Semiaromatic polyamides with enhanced charge carrier mobility

The control of local order in polymer semiconductors using non-covalent interactions may be used to engineer materials with interesting combinations of mechanical and optoelectronic properties. To investigate the possibility of preparing n-type polymer semiconductors in which hydrogen bonding plays an important role in structural order and stability, we have used solution-phase polycondensation to incorporate dicyanoperylene bisimide repeat units into an aliphatic polyamide chain backbone. The morphology and thermomechanical characteristics of the resulting polyamides, in which the aliphatic spacer length was varied systematically, were comparable with those of existing semiaromatic engineering polyamides. At the same time, the charge carrier mobility as determined by pulse-radiolysis time-resolved microwave conductivity measurements was found to be about 10-2 cm2 V-1 s-1, which is similar to that reported for low molecular weight perylene bisimides. Our results hence demonstrate that it is possible to use hydrogen bonding interactions as a means to introduce promising optoelectronic properties into high-performance engineering polymers.Peer ReviewedPostprint (author's final draft

Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B

ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers

Optimization of minimum set of protein–DNA interactions: a quasi exact solution with minimum over-fitting

Motivation: A major limitation in modeling protein interactions is the difficulty of assessing the over-fitting of the training set. Recently, an experimentally based approach that integrates crystallographic information of C2H2 zinc finger–DNA complexes with binding data from 11 mutants, 7 from EGR finger I, was used to define an improved interaction code (no optimization). Here, we present a novel mixed integer programming (MIP)-based method that transforms this type of data into an optimized code, demonstrating both the advantages of the mathematical formulation to minimize over- and under-fitting and the robustness of the underlying physical parameters mapped by the code

Leaching and decay resistance of alder and pine wood treated with copper based wood preservatives

The objective of this study was to determine the leaching and decay resistance of Alder (Alnus glutinosa subsp. barbata) and Scots pine (Pinus sylvestris) wood samples treated with copper based preservatives. Samples were treated with CCA, ACQ, Tanalith E and Wolmanit with different concentrations. Scots pine samples were exposed the mini-block test against brown rot fungi (Poria placenta) and Coniophora puteana while alder wood samples were tested against brown rot fungi (Coniophora puteana) and white rot fungi (Coriolus versicolor). Regarding to leaching test, treated samples were impregnated with 300 ml of distilled water and after 6, 24, 48 and thereafter at 48-hour intervals, the leachate was removed and replaced with fresh distilled water according to AWPA E11. Samples of each leachate were collected and retained for copper analysis. Amount of copper released from treated wood during the leaching test was chemically analyzed with Atomic Absorption spectroscopy. Perchloric acid procedure for the digestion of wood was used according to AWPA A7-97. The amount of copper component (Qd), the cumulative quantities leached (Qc) and the average daily fluxes (FLUX) were calculated. Results shows that CCA treated samples release less copper compared to other copper based preservatives used in this study. Highest mass losses were obtained from the leached samples treated with 1% of ACQ-2200 against decay fungi

Metabolic myopathy presenting with polyarteritis nodosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, we describe for the first time a patient in whom an unusual metabolic myopathy was identified after failure to respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis.</p> <p>Case presentation</p> <p>A 78-year-old African-American woman with a two-year history of progressive fatigue and exercise intolerance presented to our facility with new skin lesions and profound muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery vasculitis consistent with polyarteritis nodosa. Biochemical studies of the muscle revealed diminished cytochrome C oxidase activity (0.78 μmol/minute/g tissue; normal range 1.03 to 3.83 μmol/minute/g tissue), elevated acid maltase activity (23.39 μmol/minute/g tissue; normal range 1.74 to 9.98 μmol/minute/g tissue) and elevated neutral maltase activity (35.89 μmol/minute/g tissue; normal range 4.35 to 16.03 μmol/minute/g tissue). Treatment for polyarteritis nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic improvement. Additional management with a diet low in complex carbohydrates and ubiquinone, creatine, carnitine, folic acid, α-lipoic acid and ribose resulted in dramatic clinical improvement.</p> <p>Conclusions</p> <p>Our patient's initial symptoms of fatigue, exercise intolerance and progressive weakness were likely related to her complex metabolic myopathy involving both the mitochondrial respiratory chain and glycogen storage pathways. Management of our patient required treatment of both the polyarteritis nodosa as well as metabolic myopathy. Metabolic myopathies are common and should be considered in any patient with exercise intolerance. Metabolic myopathies may complicate the management of various disease states.</p

Tannin- caprolactam and Tannin- PEG formulations as outdoor wood preservatives: Weathering properties

International audienceAbstractKey messageThis article presents the leaching, fire and weathering resistance improvements of samples treated with tannin-based wood preservatives added of caprolactam. PEG-added formulations show limited applicability. The FT-IR and13C-NMR analyses of the caprolactam-added formulations show some evidences of copolymerization.ContextTannin-boron wood preservatives are known for their high resistance against leaching, biological attacks, fire as well as for the good mechanical properties that they impart to wood. These properties promoted these formulations for being a candidate for the protection of green buildings. However, the low elasticity of these polymers and their dark colour implied limited weathering resistances.AimsThe aim of the study is to find suitable additives for tannin-based formulations to overcome their limited weathering resistances, without compromising the other properties.MethodsTreatment, leaching and fire tests, dimensional stability as well as artificial and natural weathering of the timber treated with caprolactam-added and PEG-added formulations were performed. FT-IR and 13C-NMR of the formulations were presented.ResultsThe presence of caprolactam improved the properties of the formulation with particularly significant results in terms of resistance against leaching and dimensional stability. These enhancements were imparted also to the weathering resistance of the tannin-caprolactam formulations. Indeed, the colour changes during the artificial and natural exposures were stable for longer periods. FT-IR and 13C-NMR investigations of the advanced formulations were led, and covalent copolymerization of the caprolactam with the tannin-hexamine polymer was observed.ConclusionThe tannin formulations with caprolactam improved the durability of the wood specimens, while the PEG-tannin presented strong application drawbacks

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p <0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range

The Role of Methylation in the Intrinsic Dynamics of B- and Z-DNA

Methylation of cytosine at the 5-carbon position (5mC) is observed in both prokaryotes and eukaryotes. In humans, DNA methylation at CpG sites plays an important role in gene regulation and has been implicated in development, gene silencing, and cancer. In addition, the CpG dinucleotide is a known hot spot for pathologic mutations genome-wide. CpG tracts may adopt left-handed Z-DNA conformations, which have also been implicated in gene regulation and genomic instability. Methylation facilitates this B-Z transition but the underlying mechanism remains unclear. Herein, four structural models of the dinucleotide d(GC)5 repeat sequence in B-, methylated B-, Z-, and methylated Z-DNA forms were constructed and an aggregate 100 nanoseconds of molecular dynamics simulations in explicit solvent under physiological conditions was performed for each model. Both unmethylated and methylated B-DNA were found to be more flexible than Z-DNA. However, methylation significantly destabilized the BII, relative to the BI, state through the Gp5mC steps. In addition, methylation decreased the free energy difference between B- and Z-DNA. Comparisons of α/γ backbone torsional angles showed that torsional states changed marginally upon methylation for B-DNA, and Z-DNA. Methylation-induced conformational changes and lower energy differences may contribute to the transition to Z-DNA by methylated, over unmethylated, B-DNA and may be a contributing factor to biological function

The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury