Miracle-dz/UniFAR-FTUs huggingface dataset:
Extended 2,2′-Bipyrroles: New Monomers for Conjugated Polymers with Tailored Processability

The synthesis of 2,2′-bipyrroles substituted at positions 5,5′ with pyrrolyl, N-methyl-pyrrolyl and thienyl groups and their application in the preparation of conducting polymers is reported herein. The preparation of these monomers consisted of two synthetic steps from a functionalized 2,2′-bipyrrole: Bromination of the corresponding 2,2′-bipyrrole followed by Suzuki or Stille couplings. These monomers display low oxidation potential compared to pyrrole because of the extended length of their conjugation pathway. The resulting monomers can be polymerized through oxidative/electropolymerization. Electrical conductivity and electrochromic properties of the electrodeposited polymeric films were evaluated using 4-point probe measurements and cyclic voltammetry to evaluate their applicability in electronics.
Metabolically healthy versus unhealthy obesity and risk of fibrosis progression in non‐alcoholic fatty liver disease

Little is known about the impact of metabolically healthy obesity on fibrosis progression in non‐alcoholic fatty liver disease (NAFLD). We investigated the association of body mass index (BMI) category, body fat percentage and waist circumference with worsening of noninvasive fibrosis markers in metabolically healthy and unhealthy individuals with NAFLD.
Delivering community-led integrated HIV and sexual and reproductive health services for sex workers: A mixed methods evaluation of the DIFFER study in Mysore, South India

Introduction Women in developing countries continue to face barriers to accessing sexual and reproductive health (SRH) services, with marginalized women facing increased challenges to accessing care. The Diagonal Interventions to Fast-Forward Enhanced Reproductive Health (DIFFER) project implemented a package of interventions for female sex workers and women from the general population which integrated horizontal health services for the general population with existing vertical targeted interventions aimed at sex workers with an aim to improve SRH and HIV services. We present an outcome evaluation of the DIFFER project in terms of uptake rates for SRH services among sex workers in Mysore, India. Methods Ashodaya Samithi, a sex worker-led organization, implemented the DIFFER strategy through their community-based clinic and a Well Women Clinic (WWC), established at a partner private hospital that provided SRH services for women living with HIV. Mixed methods were used to evaluate the intervention that included a baseline (2012–13) and end of project (2015–16) cross sectional surveys (CSS), focus group discussions (FGDs), key informant interviews, and analysis of service statistics from 2013–2016. Results The CSS found that condom use, STI testing, and treatment were high before, and throughout the intervention; cervical cancer screening and treatment increased significantly, from 11.5% to 56% (aOR 9.85, p<0.001) and HIV testing in the last 3 months increased from 26.3% to 73.3% (aOR 7.25, p<0.001). The proportion of sex workers using any SRH service in the past year doubled from 25.7% to 51.4% (aOR 2.91, p<0.001). Service statistics showed similar trends. The FGDs and key informant interviews showed that women and stakeholders held high levels of satisfaction with the strategy, and affirmed potential for scale up. Conclusion The DIFFER strategy demonstrated that SRH service uptake can occur in conjuction with HIV services offered to sex workers. This model of integrated service delivery has been accepted by policy makers and needs further analysis for scaling up.
Epigenetic signature of PD-1+ TCF1+ CD8 T cells that act as resource cells during chronic viral infection and respond to PD-1 blockade

Significance PD-1+ TCF1+ stem-like CD8 T cells are critical for maintaining the T cell response during chronic viral infection and cancer, and provide the proliferative burst seen after PD-1 immunotherapy. These cells undergo a slow self-renewal and also give rise to the more terminally differentiated and exhausted CD8 T cells. Here we define the epigenetic landscape of the stem-like CD8 T cells and their more differentiated progeny. These 2 CD8 T cell subsets from chronically infected mice showed substantial differences, but also shared common features that were distinct from the epigenetic signature of effector and memory CD8 T cells generated after an acute viral infection. This information will be useful in targeting epigenetic changes to improve current immunotherapies. We have recently defined a novel population of PD-1 (programmed cell death 1)+ TCF1 (T cell factor 1)+ virus-specific CD8 T cells that function as resource cells during chronic LCMV infection and provide the proliferative burst seen after PD-1 blockade. Such CD8 T cells have been found in other chronic infections and also in cancer in mice and humans. These CD8 T cells exhibit stem-like properties undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells. Here we compared the epigenetic signature of stem-like CD8 T cells with exhausted CD8 T cells. ATAC-seq analysis showed that stem-like CD8 T cells had a unique signature implicating activity of HMG (TCF) and RHD (NF-κB) transcription factor family members in contrast to higher accessibility to ETS and RUNX motifs in exhausted CD8 T cells. In addition, regulatory regions of the transcription factors Tcf7 and Id3 were more accessible in stem-like cells whereas Prdm1 and Id2 were more accessible in exhausted CD8 T cells. We also compared the epigenetic signatures of the 2 CD8 T cell subsets from chronically infected mice with effector and memory CD8 T cells generated after an acute LCMV infection. Both CD8 T cell subsets generated during chronic infection were strikingly different from CD8 T cell subsets from acute infection. Interestingly, the stem-like CD8 T cell subset from chronic infection, despite sharing key functional properties with memory CD8 T cells, had a very distinct epigenetic program. These results show that the chronic stem-like CD8 T cell program represents a specific adaptation of the T cell response to persistent antigenic stimulation.
Satellite DNA at the Centromere Is Dispensable for Segregation Fidelity

The typical vertebrate centromeres contain long stretches of highly repeated DNA sequences (satellite DNA). We previously demonstrated that the karyotypes of the species belonging to the genus Equus are characterized by the presence of satellite-free and satellite-based centromeres and represent a unique biological model for the study of centromere organization and behavior. Using horse primary fibroblasts cultured in vitro, we compared the segregation fidelity of chromosome 11, whose centromere is satellite-free, with that of chromosome 13, which has similar size and a centromere containing long stretches of satellite DNA. The mitotic stability of the two chromosomes was compared under normal conditions and under mitotic stress induced by the spindle inhibitor, nocodazole. Two independent molecular-cytogenetic approaches were used—the interphase aneuploidy analysis and the cytokinesis-block micronucleus assay. Both assays were coupled to fluorescence in situ hybridization with chromosome specific probes in order to identify chromosome 11 and chromosome 13, respectively. In addition, we tested if the lack of centromeric satellite DNA affected chromatid cohesion under normal and stress conditions. We demonstrated that, in our system, the segregation fidelity of a chromosome is not influenced by the presence of long stretches of tandem repeats at its centromere. To our knowledge, the present study is the first analysis of the mitotic behavior of a natural satellite-free centromere.
How do technique and coordination change during learning of a whole-body task: Application to the upstart in gymnastics

ABSTRACT When learning swinging skills on a bar there has been conflicting advice in the research literature regarding whether to coach the “gold standard” technique to novices. The present study aimed to determine how technique (joint angle time histories) and (inter-limb) coordination changed as novice gymnasts learned a fundamental gymnastics skill (the upstart). It was hypothesised that both technique and coordination would become more like an expert as learning progressed. Eight novice gymnasts, unable to perform an upstart, underwent four months of training, with the number of successful upstarts out of 10 recorded at the start and then every month subsequently. In the first and last sessions motion capture was used to determine joint kinematics. Root mean squared differences for the joint angle time histories and continuous relative phase at the shoulder and hip were calculated between the novices and an expert gymnast. As training progressed technique and coordination became more like the expert gymnast. The more successful novices were better able to time their actions within the swing than the less successful novices. Gymnastics coaches teach towards a “gold standard” technique since being successful at the skill is not the only goal, as considerations for future skill development are made.
Theory of Computing: A Gentle Introduction

From the Publisher: This book focuses on fundamental issues of computation. The readers can master the content and gain lasting perspective from which to understand computers by carefully worked out examples, illustrations, and algorithmic proofs. Teaches the fundamental concepts behind computation. Hundreds of exercises marked according to the level of difficulty provide readers ample opportunity to apply concepts. Hundreds of illustrations which enhance understanding. Only algorithmic proofs are given in the text allowing readers to calibrate the mathematical depth they want to pursue. Appropriate for upper division undergraduate and graduate level courses in Computer Science Theory, Theory of Computation, and Automata and Formal Language Theory.
Beneficial role of adipose‐derived mesenchymal stem cells from microfragmented fat in a murine model of duchenne muscular dystrophy

Introduction: No etiologic therapy is available for Duchenne muscular dystrophy (DMD), but mesenchymal stem cells were shown to be effective in preclinical models of DMD. The objective of this study is to investigate the effect of microfragmented fat extracted on a murine model of DMD. Methods: Fat tissue was extracted from healthy human participants and injected IM into DMD mice. Histological analysis, cytokines, and force measurement were performed up to 4 weeks after injection. Results: Duchenne muscular dystrophy mice injected with microfragmented fat exhibited an improved muscle phenotype (decreased necrosis and fibrosis), a decrease of inflammatory cytokines, and increased strength. Discussion: Administration of microfragmented fat in key muscles may improve muscular phenotype in patients with DMD. Muscle Nerve, 2019
The enterprises simulation in second life. The case of Perting ltd

The design and evaluation of IT-systems are usually supported by different usability criteria. Our hypothesis is that criteria are predominantly formulated as supporting interaction between a user and an IT-system. We are claiming that there is a need for criteria formulated at higher levels such as communication and business processes. One example of a criterion formulated at the interaction level is “Visibility of system status” and one example of a criterion formulated at the business process level is “Quality of work”. If criteria is formulated and used on the interaction level only, the impact on design and evaluation can only take place at this level. This choice will also mean that you are only able to speculate whether the IT-system is supporting higher levels. We are not saying that criteria belonging to the interaction level are unimportant; rather we are saying that there is a need for formulating complementing criteria that resides on the communication and business process level.
A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in Candida albicans

Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system required for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire tolerance to antifungal drugs and for nonmeiotic ploidy reduction after mating. We discovered that the ancestor of C. albicans and 2 related pathogens evolved a variant of histone 2A (H2A) that lacks the conserved phosphorylation site for kinetochore-associated Bub1 kinase, a key regulator of chromosome segregation. Using engineered strains, we show that the relative gene dosage of this variant versus canonical H2A controls the fidelity of chromosome segregation and the rate of acquisition of tolerance to antifungal drugs via aneuploidy. Furthermore, whole-genome chromatin precipitation analysis reveals that Centromere Protein A/ Centromeric Histone H3-like Protein (CENP-A/Cse4), a centromeric histone H3 variant that forms the platform of the eukaryotic kinetochore, is depleted from tetraploid-mating products relative to diploid parents and is virtually eliminated from cells exposed to aneuploidy-promoting cues. We conclude that genetically programmed and environmentally induced changes in chromatin can confer the capacity for enhanced evolvability via chromosome missegregation.
Transcription factor autoregulation is required for acquisition and maintenance of neuronal identity

ABSTRACT The expression of transcription factors that initiate the specification of a unique cellular identity in multicellular organisms is often maintained throughout the life of the respective cell type via an autoregulatory mechanism. It is generally assumed that such autoregulation serves to maintain the differentiated state of a cell. To experimentally test this assumption, we used CRISPR/Cas9-mediated genome engineering to delete a transcriptional autoregulatory, cis-acting motif in the che-1 zinc-finger transcription factor locus, a terminal selector required to specify the identity of the ASE neuron pair during embryonic development of the nematode Caenorhabditis elegans. We show that che-1 autoregulation is indeed required to maintain the differentiated state of the ASE neurons but that it is also required to amplify che-1 expression during embryonic development to reach an apparent minimal threshold to initiate the ASE differentiation program. We conclude that transcriptional autoregulation fulfills two intrinsically linked purposes: one in proper initiation, the other in proper maintenance of terminal differentiation programs. This article has an associated ‘The people behind the papers’ interview. Highlighted Article: Mutation of an autoregulatory motif of che-1, a cell identity-specifying transcription factor, shows that autoregulation is required for both acquisition and maintenance of cellular identity in C. elegans.
Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons

Abstract Chimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p < .05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p < .05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH.
Identification of Surrogate Biomarkers for the Prediction of Patients at Risk of Low Macular Pigment in Type 2 Diabetes

ABSTRACT Purpose: This cross-sectional study compared macular pigment (MP) levels among persons with Type 2 diabetes relative to healthy controls. Additionally, a range of behavioral, anthropometric, clinical and serum measures were explored as possible predictors of low MP optical density (MPOD) in diabetes. Methods: Two health status groups; Group 1: Type 2 diabetes (n = 188), and Group 2: Healthy controls (n = 2,594) completed a full MP assessment using customized heterochromatic flicker photometry, as part of The Irish Longitudinal Study on Aging (TILDA). Clinical [blood pressure; cataract status; MPOD] and anthropometric [waist (cm); weight (kg); hip (cm)] measurements were taken, and a blood sample drawn for analysis of serum biomarkers [lipoproteins; inflammatory markers (C reactive protein and vitamin-D)]. Results: One-way ANOVA revealed lower MPOD in subjects with Type 2 diabetes relative to controls (p = .047). Amongst participants with diabetes, those with low serum vitamin D (≤50 nmol/L) had significantly lower mean MPOD compared to those with sufficient serum vitamin D levels >50 nmol/L (0.173(0.148) vs. 0.226(0.145); p = . 006). Concomitantly, MP was significantly lower in diabetes participants with raised serum triglyceride (TG) to high density lipoprotein (HDL) ratio (TG/HDL); values >1.74 mmol/L (0.172 (0.140) vs 0.215 (0.152); p = . 039). Body mass index, waist-to-height ratio and waist circumference, were all significantly negatively correlated with MPOD (Pearson’s correlation, p < .05 for all). Significant correlates of MPOD in the multivariate regression model included smoking, cataract, and vitamin D, which collectively contributed 18.5% of the overall variability in MPOD status amongst participants with Type 2 diabetes. Conclusions: This study provides additional evidence that low MP may indeed be a feature of Type 2 diabetes, and further identifies smoking, cataract and vitamin D status as plausible predictors of low MPOD amongst persons with Type 2 diabetes.
Asthma control and quality of life in adolescents: The role of illness perceptions, medication beliefs, and adherence

Abstract Objective: Asthma control and quality of life (QoL) are important disease outcomes for asthma patients. Illness perceptions (cognitive and emotional representations of the illness) and medication beliefs have been found to be important determinants of medication adherence, and subsequently disease control and QoL in adults with asthma. In adolescents, this issue needs further elucidation. Therefore, the aim of this study was to explore the relationship between illness perceptions, medication beliefs, medication adherence, disease control, and QoL in adolescents with asthma. Methods: In this cross-sectional study, we used baseline data of adolescents with asthma (age 12–18 years) who participated in the ADolescent Adherence Patient Tool (ADAPT) study. Questionnaires were administrated online, and included sociodemographic variables and validated questionnaires measuring self-reported illness perceptions, medication beliefs, medication adherence, disease control, and QoL. Results: Data of 243 adolescents with asthma were available; age 15.1 ± 2.0 years and 53% females. More than half of these adolescents (62%; n = 151) reported to be non-adherent (Medication Adherence Report Scale ≤23) and 77% (n = 188) had uncontrolled asthma. There was a strong positive correlation between disease control and QoL (r = 0.74). All illness perceptions items were correlated with disease control and QoL, with the strongest correlation between ‘identity’ (symptom perception) and QoL (r=–0.66). Medication adherence was correlated to medication beliefs (r = 0.38), disease control (r = 0.23), and QoL (r = 0.14), whereas medication beliefs were only associated with adherence. Conclusions: Stimulating positive illness perceptions and medication beliefs might improve adherence, which in turn might lead to improved disease control and better QoL.
Exome-wide assessment of the functional impact and pathogenicity of multinucleotide mutations

Approximately 2% of de novo single-nucleotide variants (SNVs) appear as part of clustered mutations that create multinucleotide variants (MNVs). MNVs are an important source of genomic variability as they are more likely to alter an encoded protein than a SNV, which has important implications in disease as well as evolution. Previous studies of MNVs have focused on their mutational origins and have not systematically evaluated their functional impact and contribution to disease. We identified 69,940 MNVs and 91 de novo MNVs in 6688 exome-sequenced parent–offspring trios from the Deciphering Developmental Disorders Study comprising families with severe developmental disorders. We replicated the previously described MNV mutational signatures associated with DNA polymerase zeta, an error-prone translesion polymerase, and the APOBEC family of DNA deaminases. We estimate the simultaneous MNV germline mutation rate to be 1.78 × 10−10 mutations per base pair per generation. We found that most MNVs within a single codon create a missense change that could not have been created by a SNV. MNV-induced missense changes were, on average, more physicochemically divergent, were more depleted in highly constrained genes (pLI ≥ 0.9), and were under stronger purifying selection compared with SNV-induced missense changes. We found that de novo MNVs were significantly enriched in genes previously associated with developmental disorders in affected children. This shows that MNVs can be more damaging than SNVs even when both induce missense changes, and are an important variant type to consider in relation to human disease.