A DFT Comparison of C-C Reductive Coupling from Terminal Cyanido and Cyaphido Complexes of Nickel.

The density functional theory study of the thermal C-C reductive coupling from terminal cyanido and hypothetical cyaphido complexes of [Ni(dmpe)] (dmpe = 1,2-bis(dimethylphosphino)ethane) revealed the key reaction intermediate in the reductive C-CP coupling being a σ-CC complex unlike an η2-aryl complex in the Ni C-CN system, as already observed in our previous studies. The reaction in THF is endothermic by 4.9 kcal/mol for cyanido with a 32.0 kcal/mol activation barrier and exothermic by 28.5 kcal/mol for cyaphido with an 11.3 kcal/mol activation barrier. To compare our results with the existing experimental data, we chose mesityl as the aryl group and also studied the CP reaction with [Pt(dmpe)] and [Pt(dmpm)] (dmpe = 1,2-bis(dimethylphosphino)methane) fragments. Our findings are consistent with the thermodynamically uphill photolytic C-CP bond activation in phosphaalkynes with Pt and a faster thermal back-reaction with [Pt(dmpe)] compared to that of [Pt(dmpm)]. Based on the natural population analysis, when the polarity of the C-C bond is inverted, the sign of ΔG° is also inverted.

PITX2 deficiency leads to atrial mitochondrial dysfunction.

AIM: Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation. PITX2 is restricted to left atrial cardiomyocytes in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy and atrial fibrillation are not fully understood. METHODS AND RESULTS: To identify mechanisms linking PITX2 deficiency to atrial fibrillation, we generated and characterized PITX2-deficient human atrial cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) and their controls. PITX2-deficient hiPSC-derived atrial cardiomyocytes showed shorter and disorganised sarcomeres and increased mononucleation. Electron microscopy found an increased number of smaller mitochondria compared to the control. Mitochondrial protein expression was altered in PITX2-deficient hiPSC-derived atrial cardiomyocytes. Single-nuclear RNA-sequencing found differences in cellular respiration pathways and differentially expressed mitochondrial and ion channel genes in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2 repression in hiPSC-derived atrial cardiomyocytes replicated dysregulation of cellular respiration. Mitochondrial respiration was shifted to increased glycolysis in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2-deficient human hiPSC-derived atrial cardiomyocytes showed higher spontaneous beating rates. Action potential duration was more variable with an overall prolongation of early repolarization, consistent with metabolic defects. Gene expression analyses confirmed changes in mitochondrial genes in left atria from 42 patients with atrial fibrillation compared to 43 patients in sinus rhythm. Dysregulation of left atrial mitochondrial (COX7C) and metabolic (FOXO1) genes was associated with PITX2 expression in human left atria. CONCLUSIONS: In summary, PITX2 deficiency causes mitochondrial dysfunction and a metabolic shift to glycolysis in human atrial cardiomyocytes. PITX2-dependent metabolic changes can contribute to the structural and functional defects found in PITX2-deficient atria.

Poly(benzodifurandione) Coated Silk Yarn for Thermoelectric Textiles.

Thermoelectric textile devices represent an intriguing avenue for powering wearable electronics. The lack of air-stable n-type polymers has, until now, prevented the development of n-type multifilament yarns, which are needed for textile manufacturing. Here, the thermomechanical properties of the recently reported n-type polymer poly(benzodifurandione) (PBFDO) are explored and its suitability as a yarn coating material is assessed. The outstanding robustness of the polymer facilitates the coating of silk yarn that, as a result, displays an effective bulk conductivity of 13 S cm-1, with a projected half-life of 3.2 ± 0.7 years at ambient conditions. Moreover, the n-type PBFDO coated silk yarn with a Young's modulus of E = 0.6 GPa and a strain at break of εbreak = 14% can be machine washed, with only a threefold decrease in conductivity after seven washing cycles. PBFDO and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) coated silk yarns are used to fabricate two out-of-plane thermoelectric textile devices: a thermoelectric button and a larger thermopile with 16 legs. Excellent air stability is paired with an open-circuit voltage of 17 mV and a maximum output power of 0.67 µW for a temperature difference of 70 K. Evidently, PBFDO coated multifilament silk yarn is a promising component for the realization of air stable thermoelectric textile devices.

[Cervical Spine Injuries]. / Verletzungen der oberen Halswirbelsäule.

Around a third of all cervical spine injuries occur in the upper cervical spine in the area between the occiput and the second cervical vertebra. The latter being the most common location of the injury with around 70%. But also atlas fractures, occipital condyle fractures, traumatic spondylolisthesis of C2, atypical fractures in the corpus area as well as atlantooccipital and atlantoaxial ligamentous lesions should be mentioned in connection with injuries in this area. In many cases, conservative therapy regimen is possible. In unstable or displaced injuries, however, surgical intervention is required, with various surgical procedures being used. The frequency, diagnostics, classification, and standard therapy of the individual entities are presented in detail in this continuing medical education article.

Image perception and reception in wordless picture books: Eye movements of children with intellectual disabilities.

Wordless picture books enhance comprehension and vocabulary growth and motivate children with intellectual disabilities (ID) to participate in literary activities. However, the reception of picture books can be challenging because deliberate selective attention processes and recognition of the image's meaning are often delayed. Examining eye movements may help explore these cognitive processes. Therefore, we examined eye movements in 29 children with mild and moderate ID as they explored a wordless picture book, presented on a screen and compared them to 14 typically developing children using a Tobii Pro X3-120 eye tracker. The findings showed that children with moderate ID had shorter fixation duration, fixated less often, and revisited regions of interest less frequently. Our results suggest that children with moderate ID have greater difficulties in selectively directing their attention toward regions of visual input with a high level of informativeness and expend less cognitive effort to understand their meaning.

Pnictogen Chemistry: From Light to Heavy Compounds.

Pnictogen compounds offer a broad and highly tunable set of characteristics, including pronounced Lewis acidity and basicity, privileged ligand behavior, the reversible switching between different oxidation states, the accessibility of low-valent species, and intriguing photophysical properties. In the recent renaissance of p-block chemistry, researchers are focusing their efforts to investigate and exploit these properties, to reveal unprecedented reactivity patterns and to design fascinating applications based on modern and innovative pnictogen chemistry. This special issue presents current trends in the field of pnictogen chemistry.

Prussian Blue Anchored on Reduced Graphene Oxide Substrate Achieving High Voltage in Symmetric Supercapacitor.

In this work, iron hexacyanoferrate (FeHCF-Prussian blue) particles have been grown onto a reduced graphene oxide substrate through a pulsed electrodeposition process. Thus, the prepared FeHCF electrode exhibits a specific volumetric capacitance of 88 F cm-3 (specific areal capacitance of 26.6 mF cm-2) and high cycling stability with a capacitance retention of 93.7% over 10,000 galvanostatic charge-discharge cycles in a 1 M KCl electrolyte. Furthermore, two identical FeHCF electrodes were paired up in order to construct a symmetrical supercapacitor, which delivers a wide potential window of 2 V in a 1 M KCl electrolyte and demonstrates a large energy density of 27.5 mWh cm-3 at a high power density of 330 W cm-3.

[Kratom-From natural remedy to addictive drug and back]. / Kratom ­ vom natürlichen Heilmittel zur Suchtdroge und zurück.

BACKGROUND: Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used. OBJECTIVE: The current research on kratom and its ingredients is presented. MATERIAL AND METHODS: An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed. RESULTS: Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7­hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ­opioid receptor agonism. DISCUSSION: Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment.

Sex-Based Differences in Clinical Characteristics of Patients with Acute Myocarditis: A Cohort Study.

BACKGROUND: This study investigated sex differences in acute myocarditis patients during index hospitalization. METHODS: We included 365 patients with acute myocarditis, hospitalized with continuous monitoring at the intensive care unit from 2000-2023 into the Basel Myocarditis Cohort study. We compared sex differences in clinical presentation, the presenting electrocardiogram, prior medical history, inflammatory and cardiac biomarkers, cardiac imaging, arrhythmia occurrence, and short- to midterm outcomes. RESULTS: Mean age was 41.3 years, and 26.3% were female. Compared with men, women were older (median 49.7 vs 38.3 years, P < .001) at the time of diagnosis and presented more frequently with dyspnea (41 vs 26%, P = .013) and a higher Killip class (P = .011). In the presenting electrocardiogram, men had a higher occurrence of diffuse ST-elevation (38 vs 9%, P < .001) and PQ-depression (31 vs 20%, P = .042), compared with women. Women had higher N-terminal pro B-type natriuretic peptide levels (1180 vs 387 ng/L, P = .015), lower cardiac troponin T levels (389 vs 726 ng/L, P = .006), and fewer segments with nonischemic late gadolinium enhancement on cardiac magnetic resonance imaging (1 vs 3, P = .005), but similar left ventricular ejection fraction (55 vs 55%, P = .629), compared with men. Overall, hospital stay was longer in women compared with men (7 vs 5 days, P = .018), with a similar length of intensive care unit stay (2.6 vs 2.7 days, P = .922). Women more often developed severe arrhythmia (8.3 vs 2.2%, P = .015) and heart failure during the hospitalization (31.3 vs 16.4%, P = .003). CONCLUSION: Compared with men, women with acute myocarditis were older at the time of diagnosis, presented more often with heart failure, and had an increased frequency of severe arrhythmia.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Sustained Clinical Response to Ivosidenib in Previously Treated Patients with Advanced Intrahepatic Cholangiocarcinoma Harboring an IDH1 R132 Mutation: Two Case Reports.

Introduction: Patients with progressing intrahepatic cholangiocarcinoma (iCCA) harboring an isocitrate dehydrogenase 1 (IDH1) mutation who received ivosidenib showed a median progression-free survival (PFS) benefit of 1.3 months compared to placebo in the phase 3 ClarIDHy trial. Case Presentations: We describe 2 consecutive patients with previously treated unresectable and metastatic iCCA harboring an IDH1 R132 mutation who achieved durable clinical responses with ivosidenib 500 mg once daily for >12 months until disease progression. In one case with a mixed response, a single progressive liver metastasis was additionally treated locally with interstitial brachytherapy, while ivosidenib was continued until further progression. Ivosidenib therapy resulted in long-term disease control with PFS of 20 and 13 months and duration of treatment of 26 and 13 months, respectively, with no relevant side effects. Conclusion: Patients with unresectable or metastatic IDH1-mutated iCCA can achieve sustained clinical responses for >12 months with ivosidenib. No new safety signals were observed during long-term treatment with ivosidenib.

Rare and Common Genetic Variation Underlying Atrial Fibrillation Risk.

Importance: Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution of rare variants to disease risk warrants characterization in large cohorts. Objective: To identify rare predicted loss-of-function (pLOF) variants associated with AF and elucidate their role in risk of AF, cardiomyopathy (CM), and heart failure (HF) in combination with a polygenic risk score (PRS). Design, Setting, and Participants: This was a genetic association and nested case-control study. The impact of rare pLOF variants was evaluated on the risk of incident AF. HF and CM were assessed in cause-specific Cox regressions. End of follow-up was July 1, 2022. Data were analyzed from January to October 2023. The UK Biobank enrolled 502 480 individuals aged 40 to 69 years at inclusion in the United Kingdom between March 13, 2006, and October 1, 2010. UK residents of European ancestry were included. Individuals with prior diagnosis of AF were excluded from analyses of incident AF. Exposures: Rare pLOF variants and an AF PRS. Main Outcomes and Measures: Risk of AF and incident HF or CM prior to and subsequent to AF diagnosis. Results: A total of 403 990 individuals (218 489 [54.1%] female) with a median (IQR) age of 58 (51-63) years were included; 24 447 were diagnosed with incident AF over a median (IQR) follow-up period of 13.3 (12.4-14.0) years. Rare pLOF variants in 6 genes (TTN, RPL3L, PKP2, CTNNA3, KDM5B, and C10orf71) were associated with AF. Of these, TTN, RPL3L, PKP2, CTNNA3, and KDM5B replicated in an external cohort. Combined with high PRS, rare pLOF variants conferred an odds ratio of 7.08 (95% CI, 6.03-8.28) for AF. Carriers with high PRS also had a substantial 10-year risk of AF (16% in female individuals and 24% in male individuals older than 60 years). Rare pLOF variants were associated with increased risk of CM both prior to AF (hazard ratio [HR], 3.13; 95% CI, 2.24-4.36) and subsequent to AF (HR, 2.98; 95% CI, 1.89-4.69). Conclusions and Relevance: Rare and common genetic variation were associated with an increased risk of AF. The findings provide insights into the genetic underpinnings of AF and may aid in future genetic risk stratification.

Kratom (Mitragyna speciosa) Use and Mental Health: A Systematic Review and Multilevel Meta-Analysis.

INTRODUCTION: Kratom (Mitragyna speciosa) is a medicinal tree native to Southeast Asia. The present multilevel meta-analysis describes the association between kratom use and the positive and negative indicators of mental health. METHODS: A total of thirty-six articles were included in the meta-analysis to examine the associations, using a random-effects model. RESULTS: The pooled effect size showed a very small positive association between kratom use and negative indicators of mental health {r = 0.092, 95% confidence interval (CI) = [0.020, 0.164], p < 0.05}, while no significant association was found with positive indicators of mental health (r = -0.031, 95% CI = [-0.149, 0.087], p > 0.05). Pooled effect sizes of specific mental health outcomes indicated that kratom use showed only a small positive correlation with externalizing disorders (r = 0.201, 95% CI = [0.107, 0.300], p < 0.001). No significant association was found between kratom use and quality of life (r = 0.069, 95% CI = [-0.104, 0.242], p > 0.05) and internalizing disorders (r = -0.001, 95% CI = [-0.115, 0.095], p > 0.05). Multilevel moderator analysis showed that the pooled effect size of the association between kratom use and substance use disorder was stronger in Malaysia (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001), and with the mean age (ß1 = -0.035, 95% CI = [-0.055, -0.014], p = 0.003), and the drug profile of those who were not co-using other drugs (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001). CONCLUSION: The meta-analysis supports the kratom instrumentalization concept, in that a positive gain from kratom consumption can be achieved without any significant adverse associations with mental health.

Impact of Oligoether Side-Chain Length on the Thermoelectric Properties of a Polar Polythiophene.

Conjugated polymers with oligoether side chains make up a promising class of thermoelectric materials. In this work, the impact of the side-chain length on the thermoelectric and mechanical properties of polythiophenes is investigated. Polymers with tri-, tetra-, or hexaethylene glycol side chains are compared, and the shortest length is found to result in thin films with the highest degree of order upon doping with the p-dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). As a result, a stiff material with an electrical conductivity of up to 830 ± 15 S cm-1 is obtained, resulting in a thermoelectric power factor of about 21 µW m-1 K-2 in the case of as-cast films. Aging at ambient conditions results in an initial decrease in thermoelectric properties but then yields a highly stable performance for at least 3 months, with values of about 200 S cm-1 and 5 µW m-1 K-2. Evidently, identification of the optimal side-chain length is an important criterion for the design of conjugated polymers for organic thermoelectrics.

Enhancing the diagnosis of functionally relevant coronary artery disease with machine learning.

Functionally relevant coronary artery disease (fCAD) can result in premature death or nonfatal acute myocardial infarction. Its early detection is a fundamentally important task in medicine. Classical detection approaches suffer from limited diagnostic accuracy or expose patients to possibly harmful radiation. Here we show how machine learning (ML) can outperform cardiologists in predicting the presence of stress-induced fCAD in terms of area under the receiver operating characteristic (AUROC: 0.71 vs. 0.64, p = 4.0E-13). We present two ML approaches, the first using eight static clinical variables, whereas the second leverages electrocardiogram signals from exercise stress testing. At a target post-test probability for fCAD of <15%, ML facilitates a potential reduction of imaging procedures by 15-17% compared to the cardiologist's judgement. Predictive performance is validated on an internal temporal data split as well as externally. We also show that combining clinical judgement with conventional ML and deep learning using logistic regression results in a mean AUROC of 0.74.

Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): a stepped-wedge cluster randomised quality improvement initiative.

INTRODUCTION: Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway. METHODS AND ANALYSIS: This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED. ETHICS AND DISSEMINATION: Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Maori-specific results will be disseminated to Maori stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12619001189112.

Early silent coronary bypass graft occlusion following coronary bypass surgery, implication of routine coronary computed tomography angiography.

Objective: To evaluate incidence and predictors of early silent bypass occlusion following coronary bypass surgery using cardiac computed tomography angiography. Methods: A total of 439 consecutive patients with mean age of 66 ± 10 years comprising 17% (n = 75) females underwent isolated coronary bypass surgery followed by CT scan before discharge. Graft patency was evaluated in 1,319 anastomoses where 44% (n = 580) arterial and 56% (n = 739) vein graft anastomosis were performed. Cardiovascular risk factors, demographics, and intraoperative variables were analyzed. We conducted univariable and multivariable logistic regression analyses to analyze variables potentially associated with graft occlusion following CABG. Variables included gender, surgery duration, graft flow, pulsatility index, vein vs. artery graft, and recent MI. Results: Overall incidence of graft occlusion was 2.4% (31/1,319), and it was diagnosed in 6.6% (29/439) of patients. The difference in occlusion between arterial (2.1%) and vein (2.6%) grafts was not significant, p = 0.68. The duration of intervention p = 0.034, cross clamp time p = 0.024 as well the number of distal anastomosis p = 0.034 were significantly higher in occlusion group. The univariate and multivariate logistic regression indicated duration of surgery being predictive for bypass graft occlusion with OR = 1.18; 95% CI: 1.01-1.38; p = 0.035. Conclusions: Early graft occlusion was associated with surgical factors. The number of distant anastamoses, along duration of surgical intervention were, significantly influenced the risk of EGO. Prolonged procedural time reflecting complex coronary pathology and time-consuming revascularization procedure was as well associated to the elevated risk of occlusion.

Glycan Profile and Sequence Variants of Certified Ricin Reference Material and Other Ricin Samples Yield Unique Molecular Signature Features.

A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin's origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants.

asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers.

Chromatin, the nucleoprotein complex consisting of DNA and histone proteins, plays a crucial role in regulating gene expression by controlling access to DNA. Chromatin modifications are key players in this regulation, as they help to orchestrate DNA transcription, replication, and repair. These modifications recruit epigenetic 'reader' proteins, which mediate downstream events. Most modifications occur in distinctive combinations within a nucleosome, suggesting that epigenetic information can be encoded in combinatorial chromatin modifications. A detailed understanding of how multiple modifications cooperate in recruiting such proteins has, however, remained largely elusive. Here, we integrate nucleosome affinity purification data with high-throughput quantitative proteomics and hierarchical interaction modeling to estimate combinatorial effects of chromatin modifications on protein recruitment. This is facilitated by the computational workflow asteRIa which combines hierarchical interaction modeling, stability-based model selection, and replicate-consistency checks for a stable estimation of Robust Interactions among chromatin modifications. asteRIa identifies several epigenetic reader candidates responding to specific interactions between chromatin modifications. For the polycomb protein CBX8, we independently validate our results using genome-wide ChIP-Seq and bisulphite sequencing datasets. We provide the first quantitative framework for identifying cooperative effects of chromatin modifications on protein binding.

High-mobility organic mixed conductors with a low synthetic complexity index via direct arylation polymerization.

Through direct arylation polymerization, a series of mixed ion-electron conducting polymers with a low synthetic complexity index is synthesized. A thieno[3,2-b]thiophene monomer with oligoether side chains is used in direct arylation polymerization together with a wide range of aryl bromides with varying electronic character from electron-donating thiophene to electron-accepting benzothiadiazole. The obtained polymers are less synthetically complex than other mixed ion-electron conducting polymers due to higher yield, fewer synthetic steps and less toxic reagents. Organic electrochemical transistors (OECTs) based on a newly synthesized copolymer comprising thieno[3,2-b]thiophene with oligoether side chains and bithiophene exhibit excellent device performance. A high charge-carrier mobility of up to µ = 1.8 cm2 V-1 s-1 was observed, obtained by dividing the figure of merit [µC*] from OECT measurements by the volumetric capacitance C* from electrochemical impedance spectroscopy, which reached a value of more than 215 F cm-3.