Latitude and longitude vertical disparities

The literature on vertical disparity is complicated by the fact that several different definitions of the term “vertical disparity” are in common use, often without a clear statement about which is intended or a widespread appreciation of the properties of the different definitions. Here, we examine two definitions of retinal vertical disparity: elevation-latitude and elevation-longitude disparities. Near the fixation point, these definitions become equivalent, but in general, they have quite different dependences on object distance and binocular eye posture, which have not previously been spelt out. We present analytical approximations for each type of vertical disparity, valid for more general conditions than previous derivations in the literature: we do not restrict ourselves to objects near the fixation point or near the plane of regard, and we allow for non-zero torsion, cyclovergence, and vertical misalignments of the eyes. We use these expressions to derive estimates of the latitude and longitude vertical disparities expected at each point in the visual field, averaged over all natural viewing. Finally, we present analytical expressions showing how binocular eye position—gaze direction, convergence, torsion, cyclovergence, and vertical misalignment—can be derived from the vertical disparity field and its derivatives at the fovea.

The sea-level conundrum: case studies from palaeo-archives

Uncertainties in sea-level projections for the 21st century have focused ice sheet modelling efforts to include the processes that are thought to be contributing to the recently observed rapid changes at ice sheet margins. This effort is still in its infancy, however, leaving us unable to make reliable predictions of ice sheet responses to a warming climate if such glacier accelerations were to increase in size and frequency. The geological record, however, has long identified examples of nonlinear ice sheet response to climate forcing (Shackleton NJ, Opdyke ND. 1973. Oxygen isotope and paleomagnetic stratigraphy of equatorial Pacific core V28–239, late Pliocene to latest Pleistocene. Geological Society of America Memoirs145: 449–464; Fairbanks RG. 1989. A 17,000 year glacio-eustatic sea level record: influence of glacial melting rates on the Younger Dryas event and deep ocean circulation. Nature342: 637–642; Bard E, Hamelin B, Arnold M, Montaggioni L, Cabioch G, Faure G, Rougerie F. 1996. Sea level record from Tahiti corals and the timing of deglacial meltwater discharge. Nature382: 241–244), thus suggesting an alternative strategy for constraining the rate and magnitude of sea-level change that we might expect by the end of this century. Copyright © 2009 John Wiley & Sons, Ltd.

Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: an exploratory study.

BACKGROUND: Due to the heterogeneity in the biological behavior of prostate cancer, biomarkers that can reliably distinguish indolent from aggressive disease are urgently needed to inform treatment choices. METHODS: We employed 8-plex isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to profile the proteomes of two distinct panels of isogenic prostate cancer cells with varying growth and metastatic potentials, in order to identify novel biomarkers associated with progression. The LNCaP, LNCaP-Pro5, and LNCaP-LN3 panel of cells represent a model of androgen-responsive prostate cancer, while the PC-3, PC-3M, and PC-3M-LN4 panel represent a model of androgen-insensitive disease. RESULTS: Of the 245 unique proteins identified and quantified (>or=95% confidence; >or=2 peptides/protein), 17 showed significant differential expression (>or=+/-1.5), in at least one of the variant LNCaP cells relative to parental cells. Similarly, comparisons within the PC-3 panel identified 45 proteins to show significant differential expression in at least one of the variant PC-3 cells compared with parental cells. Differential expression of selected candidates was verified by Western blotting or immunocytochemistry, and corresponding mRNA expression was determined by quantitative real-time PCR (qRT-PCR). Immunostaining of prostate tissue microarrays for ERp5, one of the candidates identified, showed a significant higher immunoexpression in pre-malignant lesions compared with non-malignant epithelium (P < 0.0001, Mann-Whitney U-test), and in high Gleason grade (4-5) versus low grade (2-3) cancers (P < 0.05). CONCLUSIONS: Our study provides proof of principle for the application of an 8-plex iTRAQ approach to uncover clinically relevant candidate biomarkers for prostate cancer progression.

Aerosol contribution to the rapid warming of near-term climate under RCP 2.6

The importance of aerosol emissions for near term climate projections is investigated by analysing simulations with the HadGEM2-ES model under two different emissions scenarios: RCP2.6 and RCP4.5. It is shown that the near term warming projected under RCP2.6 is greater than under RCP4.5, even though the greenhouse gas forcing is lower. Rapid and substantial reductions in sulphate aerosol emissions due to a reduction of coal burning in RCP2.6 lead to a reduction in the negative shortwave forcing due to aerosol direct and indirect effects. Indirect effects play an important role over the northern hemisphere oceans, especially the subtropical northeastern Pacific where an anomaly of 5-10\,Wm$^{-2}$ develops. The pattern of surface temperature change is consistent with the expected response to this surface radiation anomaly, whilst also exhibiting features that reflect redistribution of energy, and feedbacks, within the climate system. These results demonstrate the importance of aerosol emissions as a key source of uncertainty in near term projections of global and regional climate.

Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species

Conditions of stress, such as myocardial infarction, stimulate up-regulation of heme oxygenase (HO-1) to provide cardioprotection. Here, we show that CO, a product of heme catabolism by HO-1, directly inhibits native rat cardiomyocyte L-type Ca2+ currents and the recombinant alpha1C subunit of the human cardiac L-type Ca2+ channel. CO (applied via a recognized CO donor molecule or as the dissolved gas) caused reversible, voltage-independent channel inhibition, which was dependent on the presence of a spliced insert in the cytoplasmic C-terminal region of the channel. Sequential molecular dissection and point mutagenesis identified three key cysteine residues within the proximal 31 amino acids of the splice insert required for CO sensitivity. CO-mediated inhibition was independent of nitric oxide and protein kinase G but was prevented by antioxidants and the reducing agent, dithiothreitol. Inhibition of NADPH oxidase and xanthine oxidase did not affect the inhibitory actions of CO. Instead, inhibitors of complex III (but not complex I) of the mitochondrial electron transport chain and a mitochondrially targeted antioxidant (Mito Q) fully prevented the effects of CO. Our data indicate that the cardioprotective effects of HO-1 activity may be attributable to an inhibitory action of CO on cardiac L-type Ca2+ channels. Inhibition arises from the ability of CO to promote generation of reactive oxygen species from complex III of mitochondria. This in turn leads to redox modulation of any or all of three critical cysteine residues in the channel's cytoplasmic C-terminal tail, resulting in channel inhibition.

Biased interpretation in perfectionism and its modification

Perfectionism is a transdiagnostic construct associated with a range of diagnoses, including depression, eating disorders and obsessive compulsive disorder. Treatments that directly target perfectionist cognitions have been shown to successfully reduce associated pathologies. However, the way in which they do this is not clear. We set out to assess the role of one candidate mechanism of action, namely the cognitive process of interpretation of ambiguity. In one experiment we looked for associations between biased interpretation and perfectionism. In a second, we manipulated interpretations, thereby providing a strong test of their aetiological significance. Results from the first experiment confirmed the presence of biased interpretation in perfectionism and demonstrated that these are highly specific to perfection relevant information, rather than reflecting general negativity. The second experiment succeeded in manipulating these perfection relevant interpretations and demonstrated that one consequence of doing so is a change in perfectionist behaviour. Together, these data experimentally demonstrate that biased interpretation of perfection relevant ambiguity contributes to the maintenance of perfectionism, but that it is also possible to reverse this. Clinical implications include the identification of one likely mechanism of therapeutic change within existing treatments, as well as identification of an appropriate evidence based focus for future treatment development. Targeting underlying functional mechanisms, such as biased interpretation, has the potential to offer transdiagnostic benefits.

Purpose in life predicts better emotional recovery from negative stimuli

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation.

Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo

The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.

Morgawr: an experimental Bronze Age-type sewn-plank craft based on the Ferriby boats

This paper reports on the construction of a full-scale Bronze Age-type sewn-plank boat based on the Ferriby boats. The boat, which was named Morgawr, was constructed in the National Maritime Museum Cornwall in Falmouth, England, during 2012 and the first months of 2013, as part of a larger exhibition in the museum. This paper provides the background and context of the project, describes the process of building the craft, and reflects in particular on differences between Morgawr and the ‘hypothetical reconstruction of a complete sewn-plank boat’ published in 1990 by Ted Wright and John Coates which formed the basis for this project.