Dublin City University at CLEF 2004: experiments with the ImageCLEF St Andrew's collection

For the CLEF 2004 ImageCLEF St Andrew's Collection task the Dublin City University group carried out three sets of experiments: standard cross-language information retrieval (CLIR) runs using topic translation via machine translation (MT), combination of this run with image matching results from the VIPER system, and a novel document rescoring approach based on automatic MT evaluation metrics. Our standard MT-based CLIR works well on this task. Encouragingly combination with image matching lists is also observed to produce small positive changes in the retrieval output. However, rescoring using the MT evaluation metrics in their current form significantly reduced retrieval effectiveness

Dublin City University at CLEF 2004: experiments in monolingual, bilingual and multilingual retrieval

The Dublin City University group participated in the monolingual, bilingual and multilingual retrieval tasks this year. The main focus of our investigation this year was extending our retrieval system to document languages other than English, and completing the multilingual task comprising four languages: English, French, Russian and Finnish. Results from our French monolingual experiments indicate that working in French is more effective for retrieval than adopting document and topic translation to English. However, comparison of our multilingual retrieval results using different topic and document translation reveals that this result does not extend to retrieved list merging for the multilingual task in a simple predictable way

Functional plasticity in the type IV secretion system of Helicobacter pylori.

Helicobacter pylori causes clinical disease primarily in those individuals infected with a strain that carries the cytotoxin associated gene pathogenicity island (cagPAI). The cagPAI encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into epithelial cells and is required for induction of the pro-inflammatory cytokine, interleukin-8 (IL-8). CagY is an essential component of the H. pylori T4SS that has an unusual sequence structure, in which an extraordinary number of direct DNA repeats is predicted to cause rearrangements that invariably yield in-frame insertions or deletions. Here we demonstrate in murine and non-human primate models that immune-driven host selection of rearrangements in CagY is sufficient to cause gain or loss of function in the H. pylori T4SS. We propose that CagY functions as a sort of molecular switch or perhaps a rheostat that alters the function of the T4SS and "tunes" the host inflammatory response so as to maximize persistent infection

Application of the Frobenius method to the Schrodinger equation for a spherically symmetric potential: anharmonic oscillator

The power series method has been adapted to compute the spectrum of the Schrodinger equation for central potential of the form $V(r)={d_{-2}\over r^2}+{d_{-1}\over r}+\sum_{i=0}^{\infty} d_{i}r^i$. The bound-state energies are given as zeros of a calculable function, if the potential is confined in a spherical box. For an unconfined potential the interval bounding the energy eigenvalues can be determined in a similar way with an arbitrarily chosen precision. The very accurate results for various spherically symmetric anharmonic potentials are presented.Comment: 16 pages, 5 figures, published in J. Phys

Metabolic Profiling in Maturity-Onset Diabetes of the Young (MODY) and Young Onset Type 2 Diabetes Fails to Detect Robust Urinary Biomarkers

It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.publishedVersio

Island coarsening in one-dimensional models with partially and completely reversible aggregation

Using computer simulations and scaling ideas, we study one-dimensional models of diffusion, aggregation and detachment of particles from islands in the post-deposition regime, i. e. without flux. The diffusion of isolated particles takes place with unit rate, aggregation occurs immediately upon contact with another particle or island, and detachment from an island occurs with rate epsilon = exp(-E/kT), where E is the related energy barrier. In the partially reversible model, dissociation is limited to islands of size larger than a critical value i, while in the completely reversible model there is no restriction to that process (infinite i). Extending previous simulation results for the completely reversible case, we observe that a peaked island size distribution in the intermediate time regime, in which the mean island size is increasing, crosses over to the theoretically predicted exponentially decreasing distribution at long times. It contrasts with the partially reversible model, in which peaked distributions are obtained until the long time frozen state, which is attained with a crossover time $\tau \sim \frac{i^3}{\epsilon}$. The mean island size at saturation varies as $S_{sat}\approx 2i+C\epsilon$ (C constant), while the completely reversible case shows an Ahrrenius dependence of the mean island size, $S\sim \epsilon^{-1/2}$. Thus, for different coverages, the effect of the critical size i on the geometric features is much stronger than that of epsilon, which may be used to infer the relevance of size-dependent detachment rates in real systems and other models.Comment: 14 pages,8 figures, accepted for publication in Physica

Women in cardiology: past, present and future

In 2018, the Swiss Society of Cardiology celebrated its70thyear. Is this also a celebration for the achievement ofwomen in cardiology? Yes and no

A little help from residual β cells has long-lasting clinical benefits

Following type 1 diabetes (T1D) diagnosis, declining C-peptide levels reflect deteriorating β cell function. However, the precise C-peptide levels that indicate protection from severe hypoglycemia remain unknown. In this issue of the JCI, Gubitosi-Klug et al. studied participants from the landmark and ongoing Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study that had long-standing (about 35 years) T1D. The authors correlated severe hypoglycemia and other disease outcomes with residual C-peptide levels. While C-peptide secretion failed to associate with hemoglobin A1c (HbA1c) or microvascular complications, C-peptide levels greater than 0.03 nmol/L were linked with fewer episodes of severe hypoglycemia. These findings suggest that efforts to preserve finite β cell function early in T1D can have meaningful, long-standing health benefits for patients

Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome : Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine

Background/Aims Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. Methods We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient's stool microbiota composition was analysed through 16S ribosomal RNA sequencing. Results We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4's downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. Conclusions Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.Peer reviewe