Raymond Geuss’ radicalization of realism in political theory

Raymond Geuss has been viewed as one of the figureheads of the recent debates about realism in political theory. This interpretation, however, depends on a truncated understanding of his work of the past 30 years. I will offer the first sustained engagement with this work (in English and German) which allows understanding his realism as a project for reorienting political theory, particularly the relationship between political theory and politics. I interpret this reorientation as a radicalization of realismin political theory through the combination of the emphasis on the critical purpose of political theory and the provision of practical, contextual orientation. Their compatibility depends on Geuss’ understanding of criticism as negative, of power as ‘detoxified’ and of the critical purchase of political theory as based on the diagnostic engagement with its context. This radicalization particularly challenges the understanding of how political theory relates to its political context.

Finite domination and Novikov rings. Laurent polynomial rings in several variables

We present a homological characterisation of those chain complexes of modules over a Laurent polynomial ring in several indeterminates which are finitely dominated over the ground ring (that is, are a retract up to homotopy of a bounded complex of finitely generated free modules). The main tools, which we develop in the paper, are a non-standard totalisation construction for multi-complexes based on truncated products, and a high-dimensional mapping torus construction employing a theory of cubical diagrams that commute up to specified coherent homotopies.

Host Defence Peptide LL-37; Effects of truncation on antimicrobial activity

Background: The oral cavity is an ideal environment for colonisation by micro-organisms. A first line of defence against microbial infection is the secretion of broad spectrum host defence peptides (HDPs). In the current climate of antibiotic resistance, exploiting naturally occurring HDPs or synthetic derivatives (mimetics) to combat infection is particularly appealing. The human cathelicidin, LL-37 is one such HDP expressed ubiquitously by epithelial cells and neutrophils. LL-37 exhibits the ability to bind lipopolysaccharide (LPS) and displays broad spectrum activity against a wide range of bacteria. The current study focuses on truncation of LL-37 and defining the antimicrobial and LPS binding activity of the resultant mimetics. Objectives: To assess the antimicrobial and LPS binding activity of LL-37 and three truncated mimetics (KE-18, EF-14 and KR-12). Methods: Peptides were synthesised in-house by Fmoc solid phase peptide synthesis or obtained commercially. Antimicrobial activity was determined using a radial diffusion assay and ability to bind LPS was determined by indirect ELISA. Results: LL-37 and mimetics displayed antimicrobial activity against Streptococcus mutans and Enterococcus Faecalis. KE-18 and KR-12 were shown to possess antimicrobial activity against both pathogens whereas EF-14 was the least antimicrobial. In terms of LPS binding, KE-18 and KR-12 were both effective whereas EF-14 showed the least activity of the three mimetics. Conclusion: Truncation of LL-37 can yield peptides which retain antimicrobial activities and have the ability to bind LPS. Interestingly in some cases the truncation of LL-37 produced mimetics with greater potency than the parent molecule in terms of antimicrobial activity and LPS binding. This work was funded by DEL and the Diabetes Wellness Foundation.

Determinants and two-year change in anterior chamber angle width in a Chinese population

Objective: To study the population distribution and longitudinal changes in anterior chamber angle width and its determinants among Chinese adults. Design: Prospective cohort, population-based study. Participants: Persons aged 35 years or more residing in Guangzhou, China, who had not previously undergone incisional or laser eye surgery. Methods: In December 2008 and December 2010, all subjects underwent automated keratometry, and a random 50% sample had anterior segment optical coherence tomography with measurement of angle-opening distance at 500 μm (AOD500), angle recess area (ARA), iris thickness at 750 μm (IT750), iris curvature, pupil diameter, corneal thickness, anterior chamber width (ACW), lens vault (LV), and lens thickness (LT) and measurement of axial length (AL) and anterior chamber depth (ACD) by partial coherence laser interferometry. Main Outcome Measures: Baseline and 2-year change in AOD500 and ARA in the right eye. Results: A total of 745 subjects were present for full biometric testing in both 2008 and 2010 (mean age at baseline, 52.2 years; standard deviation [SD], 11.5 years; 53.7% were female). Test completion rates in 2010 varied from 77.3% (AOD500: 576/745) to 100% (AL). Mean AOD500 decreased from 0.25 mm (SD, 0.13 mm) in 2008 to 0.21 mm (SD, 13 mm) in 2010 (difference, -0.04; 95% confidence interval [CI], -0.05 to -0.03). The ARA decreased from 21.5±3.73 10^-2 mm² to 21.0±3.64 10 ^-2 mm² (difference, -0.46; 95% CI, -0.52 to -0.41). The decrease in both was most pronounced among younger subjects and those with baseline AOD500 in the widest quartile at baseline. The following baseline variables were significantly associated with a greater 2-year decrease in both AOD500 and ARA: deeper ACD, steeper iris curvature, smaller LV, greater ARA, and greater AOD500. By using simple regression models, we could explain 52% to 58% and 93% of variation in baseline AOD500 and ARA, respectively, but only 27% and 16% of variation in 2-year change in AOD500 and ARA, respectively. Conclusions: Younger persons and those with the least crowded anterior chambers at baseline have the largest 2-year decreases in AOD500 and ARA. The ability to predict change in angle width based on demographic and biometric factors is relatively poor, which may have implications for screening. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Engineered alpha-defensin peptides display antimicrobial activity against oral pathogens

Introduction: Human alpha defensins are a family of neutrophil-derived antimicrobial peptides also known as human neutrophil peptides (HNPs). The defensin family of peptides are characterised by six invariant cysteine residues forming three disulphide bridges. The formation of the correct disulphide pairs complicates the synthesis of full length human alpha defensin and limits its therapeutic potential as an antimicrobial peptide. Objectives: The aim of this study was to determine whether truncated alpha defensins displayed antimicrobial activity against a range of micro-organisms including oral pathogens. Methods: Engineered peptides were synthesised by solid-phase methods using standard Fmoc chemistry. Antibacterial assays were performed using a previously described ultra sensitive radial diffusion method. A total of five engineered defensin peptides and full length alpha defensin were tested for their sensitivity against eight micro-organisms, including Gram negative bacteria, Gram positive bacteria and fungal pathogens Results: Antimicrobial activity was identified as clear zones around peptide-containing wells. Zone diameters were used to calculate minimum inhibitory concentrations (MICs) for each peptide. There was considerable variability in the susceptibility of the micro-organisms to the truncated analogues. Bacillus subtilis and Enterococcus faecalis were sensitive to the majority of the engineered peptides whereas Staphylococcus aureus, Escherichia coli and Candida albicans displayed resistance (defined as an MIC of greater than 250 ug/ml) to the truncated defensins. Of the five engineered peptides synthesised, the 2-aminobenzoic acid (Abz)-containing analogues based on the C-terminal sequence of alpha defensin displayed MIC values closest to that of the full length defensin in 5 out of 8 micro-organisms studied. Conclusion: This study demonstrates that truncated alpha defensins display variable antimicrobial activity against a range of micro-organisms, including oral pathogens. The generation of truncated defensins without disulphide bridges simplifies their synthesis and increases their therapeutic potential.

Brightness perception: one simple model explaines most if not all effects

Few models can explain Mach bands (Pessoa, 1996 Vision Research 36 3205-3227) . Our own employs multiscale line and edge coding by simple and complex cells. Lines are interpreted by Gaussian functions, edges by bipolar, Gaussian-truncated errorfunctions. Widths of these functions are coupled to the scales of the underlying cells and the amplitudes are determined by their responses.

Structure, tissue distribution and estrogen regulation of splice variants of the sea bream estrogen receptor alpha gene

Estrogen actions are mainly mediated by specific nuclear estrogen receptors (ERs), for which different genes and a diversity of transcript variants have been identified, mainly in mammals. In this study, we investigated the presence of ER splice variants in the teleost fish gilthead sea bream (Sparus auratus), by comparison with the genomic organization of the related species Takifugu rubripes. Two exon2-deleted ERα transcript variants were isolated from liver cDNA of estradiol-treated fish. The ΔE2 variant lacks ERα exon 2, generating a premature termination codon and a putative C-terminal truncated receptor, while the ΔE2,3* variant contains an in-frame deletion of exon 2 and part of exon 3 and codes for a putative ERα protein variant lacking most of the DNA-binding domain. Both variants were expressed at very low levels in several female and male sea bream tissues, and their expression was highly inducible in liver by estradiol-17β treatment with a strong positive correlation with the typical wild-type (wt) ERα response in this tissue. These findings identify novel estrogen responsive splice variants of fish ERα, and provide the basis for future studies to investigate possible modulation of wt-ER actions by splice variants.

Effects of nanoparticles exposure in the mussel Mytilus Galloprovincialis

Tese de dout., Ciências do Mar, Terra e Ambiente (Ecotoxicologia), Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2012

Molecular bases of classic galactosemia : searching for new therapeutic strategies

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

Brain-derived neurotrophic factor and adenosine signalling on amyloid-β peptide induced toxicity : impact on hippocampal function

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2014

Molecular features of glycine-mediated neurotransmission in rat brain

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2015

Study the function of the newly discovered TrkB receptor fragment (TrkB-ICD) formed by calpain cleavage

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2016

Deciphering the mechanisms underlying the loss of BDNF neuroprotection in an Alzheimer’s disease model

Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2016

Beyond time and oblivion : Sir Robert Sidney’s autograph manuscript

Dealing with ancient manuscript or old printed texts often constitutes a difficult task, especially to philologists and editors, for two main reasons: the precarious state of preservation of the documents and the uncertainty regarding their origin, authenticity and authorship. These problems are aggravated by spurious versions, due to the publication of truncated works, poorly supervised miscellanies and non-authorised editions. Sir Robert Sidney’s literary text constitutes an exception amidst such vicissitudes, once the original corpus is wholly contained in a notebook exhibiting the organisation and unity conceived by the author himself. Today, there is no evidence that any loose poems, either autograph or copied by amanuenses, were in circulation among members of the Elizabethan court society. The notebook was kept in private collections for four centuries, which probably explains why it was so well preserved. In fact, only in 1984 would P.J. Croft’s fine edition bring the youngest Sidney’s Poems into light. In this work, I approach Croft’s perceptive, accurate philological study that eventually rescued from oblivion a remarkable piece both of the Elizabethan lyric poetry and of the English Renaissance, and, at the same time, look into Robert Sidney’s peculiar, careful and original formatting of his own autograph manuscript.

mRNA metabolism: nonsense mediated mRNA decay as a tool for gene therapy and the role of human DIS3L2 in transcript degradation

Tese de mestrado em Biologia Humana e Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015