Solvent-Responsive and Switchable Nanofiltration Membranes based on Hypercrosslinked Polymers with Permanent Porosity

Porous organic framework materials such as hypercrosslinked polymers (HCP) show a high chemical stability and dynamic behavior in a variety of solvents while their pore properties exhibit great potential for mixed matrix membrane (MMM) applications. However, their influence as porous filler in MMMs, especially for applications in liquid-phase filtration is still unexploited. Herein, we demonstrate an HCP-based MMM for molecular separation in the liquid phase by nanofiltration (NF). Depending on the solvent, the membrane changes its fractional free volume by shrinking or swelling. In connection to that, the pore size is also influenced, hence, providing a tunable permeance and molecular cut-off. The reduction of the pore volume and size directly correlates to the improvement of the NF performance, while the volume increase completely diminishes it. The extraordinary flexibility and high degree of crosslinking assure permanent porosity and render the dynamic behavior fully reversible. Thereby, a solvent-responsive “on” and “off” switching of the NF properties is enabled and was experimentally proven. Overall, this provides alternative strategies regarding the fouling and regeneration of membranes as well as the inhibition of pore blocking in membrane-derived processes by a tunable separation performance

Croconaine-Based Polymer Particles as Contrast Agents for Photoacoustic Imaging

In the development and optimization of imaging methods, photoacoustic imaging (PAI) has become a powerful tool for preclinical biomedical diagnosis and detection of cancer. PAI probes can improve contrast and help identify pathogenic tissue. Such contrast agents must meet several requirements: they need to be biocompatible, and absorb strongly in the near-infrared (NIR) range, while relaxing the photoexcited state thermally and not radiatively. In this work, polymer nanoparticles are produced with croconaine as a monomer unit. Small molecular croconaine dyes are known to act as efficient pigments, which do not show photoluminescence. Here, for the first time croconaine copolymer nanoparticles are produced from croconic acid and a range of aromatic diamines. Following a dispersion polymerization protocol, this approach yields monodisperse particles of adjustable size. All synthesized polymers exhibit broad absorption within the NIR spectrum and therefore represent suitable candidates as contrast agents for PAI. The optical properties of these polymer particles are discussed with respect to the relation between particle size and outstanding photoacoustic performance. Biocompatibility of the polymer particles is demonstrated in cell viability experiments. © The Authors. Published by Wiley-VCH Gmb

Conjugated Polyimidazole Nanoparticles as Biodegradable Electrode Materials for Organic Batteries

Conjugated polymers are promising active materials for batteries. Batteries not only need to have high energy density but should also combine safe handling with recyclability or biodegradability after reaching their end-of-life. Here, π-conjugated polyimidazole particles are developed, which are prepared using atom economic direct arylation adapted to a dispersion polymerization protocol. The synthesis yields polyimidazole nanoparticles of tunable size and narrow dispersity. In addition, the degree of crosslinking of the polymer particles can be controlled. It is demonstrated that the polyimidazole nanoparticles can be processed together with carbon black and biodegradable carboxymethyl cellulose binder as an active material for organic battery electrodes. Electrochemical characterization shows that a higher degree of crosslinking significantly improves the electrochemical performance and leads to clearer oxidation and reduction signals of the polymer. Polyimidazole as part of the composite electrode shows complete degradation by exposure to composting bacteria over the course of 72 h

Three-dimensional topology dataset of folded radar stratigraphy in northern Greenland

We present a dataset of reconstructed three-dimensional (3D) englacial stratigraphic horizons in northern Greenland. The data cover four different regions representing key ice-dynamic settings in Greenland: (i) the onset of Petermann Glacier, (ii) a region upstream of the 79° North Glacier (Nioghalvfjerdsbræ), near the northern Greenland ice divide, (iii) the onset of the Northeast Greenland Ice Stream (NEGIS) and (iv) a 700 km wide region extending across the central ice divide over the entire northern part of central Greenland. In this paper, we promote the advantages of a 3D perspective of deformed englacial stratigraphy and explain how 3D horizons provide an improved basis for interpreting and reconstructing the ice-dynamic history. The 3D horizons are provided in various formats to allow a wide range of applications and reproducibility of results

Three-dimensional topology dataset of folded radar stratigraphy in northern Greenland

We present a dataset of reconstructed three-dimensional (3D) englacial stratigraphic horizons in northern Greenland. The data cover four different regions representing key ice-dynamic settings in Greenland: (i) the onset of Petermann Glacier, (ii) a region upstream of the 79° North Glacier (Nioghalvfjerdsbræ), near the northern Greenland ice divide, (iii) the onset of the Northeast Greenland Ice Stream (NEGIS) and (iv) a 700 km wide region extending across the central ice divide over the entire northern part of central Greenland. In this paper, we promote the advantages of a 3D perspective of deformed englacial stratigraphy and explain how 3D horizons provide an improved basis for interpreting and reconstructing the ice-dynamic history. The 3D horizons are provided in various formats to allow a wide range of applications and reproducibility of results

SF3B1-mutant MDS as a distinct disease subtype:a proposal from the International Working Group for the Prognosis of MDS

The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDSas a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overtMDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement. (Blood. 2020;136(2):157-170)

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes

Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6–8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response

Solvent-Responsive and Switchable Nanofiltration Membranes based on Hypercrosslinked Polymers with Permanent Porosity

Porous organic framework materials such as hypercrosslinked polymers (HCP) show a high chemical stability and dynamic behavior in a variety of solvents while their pore properties exhibit great potential for mixed matrix membrane (MMM) applications. However, their influence as porous filler in MMMs, especially for applications in liquid-phase filtration is still unexploited. Herein, we demonstrate an HCP-based MMM for molecular separation in the liquid phase by nanofiltration (NF). Depending on the solvent, the membrane changes its fractional free volume by shrinking or swelling. In connection to that, the pore size is also influenced, hence, providing a tunable permeance and molecular cut-off. The reduction of the pore volume and size directly correlates to the improvement of the NF performance, while the volume increase completely diminishes it. The extraordinary flexibility and high degree of crosslinking assure permanent porosity and render the dynamic behavior fully reversible. Thereby, a solvent-responsive “on” and “off” switching of the NF properties is enabled and was experimentally proven. Overall, this provides alternative strategies regarding the fouling and regeneration of membranes as well as the inhibition of pore blocking in membrane-derived processes by a tunable separation performance