Roll-to-roll dip coating of three different PIMs for Organic Solvent Nanofiltration

PIM-1, PIM-7, and PIM-8 composite membranes have been fabricated for Organic Solvent Nanofiltration (OSN) on two different support membranes. Both support membranes, PAN and crosslinked Ultem 1000, displayed pore sizes within the range of 20–25 nm as characterised by gas liquid porometry. PIM layers of < 500 nm thickness were formed from dip coating on a roll-to-roll pilot line. The resultant composite membranes exhibited typical MWCOs in the region of 500–800 g mol−1. The quality of coating obtained on the crosslinked Ultem 1000 support membrane was consistently higher for all three PIMs than that obtained on the PAN membrane. The PIM composite membranes coated on to crosslinked Ultem 1000 were stable in a wider range of solvents than those on the PAN support. OSN testing in a model system with isomeric alkane solutes verified that manipulated changes to the molecular architecture of the polymer backbone resulted in a higher separation factor between straight and branched alkane isomers

Inter-individual and inter-strain differences in cognitive and social abilities of Dark Agouti and Wistar Han rats

BACKGROUND: Healthy animals showing extreme behaviours spontaneously that resemble human psychiatric symptoms are relevant models to study the natural psychobiological processes of maladapted behaviours. Healthy poor decision makers (PDMs) identified using a Rat Gambling Task, co-express a combination of cognitive and reward-based characteristics similar to symptoms observed in human patients with impulse-control disorders. The main goals of this study were to 1) confirm the existence of PDMs and their unique behavioural phenotypes in the Dark Agouti (DA) and WH, 2) to extend the behavioural profile of the PDMs to probability-based decision-making and social behaviours and 3) to discuss how the key traits of each strain could be relevant for biomedical research. METHODS: We compared cognitive abilities, natural behaviours and physiological responses in DA and WH rats using several tests. We analysed the results at the strain and the individual level. RESULTS: Previous findings in WH rats were reproduced and could be generalized to DA. Each PDM of either strain displayed a similar, naturally occurring, combination of behavioural traits, including possibly higher social rank, but no deficits in probability-based decision-making. A Random forest analysis revealed interesting discriminating traits between WH and DA. CONCLUSION: The reproducibility and conservation of the socio-cognitive and behavioural phenotypes of GDM and PDM individuals in the two genetically different strains of WH and DA support a good translational validity of these phenotypes. Both DA and WH rat strains present large phenotypic variations in behaviour pertinent for the study of the underlying mechanisms of poor decision making and associated disorders

Low energy intensity production of fuel-grade bio-butanol enabled by membrane-based extraction

Widespread use of biofuels is inhibited by the significant energy burden of recovering fuel products from aqueous fermentation systems. Here, we describe a membrane-based extraction (perstraction) system for the recovery of fuel-grade biobutanol from fermentation broths which can extract n-butanol with high purity (>99.5%) while using less than 25% of the energy of current technology options. This is achieved by combining a spray-coated thin-film composite membrane with 2-ethyl-1-hexanol as an extractant. The membrane successfully protects the micro-organisms from the extractant, which, although ideal in other respects, is a metabolic inhibitor. In contrast to water, the extractant does not form a heterogeneous azeotrope with n-butanol, and the overall energy consumption of for n-butanol production is 3.9 MJ kg−1, substantially less than other recovery processes (17.0–29.4 MJ kg−1). By (a) extracting n-butanol from the fermentation broth without a phase change, (b) breaking the heterogeneous azeotrope relationship (less energy consumption for distillation), and (c) utilizing a small volume ratio of extractant : fermentation broth (1 : 100, v/v), the need for high energy intensity processes such as pervaporation, gas stripping or liquid–liquid extraction is avoided. The application of this perstraction system to continuous production of a range of higher alcohols is explored and shown to be highly favourable

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

<p>Abstract</p> <p>Background</p> <p>Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.</p> <p>Results</p> <p>Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel <it>in silico </it>and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.</p> <p>Conclusions</p> <p>We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy <it>in vivo</it>.</p

Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities

Central serotonin appears a promising transdiagnostic marker of psychiatric disorders and a modulator of some of their key behavioral symptoms. In adult male Tph2(-/-) rats, constitutively lacking central serotonin, we tested individual's cognitive, social and non-social abilities and characterized group's social organization under classical and ethological testing conditions. Using unsupervised machine learning, we identified the functions most dependent on serotonin. Although serotonin depletion did not affect cognitive performances in classical testing, in the home-cage it induced compulsive aggression and sexual behavior, hyperactive and hypervigilant stereotyped behavior, reduced self-care and exacerbated corticosterone levels. This profile recalled symptoms of impulse control and anxiety disorders. Serotonin appeared essential for behavioral adaptation to dynamic social environments. Our animal model challenges the essential role of serotonin in decision-making, flexibility, impulsivity, and risk-taking. These findings highlight the importance of studying everyday life functions within the dynamic social living environment to model complexity in animal models

Decomposition of semigroup algebras

Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

Betti numbers for numerical semigroup rings

We survey results related to the magnitude of the Betti numbers of numerical semigroup rings and of their tangent cones.Comment: 22 pages; v2: updated references. To appear in Multigraded Algebra and Applications (V. Ene, E. Miller Eds.

Neurotensin(8–13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease

: The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders

Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.

Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin