new gas inlet and an innovative reaction chamber design. The reaction chamber consists of a tripole operated with rf voltages generating an electric field only in the radial direction. An elevated electrical field is necessary to reduce clustering of primary hydronium (H 3 O + ) and product ions with water molecules present in the sample gas. The axial movement of the ions is achieved by the sample gas flow only. Therefore, the new design allows a 30-fold longer reaction time and a 40-fold increase in pressure compared to standard PTR-TOF-MS. First calibration tests show sensitivities of up to 18000 counts per second/parts per billion and volume (cps/ppbv) at a mass resolution of >8000 m/Δm (fwhm). The new inlet using center-sampling through a critical orifice reduces wall losses of low volatility compounds. Therefore, the new PTR3 instrument is sensitive to VOC typically present in the ppbv range as well as to semivolatile organic compounds (SVOC) and even highly oxidized organic molecules (HOMs) present in the parts per quadrillion per volume (ppqv) range in the atmosphere.

Background: Various medical fields rely on detailed anatomical knowledge of the distal radius. Current studies are limited to two-dimensional analysis and biased by varying measurement locations. The aims were to 1) generate 3D shape models of the distal radius and investigate variations in the 3D shape, 2) generate and assess morphometrics in standardized cut planes, and 3) test the model's classification accuracy., Methods: The local radiographic database was screened for CT-scans of intact radii. 1) The data sets were segmented and 3D surface models generated. Statistical 3D shape models were computed (overall, gender and side separate) and the 3D shape variation assessed by evaluating the number of modes. 2) Anatomical landmarks were assigned and used to define three standardized cross-sectional cut planes perpendicular to the main axis. Cut planes were generated for the mean shape models and each individual radius. For each cut plane, the following morphometric parameters were calculated and compared: maximum width and depth, perimeter and area. 3) The overall shape model was utilized to evaluate the predictive value (leave one out cross validation) for gender and side identification within the study population., Results: Eighty-six radii (45 left, 44% female, 40 ± 18 years) were included. 1) Overall, side and gender specific statistical 3D models were successfully generated. The first mode explained 37% of the overall variance. Left radii had a higher shape variance (number of modes: 20 female / 23 male) compared to right radii (number of modes: 6 female / 6 male). 2) Standardized cut planes could be defined using anatomical landmarks. All morphometric parameters decreased from distal to proximal. Male radii were larger than female radii with no significant side difference. 3) The overall shape model had a combined median classification probability for side and gender of 80%., Conclusions: Statistical 3D shape models of the distal radius can be generated using clinical CT-data sets. These models can be used to assess overall bone variance, define and analyze standardized cut-planes, and identify the gender of an unknown sample. These data highlight the potential of shape models to assess the 3D anatomy and anatomical variance of human bones.

Hemodialysis (HD) patients face increased fracture risk, which is further associated with elevated risk of hospitalization and mortality. High-resolution peripheral computed tomography (HR-pQCT) has advanced our understanding of bone disease in chronic kidney disease by characterizing distinct changes in both the cortical and trabecular compartments. Increased cortical porosity (Ct.Po) has been shown to be associated with fracture in patients with osteopenia or in postmenopausal diabetic women. We tested whether the degree of Ct.Po identifies hemodialysis patients with prevalent fragility fractures in comparison to bone mineral density (BMD) assessed by dual X-ray absorptiometry (DXA). We performed a post-hoc analysis of a cross-sectional study in 76 prevalent hemodialysis patients. Markers of mineral metabolism, coronary calcification score, DXA-, and HR-pQCT-data were analyzed, and Ct.Po determined at radius and tibia. Ct.Po was significantly higher in patients with fracture but association was lost after adjusting for age and gender (tibia p = 0.228, radius p = 0.5). Instead, femoral (F) BMD neck area (p = 0.03), F T-score neck area (p = 0.03), radius (R) BMD (p = 0.03), R T-score (p = 0.03), and cortical HR-pQCT indices such as cortical area (Ct.Ar) (tibia: p = 0.01; radius: p = 0.02) and cortical thickness (Ct.Th) (tibia: p = 0.03; radius: p = 0.02) correctly classified patients with fragility fractures. Area under receiver operating characteristic curves (AUC) for Ct.Po (tibia AUC: 0.711; p = 0.01; radius AUC: 0.666; p = 0.04), Ct.Ar (tibia AUC: 0.832; p<0.001; radius AUC: 0.796; p<0.001), and F neck BMD (AUC: 0.758; p = 0.002) did not differ significantly among each other. In conclusion, measuring Ct.Po is not superior to BMD determined by DXA for identification of HD patients with fragility fracture.

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by [Formula: see text] (27%) to [Formula: see text] Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes., Competing Interests: The authors declare no conflict of interest.

The so-called "raspberry" model refers to the hybrid lattice-Boltzmann and Langevin molecular dynamics scheme for simulating the dynamics of suspensions of colloidal particles, originally developed by Lobaskin and Dünweg [New J. Phys. 6, 54 (2004)], wherein discrete surface points are used to achieve fluid-particle coupling. This technique has been used in many simulation studies on the behavior of colloids. However, there are fundamental questions with regards to the use of this model. In this paper, we examine the accuracy with which the raspberry method is able to reproduce Stokes-level hydrodynamic interactions when compared to analytic expressions for solid spheres in simple-cubic crystals. To this end, we consider the quality of numerical experiments that are traditionally used to establish these properties and we discuss their shortcomings. We show that there is a discrepancy between the translational and rotational mobility reproduced by the simple raspberry model and present a way to numerically remedy this problem by adding internal coupling points. Finally, we examine a non-convex shape, namely, a colloidal dumbbell, and show that the filled raspberry model replicates the desired hydrodynamic behavior in bulk for this more complicated shape. Our investigation is continued in de Graaf et al. [J. Chem. Phys. 143, 084108 (2015)], wherein we consider the raspberry model in the confining geometry of two parallel plates.

The so-called "raspberry" model refers to the hybrid lattice-Boltzmann (LB) and Langevin molecular dynamics schemes for simulating the dynamics of suspensions of colloidal particles, originally developed by Lobaskin and Dünweg [New J. Phys. 6, 54 (2004)], wherein discrete surface points are used to achieve fluid-particle coupling. In this paper, we present a follow up to our study of the effectiveness of the raspberry model in reproducing hydrodynamic interactions in the Stokes regime for spheres arranged in a simple-cubic crystal [Fischer et al., J. Chem. Phys. 143, 084107 (2015)]. Here, we consider the accuracy with which the raspberry model is able to reproduce such interactions for particles confined between two parallel plates. To this end, we compare our LB simulation results to established theoretical expressions and finite-element calculations. We show that there is a discrepancy between the translational and rotational mobilities when only surface coupling points are used, as also found in Part I of our joint publication. We demonstrate that adding internal coupling points to the raspberry can be used to correct said discrepancy in confining geometries as well. Finally, we show that the raspberry model accurately reproduces hydrodynamic interactions between a spherical colloid and planar walls up to roughly one LB lattice spacing.

Purpose: To characterize bone microarchitecture and quantify bone strength in lung transplant (LT) recipients by using high-resolution (HR) peripheral quantitative computed tomographic (CT) imaging of the ultradistal radius., Materials and Methods: After study approval by the local ethics committee, all participants provided written informed consent. Included were 118 participants (58 LT recipients [mean age, 46.8 years ± 1.9; 30 women, 28 men] and 60 control participants [mean age, 39.9 years ± 1.9; 41 women, 19 men]) between April 2010 and May 2012. HR peripheral quantitative CT of the ultradistal radius was performed and evaluated for bone mineral density and trabecular and cortical bone microarchitecture. Mechanical competence was quantified by microfinite element analysis. Differences between LT recipients and control participants were determined by using two-way factorial analysis of covariance with age adjustment., Results: Total and trabecular bone mineral density were significantly lower (-13.4% and -16.4%, respectively; P = .001) in LT recipients than in healthy control participants. LT recipients had lower trabecular number (-9.7%; P = .004) and lower trabecular thickness (-8.1%; P = .025). Trabecular separation and trabecular network heterogeneity were higher (+24.3% and +63.9%, respectively; P = .007 and P = .012, respectively) in LT recipients. Moreover, there was pronounced cortical porosity (+31.3%; P = .035) and lower cortical thickness (-10.2%, P = .005) after LT. In addition, mechanical competence was impaired, which was reflected by low stiffness (-15.0%; P < .001), low failure force (-14.8%; P < .001), and low bone strength (-14.6%; P < .001)., Conclusion: Men and women with recent LT showed severe deficits in cortical and trabecular bone microarchitecture. Poor bone microarchitecture and low bone strength are likely to contribute to high fracture susceptibility observed in LT recipients., (© RSNA, 2014.)

Cadmium is a potent inducer of programmed cell death (PCD) in plants but the morphological changes in cells exposed to cadmium are poorly characterized. Using light and transmission electron microscopy (TEM) we have investigated the changes in ultrastructure of tobacco BY-2 cells treated with 50 µM CdSO4. The cadmium-induced alterations in cell morphology occurred gradually over a period of 3-4 days and the first stages of the response resembled vacuolar type of cell death. The initial formation of numerous small cytoplasmic vacuoles and dilation of endoplasmic reticulum was followed first by fusion of smaller vacuoles with each other and with big vacuoles, and then by the appearance of autophagic vacuoles containing autophagic bodies. The final stages of cell death were accompanied by necrotic features including loss of plasmalemma integrity, shrinkage of the protoplast and unprocessed cellular components. In addition, we observed a gradual degradation of nuclear material. Our results demonstrate that cadmium-induced plant cell death is a slow process featuring elements of vacuolar cell death and terminating with necrosis., (© 2013 Scandinavian Plant Physiology Society.)