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Molecular dynamics (MD) simulation is widely used to complement ensemble-averaged experiments of intrinsically disordered proteins (IDPs). However, MD often suffers from limitations of inaccuracy. Here, we show that enhancing the sampling using Hamiltonian replica-exchange MD (HREMD) led to unbiased and accurate ensembles, reproducing small-angle scattering and NMR chemical shift experiments, for three IDPs of varying sequence properties using two recently optimized force fields, indicating the general applicability of HREMD for IDPs. We further demonstrate that, unlike HREMD, standard MD can reproduce experimental NMR chemical shifts, but not small-angle scattering data, suggesting chemical shifts are insufficient for testing the validity of IDP ensembles. Surprisingly, we reveal that despite differences in their sequence, the inter-chain statistics of all three IDPs are similar for short contour lengths ( less then 10 residues). The results suggest that the major hurdle of generating an accurate unbiased ensemble for IDPs has now been largely overcome.Jaw morphology is closely linked to both diet and biomechanical performance, and jaws are one of the most common Mesozoic mammal fossil elements. Knowledge of the dietary and functional diversity of early mammals informs on the ecological structure of palaeocommunities throughout the longest era of mammalian evolution the Mesozoic. Here, we analyse how jaw shape and mechanical advantage of the masseter (MAM) and temporalis (MAT) muscles relate to diet in 70 extant and 45 extinct mammals spanning the Late Triassic-Late Cretaceous. In extant mammals, jaw shape discriminates well between dietary groups insectivores have long jaws, carnivores intermediate to short jaws, and herbivores have short jaws. Insectivores have low MAM and MAT, carnivores have low MAM and high MAT, and herbivores have high MAM and MAT. These traits are also informative of diet among Mesozoic mammals (based on previous independent determinations of diet) and set the basis for future ecomorphological studies.Posttraumatic ankle osteoarthritis (OA) represents a significant challenge to orthopedic surgeons, especially in cases of anterior talar translation and concomitant impaction of the anterior distal tibial plafond. The aim of this study was to evaluate the clinical outcomes of an intra-articular osteotomy for the management of these patients. A total of 21 patients meeting our criteria were retrospectively reviewed. Sixteen patients sustained initial pilon fractures, while five patients had Weber type C ankle fractures. Anterior distal tibial plafond-plasty was performed to address the impaction and anterior translation of the talus. The American Orthopedic Foot and Ankle Society (AOFAS) hindfoot score and visual analog scale (VAS) score were utilized as clinical outcomes. The lateral talar station (LTS), tibial lateral surface (TLS) angle, tibial anterior surface angle and talocrural angle were evaluated pre- and postoperatively. The modified Kellgren-Lawrence score was used for the evaluation of sagittal ankle OA. The average age at surgery was 35 years, and the average follow-up duration was 34 months. The AOFAS hindfoot score increased from 26 to 71 (p  less then  0.01), and the VAS score improved from 7 to 2 (p  less then  0.01). The LTS improved from 9.0 to 2.3 mm (p  less then  0.01), and the TLS angle improved from 72° to 81° (p  less then  0.01). Of the 21 patients, 18 showed improvement in or no worsening of ankle OA on the sagittal plane, while 3 developed advanced ankle OA. A congruent ankle joint on the sagittal plane could be achieved by anterior distal tibial plafond-plasty. This is a valuable treatment option for the salvage of posttraumatic ankle OA with anterior translation of the talus.Tumor-infiltrating lymphocytes play an important, but incompletely understood role in chemotherapy response and prognosis. In breast cancer, there appear to be distinct immune responses by subtype, but most studies have used limited numbers of protein markers or bulk sequencing of RNA to characterize immune response, in which spatial organization cannot be assessed. To identify immune phenotypes of Basal-like vs. Luminal breast cancer we used the GeoMx® (NanoString) platform to perform digital spatial profiling of immune-related proteins in tumor whole sections and tissue microarrays (TMA). Visualization of CD45, CD68, or pan-Cytokeratin by immunofluorescence was used to select regions of interest in formalin-fixed paraffin embedded tissue sections. Forty-four antibodies representing stromal markers and multiple immune cell types were applied to quantify the tumor microenvironment. In whole tumor slides, immune hot spots (CD45+) had increased expression of many immune markers, suggesting a diverse and robust immune response. In epithelium-enriched areas, immune signals were also detectable and varied by subtype, with regulatory T-cell (Treg) markers (CD4, CD25, and FOXP3) being higher in Basal-like vs. Luminal breast cancer. Extending these findings to TMAs with more patients (n = 75), we confirmed subtype-specific immune profiles, including enrichment of Treg markers in Basal-likes. This work demonstrated that immune responses can be detected in epithelium-rich tissue, and that TMAs are a viable approach for obtaining important immunoprofiling data. In addition, we found that immune marker expression is associated with breast cancer subtype, suggesting possible prognostic, or targetable differences.Fine line screen printing for solar cell metallization is one of the most critical steps in the entire production chain of solar cells, facing the challenge of providing a conductive grid with a minimum amount of resource consumption at an ever increasing demand for higher production speeds. The continuous effort of the industrial and scientific community has led to tremendous progress over the last 20 years, demonstrating an average reduction rate for the finger width of approximately 7 µm per year with the latest highlight of achieving widths of 19 µm. However, further reductions will become a major challenge because commonly used metal pastes are not able to penetrate arbitrary small screen opening structures. learn more Therefore, this study introduces the novel dimensionless parameter screen utility index SUI which quantifies the expected printability of any 2-dimensional screen architecture in reference to a given paste. Further, we present a full theoretical derivation of the SUI, a correlation to experimental results and an in-depth simulation over a broad range of screen manufacturing parameters.