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This study presents the performance assessment of a novel hybrid pixel detector. The electron counting application-specific integrated circuit (ASIC), named KITE, was optimized for 4D STEM applications and bump-bonded to a silicon sensor that is suitable for electron energies in the range 30-200 keV. The KITE ASIC was developed for high frame rates, currently up to 120 kfps, and high count rates, owing to fast signal shaping times and instant retrigger technology, which allows operation in a unique non-paralyzable counting mode. Investigated quantities include the spectral response, the identification of optimal threshold energies, an estimation of the threshold trimming accuracy, the analysis of the single-event multiplicity distributions, the count rate capabilities, and imaging performance metrics MTF and DQE. To highlight the capabilities of the detector, the best value of 10% of linearity loss was achieved at 84 Mcts/s/pix, the best value of count rate "cutoff" at nearly 150 Mcts/s/pix, and DQE (0) between 0.75 and 0.82 up to the electron energy of 160 keV. [ABSTRACT FROM AUTHOR]

The two-dimensional electron system (2DES) in LaAlO3/SrTiO3 (LAO/STO) heterostructures, showing superconductivity below 200 mK at ambient pressure, displays incipient localization under hydrostatic pressure p. Even small p significantly affects the transport properties for 10K

Background: The basolateral complex of the amygdala is a crucial neurobiological site for Pavlovian conditioning. Investigations into volumetric alterations of the basolateral amygdala in individuals with major depressive disorder (MDD) have yielded conflicting results. These may be reconciled in an inverted U-shape allostatic growth trajectory. This hypothesized trajectory unfolds with an initial phase of volumetric expansion, driven by enhanced dendritic arborization and synaptic plasticity. The increase in volume is followed by a reduction phase, as glucocorticoid exposure cumulatively results in excitotoxic damage, reflecting allostatic load., Methods: 7T magnetic resonance brain imaging was conducted on a total of 84 participants (mean age 38 ± 12 years), comprising 20 unmedicated and 20 medicated individuals with MDD, 21 individuals suffering from bipolar disorder and 23 healthy controls. We employed FreeSurfer 7.3.2 for automatic high-resolution segmentation of nine amygdala subnuclei. We conducted analyses of covariance, with volumes of the basolateral complex, the lateral nucleus and, exploratively, the whole amygdala, as dependent variables, while controlling for the total intracranial volume and sex. Quadratic regressions were computed within the MDD group and in relevant subgroups to investigate the presence of a U-shaped relationship between the number of preceding major depressive episodes or the duration of the disease since the first episode and the dependent variables., Results: Diagnostic groups did not exhibit statistically significant differences in the volumes of the basolateral amygdala (left F (3,75) = 0.66, p >.05; right F (3,76) = 1.80, p >.05), the lateral nucleus (left F (3,75) = 1.22, p >.05; right F (3,76) = 2.30, p >.05)), or the whole amygdala (left F (3,75) = 0.48, p >.05; right F (3,76) = 1.58, p >.05). No quadratic associations were observed between surrogate parameters of disease progression and any of the examined amygdala volumes. There were no significant correlations between subregion volumes and clinical characteristics., Conclusion: We found no evidence for the hypothesis of an inverted U-shaped volumetric trajectory of the basolateral amygdala in MDD. Future research with larger sample sizes, including the measurement of genetic and epigenetic markers, will hopefully further elucidate this compelling paradigm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Kürzinger, Schindler, Meffert, Rosenhahn, Trampel, Turner and Schoenknecht.)

Background: The subgenual Anterior Cingulate Cortex (sgACC), as a part of the Anterior Cingulate Cortex and the limbic system plays a crucial role in mood regulation. Previous structural and functional brain imaging studies of the sgACC have revealed alterations of Gray Matter (GM) volumes and Blood Oxygenation Level Dependent signals (BOLD) in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD), suggesting potential biomarker traits for affective disorders., Method: In this study we investigated the gray matter volume of the sgACC in 3 different patient groups: 40 MDD patients, of which 20 were medicated (MDDm) and 20 were unmedicated (MDDu), and 21 medicated BD patients, and compared them with 23 healthy volunteers. We examined GM volume alteration using high-resolution 7T Magnetic Resonance Imaging (MRI) which produced quantitative maps of the spin-lattice relaxation time (T1). T1 maps provide high contrast between gray and white matter, and at 7 Tesla voxels with submillimeter resolution can be acquired in a reasonable scan time. We developed a semi-automatic segmentation protocol based on refined landmarks derived from previous volumetric studies using quantitative T1 maps as raw input data for automatic tissue segmentation of GM, WM and CSF (cerebrospinal fluid) tissue. The sgACC ROI was then superimposed on these tissue probability maps and traced manually by two independent raters (F.B., M.M.) following our semi-automatic segmentation protocol. Interrater reliability was calculated on a subset of 10 brain scans for each hemisphere, showing an Intra-Class Correlation coefficient (ICC) r = 0.96 for left sgACC and r = 0.84 for right sgACC respectively. In summary, we have developed a reproducible and reliable semi-automatic segmentation protocol to measure gray matter volume in the sgACC. Based on previous findings from meta-analyses on morphometric studies of the sgACC, we hypothesized that patients with MDD would have lower gray matter sgACC volumes compared to healthy subjects., Results: Post-hoc analysis revealed smaller subgenual volumes for the left hemisphere in both the medicated (MDDm) and non-medicated (MDDu) group versus healthy controls (p = .001, p = .008) respectively. For the right hemisphere, the (MDDu) and BD group exhibited significantly lower subgenual volumes than healthy controls (p < .001, p = .004) respectively., Conclusion: To our knowledge, this is the first morphometric MRI study using T1 maps obtained in high-resolution 7 Tesla MRI to compare MDD and BD patients with healthy controls., Competing Interests: Author P-LB was employed by company Full Brain Picture Analytics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Buchholz, Meffert, Bazin, Trampel, Turner and Schönknecht.)

Electron cryomicroscopy can, in principle, determine the structures of most biological molecules but is currently limited by access, specimen preparation difficulties, and cost. We describe a purpose-built instrument operating at 100 keV-including advances in electron optics, detection, and processing-that makes structure determination fast and simple at a fraction of current costs. The instrument attains its theoretical performance limits, allowing atomic resolution imaging of gold test specimens and biological molecular structure determination in hours. We demonstrate its capabilities by determining the structures of eleven different specimens, ranging in size from 140 kDa to 2 MDa, using a fraction of the data normally required. CryoEM with a microscope designed specifically for high-efficiency, on-the-spot imaging of biological molecules will expand structural biology to a wide range of previously intractable problems., Competing Interests: Competing interests statement:T.W. and M.M.E.-G. are employees of YPS, Ltd. J.D. was an employee of JEOL, UK during this work. M.M. and C.S.-B. are employees of DECTRIS, Ltd. G.M., R.H., and C.J.R. are inventors on a patent application EP No. 20789961.8 filed by UKRI related to this work.

Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine-modified silica NPs trigger cell death in RAW 264.7 macrophages. The in vitro results can be confirmed in vivo and are predictive for the inflammatory potential in murine lungs. In the presence of serum proteins, on the other hand, a replacement of only 10% of surface-active silanol groups by amines is sufficient to suppress cytotoxicity, emphasizing the relevance of exposure conditions. Mechanistic investigations identify a key role of lysosomal injury for cytotoxicity only in the presence, but not in the absence, of serum proteins. In conclusion, this work shows the critical need to rigorously characterize the surface coverage of NPs by their constituent functional groups, as well as the impact of serum, to reliably establish quantitative nanostructure activity relationships and develop safe nanomaterials., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transmission electron microscopy (TEM) with low-energy electrons has been recognized as an important addition to the family of electron microscopies as it may avoid knock-on damage and increase the contrast of weakly scattering objects. Scanning electron microscopes (SEMs) are well suited for low-energy electron microscopy with maximum electron energies of 30 keV, but they are mainly used for topography imaging of bulk samples. Implementation of a scanning transmission electron microscopy (STEM) detector and a charge-coupled-device camera for the acquisition of on-axis transmission electron diffraction (TED) patterns, in combination with recent resolution improvements, make SEMs highly interesting for structure analysis of some electron-transparent specimens which are traditionally investigated by TEM. A new aspect is correlative SEM, STEM, and TED imaging from the same specimen region in a SEM which leads to a wealth of information. Simultaneous image acquisition gives information on surface topography, inner structure including crystal defects and qualitative material contrast. Lattice-fringe resolution is obtained in bright-field STEM imaging. The benefits of correlative SEM/STEM/TED imaging in a SEM are exemplified by structure analyses from representative sample classes such as nanoparticulates and bulk materials.

While galvanic exchange is commonly applied to metallic nanoparticles, recently its applicability was expanded to metal-oxides. Here the galvanic exchange is studied in metal/metal-oxide core/shell nanocrystals. In particular Sn/SnO 2 is treated by Ag + , Pt 2+ , Pt 4+ , and Pd 2+ . The conversion dynamics is monitored by in situ synchrotron X-ray diffraction. The Ag + treatment converts the Sn cores to the intermetallic Ag x Sn ( x ∼ 4) phase, by changing the core's crystal structure. For the analogous treatment by Pt 2+ , Pt 4+ , and Pd 2+ , such a galvanic exchange is not observed. This different behavior is caused by the semipermeability of the naturally formed SnO 2 shell, which allows diffusion of Ag + but protects the nanocrystal cores from oxidation by Pt and Pd ions.

(Ba0.5Sr0.5)(Co0.8Fe0.2)O3-δ (BSCF) is a promising material with mixed ionic and electronic conductivity which is considered for oxygen separation membranes. Selective improvement of material properties, e.g. oxygen diffusivity or suppression of secondary phase formation, can be achieved by B-site doping. This study is concerned with the formation of Co-oxide precipitates in undoped BSCF at typical homogenization temperatures of 1,000°C, which act as undesirable nucleation sites for other secondary phases in the application-relevant temperature range. Y-doping successfully suppresses Co-oxide formation, whereas only minor improvements are achieved by Sc-doping. To understand the reason for the different behavior of Y and Sc, the lattice sites of dopant cations in BSCF were experimentally determined in this work. Energy-dispersive X-ray spectroscopy in a transmission electron microscope was applied to locate dopant sites exploiting the atom location by channeling enhanced microanalysis technique. It is shown that Sc exclusively occupies B-cation sites, whereas Y is detected on A- and B-cation sites in Y-doped BSCF, although solely B-site doping was intended. A model is presented for the suppression of Co-oxide formation in Y-doped BSCF based on Y double-site occupancy.

A fast method for determination of the Co-valence state by electron energy loss spectroscopy in a transmission electron microscope is presented. We suggest the distance between the Co-L3 and Co-L2 white-lines as a reliable property for the determination of Co-valence states between 2+ and 3+. The determination of the Co-L2,3 white-line distance can be automated and is therefore well suited for the evaluation of large data sets that are collected for line scans and mappings. Data with a low signal-to-noise due to short acquisition times can be processed by applying principal component analysis. The new technique was applied to study the Co-valence state of Ba0.5Sr0.5Co0.8Fe0.2O3-d (BSCF), which is hampered by the superposition of the Ba-M4,5 white-lines on the Co-L2,3 white-lines. The Co-valence state of the cubic BSCF phase was determined to be 2.2+ (±0.2) after annealing for 100 h at 650°C, compared to an increased valence state of 2.8+ (±0.2) for the hexagonal phase. These results support models that correlate the instability of the cubic BSCF phase with an increased Co-valence state at temperatures below 840°C.

Purpose: This study examined the reliability and validity of the Test of Infant Motor Performance Screening Items (TIMPSI) in infants with type I spinal muscular atrophy (SMA)., Methods: After training, 12 evaluators scored 4 videos of infants with type I SMA to assess interrater reliability. Intrarater and test-retest reliability was further assessed for 9 evaluators during a SMA type I clinical trial, with 9 evaluators testing a total of 38 infants twice. Relatedness of the TIMPSI score to ability to reach and ventilatory support was also examined., Results: Excellent interrater video score reliability was noted (intraclass correlation coefficient, 0.97-0.98). Intrarater reliability was excellent (intraclass correlation coefficient, 0.91-0.98) and test-retest reliability ranged from r = 0.82 to r = 0.95. The TIMPSI score was related to the ability to reach (P ≤ .05)., Conclusion: The TIMPSI can reliably be used to assess motor function in infants with type I SMA. In addition, the TIMPSI scores are related to the ability to reach, an important functional skill in children with type I SMA.

Genetic and immunological factors may play a role as possible causes for gestational diabetes. Autoantibodies to glutamic acid decarboxylase (GADA) are frequently found in patients with insulin dependent diabetes, but have only rarely been analyzed with regard to the carbohydrate tolerance in pregnancy. An oral glucose tolerance test (oGTT) with 75 g glucose was performed in 110 pregnant patients during the third trimenon. Glucose (glucose dehydrogenase method) and insulin (RIA) concentrations were measured after 0, 30, 60, 120, and 180 minutes. Patients were divided into five groups of increasing glucose intolerance based on the highest glucose concentration reached during the oGTT. GADA were measured using a quantitative enzyme-immunoassay. Only a single patient showed pathologically elevated GADA, and her oGTT results were within the normal range. GADA in subjects with normal pathological glucose tolerance showed no significant difference (276.6 +/- 151.6 and 263.0 +/- 107.1 mU/ml respectively). There was a tendency of positive correlations between high GADA-levels and higher concentrations of insulin as well as an increased insulin-glucose-index. These findings suggest that pregnant patients with higher GADA-levels may have an increased insulin resistance. In conclusion, the concentration of GADA was not found to be helpful in evaluating the current metabolic situation in gestational diabetes. It remains unclear whether elevated GADA during pregnancy have a prognostic value regarding the manifestation of overt diabetes mellitus later in life.

Objective: In comparison a higher insulin-glucose-index is usually associated with an increased insulin resistance. In the present study changes in insulin-glucose-indices were examined in relation to a defined glucose tolerance in the last trimester of pregnancy., Material and Methods: 249 pregnant women were challenged with a 75 gm oral glucose tolerance test (oGTT). Serum samples for glucose (glucose-dehydrogenase-method) and insulin measurements (RIA) were drawn before and at 30, 60, 120, and 180 minutes after glucose load during oGTT. Patients were assigned to five groups with increasing glucose intolerance according to maximal glucose levels during the test., Results: There were no significant differences in insulin-glucose-indices prior to glucose load. Pregnant women with gestational diabetes were shown to have significantly lower insulin-glucose-indices in the early and intermediate phase of the challenge test while the indices were higher in the final phase of the test., Conclusions: Women with gestational diabetes demonstrated an initial delay in insulin secretion in combination with a higher insulin-glucose-index, corresponding to an increased insulin resistance, only in the end of the test. These characteristics may possibly be a cause of the observed disorder in glucose metabolism in these patients.

Human recombinant interleukin-2 (rIL-2) induced interferon-gamma (IFN-gamma) release in vivo was studied in 16 renal cell carcinoma patients treated with low-dose s.c. rIL-2. The s.c. administration of rIL-2 resulted in a significant increase in circulating IFN-gamma in all patients within 6 to 8 hours as measured by enzyme-linked immunosorbent assay (ELISA). Total IFN-gamma release, as expressed by the area under the concentration curve (AUC), and IFN-gamma serum peaks following repetitive s.c. rIL-2 injection showed a direct dose distribution dependancy, whereby significantly higher levels of secondary IFN-gamma were achieved in patients treated with 10 million IU rIL-2/m2 q 12 hours when compared with patients treated with 20 million IU rIL-2/m2 q 24 hours. IFN-gamma release was suppressed significantly in one patient who had been pretreated with corticosteroids, while prior immunotherapy with rIL-2 had no measurable effect on secondary IFN-gamma release in this study. Cumulative secondary IFN-gamma secretion, as expressed by the AUC, and IFN-gamma serum peak concentrations in response to s.c. rIL-2 did not correlate with response to therapy or survival of rIL-2 treated renal cell carcinoma patients.

Nitric oxide (NO) stimulates calcium-independent neurotransmitter release from synaptosomes. NO-stimulated release was found to be inhibited by Botulinum neurotoxins that inactivate the core complex of synaptic proteins involved in the docking and fusion of synaptic vesicles. In experiments using recombinant proteins, NO donors increased formation of the VAMP/SNAP-25/syntaxin 1a core complex and inhibited the binding of n-sec1 to syntaxin 1a. The combined effects of these activities is predicted to promote vesicle docking/fusion. The sulfhydryl reagent NEM inhibited the binding of n-sec1 to syntaxin 1a, while beta-ME could reverse the NO-enhanced association of VAMP/SNAP-25/syntaxin 1a. These data suggest that post-translational modification of sulfhydryl groups by a nitrogen monoxide (likely to be NO+) alters the synaptic protein interactions that regulate neurotransmitter release and synaptic plasticity.