The Underestimation Of Egocentric Distance: Evidence From Frontal Matching Tasks

There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Does shear wave ultrasound independently predict axillary lymph node metastasis in women with invasive breast cancer?

Shear wave elastography (SWE) shows promise as an adjunct to greyscale ultrasound examination in assessing breast masses. In breast cancer, higher lesion stiffness on SWE has been shown to be associated with features of poor prognosis. The purpose of this study was to assess whether lesion stiffness at SWE is an independent predictor of lymph node involvement. Patients with invasive breast cancer treated by primary surgery, who had undergone SWE examination were eligible. Data were retrospectively analysed from 396 consecutive patients. The mean stiffness values were obtained using the Aixplorer(®) ultrasound machine from SuperSonic Imagine Ltd. Measurements were taken from a region of interest positioned over the stiffest part of the abnormality. The average of the mean stiffness value obtained from each of two orthogonal image planes was used for analysis. Associations between lymph node involvement and mean lesion stiffness, invasive cancer size, histologic grade, tumour type, ER expression, HER-2 status and vascular invasion were assessed using univariate and multivariate logistic regression. At univariate analysis, invasive size, histologic grade, HER-2 status, vascular invasion, tumour type and mean stiffness were significantly associated with nodal involvement. Nodal involvement rates ranged from 7 % for tumours with mean stiffness <50 kPa to 41 % for tumours with a mean stiffness of >150 kPa. At multivariate analysis, invasive size, tumour type, vascular invasion, and mean stiffness maintained independent significance. Mean stiffness at SWE is an independent predictor of lymph node metastasis and thus can confer prognostic information additional to that provided by conventional preoperative tumour assessment and staging

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Irish general practitioner attitudes toward decriminalisation and medical use of cannabis: results from a national survey.

BACKGROUND: Governmental debate in Ireland on the de facto decriminalisation of cannabis and legalisation for medical use is ongoing. A cannabis-based medicinal product (Sativex®) has recently been granted market authorisation in Ireland. This unique study aimed to investigate Irish general practitioner (GP) attitudes toward decriminalisation of cannabis and assess levels of support for use of cannabis for therapeutic purposes (CTP). METHODS: General practitioners in the Irish College of General Practitioner (ICGP) database were invited to complete an online survey. Anonymous data yielded descriptive statistics (frequencies, percentages) to summarise participant demographic information and agreement with attitudinal statements. Chi-square tests and multi-nominal logistic regression were included. RESULTS: The response rate was 15% (n = 565) which is similar to other Irish national GP attitudinal surveys. Over half of Irish GPs did not support the decriminalisation of cannabis (56.8%). In terms of gender, a significantly higher proportion of males compared with females (40.6 vs. 15%; p < 0.0001) agreed or strongly agreed with this drug policy approach. A higher percentage of GPs with advanced addiction specialist training (level 2) agreed/strongly agreed that cannabis should be decriminalised (54.1 vs. 31.5%; p = 0.021). Over 80% of both genders supported the view that cannabis use has a significant effect on patients' mental health and increases the risk of schizophrenia (77.3%). Over half of Irish GPs supported the legalisation of cannabis for medical use (58.6%). A higher percentage of those who were level 1-trained (trained in addiction treatment but not to an advanced level) agreed/strongly agreed cannabis should be legalised for medical use (p = 0.003). Over 60% agreed that cannabis can have a role in palliative care, pain management and treatment of multiple sclerosis (MS). In the regression response predicator analysis, females were 66.2% less likely to agree that cannabis should be decriminalised, 42.5% less likely to agree that cannabis should be legalised for medical use and 59.8 and 37.6% less likely to agree that cannabis has a role in palliative care and in the treatment of multiple sclerosis (respectively) than males. CONCLUSIONS: The majority of Irish GPs do not support the present Irish governmental drug policy of decriminalisation of cannabis but do support the legalisation of cannabis for therapeutic purposes. Male GPs and those with higher levels of addiction training are more likely to support a more liberal drug policy approach to cannabis for personal use. A clear majority of GPs expressed significant concerns regarding both the mental and physical health risks of cannabis use. Ongoing research into the health and other effects of drug policy changes on cannabis use is required

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?

[EN] Academic spin-offs (ASOs) help universities transfer knowledge or technology through business projects developed by academic staff. This investigation aims at analyzing the critical factors for spin-off creation at universities operating in crisis-raven, entrepreneurship-unfriendly environments. Such factors revolve around four types of resources: environmental, institutional, organizational, and personal. Focusing on a Southern European context, as an example of an unfriendly environment affected by economic crisis, an entrepreneurial university (the Technical University of Valencia in Spain, UPV) is our research setting. Through a case study approach, we examine the potential of UPV as a springboard for ASOs. Our results show an adverse local environment, a rather favorable influence of institutional and organizational drivers, and a mixed role of personal factors. Our findings illustrate that UPV consistently supports spin-off creation due to a greater (rather positive) reflexivity from its institutional, organizational and personal resources than the (negative) imprinting of the unfriendly environment. This helps counter-balance the structural unfriendliness for academic entrepreneurship, and trigger a crisis-led risk-taking attitude by academic staff. Hence, UPV should continue with its current strategy of supporting academic entrepreneurship, and might transfer best practices to other universities also affected by unfavorable environmental conditions. Generally speaking, we would advise universities facing adverse circumstances to develop rules and mechanisms for academic entrepreneurship, carefully revise and improve malfunctions, and become involved throughout the whole process of spin-off development. All in all, our study advances understanding of how the different drivers for ASO creation can be revamped by universities located in unfriendly environments, having in mind the key role that universities play in fostering social and economic development through academic entrepreneurship in such environments.The authors would like to thank the Universitat Politecnica de Valencia (grant PAID-06-12-0916), and the Spanish Ministry of Economy and Competitiveness (grant ECO2011-29863), for their financial support for this research.Seguí-Mas, E.; Oltra, V.; Tormo-Carbó, G.; Sarrión Viñes, F. (2017). Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?. International Entrepreneurship and Management Journal. 1-42. doi:10.1007/s11365-017-0478-zS142Acs, Z. J., Audretsch, D. B., & Lehmann, E. E. (2013). The knowledge spillover theory of entrepreneurship. Small Business Economics, 41, 757–774.Alemany, L. (2011). 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Contribution of DEAF1 Structural Domains to the Interaction with the Breast Cancer Oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1