Regulation of pancreatic cancer aggressiveness by stromal stiffening

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Contact Manifolds, Contact Instantons, and Twistor Geometry

Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

Search for electric dipole moments at storage rings

Permanent electric dipole moments (EDMs) violate parity and time reversal symmetry. Within the Standard Model (SM) they are many orders of magnitude below present experimental sensitivity. Many extensions of the SM predict much larger EDMs, which are therefore an excellent probe for the existence of "new physics". Until recently it was believed that only electrically neutral systems could be used for sensitive searches of EDMs. With the introduction of a novel experimental method, high precision for charged systems will be within reach as well. The features of this method and its possibilities are discussed.Comment: Proc. EXA2011, 6 pages; http://www.springerlink.com/content/45l35376832vhrg0

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Understanding the threats posed by non-native species: public vs. conservation managers.

Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Why grit requires perseverance and passion to positively predict performance

This is the final version. Available from the publisher via the DOI in this record.Data deposition: Data and scripts related to this paper are available at https://osf.io/ kp7cb/Prior studies linking grit—defined as perseverance and passion for long-term goals—to performance are beset by contradictory evidence. As a result, commentators have increasingly declared that grit has limited effects. We propose that this inconsistent evidence has occurred because prior research has emphasized perseverance and ignored, both theoretically and empirically, the critical role of passion, which we define as a strong feeling toward a personally important value/preference that motivates intentions and behaviors to express that value/preference. We suggest that combining the grit scale— which only captures perseverance—with a measure that assesses whether individuals attain desired levels of passion will predict performance. We first metaanalyzed 127 studies (n = 45,485) that used the grit scale and assessed performance, and found that effect sizes are larger in studies where participants were more passionate for the performance domain. Second, in a survey of employees matched to supervisor-rated job performance (n = 422), we found that the combination of perseverance, measured through the grit scale, and passion attainment, measured through a new scale, predicted higher performance. A final study measured perseverance and passion attainment in a sample of students (n = 248) and linked these to their grade-point average (GPA), finding that the combination of perseverance and passion attainment predicted higher GPAs in part through increased immersion. The present results help resolve the mixed evidence of grit’s relationship with performance by highlighting the important role that passion plays in predicting performance. By adequately measuring both perseverance and passion, the present research uncovers grit’s true predictive power