Generalized Shortest Path Kernel on Graphs

We consider the problem of classifying graphs using graph kernels. We define a new graph kernel, called the generalized shortest path kernel, based on the number and length of shortest paths between nodes. For our example classification problem, we consider the task of classifying random graphs from two well-known families, by the number of clusters they contain. We verify empirically that the generalized shortest path kernel outperforms the original shortest path kernel on a number of datasets. We give a theoretical analysis for explaining our experimental results. In particular, we estimate distributions of the expected feature vectors for the shortest path kernel and the generalized shortest path kernel, and we show some evidence explaining why our graph kernel outperforms the shortest path kernel for our graph classification problem.Comment: Short version presented at Discovery Science 2015 in Banf

Bridging the gap between goal intentions and actions: a systematic review in patient populations.

To evaluate the evidence for the effectiveness of if-then implementation intentions (if-then plans) in adult patient populations. Outcomes of interest included adherence, goal pursuit and physical health outcomes.Keywords were used to search electronic databases without date or language restrictions (up to 30 April 2014). Studies were included if they (1) concerned a patient population; (2) used if-then plans as a sole intervention or as part of treatment, therapy or rehabilitation; (3) if they were randomised controlled trials. The PEDro scale was used to evaluate study quality. Guidance as set out by the Cochrane Collaboration was used. Two reviewers independently extracted data, discrepancies were discussed and if required referred to a third reviewer.In total, 18 of the 2141 articles were identified as potentially relevant and four studies of people with epilepsy, chronic back pain, stroke and obesity met the inclusion criteria. People who form if-then plans achieved better outcomes on epilepsy and stroke medication adherence and physical capacity than controls.Of the four studies that used an if-then plan, only one (people with epilepsy) looked at the intervention as a stand-alone strategy. Further research needs to explore if this simple approach improves rehabilitation outcomes and is a helpful and feasible strategy for people experiencing disabilities. Implications for Rehabilitation Steps involved in achieving goals, such as doing exercises or completing other goal related tasks, can be compromised for people with chronic health conditions particularly resulting from difficulties in self-regulating behaviour. If-then plans are implementation intention tools aimed at supporting people to deal more effectively with self-regulatory problems that might undermine goal striving and goal attainment, and have been found to be effective in health promotion and health behaviour change. This systematic literature review identified four studies completed with patient populations, with three demonstrating effectiveness. If-then plans provide an opportunity for clinicians to develop better ways of implementing rehabilitation

Bad expression influences time to androgen escape in prostate cancer

<b>OBJECTIVE</b>: To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18–24 months. <b>PATIENTS, MATERIALS AND METHODS</b>: The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables. <b>RESULTS</b>: High Bad expression in AD tumours was associated with an increased time to biochemical relapse (<i>P</i> = 0.007) and a trend towards improved overall survival (<i>P</i> = 0.053). There were also trends towards a decrease in Bad (<i>P</i> = 0.068) and Bax (<i>P</i> = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL. <b>CONCLUSION</b>: There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future

Large adiabatic temperature and magnetic entropy changes in EuTiO3

We have investigated the magnetocaloric effect in single and polycrystalline samples of quantum paraelectric EuTiO3 by magnetization and heat capacity measurements. Single crystalline EuTiO3 shows antiferromagnetic ordering due to Eu2+ magnetic moments below TN = 5.6 K. This compound shows a giant magnetocaloric effect around its Neel temperature. The isothermal magnetic entropy change is 49 Jkg-1K-1, the adiabatic temperature change is 21 K and the refrigeration capacity is 500 JKg-1 for a field change of 7 T at TN. The single crystal and polycrystalline samples show similar values of the magnetic entropy change and adiabatic temperature changes. The large magnetocaloric effect is due to suppression of the spin entropy associated with localized 4f moment of Eu2+ ions. The giant magnetocaloric effect together with negligible hysteresis, suggest that EuTiO3 could be a potential material for magnetic refrigeration below 20 K.Comment: 12 pages, 4 figure

The ducky^{2J} Mutation in Cacna2d2 Results in Reduced Spontaneous Purkinje Cell Activity and Altered Gene Expression

The mouse mutant ducky and its allele ducky^{2J} represent a model for absence epilepsy characterized by spike-wave seizures and cerebellar ataxia. These mice have mutations in Cacna2d2, which encodes the α₂δ-2 calcium channel subunit. Of relevance to the ataxic phenotype, α₂δ-2 mRNA is strongly expressed in cerebellar Purkinje cells (PCs). The Cacna2d2du2J mutation results in a 2 bp deletion in the coding region and a complete loss of α₂δ-2 protein. Here we show that du^{2J}/du^{2J} mice have a 30% reduction in somatic calcium current and a marked fall in the spontaneous PC firing rate at 22°C, accompanied by a decrease in firing regularity, which is not affected by blocking synaptic input to PCs. At 34°C, du^{2J}/du^{2J} PCs show no spontaneous intrinsic activity. DU^{2J}/du^{2J} mice also have alterations in the cerebellar expression of several genes related to PC function. At postnatal day 21, there is an elevation of tyrosine hydroxylase mRNA and a reduction in tenascin-C gene expression. Although du^{2J}/+ mice have a marked reduction in α₂δ-2 protein, they show no fall in PC somatic calcium currents or increase in cerebellar tryrosine hydroxylase gene expression. However, du^{2J}/+ PCs do exhibit a significant reduction in firing rate, correlating with the reduction in α₂δ-2. A hypothesis for future study is that effects on gene expression occur as a result of a reduction in somatic calcium currents, whereas effects on PC firing occur as a long-term result of loss of α₂δ-2 and/or a reduction in calcium currents and calcium-dependent processes in regions other than the soma

Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab

Background: The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed might be able to predict patients' clinical outcome more accurately than RAS status alone. Methods: K-RAS (exons 2, 3, 4) wild type colorectal cancer patients, candidates to second/third-line cetuximab with chemotherapy were prospectively allocated into 2 groups on the basis of their profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2) or unfavourable (any of the previous markers altered or mutated). After the introduction of N-RAS status (exons 2, 3, 4) only RAS wild type patients were considered eligible. Results: Forty-six patients were enrolled. Seventeen patients (37%) were allocated to the favourable and 29 patients (63%) to the unfavourable profile. RR in the favourable and unfavourable group was 11/17 (65%) and 2/29 (7%) (p = 0.007) respectively. The favourable group also showed an improved PFS (8months vs. 3months, p < 0.0001) and OS (15months vs. 6months, p < 0.0001). Conclusions: Our results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcom

K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent

Exploring the socio-cultural contexts of fishers and fishing: Developing the concept of the ‘good fisher’

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Recent calls have been made to pay greater attention to the social and cultural contexts of fisheries and their management. This paper explores how the recent Bourdieusian-inspired literature on the ‘good farmer’ might inform our discussion of fishers and their activities. Bourdieu’s ideas of habitus, field and capital(s), and how these interact in (re)shaping the positioning as a ‘good fisher’, allows us to move beyond the myopic, economic, framing of fishers seen in much previous literature and fishing policy. Through in-depth interviews and participant observations in a small-scale fishing community in North Wales (UK), the paper explores the particularity of the fishing field, and notes the multiple performances and demonstrations required in order for individuals to position as a ‘good fisher’. It goes on to highlight the importance of these performances in developing social capital and the associated access to networks of support and reciprocity at sea. Central to these interrelations, the paper observes, is adhering to and internalising various ‘rules of the game’ – which include managing territories, respecting fishing gear, maintaining safety at sea, and the importance of keeping secrets. The paper moves on to consider the implications of these observations for the current and future management of fishing in such areas – noting how pre-existing and context-specific relations between fishers offer boundaries to what change might be achieved by new policies – before examining future agendas for research in this field

Human exercise-induced circulating progenitor cell mobilization is nitric oxide-dependent and is blunted in South Asian men

This article is available open access through the publisher’s website. Copyright @ 2010 American Heart Foundation.Objective— Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPC. We assessed CPC mobilization in response to exercise in Asian men and examined the role of NO in CPC mobilization per se. Methods and Results— In 15 healthy, white European men and 15 matched South Asian men, CPC mobilization was assessed during moderate-intensity exercise. Brachial artery flow-mediated vasodilatation was used to assess NO bioavailability. To determine the role of NO in CPC mobilization, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor l-NMMA, and norepinephrine.  Flow-mediated vasodilatation (5.8%±0.4% vs 7.9%±0.5%; P=0.002) and CPC mobilization (CD34+/KDR+ 53.2% vs 85.4%; P=0.001; CD133+/CD34+/KDR+ 48.4% vs 73.9%; P=0.05; and CD34+/CD45− 49.3% vs 78.4; P=0.006) was blunted in the South Asian group. CPC mobilization correlated with flow-mediated vasodilatation and l-NMMA significantly reduced exercise-induced CPC mobilization (CD34+/KDR+ −3.3% vs 68.4%; CD133+/CD34+/KDR+ 0.7% vs 71.4%; and CD34+/CD45− −30.5% vs 77.8%; all P<0.001). Conclusion— In humans, NO is critical for CPC mobilization in response to exercise. Reduced NO bioavailability may contribute to imbalance between vascular damage and repair mechanisms in South Asian men.British Heart Foundatio